AiPD: Autoinhibited Protein Database

P31749

Gene name	AKT1 (PKB, RAC)
Protein name	RAC-alpha serine/threonine-protein kinase
Names	Protein kinase B, PKB, Protein kinase B alpha, PKB alpha, Proto-oncogene c-Akt, RAC-PK-alpha
Species	Homo sapiens (Human)
KEGG Pathway	hsa:207
EC number	2.7.11.1: Protein-serine/threonine kinases
Protein Class	RIBOSOMAL PROTEIN S6 KINASE (PTHR24351)

Descriptions

The protein kinase Akt is one of the primary effectors of growth factor signaling in the cell. Akt responds specifically to the lipid second messengers phosphatidylinositol-3,4,5-trisphosphate [PI(3,4,5)P3] and phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2] via its autoinhibitory domain (PH domain). Recruitment of Akt to PI(3,4,5)P3 in the plasma membrane promotes its phosphorylation by phosphoinositide-dependent kinase 1 (PDK1) in its activation loop (T308). Phosphorylation of S473 within AGC kinase C-terminal domain activates Akt through the formation of an electrostatic interaction with a conserved basic residue (R144) in the PH-kinase domain linker, thereby relieving PH domain- mediated autoinhibition.

Autoinhibitory domains (AIDs)

Target domain	150-408 (Protein kinase domain)
Relief mechanism	Ligand binding, PTM
Assay	Structural analysis, Mutagenesis experiment, Deletion assay

AID

7-106 (PH domain)

Target domain

150-408 (Protein kinase domain)

Relief mechanism

Ligand binding (Binding of phosphatidylinositol-3, 4, 5-trisphosphate and phosphatidylinositol-3, 4-bisphosphate to PH domain), PTM (Phosphorylation of S473 within AGC kinase C-terminal domain)

Assay

Structural analysis, Mutagenesis experiment, Deletion assay

Accessory elements

291-314 (Activation loop from InterPro)

Target domain	124-479 (Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha, also called Akt1)
Relief mechanism
Assay

References

Huang X et al. (2003) "Crystal structure of an inactive Akt2 kinase domain", Structure (London, England : 1993), 11, 21-30

Truebestein L et al. (2021) "Structure of autoinhibited Akt1 reveals mechanism of PIP(3)-mediated activation", Proceedings of the National Academy of Sciences of the United States of America, 118,

Lučić I et al. (2018) "Conformational sampling of membranes by Akt controls its activation and inactivation", Proceedings of the National Academy of Sciences of the United States of America, 115, E3940-E3949

Ashwell MA et al. (2012) "Discovery and optimization of a series of 3-(3-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amines: orally bioavailable, selective, and potent ATP-independent Akt inhibitors", Journal of medicinal chemistry, 55, 5291-310

Autoinhibited structure

Activated structure

37 structures for P31749

Entry ID	Method	Resolution	Chain	Position	Source
1H10	X-ray	140 A	A	1-123	PDB
1UNP	X-ray	165 A	A	1-121	PDB
1UNQ	X-ray	098 A	A	1-123	PDB
1UNR	X-ray	125 A	A	1-123	PDB
2UVM	X-ray	194 A	A	1-123	PDB
2UZR	X-ray	194 A	A	1-123	PDB
2UZS	X-ray	246 A	A	1-123	PDB
3CQU	X-ray	220 A	A	144-480	PDB
3CQW	X-ray	200 A	A	144-480	PDB
3MV5	X-ray	247 A	A	144-480	PDB
3MVH	X-ray	201 A	A	144-480	PDB
3O96	X-ray	270 A	A	2-443	PDB
3OCB	X-ray	270 A	A/B	144-480	PDB
3OW4	X-ray	260 A	A/B	144-480	PDB
3QKK	X-ray	230 A	A	144-480	PDB
3QKL	X-ray	190 A	A	144-480	PDB
3QKM	X-ray	220 A	A	144-480	PDB
4EJN	X-ray	219 A	A	2-446	PDB
4EKK	X-ray	280 A	A/B	144-480	PDB
4EKL	X-ray	200 A	A	144-480	PDB
4GV1	X-ray	149 A	A	144-480	PDB
5KCV	X-ray	270 A	A	2-446	PDB
6BUU	X-ray	240 A	A/B	144-480	PDB
6CCY	X-ray	218 A	A	144-466	PDB
6HHF	X-ray	290 A	A	2-446	PDB
6HHG	X-ray	230 A	A	2-446	PDB
6HHH	X-ray	270 A	A	2-446	PDB
6HHI	X-ray	270 A	A	2-446	PDB
6HHJ	X-ray	230 A	A	2-446	PDB
6NPZ	X-ray	212 A			PDB
6S9W	X-ray	230 A	A	2-446	PDB
6S9X	X-ray	260 A	A	2-446	PDB
7APJ	X-ray	205 A			PDB
7MYX	X-ray	139 A	A	1-121	PDB
7NH4	X-ray	230 A	A	2-446	PDB
7NH5	X-ray	190 A	A	2-446	PDB
AF-P31749-F1	Predicted				AlphaFoldDB

261 variants for P31749

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA391223990 RCV000688933 rs1566826869	2	S>G	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs140532443 CA7374951 RCV000461062	3	D>N	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV000472618 rs754031503 CA7374949	4	V>M	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000421850 RCV000436698 rs121434592 RCV000431237 RCV000434120 RCV000421696 RCV000439982 RCV000444311 VAR_055422 RCV000445271 CA123660 RCV000440828 RCV000426386 RCV000419412 RCV000421009 RCV000438154 COSM33765 RCV000015017 RCV000031926 RCV000443761 RCV000430173 RCV000015018 RCV000431723 RCV000427484 RCV000015019 RCV000429060	17	E>K	thymus upper_aerodigestive_tract PROTEUSS and breast cancer; also detected in colorectal and ovarian cancer; somatic mutation; results in increased phosphorylation at T-308 and higher basal ubiquitination; the mutant protein is more efficiently recruited to the plasma membrane; alters phosphatidylinositiol phosphates lipid specificity of the AKT1 PH domain NS Neoplasm of uterine cervix central_nervous_system skin Hepatocellular carcinoma Lung adenocarcinoma Proteus syndrome soft_tissue Neoplasm of the large intestine haematopoietic_and_lymphoid_tissue meninges Prostate neoplasm Carcinoma of colon Bone osteosarcoma Endometrial Endometrioid Adenocarcinoma, Variant with Squamous Differentiation Small cell lung carcinoma Breast adenocarcinoma endometrium urinary_tract Non-small cell lung carcinoma bone Gastric adenocarcinoma Prostate adenocarcinoma Thyroid tumor lung Squamous cell carcinoma of the head and neck ovary thyroid Squamous cell lung carcinoma large_intestine Tumor of meninges prostate Neoplasm of ovary breast Malignant melanoma of skin Breast neoplasm [Cosmic, UniProt, ClinVar]	Yes	ClinGen cosmic curated ClinVar UniProt ExAC dbSNP gnomAD
RCV000984546 CA915946437 rs1595251483	17	E>R	Proteus syndrome [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA130749 rs397514644 RCV000033177 VAR_069791	25	R>C	Cowden syndrome 6 CWS6 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt TOPMed dbSNP
RCV000686512 rs758157217 CA7374904	36	I>T	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs781339141 CA7374905 RCV000465998	36	I>V	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
CA156577 rs146875699 RCV000231031 RCV000119959	46	D>E	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs374093099 RCV000531301 CA7374896	48	R>C	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
CA7374895 COSM1368558 rs774836044 RCV000695576	48	R>H	Cowden syndrome 6 large_intestine [ClinVar, Cosmic]	Yes	ClinGen cosmic curated ClinVar ExAC TOPMed dbSNP gnomAD
CA7374855 RCV000543771 rs183989506	69	R>Q	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
rs587778019 RCV001854593 RCV000119960 CA156582	75	I>M	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
rs771065764 RCV000556163 CA7374853	76	R>H	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP
RCV000422108 COSM159008 CA16602625 rs1057519804	79	Q>K	Melanoma endometrium breast [ClinVar, Cosmic]	Yes	ClinGen cosmic curated ClinVar Ensembl dbSNP
CA16042842 RCV000413604 rs1057518602 RCV001851003	79	Q>R	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000709351 CA391220214 rs1566818099	119	D>G	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs778376616 RCV000231420 CA7374803	136	V>M	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA7374801 rs375990114 RCV000704448	144	R>C	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV000457583 rs1060503071 CA16614120	144	R>H	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
rs758456890 CA7374773 RCV000651047	147	M>T	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA267349921 RCV000532235 rs983007851	174	R>C	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
CA391219354 RCV000651044 rs1555383695	182	K>R	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000456495 CA7374656 rs768606668	241	R>W	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000691797 CA7374651 rs780571834	251	R>C	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000472766 rs375395037 CA7374648	255	A>T	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV000558043 CA391218330 rs1555383511	257	I>T	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000651043 rs1555383471 CA391217685	306	M>T	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs762705090 CA7374571 RCV000651045	367	R>S	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000706299 rs746272761 CA7374568	370	R>H	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs1566816289 RCV000699382 CA391216555	387	D>N	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs1334042967 RCV000525011 CA391216366	397	E>D	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
RCV000232840 CA7374522 rs146483593	410	G>S	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV000525815 CA391216125 rs1555383354	414	Q>H	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000690076 rs1566815164 CA391214816	421	L>F	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
VAR_069792 RCV000033178 rs397514645 CA130755	435	T>P	Cowden syndrome 6 CWS6 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs1159942120 CA391214538 RCV000538250	440	E>D	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
rs1892340313 RCV001333360	451	P>S	Cowden syndrome 6 [ClinVar]	Yes	ClinVar dbSNP
rs759702315 CA7374469 RCV000651046	454	Q>R	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs587778018 CA156572 RCV000119958 RCV000464381	458	M>T	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000709350 CA7374441 rs745803788	464	E>K	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA349773 RCV000205643 rs113547523	465	R>H	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs1205616929 CA391214217 RCV000697095	478	G>S	Cowden syndrome 6 [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
rs754031503 CA391223958 COSM3814333	4	V>L	breast [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA391223941 rs1338237897	5	A>G		No	ClinGen gnomAD
CA7374948 rs766546254	5	A>T		No	ClinGen ExAC gnomAD
rs1404637346 CA391223931	6	I>T		No	ClinGen gnomAD
CA391223907 rs1173631887	8	K>R		No	ClinGen gnomAD
CA7374947 rs760853972	11	W>*		No	ClinGen ExAC gnomAD
rs1235749501 CA391223843	13	H>Y		No	ClinGen TOPMed
rs368797346 CA7374946	15	R>Q		No	ClinGen ESP ExAC gnomAD
rs1380514442 CA391221825	20	K>E		No	ClinGen gnomAD
CA391221755 rs1184173073	25	R>H		No	ClinGen TOPMed
CA267352474 rs990046031	28	L>F		No	ClinGen TOPMed
CA7374908 rs780173607	31	N>S		No	ClinGen ExAC gnomAD
rs201636005 CA267352457	32	D>E		No	ClinGen 1000Genomes ExAC gnomAD
rs750653493 CA7374906	34	T>N		No	ClinGen ExAC TOPMed gnomAD
rs1223729648 CA391221585	38	Y>H		No	ClinGen gnomAD
CA7374902 rs764931115	39	K>E		No	ClinGen ExAC gnomAD
CA7374899 rs766000895	41	R>Q		No	ClinGen ExAC gnomAD
CA7374900 rs753765116	41	R>W		No	ClinGen ExAC gnomAD
CA267352414 rs11555436	43	Q>*		No	ClinGen Ensembl
rs1301434623 CA391221539	44	D>A		No	ClinGen TOPMed
CA391221517 rs532268608	47	Q>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs532268608 CA391221516	47	Q>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1358103245 CA391221499	49	E>G		No	ClinGen TOPMed
rs768898540 CA7374894	50	A>V		No	ClinGen ExAC gnomAD
rs1476861882 CA391221464	52	L>F		No	ClinGen gnomAD
CA267350804 rs923841704	60	C>Y		No	ClinGen Ensembl
rs1566818959 CA391220816	63	M>I		No	ClinGen Ensembl
CA7374859 COSM1368556 rs751243134	65	T>M	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1396308032 CA391220792	67	R>Q		No	ClinGen TOPMed
rs762559261 CA7374857	67	R>W		No	ClinGen ExAC TOPMed gnomAD
rs775892860 CA7374856	69	R>W		No	ClinGen ExAC gnomAD
CA391220779 rs1316268769	70	P>A		No	ClinGen gnomAD
CA7374854 rs760044481	72	T>A		No	ClinGen ExAC gnomAD
CA391220765 rs760044481	72	T>P		No	ClinGen ExAC gnomAD
rs1012676649 CA267350765	76	R>C		No	ClinGen Ensembl
CA391220683 rs1566818890	85	E>K		No	ClinGen Ensembl
rs772473246 CA7374850	86	R>C		No	ClinGen ExAC gnomAD
rs773971502 CA267350748	86	R>H		No	ClinGen TOPMed
rs1296782302 CA391220625	93	P>H		No	ClinGen TOPMed gnomAD
rs1296782302 CA391220624	93	P>R		No	ClinGen TOPMed gnomAD
CA267350738 rs897360247	96	R>Q		No	ClinGen Ensembl
rs760536822 COSM1133358 CA267350741	96	R>W	large_intestine [Cosmic]	No	ClinGen cosmic curated Ensembl
CA7374817 rs761151169	101	T>A		No	ClinGen ExAC gnomAD
rs1298334491 CA391220462	101	T>I		No	ClinGen gnomAD
rs1281415838 CA391220450	103	I>V		No	ClinGen gnomAD
CA267350233 rs1038322721	105	T>A		No	ClinGen gnomAD
CA7374813 rs774745066	108	D>A		No	ClinGen ExAC gnomAD
CA391220383 rs774745066	108	D>G		No	ClinGen ExAC gnomAD
rs768800433 CA391220374	109	G>C		No	ClinGen ExAC gnomAD
rs768800433 CA391220375	109	G>R		No	ClinGen ExAC gnomAD
rs768800433 CA7374812	109	G>S		No	ClinGen ExAC gnomAD
rs908575682 CA267350218	113	Q>E		No	ClinGen TOPMed
rs1338783398 CA391220287	115	E>K		No	ClinGen TOPMed gnomAD
rs1595245738 CA391220269	116	E>K		No	ClinGen Ensembl
rs1268659696 CA391220244	117	E>D		No	ClinGen TOPMed gnomAD
rs776345122 CA7374810	117	E>K		No	ClinGen ExAC gnomAD
CA391220195 rs1457484217	121	R>Q		No	ClinGen gnomAD
COSM252336 rs369198922 CA7374808	121	R>W	ovary large_intestine [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs746934495 CA7374807	122	S>L		No	ClinGen ExAC TOPMed gnomAD
CA7374805 rs759031755	125	P>L		No	ClinGen ExAC TOPMed gnomAD
CA391220078 rs1319030326	132	E>K		No	ClinGen TOPMed gnomAD
rs1230091567 CA391220031	134	M>I		No	ClinGen TOPMed
CA391220002 rs1324208253	137	S>A		No	ClinGen Ensembl
rs1566818045 CA391219986	139	A>P		No	ClinGen Ensembl
CA391219980 rs1445658903	139	A>V		No	ClinGen gnomAD
rs142843688 CA7374802	143	H>Y		No	ClinGen ESP ExAC gnomAD
CA391219919 rs375990114	144	R>G		No	ClinGen ESP ExAC TOPMed gnomAD
CA391219908 rs1166659979	145	V>M		No	ClinGen gnomAD
CA391219828 rs1371607114	146	T>I		No	ClinGen TOPMed
CA391219821 rs1277434432	147	M>I		No	ClinGen gnomAD
CA7374770 rs568870136	157	G>R		No	ClinGen 1000Genomes ExAC gnomAD
rs866169013 CA267349941	159	G>V		No	ClinGen Ensembl
CA267349938 rs980441042	160	T>A		No	ClinGen Ensembl
CA391219564 rs1352687393	163	K>M		No	ClinGen gnomAD
CA391219543 rs1244026143	164	V>G		No	ClinGen TOPMed
CA267349931 VAR_051617 rs11555433	167	V>A		No	ClinGen UniProt Ensembl dbSNP
rs1183083759 CA391219506	168	K>E		No	ClinGen Ensembl
CA7374766 rs774284624	170	K>N		No	ClinGen ExAC gnomAD
CA391219458 rs1016707349	171	A>S		No	ClinGen TOPMed gnomAD
CA267349927 rs1016707349	171	A>T		No	ClinGen TOPMed gnomAD
CA7374765 rs768070795	171	A>V		No	ClinGen ExAC gnomAD
rs748789094 CA7374764	172	T>I		No	ClinGen ExAC gnomAD
rs1200003171 CA391219421	174	R>H		No	ClinGen TOPMed gnomAD
rs1200003171 CA391219417	174	R>L		No	ClinGen TOPMed gnomAD
rs769619023 CA7374762	178	M>T		No	ClinGen ExAC gnomAD
rs745500951 CA7374761	185	V>G		No	ClinGen ExAC gnomAD
rs1216778719 CA391219322	187	V>M		No	ClinGen gnomAD
CA7374758 rs144128670	188	A>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs780207480 CA391219284	190	D>E		No	ClinGen ExAC TOPMed gnomAD
CA7374732 rs756293014	193	A>V		No	ClinGen ExAC
CA7374731 rs751416672	196	L>H		No	ClinGen ExAC gnomAD
rs1595244672 CA391219244	197	T>P		No	ClinGen Ensembl
CA391219221 rs1176264024	200	R>C		No	ClinGen gnomAD
rs1462219795 CA391219220	200	R>H		No	ClinGen gnomAD
rs774360915 CA7374728	201	V>I		No	ClinGen ExAC TOPMed gnomAD
rs1240566715 CA391219186	205	S>C		No	ClinGen TOPMed gnomAD
CA391219188 rs1240566715	205	S>F		No	ClinGen TOPMed gnomAD
CA267349818 rs941063820	206	R>G		No	ClinGen Ensembl
CA391218974 rs1163499100	212	A>G		No	ClinGen gnomAD
CA391218973 rs1163499100	212	A>V		No	ClinGen gnomAD
rs760384228 CA7374705	215	Y>C		No	ClinGen ExAC gnomAD
rs971568277 CA391218920	217	F>L		No	ClinGen TOPMed gnomAD
rs971568277 CA267349483	217	F>L		No	ClinGen TOPMed gnomAD
rs1489605167 CA391218919	218	Q>*		No	ClinGen gnomAD
CA7374701 rs762040581	221	D>H		No	ClinGen ExAC TOPMed gnomAD
COSM301664 rs762040581 CA267349477	221	D>N	central_nervous_system [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs551254461 CA7374700	222	R>C		No	ClinGen 1000Genomes ExAC gnomAD
CA7374699 rs369698909	222	R>H		No	ClinGen ESP ExAC gnomAD
rs775612804 CA7374697	227	M>T		No	ClinGen ExAC gnomAD
rs1276744835 CA391218774	228	E>D		No	ClinGen gnomAD
rs1367895795 CA391218754	230	A>T		No	ClinGen gnomAD
rs1595243377 CA391218733	231	N>S		No	ClinGen Ensembl
rs781232725 CA7374694	232	G>R		No	ClinGen ExAC TOPMed gnomAD
CA7374691 rs778838358	234	E>K		No	ClinGen ExAC gnomAD
rs770980034 CA7374659	235	L>V		No	ClinGen ExAC TOPMed gnomAD
rs773520823 CA7374657	240	S>C		No	ClinGen ExAC gnomAD
rs1244832277 CA391218526	241	R>Q		No	ClinGen gnomAD
rs1310418829 CA391218516	242	E>G		No	ClinGen gnomAD
rs1339827175 CA391218522	242	E>K		No	ClinGen gnomAD
CA391218506 rs1340970650	243	R>C		No	ClinGen gnomAD
rs1297345295 CA391218497	244	V>M		No	ClinGen gnomAD
rs779874420 CA7374654	246	S>A		No	ClinGen ExAC gnomAD
CA391218463 rs1165092690	247	E>K		No	ClinGen gnomAD
CA7374652 rs745809388	249	R>Q		No	ClinGen ExAC gnomAD
rs1458420660 CA391218431 COSM3983126	249	R>W	ovary [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA7374650 rs756697784	251	R>H		No	ClinGen ExAC gnomAD
rs751232562 CA7374649	253	Y>C		No	ClinGen ExAC gnomAD
CA391218308 rs1209929395	260	A>T		No	ClinGen gnomAD
CA7374647 rs758025607	261	L>V		No	ClinGen ExAC gnomAD
rs371467719 CA7374645	262	D>E		No	ClinGen ESP ExAC gnomAD
CA391218277 rs1397852501	265	H>Y		No	ClinGen gnomAD
CA7374642 rs549083521	266	S>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA391218251 rs1566816661	268	K>N		No	ClinGen Ensembl
CA391218248 rs1167819752	269	N>D		No	ClinGen TOPMed
rs1390179436 CA391218234	270	V>M		No	ClinGen gnomAD
CA391218194 rs1424916218	273	R>Q		No	ClinGen TOPMed gnomAD
rs955764429 CA267349217	288	I>T		No	ClinGen Ensembl
CA7374618 rs767699129	288	I>V		No	ClinGen ExAC gnomAD
rs1360111387 CA391217718	303	G>S		No	ClinGen TOPMed
CA391217704 rs1377831067	304	A>V		No	ClinGen gnomAD
rs12881616 CA267349193	319	E>G		No	ClinGen Ensembl
CA391217444 rs1454909926	321	L>P		No	ClinGen TOPMed
rs746397537 CA7374585	324	N>S		No	ClinGen ExAC TOPMed gnomAD
rs781749630 CA7374584	325	D>N		No	ClinGen ExAC gnomAD
CA391217360 rs1171160211	327	G>S		No	ClinGen TOPMed gnomAD
CA391217351 rs1274533572	327	G>V		No	ClinGen TOPMed
rs1197941200 CA391217239	336	G>D		No	ClinGen TOPMed
rs1595242014 CA391217231	337	V>G		No	ClinGen Ensembl
CA391217235 rs1247419183	337	V>M		No	ClinGen gnomAD
CA391217186 rs1340200537	341	E>K		No	ClinGen TOPMed gnomAD
CA391217111 rs1168658858	346	R>C		No	ClinGen TOPMed
CA391217109 rs1219649544	346	R>H		No	ClinGen gnomAD
CA267349088 rs976500042	351	N>D		No	ClinGen TOPMed
CA391217044 rs1170677405	351	N>S		No	ClinGen TOPMed
rs1438024792 CA391216981	355	E>G		No	ClinGen gnomAD
CA391216973 rs1335182846	356	K>Q		No	ClinGen TOPMed
CA267349080 rs11555432	357	L>P		No	ClinGen Ensembl
CA267349077 rs372502847	363	M>V		No	ClinGen ESP
CA391216843 rs1359340183	365	E>K		No	ClinGen TOPMed
rs762705090 COSM1235769 CA7374572	367	R>C	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA267349072 rs369520527	367	R>H		No	ClinGen ESP TOPMed gnomAD
COSM268636 CA7374569 rs549370342	370	R>C	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs746272761 CA391216771	370	R>P		No	ClinGen ExAC TOPMed gnomAD
rs549370342 CA391216776	370	R>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA267349064 rs781388586	371	T>K		No	ClinGen ExAC TOPMed gnomAD
CA7374567 COSM3983124 rs781388586	371	T>M	ovary [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs889182971 CA267349057	373	G>D		No	ClinGen Ensembl
CA7374563 rs373253729	375	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA267349053 rs1050565251	376	A>S		No	ClinGen Ensembl
CA391216684 rs1480573852	377	K>R		No	ClinGen gnomAD
CA391216601 rs1302148730	384	L>F		No	ClinGen gnomAD
rs11555431 CA267349033	388	P>T		No	ClinGen Ensembl
CA391216526 rs1390801321	389	K>R		No	ClinGen gnomAD
CA391216508 rs1394191738	391	R>G		No	ClinGen gnomAD
CA7374531 rs766798551	397	E>A		No	ClinGen ExAC gnomAD
CA7374532 rs531850885	397	E>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA267348821 rs188580689	399	A>T		No	ClinGen 1000Genomes
rs773607483 CA7374529	400	K>E		No	ClinGen ExAC TOPMed gnomAD
rs1342613654 CA391216337	400	K>R		No	ClinGen gnomAD
rs774414969 CA7374526	403	M>I		No	ClinGen ExAC gnomAD
CA391216266 rs1295342651	404	Q>R		No	ClinGen gnomAD
rs768660759 CA7374525	405	H>P		No	ClinGen ExAC gnomAD
rs749544983 CA7374524	406	R>C		No	ClinGen ExAC TOPMed gnomAD
CA267348800 rs143266084	406	R>H		No	ClinGen ESP TOPMed gnomAD
CA391216184 rs1373983688	410	G>A		No	ClinGen gnomAD
rs937869519 CA267348790	412	V>G		No	ClinGen TOPMed
CA391216165 rs1444891733	412	V>M		No	ClinGen TOPMed gnomAD
rs1295857274 CA391216137	414	Q>K		No	ClinGen TOPMed
CA391216111 rs758476416	415	H>Q		No	ClinGen ExAC TOPMed gnomAD
CA7374520 rs777696700	415	H>Y		No	ClinGen ExAC TOPMed gnomAD
CA391216108 rs1308190883	416	V>M		No	ClinGen TOPMed
CA391216092 rs1468001776	417	Y>D		No	ClinGen gnomAD
rs764863282 RCV000585255 CA7374518	418	E>K		No	ClinGen ClinVar ExAC dbSNP gnomAD
rs754500025 CA7374517	419	K>R		No	ClinGen ExAC gnomAD
rs753360468 CA7374516	420	K>E		No	ClinGen ExAC gnomAD
rs913653954 CA267348195	421	L>P		No	ClinGen Ensembl
CA391214757 rs1369639631	425	F>L		No	ClinGen TOPMed
rs749186394 CA7374480	430	T>M		No	ClinGen ExAC TOPMed gnomAD
rs755597789 CA7374478	431	S>L		No	ClinGen ExAC gnomAD
CA391214608 rs1373202839	436	R>K		No	ClinGen gnomAD
CA7374474 rs751976958	446	M>I		No	ClinGen ExAC TOPMed gnomAD
CA7374473 rs764514218	447	I>V		No	ClinGen ExAC gnomAD
rs1595239049 CA391214440	448	T>P		No	ClinGen Ensembl
CA7374471 rs753190812	452	P>H		No	ClinGen ExAC gnomAD
CA7374470 rs765264778	453	D>E		No	ClinGen ExAC gnomAD
rs754040453 CA7374448	455	D>G		No	ClinGen ExAC
CA267348057 rs759902535	457	S>R		No	ClinGen Ensembl
CA7374447 rs587778018	458	M>K		No	ClinGen ExAC TOPMed gnomAD
CA391214353 rs1360782672	458	M>V		No	ClinGen gnomAD
rs1431676094 CA391214343	459	E>G		No	ClinGen gnomAD
rs11555435 CA267348052	461	V>L		No	ClinGen Ensembl
rs144112075 CA7374443	463	S>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs770370100 COSM324690 CA7374439	465	R>C	lung [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs770370100 CA7374440	465	R>G		No	ClinGen ExAC TOPMed gnomAD
rs1418994529 CA391214300	466	R>W		No	ClinGen gnomAD
rs757963528 CA7374437	474	Y>S		No	ClinGen ExAC gnomAD
CA391214226 rs1467510263	476	A>V		No	ClinGen gnomAD
rs201291259 CA7374434	479	T>M		No	ClinGen 1000Genomes ExAC gnomAD

5 associated diseases with P31749

[MIM: 114480]: Breast cancer (BC)

A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:17611497}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

[MIM: 114500]: Colorectal cancer (CRC)

A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note=The gene represented in this entry may be involved in disease pathogenesis.

[MIM: 176920]: Proteus syndrome (PROTEUSS)

A highly variable, severe disorder of asymmetric and disproportionate overgrowth of body parts, connective tissue nevi, epidermal nevi, dysregulated adipose tissue, and vascular malformations. Many features of Proteus syndrome overlap with other overgrowth syndromes. {ECO:0000269|PubMed:18954143, ECO:0000269|PubMed:21793738}. Note=The disease is caused by variants affecting the gene represented in this entry.

[MIM: 615109]: Cowden syndrome 6 (CWS6)

A form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid. {ECO:0000269|PubMed:23246288}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:17611497}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note=The gene represented in this entry may be involved in disease pathogenesis.
A highly variable, severe disorder of asymmetric and disproportionate overgrowth of body parts, connective tissue nevi, epidermal nevi, dysregulated adipose tissue, and vascular malformations. Many features of Proteus syndrome overlap with other overgrowth syndromes. {ECO:0000269|PubMed:18954143, ECO:0000269|PubMed:21793738}. Note=The disease is caused by variants affecting the gene represented in this entry.
A form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid. {ECO:0000269|PubMed:23246288}. Note=The disease is caused by variants affecting the gene represented in this entry.

8 regional properties for P31749

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	150 - 408	IPR000719
domain	AGC-kinase, C-terminal	409 - 480	IPR000961
domain	Pleckstrin homology domain	5 - 110	IPR001849
active_site	Serine/threonine-protein kinase, active site	270 - 282	IPR008271
binding_site	Protein kinase, ATP binding site	156 - 189	IPR017441
domain	Protein kinase, C-terminal	429 - 474	IPR017892
domain	Protein kinase B alpha, catalytic domain	124 - 479	IPR034676
domain	Protein Kinase B, pleckstrin homology domain	4 - 111	IPR039026

Functions

		Description
EC Number	2.7.11.1	Protein-serine/threonine kinases
Subcellular Localization	Cytoplasm Nucleus Cell membrane	Nucleus after activation by integrin-linked protein kinase 1 (ILK1) Nuclear translocation is enhanced by interaction with TCL1A Phosphorylation on Tyr-176 by TNK2 results in its localization to the cell membrane where it is targeted for further phosphorylations on Thr-308 and Ser-473 leading to its activation and the activated form translocates to the nucleus Colocalizes with WDFY2 in intracellular vesicles (PubMed:16792529)
PANTHER Family	PTHR24351	RIBOSOMAL PROTEIN S6 KINASE
PANTHER Subfamily	PTHR24351:SF200	NON-SPECIFIC SERINE_THREONINE PROTEIN KINASE
PANTHER Protein Class	protein modifying enzyme
PANTHER Pathway Category	Ras Pathway AKT Angiogenesis Akt Inflammation mediated by chemokine and cytokine signaling pathway AKT p53 pathway Akt Interleukin signaling pathway PKB Huntington disease Akt Apoptosis signaling pathway AKT p53 pathway by glucose deprivation Akt FGF signaling pathway Akt VEGF signaling pathway Akt/PKB p53 pathway feedback loops 2 AKT EGF receptor signaling pathway Akt Hypoxia response via HIF activation AKT T cell activation Akt PI3 kinase pathway PKB FAS signaling pathway ASK1 Endothelin signaling pathway Akt

15 GO annotations of cellular component

Name	Definition
cell-cell junction	A cell junction that forms a connection between two or more cells of an organism; excludes direct cytoplasmic intercellular bridges, such as ring canals in insects.
ciliary basal body	A membrane-tethered, short cylindrical array of microtubules and associated proteins found at the base of a eukaryotic cilium (also called flagellum) that is similar in structure to a centriole and derives from it. The cilium basal body is the site of assembly and remodelling of the cilium and serves as a nucleation site for axoneme growth. As well as anchoring the cilium, it is thought to provide a selective gateway regulating the entry of ciliary proteins and vesicles by intraflagellar transport.
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
extrinsic component of cytoplasmic side of plasma membrane	The component of a plasma membrane consisting of gene products and protein complexes that are loosely bound to its cytoplasmic surface, but not integrated into the hydrophobic region.
lamellipodium	A thin sheetlike process extended by the leading edge of a migrating cell or extending cell process; contains a dense meshwork of actin filaments.
microtubule cytoskeleton	The part of the cytoskeleton (the internal framework of a cell) composed of microtubules and associated proteins.
mitochondrion	A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
postsynapse	The part of a synapse that is part of the post-synaptic cell.
protein-containing complex	A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.
spindle	The array of microtubules and associated molecules that forms between opposite poles of a eukaryotic cell during mitosis or meiosis and serves to move the duplicated chromosomes apart.
vesicle	Any small, fluid-filled, spherical organelle enclosed by membrane.

16 GO annotations of molecular function

Name	Definition
14-3-3 protein binding	Binding to a 14-3-3 protein. A 14-3-3 protein is any of a large family of approximately 30kDa acidic proteins which exist primarily as homo- and heterodimers within all eukaryotic cells, and have been implicated in the modulation of distinct biological processes by binding to specific phosphorylated sites on diverse target proteins, thereby forcing conformational changes or influencing interactions between their targets and other molecules. Each 14-3-3 protein sequence can be roughly divided into three sections: a divergent amino terminus, the conserved core region and a divergent carboxy-terminus. The conserved middle core region of the 14-3-3s encodes an amphipathic groove that forms the main functional domain, a cradle for interacting with client proteins.
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
calmodulin binding	Binding to calmodulin, a calcium-binding protein with many roles, both in the calcium-bound and calcium-free states.
enzyme binding	Binding to an enzyme, a protein with catalytic activity.
identical protein binding	Binding to an identical protein or proteins.
kinase activity	Catalysis of the transfer of a phosphate group, usually from ATP, to a substrate molecule.
nitric-oxide synthase regulator activity	Binds to and modulates the activity of nitric oxide synthase.
phosphatidylinositol-3,4,5-trisphosphate binding	Binding to phosphatidylinositol-3,4,5-trisphosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 3', 4' and 5' positions.
phosphatidylinositol-3,4-bisphosphate binding	Binding to phosphatidylinositol-3,4-bisphosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 3' and 4' positions.
potassium channel activator activity	Binds to and increases the activity of a potassium channel, resulting in its opening.
protein homodimerization activity	Binding to an identical protein to form a homodimer.
protein kinase activity	Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP.
protein kinase binding	Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
protein serine kinase activity	Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine kinase activity	Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.
protein serine/threonine/tyrosine kinase activity	Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.

131 GO annotations of biological process

Name	Definition
activation-induced cell death of T cells	A T cell apoptotic process that occurs towards the end of the expansion phase following the initial activation of mature T cells by antigen and is triggered by T cell receptor stimulation and signals transmitted via various surface-expressed members of the TNF receptor family such as Fas ligand, Fas, and TNF and the p55 and p75 TNF receptors.
anoikis	Apoptosis triggered by inadequate or inappropriate adherence to substrate e.g. after disruption of the interactions between normal epithelial cells and the extracellular matrix.
apoptotic mitochondrial changes	The morphological and physiological alterations undergone by mitochondria during apoptosis.
behavioral response to pain	Any process that results in a change in the behavior of an organism as a result of a pain stimulus. Pain stimuli cause activation of nociceptors, peripheral receptors for pain, include receptors which are sensitive to painful mechanical stimuli, extreme heat or cold, and chemical stimuli.
carbohydrate transport	The directed movement of carbohydrate into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Carbohydrates are a group of organic compounds based of the general formula Cx(H2O)y.
cell differentiation	The process in which relatively unspecialized cells, e.g. embryonic or regenerative cells, acquire specialized structural and/or functional features that characterize the cells, tissues, or organs of the mature organism or some other relatively stable phase of the organism's life history. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state.
cell migration involved in sprouting angiogenesis	The orderly movement of endothelial cells into the extracellular matrix in order to form new blood vessels involved in sprouting angiogenesis.
cell population proliferation	The multiplication or reproduction of cells, resulting in the expansion of a cell population.
cellular response to cadmium ion	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cadmium (Cd) ion stimulus.
cellular response to decreased oxygen levels	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus reflecting a decline in the level of oxygen.
cellular response to epidermal growth factor stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an epidermal growth factor stimulus.
cellular response to granulocyte macrophage colony-stimulating factor stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a granulocyte macrophage colony-stimulating factor stimulus.
cellular response to insulin stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an insulin stimulus. Insulin is a polypeptide hormone produced by the islets of Langerhans of the pancreas in mammals, and by the homologous organs of other organisms.
cellular response to nerve growth factor stimulus	A process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a nerve growth factor stimulus.
cellular response to oxidised low-density lipoprotein particle stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an oxidized lipoprotein particle stimulus.
cellular response to prostaglandin E stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a prostagladin E stimulus.
cellular response to reactive oxygen species	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a reactive oxygen species stimulus. Reactive oxygen species include singlet oxygen, superoxide, and oxygen free radicals.
cellular response to tumor necrosis factor	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a tumor necrosis factor stimulus.
cellular response to vascular endothelial growth factor stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a vascular endothelial growth factor stimulus.
cytokine-mediated signaling pathway	The series of molecular signals initiated by the binding of a cytokine to a receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
epidermal growth factor receptor signaling pathway	The series of molecular signals initiated by binding of a ligand to the tyrosine kinase receptor EGFR (ERBB1) on the surface of a cell. The pathway ends with regulation of a downstream cellular process, e.g. transcription.
establishment of protein localization to mitochondrion	The directed movement of a protein to the mitochondrion or a part of the mitochondrion.
excitatory postsynaptic potential	A process that leads to a temporary increase in postsynaptic potential due to the flow of positively charged ions into the postsynaptic cell. The flow of ions that causes an EPSP is an excitatory postsynaptic current (EPSC) and makes it easier for the neuron to fire an action potential.
execution phase of apoptosis	A stage of the apoptotic process that starts with the controlled breakdown of the cell through the action of effector caspases or other effector molecules (e.g. cathepsins, calpains etc.). Key steps of the execution phase are rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
fibroblast migration	Cell migration that is accomplished by extension and retraction of a fibroblast pseudopodium. A fibroblast is a connective tissue cell which secretes an extracellular matrix rich in collagen and other macromolecules.
G protein-coupled receptor signaling pathway	The series of molecular signals initiated by a ligand binding to its receptor, in which the activated receptor promotes the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The GTP-bound activated alpha-G-protein then dissociates from the beta- and gamma-subunits to further transmit the signal within the cell. The pathway begins with receptor-ligand interaction, and ends with regulation of a downstream cellular process. The pathway can start from the plasma membrane, Golgi or nuclear membrane.
gene expression	The process in which a gene's sequence is converted into a mature gene product (protein or RNA). This includes the production of an RNA transcript and its processing, translation and maturation for protein-coding genes.
germ cell development	The process whose specific outcome is the progression of an immature germ cell over time, from its formation to the mature structure (gamete). A germ cell is any reproductive cell in a multicellular organism.
glucose homeostasis	Any process involved in the maintenance of an internal steady state of glucose within an organism or cell.
glucose metabolic process	The chemical reactions and pathways involving glucose, the aldohexose gluco-hexose. D-glucose is dextrorotatory and is sometimes known as dextrose; it is an important source of energy for living organisms and is found free as well as combined in homo- and hetero-oligosaccharides and polysaccharides.
glycogen biosynthetic process	The chemical reactions and pathways resulting in the formation of glycogen, a polydisperse, highly branched glucan composed of chains of D-glucose residues.
glycogen cell differentiation involved in embryonic placenta development	The process in which a relatively unspecialized cell acquires specialized features of a glycogen cell of the placenta. A glycogen cell is a vacuolated glycogen-rich cell that appears in compact cell islets of the spongiotrophoblast layer.
I-kappaB kinase/NF-kappaB signaling	The process in which a signal is passed on to downstream components within the cell through the I-kappaB-kinase (IKK)-dependent activation of NF-kappaB. The cascade begins with activation of a trimeric IKK complex (consisting of catalytic kinase subunits IKKalpha and/or IKKbeta, and the regulatory scaffold protein NEMO) and ends with the regulation of transcription of target genes by NF-kappaB. In a resting state, NF-kappaB dimers are bound to I-kappaB proteins, sequestering NF-kappaB in the cytoplasm. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing the NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription.
inflammatory response	The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages.
insulin receptor signaling pathway	The series of molecular signals generated as a consequence of the insulin receptor binding to insulin.
insulin-like growth factor receptor signaling pathway	The series of molecular signals initiated by a ligand binding to an insulin-like growth factor receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
interleukin-18-mediated signaling pathway	The series of molecular signals initiated by interleukin-18 binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
intracellular signal transduction	The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
labyrinthine layer blood vessel development	The process whose specific outcome is the progression of a blood vessel of the labyrinthine layer of the placenta over time, from its formation to the mature structure. The embryonic vessels grow through the layer to come in close contact with the maternal blood supply.
lipopolysaccharide-mediated signaling pathway	The series of molecular signals initiated by the binding of a lipopolysaccharide (LPS) to a receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. Lipopolysaccharides are major components of the outer membrane of Gram-negative bacteria, making them prime targets for recognition by the immune system.
maintenance of protein location in mitochondrion	Any process in which a protein is maintained in a specific location in a mitochondrion, and is prevented from moving elsewhere.
mammary gland epithelial cell differentiation	The process in which a relatively unspecialized epithelial cell becomes a more specialized epithelial cell of the mammary gland.
maternal placenta development	Maternally driven process whose specific outcome is the progression of the placenta over time, from its formation to the mature structure. The placenta is an organ of metabolic interchange between fetus and mother, partly of embryonic origin and partly of maternal origin.
negative regulation of apoptotic process	Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.
negative regulation of autophagy	Any process that stops, prevents, or reduces the frequency, rate or extent of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm.
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	Any process that stops, prevents, or reduces the frequency, rate or extent of a cysteine-type endopeptidase activity involved in the apoptotic process.
negative regulation of endopeptidase activity	Any process that decreases the frequency, rate or extent of endopeptidase activity, the endohydrolysis of peptide bonds within proteins.
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	Any process that stops, prevents or reduces the frequency, rate or extent of extrinsic apoptotic signaling pathway in absence of ligand.
negative regulation of fatty acid beta-oxidation	Any process that stops, prevents, or reduces the frequency, rate or extent of fatty acid beta-oxidation.
negative regulation of gene expression	Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
negative regulation of leukocyte cell-cell adhesion	Any process that stops, prevents or reduces the frequency, rate or extent of leukocyte cell-cell adhesion.
negative regulation of long-chain fatty acid import across plasma membrane	Any process that decreases the rate, frequency or extent of plasma membrane long-chain fatty acid transport. Plasma membrane long-chain fatty acid transport is the directed movement of long-chain fatty acids across the plasma membrane.
negative regulation of lymphocyte migration	Any process that stops, prevents or reduces the frequency, rate or extent of lymphocyte migration.
negative regulation of macroautophagy	Any process that stops, prevents, or reduces the frequency, rate or extent of macroautophagy.
negative regulation of neuron death	Any process that stops, prevents or reduces the frequency, rate or extent of neuron death.
negative regulation of Notch signaling pathway	Any process that stops, prevents, or reduces the frequency, rate or extent of the Notch signaling pathway.
negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	Any process that stops, prevents or reduces the frequency, rate or extent of an oxidative stress-induced intrinsic apoptotic signaling pathway.
negative regulation of protein binding	Any process that stops, prevents, or reduces the frequency, rate or extent of protein binding.
negative regulation of protein kinase activity	Any process that stops, prevents, or reduces the frequency, rate or extent of protein kinase activity.
negative regulation of protein kinase activity by protein phosphorylation	Any protein phosphorylation process that negatively regulates protein kinase activity.
negative regulation of protein serine/threonine kinase activity	Any process that decreases the rate, frequency, or extent of protein serine/threonine kinase activity.
negative regulation of protein ubiquitination	Any process that stops, prevents, or reduces the frequency, rate or extent of the addition of ubiquitin groups to a protein.
negative regulation of proteolysis	Any process that stops, prevents, or reduces the frequency, rate or extent of the hydrolysis of a peptide bond or bonds within a protein.
negative regulation of release of cytochrome c from mitochondria	Any process that decreases the rate, frequency or extent of release of cytochrome c from mitochondria, the process in which cytochrome c is enabled to move from the mitochondrial intermembrane space into the cytosol, which is an early step in apoptosis and leads to caspase activation.
NIK/NF-kappaB signaling	The process in which a signal is passed on to downstream components within the cell through the NIK-dependent processing and activation of NF-KappaB. Begins with activation of the NF-KappaB-inducing kinase (NIK), which in turn phosphorylates and activates IkappaB kinase alpha (IKKalpha). IKKalpha phosphorylates the NF-Kappa B2 protein (p100) leading to p100 processing and release of an active NF-KappaB (p52).
nitric oxide biosynthetic process	The chemical reactions and pathways resulting in the formation of nitric oxide, nitrogen monoxide (NO), a colorless gas only slightly soluble in water.
osteoblast differentiation	The process whereby a relatively unspecialized cell acquires the specialized features of an osteoblast, a mesodermal or neural crest cell that gives rise to bone.
peptidyl-serine phosphorylation	The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
peptidyl-threonine phosphorylation	The phosphorylation of peptidyl-threonine to form peptidyl-O-phospho-L-threonine.
peripheral nervous system myelin maintenance	The process in which the structure and material content of mature peripheral nervous system myelin is kept in a functional state.
phosphatidylinositol 3-kinase signaling	A series of reactions within the signal-receiving cell, mediated by the intracellular phosphatidylinositol 3-kinase (PI3K). Many cell surface receptor linked signaling pathways signal through PI3K to regulate numerous cellular functions.
phosphorylation	The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide.
positive regulation of blood vessel endothelial cell migration	Any process that activates or increases the frequency, rate or extent of the migration of the endothelial cells of blood vessels.
positive regulation of cell growth	Any process that activates or increases the frequency, rate, extent or direction of cell growth.
positive regulation of cell population proliferation	Any process that activates or increases the rate or extent of cell proliferation.
positive regulation of cyclin-dependent protein serine/threonine kinase activity	Any process that activates or increases the frequency, rate or extent of CDK activity.
positive regulation of DNA-binding transcription factor activity	Any process that activates or increases the frequency, rate or extent of activity of a transcription factor, any factor involved in the initiation or regulation of transcription.
positive regulation of endodeoxyribonuclease activity	Any process that activates or increases the frequency, rate or extent of endodeoxyribonuclease activity, the hydrolysis of ester linkages within deoxyribonucleic acid by creating internal breaks.
positive regulation of endothelial cell migration	Any process that increases the rate, frequency, or extent of the orderly movement of an endothelial cell into the extracellular matrix to form an endothelium.
positive regulation of endothelial cell proliferation	Any process that activates or increases the rate or extent of endothelial cell proliferation.
positive regulation of fat cell differentiation	Any process that activates or increases the frequency, rate or extent of adipocyte differentiation.
positive regulation of fibroblast migration	Any process that increases the rate, frequency or extent of fibroblast cell migration. Fibroblast cell migration is accomplished by extension and retraction of a pseudopodium.
positive regulation of G1/S transition of mitotic cell cycle	Any signalling pathway that increases or activates a cell cycle cyclin-dependent protein kinase to modulate the switch from G1 phase to S phase of the mitotic cell cycle.
positive regulation of gene expression	Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
positive regulation of glucose import	Any process that activates or increases the frequency, rate or extent of the import of the hexose monosaccharide glucose into a cell or organelle.
positive regulation of glucose metabolic process	Any process that increases the rate, frequency or extent of glucose metabolism. Glucose metabolic processes are the chemical reactions and pathways involving glucose, the aldohexose gluco-hexose.
positive regulation of glycogen biosynthetic process	Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of glycogen.
positive regulation of I-kappaB phosphorylation	Any process that activates or increases the frequency, rate or extent of I-kappaB phosphorylation.
positive regulation of lipid biosynthetic process	Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of lipids.
positive regulation of mitochondrial membrane potential	Any process that activates or increases the frequency, rate or extent of establishment or extent of a mitochondrial membrane potential, the electric potential existing across any mitochondrial membrane arising from charges in the membrane itself and from the charges present in the media on either side of the membrane.
positive regulation of nitric oxide biosynthetic process	Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of nitric oxide.
positive regulation of nitric-oxide synthase activity	Any process that activates or increases the activity of the enzyme nitric-oxide synthase.
positive regulation of organ growth	Any process that activates or increases the frequency, rate or extent of growth of an organ of an organism.
positive regulation of peptidyl-serine phosphorylation	Any process that activates or increases the frequency, rate or extent of the phosphorylation of peptidyl-serine.
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	Any process that activates or increases the frequency, rate or extent of the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome.
positive regulation of protein localization to cell surface	Any process that activates or increases the frequency, rate or extent of protein localization to the cell surface.
positive regulation of protein localization to nucleus	Any process that activates or increases the frequency, rate or extent of protein localization to nucleus.
positive regulation of protein localization to plasma membrane	Any process that activates or increases the frequency, rate or extent of protein localization to plasma membrane.
positive regulation of protein phosphorylation	Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein.
positive regulation of smooth muscle cell proliferation	Any process that activates or increases the rate or extent of smooth muscle cell proliferation.
positive regulation of sodium ion transport	Any process that increases the frequency, rate or extent of the directed movement of sodium ions (Na+) into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
positive regulation of transcription by RNA polymerase II	Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
positive regulation of transcription, DNA-templated	Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription.
protein autophosphorylation	The phosphorylation by a protein of one or more of its own amino acid residues (cis-autophosphorylation), or residues on an identical protein (trans-autophosphorylation).
protein catabolic process	The chemical reactions and pathways resulting in the breakdown of a protein by the destruction of the native, active configuration, with or without the hydrolysis of peptide bonds.
protein import into nucleus	The directed movement of a protein from the cytoplasm to the nucleus.
protein kinase B signaling	A series of reactions, mediated by the intracellular serine/threonine kinase protein kinase B (also called AKT), which occurs as a result of a single trigger reaction or compound.
protein phosphorylation	The process of introducing a phosphate group on to a protein.
protein ubiquitination	The process in which one or more ubiquitin groups are added to a protein.
regulation of apoptotic process	Any process that modulates the occurrence or rate of cell death by apoptotic process.
regulation of cell migration	Any process that modulates the frequency, rate or extent of cell migration.
regulation of glycogen biosynthetic process	Any process that modulates the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of glycogen.
regulation of mRNA stability	Any process that modulates the propensity of mRNA molecules to degradation. Includes processes that both stabilize and destabilize mRNAs.
regulation of myelination	Any process that modulates the frequency, rate or extent of the formation of a myelin sheath around nerve axons.
regulation of neuron projection development	Any process that modulates the rate, frequency or extent of neuron projection development. Neuron projection development is the process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites).
regulation of signal transduction by p53 class mediator	Any process that modulates the frequency, rate or extent of signal transduction by p53 class mediator.
regulation of translation	Any process that modulates the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of proteins by the translation of mRNA or circRNA.
regulation of type B pancreatic cell development	Any process that modulates the frequency, rate or extent of pancreatic B cell development.
response to fluid shear stress	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a fluid shear stress stimulus. Fluid shear stress is the force acting on an object in a system where the fluid is moving across a solid surface.
response to food	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a food stimulus; food is anything which, when taken into the body, serves to nourish or build up the tissues or to supply body heat.
response to growth factor	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a growth factor stimulus.
response to growth hormone	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a growth hormone stimulus. Growth hormone is a peptide hormone that binds to the growth hormone receptor and stimulates growth.
response to heat	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a heat stimulus, a temperature stimulus above the optimal temperature for that organism.
response to insulin-like growth factor stimulus	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an insulin-like growth factor stimulus.
response to oxidative stress	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals.
response to UV-A	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a UV-A radiation stimulus. UV-A radiation (UV-A light) spans the wavelengths 315 to 400 nm.
signal transduction	The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.
sphingosine-1-phosphate receptor signaling pathway	A G protein-coupled receptor signaling pathway initiated by sphingosine-1-phosphate binding to its receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
striated muscle cell differentiation	The process in which a relatively unspecialized cell acquires specialized features of a striated muscle cell; striated muscle fibers are divided by transverse bands into striations, and cardiac and voluntary muscle are types of striated muscle.
T cell costimulation	The process of providing, via surface-bound receptor-ligand pairs, a second, antigen-independent, signal in addition to that provided by the T cell receptor to augment T cell activation.
TOR signaling	The series of molecular signals mediated by TOR (Target of rapamycin) proteins, members of the phosphoinositide (PI) 3-kinase related kinase (PIKK) family that act as serine/threonine kinases in response to nutrient availability or growth factors.

32 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q01314	AKT1	RAC-alpha serine/threonine-protein kinase	Bos taurus (Bovine)	SS
Q8INB9	Akt	RAC serine/threonine-protein kinase	Drosophila melanogaster (Fruit fly)	SS
O15530	PDPK1	3-phosphoinositide-dependent protein kinase 1	Homo sapiens (Human)	EV
Q05513	PRKCZ	Protein kinase C zeta type	Homo sapiens (Human)	SS
P41743	PRKCI	Protein kinase C iota type	Homo sapiens (Human)	EV
Q16512	PKN1	Serine/threonine-protein kinase N1	Homo sapiens (Human)	EV
Q6P5Z2	PKN3	Serine/threonine-protein kinase N3	Homo sapiens (Human)	SS
Q16513	PKN2	Serine/threonine-protein kinase N2	Homo sapiens (Human)	EV
P24723	PRKCH	Protein kinase C eta type	Homo sapiens (Human)	SS
Q02156	PRKCE	Protein kinase C epsilon type	Homo sapiens (Human)	SS
Q04759	PRKCQ	Protein kinase C theta type	Homo sapiens (Human)	PR
Q05655	PRKCD	Protein kinase C delta type	Homo sapiens (Human)	SS
P17252	PRKCA	Protein kinase C alpha type	Homo sapiens (Human)	EV
P05129	PRKCG	Protein kinase C gamma type	Homo sapiens (Human)	SS
P05771	PRKCB	Protein kinase C beta type	Homo sapiens (Human)	SS
P31751	AKT2	RAC-beta serine/threonine-protein kinase	Homo sapiens (Human)	EV SS
Q9Y243	AKT3	RAC-gamma serine/threonine-protein kinase	Homo sapiens (Human)	SS
Q96BR1	SGK3	Serine/threonine-protein kinase Sgk3	Homo sapiens (Human)	SS
Q9HBY8	SGK2	Serine/threonine-protein kinase Sgk2	Homo sapiens (Human)	SS
O00141	SGK1	Serine/threonine-protein kinase Sgk1	Homo sapiens (Human)	PR
Q15208	STK38	Serine/threonine-protein kinase 38	Homo sapiens (Human)	EV
Q9Y2H1	STK38L	Serine/threonine-protein kinase 38-like	Homo sapiens (Human)	EV
Q6A1A2	PDPK2P	Putative 3-phosphoinositide-dependent protein kinase 2	Homo sapiens (Human)	PR
Q60823	Akt2	RAC-beta serine/threonine-protein kinase	Mus musculus (Mouse)	PR
Q9WUA6	Akt3	RAC-gamma serine/threonine-protein kinase	Mus musculus (Mouse)	PR
P31750	Akt1	RAC-alpha serine/threonine-protein kinase	Mus musculus (Mouse)	PR
P47197	Akt2	RAC-beta serine/threonine-protein kinase	Rattus norvegicus (Rat)	SS
Q63484	Akt3	RAC-gamma serine/threonine-protein kinase	Rattus norvegicus (Rat)	PR
P47196	Akt1	RAC-alpha serine/threonine-protein kinase	Rattus norvegicus (Rat)	PR
Q9XTG7	akt-2	Serine/threonine-protein kinase akt-2	Caenorhabditis elegans	SS
Q17941	akt-1	Serine/threonine-protein kinase akt-1	Caenorhabditis elegans	PR
Q9SUA3	D6PKL1	Serine/threonine-protein kinase D6PKL1	Arabidopsis thaliana (Mouse-ear cress)	PR

10	20	30	40	50	60
MSDVAIVKEG	WLHKRGEYIK	TWRPRYFLLK	NDGTFIGYKE	RPQDVDQREA	PLNNFSVAQC
70	80	90	100	110	120
QLMKTERPRP	NTFIIRCLQW	TTVIERTFHV	ETPEEREEWT	TAIQTVADGL	KKQEEEEMDF
130	140	150	160	170	180
RSGSPSDNSG	AEEMEVSLAK	PKHRVTMNEF	EYLKLLGKGT	FGKVILVKEK	ATGRYYAMKI
190	200	210	220	230	240
LKKEVIVAKD	EVAHTLTENR	VLQNSRHPFL	TALKYSFQTH	DRLCFVMEYA	NGGELFFHLS
250	260	270	280	290	300
RERVFSEDRA	RFYGAEIVSA	LDYLHSEKNV	VYRDLKLENL	MLDKDGHIKI	TDFGLCKEGI
310	320	330	340	350	360
KDGATMKTFC	GTPEYLAPEV	LEDNDYGRAV	DWWGLGVVMY	EMMCGRLPFY	NQDHEKLFEL
370	380	390	400	410	420
ILMEEIRFPR	TLGPEAKSLL	SGLLKKDPKQ	RLGGGSEDAK	EIMQHRFFAG	IVWQHVYEKK
430	440	450	460	470
LSPPFKPQVT	SETDTRYFDE	EFTAQMITIT	PPDQDDSMEC	VDSERRPHFP	QFSYSASGTA