AiPD: Autoinhibited Protein Database

P31751

EV SS

Gene name	AKT2
Protein name	RAC-beta serine/threonine-protein kinase
Names	Protein kinase Akt-2, Protein kinase B beta, PKB beta, RAC-PK-beta
Species	Homo sapiens (Human)
KEGG Pathway	hsa:208
EC number	2.7.11.1: Protein-serine/threonine kinases
Protein Class	RIBOSOMAL PROTEIN S6 KINASE (PTHR24351)

Descriptions

Akt is a serine/threonine kinase that belongs to a group of proteins called the AGC superfamily. It is involved in various biological responses through the phosphatidylinositol 3-kinase (PI3K) signal transduction pathway. Akt2, in particular, is regulated by different regions of the protein.
The N-terminal PH domain of Akt2 plays a regulatory role in its activation. Phosphorylation of Ser474 in the C-terminal regulatory domain is also necessary for full activation of Akt2. These modifications help activate the kinase and enable it to carry out its functions.
The linker region between the N-lobe and C-lobe of Akt2 occupies the ATP binding site. Additionally, the activation loop within Akt2 aids in autoinhibition by blocking the binding of peptide substrates, while still allowing access to the ATP binding site.

Autoinhibitory domains (AIDs)

5-108 (PH domain) SS

Target domain	143-481 (Kinase domain)
Relief mechanism	PTM, Ligand binding
Assay

AID

5-108 (PH domain)

Target domain

143-481 (Kinase domain)

Relief mechanism

PTM (Phosphorylation of Ser474 or Thr309), Ligand binding (Binding of PIP3 and PIP2 to PH domain)

Assay

Target domain	143-481 (Kinase domain)
Relief mechanism	PTM
Assay	Mutagenesis experiment, Structural analysis

AID

146-440 (Linker region between N- and C-lobes)

Target domain

143-481 (Kinase domain)

Relief mechanism

PTM (Phosphorylation of Ser474 or Thr309)

Assay

Mutagenesis experiment, Structural analysis

Accessory elements

292-315 (Activation loop from InterPro)

Target domain	156-478 (Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta, also called Akt2)
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

Autoinhibited structure

Activated structure

19 structures for P31751

Entry ID	Method	Resolution	Chain	Position	Source
1GZK	X-ray	230 A	A	146-460	PDB
1GZN	X-ray	250 A	A	146-480	PDB
1GZO	X-ray	275 A	A	146-460	PDB
1MRV	X-ray	280 A	A	143-481	PDB
1MRY	X-ray	280 A	A	143-481	PDB
1O6K	X-ray	170 A	A	146-481	PDB
1O6L	X-ray	160 A	A	146-467	PDB
1P6S	NMR	-	A	1-111	PDB
2JDO	X-ray	180 A	A	146-467	PDB
2JDR	X-ray	230 A	A	146-467	PDB
2UW9	X-ray	210 A	A	146-467	PDB
2X39	X-ray	193 A	A	146-467	PDB
2XH5	X-ray	272 A	A	146-479	PDB
3D0E	X-ray	200 A	A/B	146-480	PDB
3E87	X-ray	230 A	A/B	146-480	PDB
3E88	X-ray	250 A	A/B	146-480	PDB
3E8D	X-ray	270 A	A/B	146-480	PDB
8Q61	X-ray	232 A	A	1-481	PDB
AF-P31751-F1	Predicted				AlphaFoldDB

282 variants for P31751

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs1976263420 RCV001335851	15	R>H	Type 2 diabetes mellitus [ClinVar]	Yes	ClinVar dbSNP
CA128662 VAR_067309 RCV000022676 rs387906659 COSM159009	17	E>K	Hypoinsulinemic hypoglycemia and body hemihypertrophy breast HIHGHH; exhibits plasma membrane localization in serum-starved cells and produced inappropriate tonic nuclear exclusion of FOXO1 in preadipocytes [ClinVar, Cosmic, UniProt]	Yes	ClinGen cosmic curated ClinVar UniProt Ensembl dbSNP
VAR_067310 rs121434593 RCV000015016 CA123659	274	R>H	NIDDM; associated with typical metabolic dyslipidemia with elevated fastin triglyceride, high VLDL triglyceride/cholesterol ratios, low HDL cholesterol levels and high small dense LDL levels; de novo lipogenesis and liver fat are also significantly elevated in this subject Type 2 diabetes mellitus [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
RCV000423006 rs1057519754 CA16602506	302	S>G	Neoplasm of the large intestine [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
COSM3960070 rs778561687 RCV000441898 CA16602505	371	R>H	lung Non-small cell lung carcinoma [Cosmic, ClinVar]	Yes	ClinGen cosmic curated ClinVar ExAC dbSNP gnomAD
CA9441513 rs771065673 RCV000624382	416	D>N	Inborn genetic diseases [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA405874606 rs1227207335	2	N>S		No	ClinGen gnomAD
CA405874554 rs1386086141	6	V>F		No	ClinGen gnomAD
rs199748431 CA405874542	7	I>F		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs199748431 CA9442020	7	I>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1405458685 CA405874523	8	K>R		No	ClinGen gnomAD
rs748173515 CA9442019	9	E>K		No	ClinGen ExAC gnomAD
rs1476241262 CA405874462	14	K>T		No	ClinGen gnomAD
CA9442017 rs781407242	15	R>C		No	ClinGen ExAC gnomAD
rs387906659 CA308392149	17	E>*		No	ClinGen Ensembl
rs1438443076 CA405873281	19	I>F		No	ClinGen TOPMed
CA405873280 rs1600058964	19	I>T		No	ClinGen Ensembl
rs1272565080 CA405873213	24	P>L		No	ClinGen gnomAD
rs1185991201 CA405873218	24	P>S		No	ClinGen TOPMed
CA9441993 rs746989021	25	R>Q		No	ClinGen ExAC gnomAD
rs1371021819 CA405873198	26	Y>S		No	ClinGen gnomAD
CA9441992 rs779811637	31	S>N		No	ClinGen ExAC gnomAD
rs1360665207 CA405873136	32	D>N		No	ClinGen TOPMed gnomAD
rs1197293098 CA405872995	41	R>K		No	ClinGen gnomAD
CA9441986 rs763646270	45	P>S		No	ClinGen ExAC gnomAD
CA9441985 rs201917021	49	L>P		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA9441984 rs201917021	49	L>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs184042322 CA9441982	50	P>A		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs184042322 CA9441981	50	P>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA16040265 rs201145928	51	P>A		No	ClinGen TOPMed gnomAD
rs770250877 CA9441980	51	P>L		No	ClinGen ExAC TOPMed gnomAD
rs770250877 CA405872815	51	P>R		No	ClinGen ExAC TOPMed gnomAD
rs1407888862 CA405872708	57	V>I		No	ClinGen TOPMed gnomAD
rs1380555769 CA405871665	61	Q>R		No	ClinGen gnomAD
CA9441947 rs747803532	66	E>K		No	ClinGen ExAC gnomAD
rs1410236931 CA405871546	68	P>L		No	ClinGen gnomAD
CA405871540 rs1287086134	69	R>*		No	ClinGen TOPMed
COSM996631 CA405871534 rs1485745630	69	R>Q	endometrium [Cosmic]	No	ClinGen cosmic curated TOPMed
CA405871530 rs1170693725	70	P>A		No	ClinGen gnomAD
rs200272953 CA9441945	71	N>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs200272953 CA405871507	71	N>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs765768303 CA9441943	72	T>I		No	ClinGen ExAC gnomAD
CA405871491 rs765768303	72	T>S		No	ClinGen ExAC gnomAD
CA405871482 rs1190606056	73	F>V		No	ClinGen gnomAD
CA9441941 rs754309980	74	V>F		No	ClinGen ExAC TOPMed gnomAD
CA405871469 rs754309980	74	V>I		No	ClinGen ExAC TOPMed gnomAD
CA405871326 rs1393896368	85	E>K		No	ClinGen TOPMed
CA405871278 rs1489834693	88	F>L		No	ClinGen gnomAD
CA405871240 rs1160079555	90	V>M		No	ClinGen TOPMed
CA405871223 rs1205519703	91	D>Y		No	ClinGen gnomAD
rs764512283 CA9441940	92	S>F		No	ClinGen ExAC gnomAD
CA308390831 rs965617770	93	P>L		No	ClinGen Ensembl
rs374073998 CA9441938	95	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA405869652 rs1434565896	97	E>G		No	ClinGen gnomAD
CA9441916 rs369128708	100	M>L		No	ClinGen ESP ExAC gnomAD
CA405869602 rs761956794	101	R>G		No	ClinGen ExAC TOPMed gnomAD
CA308381827 rs968169579	101	R>Q		No	ClinGen TOPMed gnomAD
rs761956794 CA9441915	101	R>W		No	ClinGen ExAC TOPMed gnomAD
rs1186768719 CA405869582	103	I>F		No	ClinGen TOPMed
rs1599985751 CA405869579	103	I>T		No	ClinGen Ensembl
CA405869567 rs1260732312	104	Q>R		No	ClinGen TOPMed
CA9441914 rs762920486	105	M>T		No	ClinGen ExAC gnomAD
rs761598534 CA9441911	107	A>T		No	ClinGen ExAC TOPMed gnomAD
rs1599985609 CA405869522	108	N>T		No	ClinGen Ensembl
CA405869509 rs1231123715	109	S>N		No	ClinGen gnomAD
CA9441910 rs776161532	113	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA308381804 rs1054914884	113	R>W		No	ClinGen TOPMed gnomAD
rs1257065618 CA405869451	114	A>S		No	ClinGen gnomAD
CA405869454 rs1257065618	114	A>T		No	ClinGen gnomAD
CA308381793 rs937810724	114	A>V		No	ClinGen TOPMed
rs1203244050 CA405869436	115	P>L		No	ClinGen gnomAD
rs141209878 CA9441909	116	G>A		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs148339167 CA9441908	117	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA9441906 rs771687909	118	D>G		No	ClinGen ExAC gnomAD
rs779749219 CA9441907	118	D>N		No	ClinGen ExAC gnomAD
CA9441904 rs778304096	119	P>L		No	ClinGen ExAC gnomAD
CA9441905 rs749837210	119	P>S		No	ClinGen ExAC TOPMed gnomAD
CA9441902 rs753052094	120	M>I		No	ClinGen ExAC gnomAD
CA405869381 rs1390462628	120	M>R		No	ClinGen gnomAD
CA405869374 rs1284479566	121	D>N		No	ClinGen TOPMed
rs201717577 CA9441900	122	Y>C		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA9441901 rs781400894	122	Y>H		No	ClinGen ExAC gnomAD
CA405869336 rs1473114374	124	C>R		No	ClinGen gnomAD
CA9441899 rs751752149	126	S>F		No	ClinGen ExAC gnomAD
rs1217996479 CA405869300	127	P>L		No	ClinGen TOPMed
CA308381669 rs908489075	128	S>R		No	ClinGen Ensembl
rs1460139068 CA405869288	129	D>G		No	ClinGen gnomAD
rs984104264 CA308381668	130	S>C		No	ClinGen TOPMed
rs1209358799 CA405869269	131	S>F		No	ClinGen gnomAD
CA9441898 rs768885006	132	T>A		No	ClinGen ExAC TOPMed gnomAD
CA9441897 rs143335817	132	T>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA308381646 rs1028818887	134	E>A		No	ClinGen TOPMed gnomAD
CA9441895 rs765159398	134	E>D		No	ClinGen ExAC gnomAD
rs1028818887 CA405869237	134	E>V		No	ClinGen TOPMed gnomAD
rs761642183 CA9441894	136	M>L		No	ClinGen ExAC gnomAD
rs776555398 CA9441893	138	V>L		No	ClinGen ExAC TOPMed gnomAD
rs768539227 CA9441892 COSM189287	139	A>V	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs1158640193 CA405869165	140	V>I		No	ClinGen TOPMed
CA308381614 rs867449500	144	R>Q		No	ClinGen Ensembl
CA9441889 rs575460456 COSM996625	144	R>W	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA308381604 rs879199809	146	K>T		No	ClinGen Ensembl
CA405869078 rs1477451871	147	V>A		No	ClinGen gnomAD
CA308381211 rs886949760	149	M>T		No	ClinGen Ensembl
rs1409596764 CA405868549	151	D>N		No	ClinGen gnomAD
rs1599981496 CA405868446	156	K>N		No	ClinGen Ensembl
CA9441866 rs777080235	156	K>R		No	ClinGen ExAC TOPMed gnomAD
CA9441864 rs747313418	168	L>R		No	ClinGen ExAC gnomAD
CA405868318 rs1305342088	169	V>M		No	ClinGen gnomAD
CA9441862 rs572670425 COSM996623	170	R>W	endometrium [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs1599981195 CA405868264	174	T>P		No	ClinGen Ensembl
CA405868252 rs1280863854	175	G>D		No	ClinGen gnomAD
rs398123625 COSM1645332 CA221735	175	G>S	large_intestine [Cosmic]	No	ClinGen cosmic curated Ensembl
CA9441859 rs757233968	176	R>C		No	ClinGen ExAC TOPMed gnomAD
rs764058037 CA9441857	176	R>H		No	ClinGen ExAC TOPMed gnomAD
rs764058037 CA9441858	176	R>L		No	ClinGen ExAC TOPMed gnomAD
CA405868222 rs755987647	178	Y>*		No	ClinGen ExAC TOPMed gnomAD
rs991833403 CA308381157	179	A>T		No	ClinGen TOPMed
CA308381155 rs959871626	180	M>V		No	ClinGen TOPMed
rs1352944542 CA405868172	183	L>Q		No	ClinGen gnomAD
rs1470454115 CA405868165	184	R>Q		No	ClinGen gnomAD
rs752597471 CA9441855	184	R>W		No	ClinGen ExAC gnomAD
rs55859611 CA308381142 VAR_040356	188	I>V		No	ClinGen UniProt TOPMed dbSNP gnomAD
CA9441853 rs759277032	191	K>R		No	ClinGen ExAC TOPMed gnomAD
rs774646421 CA9441805	192	D>E		No	ClinGen ExAC gnomAD
CA405868010 rs1225273209	192	D>N		No	ClinGen gnomAD
rs763319755 CA9441803 COSM3422825	195	A>T	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA405867975 rs1568526119	197	T>A		No	ClinGen Ensembl
rs371943261 CA9441802	198	V>I		No	ClinGen ESP ExAC gnomAD
CA9441800 rs748177849	202	R>W		No	ClinGen ExAC gnomAD
CA9441798 rs549648922	207	T>S		No	ClinGen 1000Genomes ExAC gnomAD
rs35817154 VAR_040357 CA9441797	208	R>K		No	ClinGen UniProt ESP ExAC TOPMed dbSNP gnomAD
rs1599969539 CA405867889	210	P>R		No	ClinGen Ensembl
rs1175170174 CA405867875	212	L>P		No	ClinGen gnomAD
rs758767505 CA9441736	214	A>E		No	ClinGen ExAC TOPMed gnomAD
rs758767505 CA9441737	214	A>V		No	ClinGen ExAC TOPMed gnomAD
rs1189807846 CA405867850	215	L>V		No	ClinGen gnomAD
rs1599963715 CA405867808	221	T>P		No	ClinGen Ensembl
CA9441732 rs769554060	222	H>D		No	ClinGen ExAC gnomAD
rs1599963532 CA405867793	223	D>A		No	ClinGen Ensembl
CA9441729 rs545889598	223	D>E		No	ClinGen 1000Genomes ExAC gnomAD
rs780894376 CA9441730	223	D>N		No	ClinGen ExAC gnomAD
rs1322643388 CA405867789	224	R>C		No	ClinGen gnomAD
CA405867786 rs746407532	224	R>H		No	ClinGen ExAC gnomAD
CA9441728 rs746407532	224	R>L		No	ClinGen ExAC gnomAD
CA405867774 rs1373751808	226	C>Y		No	ClinGen gnomAD
rs754286414 CA9441725	231	Y>H		No	ClinGen ExAC gnomAD
rs1227145174 CA405867726	233	N>D		No	ClinGen gnomAD
rs988297708 CA308378294	233	N>S		No	ClinGen TOPMed gnomAD
rs1363221582 CA405867219	243	R>Q		No	ClinGen gnomAD
rs763896696 CA9441694	243	R>W		No	ClinGen ExAC gnomAD
CA9441693 rs760399082	245	R>C		No	ClinGen ExAC gnomAD
rs775105991 CA9441692	245	R>H		No	ClinGen ExAC TOPMed gnomAD
CA405867173 rs1367814764	248	T>A		No	ClinGen gnomAD
CA9441691 rs771461640	248	T>I		No	ClinGen ExAC gnomAD
CA308377603 rs1044041105	250	E>*		No	ClinGen TOPMed
CA308377581 rs751522812	251	R>Q		No	ClinGen TOPMed
CA9441689 rs773553776	251	R>W		No	ClinGen ExAC gnomAD
rs1428621686 CA405867132	252	A>G		No	ClinGen gnomAD
CA9441688 rs770151213	252	A>T		No	ClinGen ExAC gnomAD
CA405867128 rs781527200	253	R>G		No	ClinGen ExAC gnomAD
CA9441685 rs145907048	253	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs781527200 CA9441686	253	R>W		No	ClinGen ExAC gnomAD
rs1207387979 CA405867059	259	I>V		No	ClinGen gnomAD
CA9441684 rs747207035	261	S>L		No	ClinGen ExAC
CA9441682 rs758367800	262	A>G		No	ClinGen ExAC gnomAD
CA308377549 rs1804324	265	Y>N		No	ClinGen Ensembl
CA405866958 rs757245351	268	S>*		No	ClinGen ExAC gnomAD
rs757245351 CA9441679	268	S>L		No	ClinGen ExAC gnomAD
CA308377525 rs761347839	269	R>Q		No	ClinGen TOPMed gnomAD
CA9441677 rs763951605	269	R>W		No	ClinGen ExAC gnomAD
rs1347953319 CA405866933	271	V>M		No	ClinGen gnomAD
rs1304063423 CA405866923	272	V>I		No	ClinGen gnomAD
CA9441675 rs774959037	274	R>C		No	ClinGen ExAC TOPMed gnomAD
rs1240210533 CA405866828	281	L>V		No	ClinGen gnomAD
CA405866809 rs1473345359	284	D>N		No	ClinGen TOPMed
CA9441636 rs369596328	290	K>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA9441635 rs762379584	291	I>V		No	ClinGen ExAC gnomAD
CA405866699 rs1333003888	299	E>*		No	ClinGen gnomAD
CA9441634 rs376326333	305	A>V		No	ClinGen ESP ExAC gnomAD
CA9441633 rs777865319	306	T>S		No	ClinGen ExAC gnomAD
rs1378308963 CA405866648	307	M>V		No	ClinGen gnomAD
rs1243812798 CA405866597	314	P>A		No	ClinGen gnomAD
rs140987550 CA308376544	314	P>L		No	ClinGen ESP TOPMed
CA405866589 rs1441119595	315	E>G		No	ClinGen gnomAD
CA405866567 rs1206035617	318	A>V		No	ClinGen gnomAD
rs374756725 CA308376460	325	N>S		No	ClinGen ESP TOPMed gnomAD
CA308376457 rs980537301	326	D>Y		No	ClinGen Ensembl
rs144395843 CA9441610	329	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs763266151 CA9441609	330	A>T		No	ClinGen ExAC gnomAD
rs1323113005 CA405866456 COSM1481073	333	W>*	breast [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1323113005 CA405866455	333	W>C		No	ClinGen gnomAD
CA405866443 rs1568519097	335	G>R		No	ClinGen Ensembl
rs1004075798 CA308376430	340	M>I		No	ClinGen Ensembl
rs776561628 CA9441605	340	M>T		No	ClinGen ExAC gnomAD
CA9441603 rs372625056	344	M>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs1166756826 CA405866379	344	M>K		No	ClinGen TOPMed gnomAD
rs1422114933 COSM996621 CA405866381	344	M>V	endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1169786300 CA405866366	346	G>S		No	ClinGen TOPMed
rs145305228 CA9441601	347	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs202125073 CA308376418	347	R>H		No	ClinGen 1000Genomes
rs745497338 CA9441600	349	P>L		No	ClinGen ExAC gnomAD
rs1020231672 COSM1579112 CA308376415	351	Y>C	upper_aerodigestive_tract [Cosmic]	No	ClinGen cosmic curated TOPMed
CA9441598 rs756750912	352	N>H		No	ClinGen ExAC TOPMed gnomAD
CA308376411 rs886899893	352	N>S		No	ClinGen TOPMed gnomAD
CA9441597 rs753149827	353	Q>E		No	ClinGen ExAC gnomAD
CA405866323 rs1195945663	353	Q>R		No	ClinGen gnomAD
COSM439520 CA405866302 rs1568518786	356	E>K	breast [Cosmic]	No	ClinGen cosmic curated Ensembl
rs1026908617 CA308376403	357	R>C		No	ClinGen TOPMed gnomAD
CA9441594 rs752039318	357	R>H		No	ClinGen ExAC TOPMed gnomAD
rs200433217 CA9441591	360	E>A		No	ClinGen ExAC TOPMed gnomAD
rs930976777 CA308376396	360	E>K		No	ClinGen TOPMed gnomAD
CA405866251 rs1568518681	364	M>V		No	ClinGen Ensembl
CA9441590 rs765232271	366	E>K		No	ClinGen ExAC gnomAD
CA405866226 rs1470923617	367	I>V		No	ClinGen gnomAD
rs144444132 COSM268637 CA9441588	368	R>C	large_intestine [Cosmic]	No	ClinGen cosmic curated ESP ExAC gnomAD
CA9441587 rs768703735 COSM996619	368	R>H	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA405866205 rs1204214325	370	P>L		No	ClinGen gnomAD
CA9441583 rs745550650	371	R>C		No	ClinGen ExAC gnomAD
CA9441582 rs778561687 COSM318640	371	R>L	lung [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs139506765 CA9441581	372	T>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs777146223 CA9441579	373	L>V		No	ClinGen ExAC gnomAD
CA308376337 rs200395003	376	E>D		No	ClinGen Ensembl
rs1466949645 CA405866175	376	E>K		No	ClinGen gnomAD
CA9441575 rs758765375	377	A>V		No	ClinGen ExAC gnomAD
rs765549797 CA9441573	378	K>E		No	ClinGen ExAC gnomAD
rs529742537 CA405866160	378	K>M		No	ClinGen 1000Genomes ExAC gnomAD
rs529742537 CA9441572	378	K>R		No	ClinGen 1000Genomes ExAC gnomAD
rs753989242 CA9441571	382	A>S		No	ClinGen ExAC TOPMed gnomAD
rs1437512007 CA405866121	385	L>H		No	ClinGen gnomAD
CA405866043 rs1458251691	394	G>C		No	ClinGen gnomAD
rs1257580103 CA405866039	395	G>W		No	ClinGen gnomAD
CA9441524 rs765026585	396	G>R		No	ClinGen ExAC TOPMed gnomAD
CA405866033 rs765026585	396	G>R		No	ClinGen ExAC TOPMed gnomAD
rs1319165364 CA405866014	399	D>N		No	ClinGen TOPMed
rs1256885928 CA405865995	401	K>R		No	ClinGen gnomAD
CA405865980 rs1599949801	403	V>G		No	ClinGen Ensembl
rs767995122 CA9441521	404	M>T		No	ClinGen ExAC gnomAD
CA405865977 rs1328944283	404	M>V		No	ClinGen gnomAD
CA405865964 rs1485158704	405	E>A		No	ClinGen TOPMed
CA405865916 rs1198321649	412	I>L		No	ClinGen TOPMed
CA405865906 rs1470884234	413	N>S		No	ClinGen gnomAD
rs749701848 CA9441515	415	Q>K		No	ClinGen ExAC gnomAD
CA9441511 rs781260194	417	V>M		No	ClinGen ExAC gnomAD
CA9441510 rs754942500	418	V>F		No	ClinGen ExAC gnomAD
rs1159523716 CA405865869	418	V>G		No	ClinGen TOPMed
rs779909600 CA9441508	419	Q>H		No	ClinGen ExAC gnomAD
CA308375887 rs1010551997	425	P>H		No	ClinGen TOPMed
CA9441483 rs752215436	428	P>S		No	ClinGen ExAC gnomAD
CA405865783 rs767039609	429	Q>H		No	ClinGen ExAC TOPMed gnomAD
CA405865784 rs767039609	429	Q>H		No	ClinGen ExAC TOPMed gnomAD
rs1399189737 CA405865786	429	Q>R		No	ClinGen gnomAD
CA9441481 rs375739695	431	T>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs867381867 CA308375876	432	S>C		No	ClinGen Ensembl
CA405865675 rs1371711287	445	A>P		No	ClinGen TOPMed
rs1316408057 CA405865642	450	I>V		No	ClinGen TOPMed
CA405865630 rs1207581157	452	P>T		No	ClinGen gnomAD
CA405865622 rs1278736092	453	P>S		No	ClinGen gnomAD
rs1278736092 CA405865624	453	P>T		No	ClinGen gnomAD
rs757239082 CA405865609	455	R>C		No	ClinGen ExAC TOPMed gnomAD
rs757239082 CA405865610	455	R>G		No	ClinGen ExAC TOPMed gnomAD
CA9441469 rs778976738	455	R>H		No	ClinGen ExAC TOPMed gnomAD
rs778976738 CA308375838	455	R>L		No	ClinGen ExAC TOPMed gnomAD
CA9441470 rs757239082	455	R>S		No	ClinGen ExAC TOPMed gnomAD
CA405865184 rs1468068048	457	D>G		No	ClinGen TOPMed gnomAD
CA9441422 rs756547812	458	S>C		No	ClinGen ExAC gnomAD
rs753179882 CA405865173	458	S>R		No	ClinGen ExAC TOPMed gnomAD
rs1173481204 CA405865151	462	L>P		No	ClinGen TOPMed
CA405865149 rs1251045508	463	E>K		No	ClinGen TOPMed gnomAD
CA405865148 rs1251045508	463	E>Q		No	ClinGen TOPMed gnomAD
CA405865121 rs1413205437	466	Q>H		No	ClinGen TOPMed
rs759851333 CA9441419	467	R>Q		No	ClinGen ExAC gnomAD
CA9441420 rs142926499	467	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs1385936959 CA405865111	469	H>Y		No	ClinGen gnomAD
CA405865101 rs1368133745	470	F>I		No	ClinGen gnomAD
CA405865063 rs1447335111	475	Y>C		No	ClinGen gnomAD
CA405865062 rs1447335111	475	Y>S		No	ClinGen gnomAD
rs766596535 CA9441417	476	S>L		No	ClinGen ExAC gnomAD
CA405865044 rs1297243797	478	S>N		No	ClinGen TOPMed
CA9441414 rs769806554	480	R>C		No	ClinGen ExAC TOPMed gnomAD
CA405865032 rs769806554	480	R>G		No	ClinGen ExAC TOPMed gnomAD
CA308375219 rs1017033490	480	R>H		No	ClinGen TOPMed gnomAD
CA308375208 rs1044344132	481	E>K		No	ClinGen Ensembl

No associated diseases with P31751

No regional properties for P31751

Type	Name	Position	InterPro Accession
No domain, repeats, and functional sites for P31751

Functions

		Description
EC Number	2.7.11.1	Protein-serine/threonine kinases
Subcellular Localization	Cytoplasm Nucleus Cell membrane; Peripheral membrane protein Early endosome	Through binding of the N-terminal PH domain to phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) or phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)P2), recruited to the plasma membrane Cell membrane recruitment is facilitated by interaction with CLIP3 Colocalizes with WDFY2 in early endosomes (By similarity) Localizes within both nucleus and cytoplasm in proliferative primary myoblasts and mostly within the nucleus of differentiated primary myoblasts (PubMed:17565718)
PANTHER Family	PTHR24351	RIBOSOMAL PROTEIN S6 KINASE
PANTHER Subfamily	PTHR24351:SF192	PROTEIN KINASE C
PANTHER Protein Class	protein modifying enzyme
PANTHER Pathway Category	No pathway information available

9 GO annotations of cellular component

Name	Definition
cell cortex	The region of a cell that lies just beneath the plasma membrane and often, but not always, contains a network of actin filaments and associated proteins.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
early endosome	A membrane-bounded organelle that receives incoming material from primary endocytic vesicles that have been generated by clathrin-dependent and clathrin-independent endocytosis; vesicles fuse with the early endosome to deliver cargo for sorting into recycling or degradation pathways.
intracellular membrane-bounded organelle	Organized structure of distinctive morphology and function, bounded by a single or double lipid bilayer membrane and occurring within the cell. Includes the nucleus, mitochondria, plastids, vacuoles, and vesicles. Excludes the plasma membrane.
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.
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.
ruffle membrane	The portion of the plasma membrane surrounding a ruffle.

5 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
metal ion binding	Binding to a metal ion.
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.

32 GO annotations of biological process

Name	Definition
activation of GTPase activity	Any process that initiates the activity of an inactive GTPase through the replacement of GDP by GTP.
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.
cellular response to high light intensity	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 high light intensity 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.
fat cell differentiation	The process in which a relatively unspecialized cell acquires specialized features of an adipocyte, an animal connective tissue cell specialized for the synthesis and storage of fat.
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.
insulin receptor signaling pathway	The series of molecular signals generated as a consequence of the insulin receptor binding to insulin.
intracellular protein transmembrane transport	The directed movement of proteins in a cell, from one side of a membrane to another by means of some agent such as a transporter or pore.
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.
mammary gland epithelial cell differentiation	The process in which a relatively unspecialized epithelial cell becomes a more specialized epithelial cell of the mammary gland.
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 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.
peptidyl-serine phosphorylation	The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
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.
positive regulation of cell migration	Any process that activates or increases the frequency, rate or extent of cell migration.
positive regulation of cell motility	Any process that activates or increases the frequency, rate or extent of cell motility.
positive regulation of cell population proliferation	Any process that activates or increases the rate or extent of cell proliferation.
positive regulation of fatty acid beta-oxidation	Any process that activates or increases the frequency, rate or extent of fatty acid beta-oxidation.
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 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 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 protein targeting to membrane	Any process that increases the frequency, rate or extent of the process of directing proteins towards a membrane, usually using signals contained within the protein.
positive regulation of vesicle fusion	Any process that activates or increases the frequency, rate or extent of vesicle fusion.
protein localization to plasma membrane	A process in which a protein is transported to, or maintained in, a specific location in the plasma membrane.
regulation of cell cycle	Any process that modulates the rate or extent of progression through the cell cycle.
regulation of cell migration	Any process that modulates the frequency, rate or extent of cell migration.
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.
retinal rod cell apoptotic process	Any apoptotic process in a retinal rod cell, one of the two photoreceptor cell types of the vertebrate retina.
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.

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
P31749	AKT1	RAC-alpha serine/threonine-protein kinase	Homo sapiens (Human)	EV
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
P31750	Akt1	RAC-alpha serine/threonine-protein kinase	Mus musculus (Mouse)	PR
Q9WUA6	Akt3	RAC-gamma serine/threonine-protein kinase	Mus musculus (Mouse)	PR
Q60823	Akt2	RAC-beta serine/threonine-protein kinase	Mus musculus (Mouse)	PR
P47196	Akt1	RAC-alpha serine/threonine-protein kinase	Rattus norvegicus (Rat)	PR
Q63484	Akt3	RAC-gamma serine/threonine-protein kinase	Rattus norvegicus (Rat)	PR
P47197	Akt2	RAC-beta serine/threonine-protein kinase	Rattus norvegicus (Rat)	SS
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
MNEVSVIKEG	WLHKRGEYIK	TWRPRYFLLK	SDGSFIGYKE	RPEAPDQTLP	PLNNFSVAEC
70	80	90	100	110	120
QLMKTERPRP	NTFVIRCLQW	TTVIERTFHV	DSPDEREEWM	RAIQMVANSL	KQRAPGEDPM
130	140	150	160	170	180
DYKCGSPSDS	STTEEMEVAV	SKARAKVTMN	DFDYLKLLGK	GTFGKVILVR	EKATGRYYAM
190	200	210	220	230	240
KILRKEVIIA	KDEVAHTVTE	SRVLQNTRHP	FLTALKYAFQ	THDRLCFVME	YANGGELFFH
250	260	270	280	290	300
LSRERVFTEE	RARFYGAEIV	SALEYLHSRD	VVYRDIKLEN	LMLDKDGHIK	ITDFGLCKEG
310	320	330	340	350	360
ISDGATMKTF	CGTPEYLAPE	VLEDNDYGRA	VDWWGLGVVM	YEMMCGRLPF	YNQDHERLFE
370	380	390	400	410	420
LILMEEIRFP	RTLSPEAKSL	LAGLLKKDPK	QRLGGGPSDA	KEVMEHRFFL	SINWQDVVQK
430	440	450	460	470	480
KLLPPFKPQV	TSEVDTRYFD	DEFTAQSITI	TPPDRYDSLG	LLELDQRTHF	PQFSYSASIR

E