AiPD: Autoinhibited Protein Database

Q9Y243

Gene name	AKT3 (PKBG)
Protein name	RAC-gamma serine/threonine-protein kinase
Names	Protein kinase Akt-3, Protein kinase B gamma, PKB gamma, RAC-PK-gamma, STK-2
Species	Homo sapiens (Human)
KEGG Pathway	hsa:10000
EC number
Protein Class

Descriptions

Akt belongs to the AGC superfamily of serine/threonine kinases, which also includes SGK and the ribosomal S6 protein kinase. Akt has been implicated as the central mediator of many biological responses associated with the phosphatidylinositol 3-kinase (PI3K) signal transduction pathway. In human AKT2 (P31751), the N-terminal PH domain plays a regulatory role in Akt2 activation. In addition, phosphorylation of Ser474 in the C-terminal regulatory domain is required for full activation of Akt2.

Autoinhibitory domains (AIDs)

5-107 (PH domain) SS

Target domain	148-479 (Protein kinase domain)
Relief mechanism	PTM
Assay

AID

5-107 (PH domain)

Target domain

148-479 (Protein kinase domain)

Relief mechanism

PTM (Phosphorylation of Ser474 or Thr309)

Assay

406-479 (C-terminal regulatory region) SS

Target domain	148-479 (Protein kinase domain)
Relief mechanism	PTM
Assay

AID

406-479 (C-terminal regulatory region)

Target domain

148-479 (Protein kinase domain)

Relief mechanism

PTM (Phosphorylation of Ser474 or Thr309)

Assay

Accessory elements

288-311 (Activation loop from InterPro)

Target domain	148-405 (Protein kinase domain)
Relief mechanism
Assay

References

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

Bichsel SJ et al. (2004) "Mechanism of activation of NDR (nuclear Dbf2-related) protein kinase by the hMOB1 protein", The Journal of biological chemistry, 279, 35228-35

Stegert MR et al. (2004) "Regulation of NDR2 protein kinase by multi-site phosphorylation and the S100B calcium-binding protein", The Journal of biological chemistry, 279, 23806-12

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

Steinberg SF (2008) "Structural basis of protein kinase C isoform function", Physiological reviews, 88, 1341-78

Sommese RF et al. (2017) "The Role of Regulatory Domains in Maintaining Autoinhibition in the Multidomain Kinase PKCα", The Journal of biological chemistry, 292, 2873-2880

Pears CJ et al. (1990) "Mutagenesis of the pseudosubstrate site of protein kinase C leads to activation", European journal of biochemistry, 194, 89-94

Smith MK et al. (1990) "Specificities of autoinhibitory domain peptides for four protein kinases. Implications for intact cell studies of protein kinase function", The Journal of biological chemistry, 265, 1837-40

Yoshinaga C et al. (1999) "Mutational analysis of the regulatory mechanism of PKN: the regulatory region of PKN contains an arachidonic acid-sensitive autoinhibitory domain", Journal of biochemistry, 126, 475-84

Ivey RA et al. (2014) "Requirements for pseudosubstrate arginine residues during autoinhibition and phosphatidylinositol 3,4,5-(PO₄)₃-dependent activation of atypical PKC", The Journal of biological chemistry, 289, 25021-30

Masters TA et al. (2010) "Regulation of 3-phosphoinositide-dependent protein kinase 1 activity by homodimerization in live cells", Science signaling, 3, ra78

Autoinhibited structure

Activated structure

2 structures for Q9Y243

Entry ID	Method	Resolution	Chain	Position	Source
2X18	X-ray	146 A	A/B/C/D/E/F/G/H	1-118	PDB
AF-Q9Y243-F1	Predicted				AlphaFoldDB

277 variants for Q9Y243

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs1553462330 CA345671785 RCV000623779	13	Q>R	Inborn genetic diseases [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
COSM1134860 rs397514606 VAR_065830 COSM1134859 COSM224779 CA130584	17	E>K	kidney MPPH2 and melanoma; results in activation of AKT skin [Cosmic, UniProt]	Yes	ClinGen cosmic curated UniProt Ensembl dbSNP
RCV000533230 rs1553428545 CA345669292	75	R>K	Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV001249248 rs1680073345	182	E>missing	AKT3-Related Disorder [ClinVar]	Yes	ClinVar dbSNP
rs886041100 CA10602705 RCV000258932	183	V>D	Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000416600 VAR_069260 RCV000033036 CA130581 rs397514605	229	N>S	MPPH2 Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 Megalencephaly-capillary malformation-polymicrogyria syndrome [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV001364473 RCV001091228 rs1674673024	268	V>A	Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 [ClinVar]	Yes	ClinVar dbSNP
RCV001289464 rs1673171921	321	N>K	Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 [ClinVar]	Yes	ClinVar dbSNP
rs1048970120 CA41022931 RCV001198092	414	Y>C	Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
CA345668745 RCV000557906 rs868556430	426	V>L	Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV001172028 RCV000995482 rs1574509510 CA345668622	444	I>V	Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs587776935 CA130580 VAR_069261	465	R>W	MPPH2; disease phenotype overlaps with megalencephaly-capillary malformation syndrome [UniProt]	Yes	ClinGen UniProt Ensembl dbSNP
rs1182345628 CA345671841	5	T>A		No	ClinGen gnomAD
rs1182345628	5	T>A		No	gnomAD
rs758329804	5	T>I		No	ExAC gnomAD
rs758329804 CA1484213	5	T>I		No	ClinGen ExAC gnomAD
rs750279631 CA1484212	6	I>V		No	ClinGen ExAC gnomAD
rs750279631	6	I>V		No	ExAC gnomAD
rs377541484	9	E>A		No	ESP ExAC gnomAD
CA1484210 rs377541484	9	E>A		No	ClinGen ESP ExAC gnomAD
rs1553462330	13	Q>R		No	Ensembl
rs397514606	17	E>K		No	Ensembl
CA345671412 rs1459278370	21	N>Y		No	ClinGen TOPMed
rs1459278370	21	N>Y		No	TOPMed
rs1199307351	22	W>*		No	TOPMed
CA345671398 rs1199307351	22	W>*		No	ClinGen TOPMed
rs1261943456	26	Y>F		No	gnomAD
CA345671372 rs1261943456	26	Y>F		No	ClinGen gnomAD
rs866042852	33	G>V		No	Ensembl
rs866042852 CA41040445	33	G>V		No	ClinGen Ensembl
rs1210004922 CA345671314	34	S>L		No	ClinGen gnomAD
rs1210004922	34	S>L		No	gnomAD
rs1346589083	36	I>V		No	gnomAD
rs1346589083 CA345671304	36	I>V		No	ClinGen gnomAD
CA345671280 rs1281393478	39	K>R		No	ClinGen gnomAD
rs1281393478	39	K>R		No	gnomAD
CA345671241 rs1220113079	44	D>G		No	ClinGen gnomAD
rs1220113079	44	D>G		No	gnomAD
rs866698621	51	L>R		No	Ensembl
rs866698621 COSM309035 CA41040442	51	L>R	lung [Cosmic]	No	ClinGen cosmic curated Ensembl
rs1402121409 CA345671161	56	V>M		No	ClinGen gnomAD
rs1402121409	56	V>M		No	gnomAD
rs761062123	60	Q>H		No	ExAC gnomAD
CA1484161 rs761062123 COSM369229	60	Q>H	lung [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
COSM1473714 CA345669353 COSM425791 rs1399248274 COSM1473715	66	R>*	breast [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1399248274	66	R>*		No	gnomAD
CA345669351 rs1328985736	66	R>Q		No	ClinGen gnomAD
rs1328985736	66	R>Q		No	gnomAD
rs771617244 CA1484159	69	P>S		No	ClinGen ExAC gnomAD
rs771617244	69	P>S		No	ExAC gnomAD
rs1553428545	75	R>K		No	Ensembl
rs773758145 CA1484157	81	T>A		No	ClinGen ExAC gnomAD
rs773758145	81	T>A		No	ExAC gnomAD
CA345669238 rs1415378343	83	I>V		No	ClinGen gnomAD
rs1415378343	83	I>V		No	gnomAD
CA345669211 rs1182923739	87	F>L		No	ClinGen TOPMed gnomAD
rs1182923739	87	F>L		No	TOPMed gnomAD
rs1216797938 CA345669172	92	P>Q		No	ClinGen gnomAD
rs1216797938	92	P>Q		No	gnomAD
CA1484155 rs749228367	94	E>K		No	ClinGen ExAC gnomAD
rs749228367	94	E>K		No	ExAC gnomAD
rs1024318873	99	T>A		No	TOPMed
rs1024318873 CA41034427	99	T>A		No	ClinGen TOPMed
rs762440650	101	A>T		No	ExAC gnomAD
rs762440650 CA1484138	101	A>T		No	ClinGen ExAC gnomAD
rs1300272660 CA345670756	105	V>I		No	ClinGen gnomAD
rs1300272660	105	V>I		No	gnomAD
rs1255579371	106	A>T		No	TOPMed
CA345670750 rs1255579371	106	A>T		No	ClinGen TOPMed
rs1384888633	108	R>S		No	gnomAD
rs1384888633 CA345670730	108	R>S		No	ClinGen gnomAD
rs201189866	111	R>S		No	1000Genomes ExAC TOPMed gnomAD
rs201189866 CA41034426	111	R>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA1484134 rs780868494	117	M>I		No	ClinGen ExAC gnomAD
rs780868494	117	M>I		No	ExAC gnomAD
CA1484133 rs371339772	122	T>A		No	ClinGen ESP ExAC TOPMed gnomAD
rs371339772	122	T>A		No	ESP ExAC TOPMed gnomAD
rs367585326	122	T>I		No	ESP ExAC TOPMed gnomAD
CA345670630 rs367585326	122	T>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs367585326	122	T>N		No	ESP ExAC TOPMed gnomAD
rs367585326 CA345670631	122	T>N		No	ClinGen ESP ExAC TOPMed gnomAD
rs367585326 CA1484132	122	T>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs367585326	122	T>S		No	ESP ExAC TOPMed gnomAD
rs757469708	125	I>M		No	ExAC gnomAD
CA1484130 rs757469708	125	I>M		No	ClinGen ExAC gnomAD
rs200534356 CA1484131	125	I>T		No	ClinGen ExAC gnomAD
rs200534356	125	I>T		No	ExAC gnomAD
CA41034424 RCV000493181 rs374658863	128	I>M		No	ClinGen ClinVar 1000Genomes ESP TOPMed dbSNP
rs374658863	128	I>M		No	1000Genomes ESP TOPMed
rs1487348762	128	I>T		No	gnomAD
CA345670591 rs1487348762	128	I>T		No	ClinGen gnomAD
rs984642349	128	I>V		No	gnomAD
CA41034425 rs984642349	128	I>V		No	ClinGen gnomAD
CA345670585 rs1429439523	129	G>A		No	ClinGen TOPMed
rs1429439523	129	G>A		No	TOPMed
rs1217463895 CA345670531	136	S>F		No	ClinGen gnomAD
rs1217463895	136	S>F		No	gnomAD
rs1351256745 CA345670529	137	T>A		No	ClinGen TOPMed gnomAD
rs1351256745	137	T>A		No	TOPMed gnomAD
CA1484128 rs202064755	137	T>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs202064755	137	T>I		No	1000Genomes ExAC TOPMed gnomAD
rs1230714185 CA345670522	138	T>I		No	ClinGen gnomAD
rs1230714185	138	T>I		No	gnomAD
COSM1139119 COSM533998 rs1173790414 CA345670517 COSM1139120	139	H>Y	lung [Cosmic]	No	ClinGen cosmic curated TOPMed
rs1173790414	139	H>Y		No	TOPMed
rs756197145	150	Y>C		No	ExAC gnomAD
CA1484107 rs756197145	150	Y>C		No	ClinGen ExAC gnomAD
rs1426791205	152	K>R		No	TOPMed gnomAD
CA345669881 rs1426791205	152	K>R		No	ClinGen TOPMed gnomAD
rs1085307712	161	K>Q		No	Ensembl
CA345669825 RCV000490118 rs1085307712	161	K>Q		No	ClinGen ClinVar Ensembl dbSNP
CA1484104 rs755369410	167	E>D		No	ClinGen ExAC gnomAD
rs755369410	167	E>D		No	ExAC gnomAD
CA345669765 rs1572072780	170	S>C		No	ClinGen Ensembl
rs1572072780	170	S>C		No	Ensembl
rs1402272180	171	G>R		No	TOPMed
COSM13303 VAR_040358 rs1402272180 CA345669759	171	G>R	central_nervous_system a glioblastoma multiforme sample; somatic mutation [Cosmic, UniProt]	No	ClinGen cosmic curated UniProt TOPMed dbSNP
rs1472506491	173	Y>C		No	gnomAD
rs1472506491 CA345669741	173	Y>C		No	ClinGen gnomAD
rs1187260557 CA345669736	174	Y>H		No	ClinGen gnomAD
rs1187260557	174	Y>H		No	gnomAD
rs80155418	180	K>N		No	Ensembl
CA41033285 rs80155418	180	K>N		No	ClinGen Ensembl
rs1446319397 CA345669689	180	K>R		No	ClinGen gnomAD
rs1446319397	180	K>R		No	gnomAD
rs886041100	183	V>D		No	Ensembl
rs1243709826	183	V>I		No	gnomAD
CA345669671 rs1243709826	183	V>I		No	ClinGen gnomAD
rs758066333	184	I>V		No	ExAC gnomAD
CA1484101 rs758066333	184	I>V		No	ClinGen ExAC gnomAD
CA345669136 rs1436246295	188	D>N		No	ClinGen gnomAD
rs1436246295	188	D>N		No	gnomAD
rs1343245309	190	V>M		No	gnomAD
CA345669119 rs1343245309	190	V>M		No	ClinGen gnomAD
rs767433650	191	A>V		No	ExAC gnomAD
rs767433650 CA1484073	191	A>V		No	ClinGen ExAC gnomAD
rs887159202 CA41030717	194	L>V		No	ClinGen TOPMed gnomAD
rs887159202	194	L>V		No	TOPMed gnomAD
rs1360057195 CA345669072	197	S>N		No	ClinGen gnomAD
rs1360057195	197	S>N		No	gnomAD
rs993297588	200	L>F		No	TOPMed gnomAD
CA41030716 rs993297588	200	L>F		No	ClinGen TOPMed gnomAD
rs200428825	220	R>H		No	ESP ExAC TOPMed gnomAD
CA1484058 rs200428825	220	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
CA1484057 rs753382585	221	L>F		No	ClinGen ExAC gnomAD
rs753382585	221	L>F		No	ExAC gnomAD
rs530590989	229	N>D		No	1000Genomes
rs530590989 CA41030554	229	N>D		No	ClinGen 1000Genomes
rs397514605	229	N>S		No	Ensembl
rs771134997	238	S>L		No	ExAC TOPMed gnomAD
rs771134997 CA1484041	238	S>L		No	ClinGen ExAC TOPMed gnomAD
rs755752354	241	R>L		No	ExAC gnomAD
rs755752354 CA1484038	241	R>L		No	ClinGen ExAC gnomAD
rs752227326	242	V>L		No	ExAC gnomAD
rs752227326 CA1484037	242	V>L		No	ClinGen ExAC gnomAD
rs754990008	247	R>C		No	ExAC gnomAD
CA1484035 rs754990008	247	R>C		No	ClinGen ExAC gnomAD
rs568298910	249	R>H		No	1000Genomes ExAC TOPMed gnomAD
CA1484034 rs568298910	249	R>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1226713181 CA345671618	250	F>S		No	ClinGen gnomAD
rs1226713181	250	F>S		No	gnomAD
rs766197531	251	Y>C		No	ExAC TOPMed gnomAD
CA1484033 rs766197531	251	Y>C		No	ClinGen ExAC TOPMed gnomAD
CA1484031 rs78293563	253	A>V		No	ClinGen 1000Genomes ExAC gnomAD
rs78293563	253	A>V		No	1000Genomes ExAC gnomAD
rs764214500	257	S>C		No	ExAC gnomAD
rs764214500 CA1484030	257	S>C		No	ClinGen ExAC gnomAD
rs772090769	265	G>R		No	ExAC gnomAD
CA1484027 COSM1340762 rs772090769	265	G>R	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1439435818	270	R>S		No	gnomAD
rs1439435818 CA345671488	270	R>S		No	ClinGen gnomAD
CA1484003 rs752876589	280	D>G		No	ClinGen ExAC gnomAD
rs752876589	280	D>G		No	ExAC gnomAD
rs1216018093 CA345671050	285	I>M		No	ClinGen gnomAD
rs1216018093	285	I>M		No	gnomAD
rs774991430	285	I>V		No	ExAC gnomAD
rs774991430 CA1484000	285	I>V		No	ClinGen ExAC gnomAD
CA41024856 rs778412034	288	T>K		No	ClinGen Ensembl
rs778412034	288	T>K		No	Ensembl
rs773474217	300	A>T		No	ExAC gnomAD
CA1483997 COSM1501945 rs773474217	300	A>T	lung [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1168181651	304	K>R		No	TOPMed
CA345670919 rs1168181651	304	K>R		No	ClinGen TOPMed
rs1303187078 CA345670890	308	G>D		No	ClinGen gnomAD
rs1303187078	308	G>D		No	gnomAD
rs1064795602	322	D>N		No	Ensembl
RCV000487269 rs1064795602 CA16617120	322	D>N		No	ClinGen ClinVar Ensembl dbSNP
rs1247342442	326	A>T		No	TOPMed
rs1247342442 CA345670405	326	A>T		No	ClinGen TOPMed
rs773792621	336	M>I		No	ExAC gnomAD
rs773792621 CA1483979	336	M>I		No	ClinGen ExAC gnomAD
rs763403101	336	M>V		No	ExAC gnomAD
CA1483980 rs763403101	336	M>V		No	ClinGen ExAC gnomAD
CA345670270 rs1019736328	344	L>F		No	ClinGen TOPMed gnomAD
rs1019736328	344	L>F		No	TOPMed gnomAD
rs1251119164	349	Q>R		No	gnomAD
CA345670235 rs1251119164	349	Q>R		No	ClinGen gnomAD
rs768388837 CA1483975	360	M>T		No	ClinGen ExAC gnomAD
rs768388837	360	M>T		No	ExAC gnomAD
rs760280114 CA1483974	361	E>G		No	ClinGen ExAC TOPMed gnomAD
rs760280114	361	E>G		No	ExAC TOPMed gnomAD
rs1198994311 CA345670140	362	D>N		No	ClinGen TOPMed
rs1198994311	362	D>N		No	TOPMed
rs1257968510	363	I>T		No	TOPMed
rs1257968510 CA345670129	363	I>T		No	ClinGen TOPMed
rs771570730	374	K>E		No	ExAC gnomAD
CA1483972 rs771570730	374	K>E		No	ClinGen ExAC gnomAD
rs1376625347	384	D>G		No	TOPMed
CA345669991 rs1376625347	384	D>G		No	ClinGen TOPMed
rs942187513 CA41022937	394	D>N		No	ClinGen Ensembl
rs942187513	394	D>N		No	Ensembl
rs1558604096	397	K>R		No	Ensembl
rs1558604096 CA345669574	397	K>R		No	ClinGen Ensembl
rs1195814923	400	M>I		No	gnomAD
rs1195814923 CA345669548	400	M>I		No	ClinGen gnomAD
rs771494754	401	R>K		No	ExAC TOPMed gnomAD
CA1483955 rs771494754	401	R>K		No	ClinGen ExAC TOPMed gnomAD
rs910742701	402	H>R		No	Ensembl
CA41022935 rs910742701	402	H>R		No	ClinGen Ensembl
rs777060434	402	H>Y		No	Ensembl
CA41022936 rs777060434	402	H>Y		No	ClinGen Ensembl
rs986720230	409	N>K		No	gnomAD
rs986720230	409	N>K		No	gnomAD
CA345669486 rs986720230	409	N>K		No	ClinGen gnomAD
CA41022933 rs986720230	409	N>K		No	ClinGen gnomAD
rs113943363 CA41022934	409	N>S		No	ClinGen Ensembl
rs113943363	409	N>S		No	Ensembl
rs769299773	413	V>I		No	TOPMed
rs769299773 CA41022932	413	V>I		No	ClinGen TOPMed
rs1048970120	414	Y>C		No	TOPMed gnomAD
rs1344843803 CA345668793	418	L>P		No	ClinGen TOPMed
rs1344843803	418	L>P		No	TOPMed
rs762883936 CA1483932	420	P>S		No	ClinGen ExAC gnomAD
rs762883936	420	P>S		No	ExAC gnomAD
rs769538692	421	P>A		No	ExAC gnomAD
CA1483930 rs769538692	421	P>A		No	ClinGen ExAC gnomAD
rs1290444154	424	P>L		No	TOPMed
rs1290444154 CA345668755	424	P>L		No	ClinGen TOPMed
rs868556430	426	V>I		No	Ensembl
rs868556430 CA41019244	426	V>I		No	ClinGen Ensembl
rs868556430	426	V>L		No	Ensembl
rs775611627	427	T>I		No	ExAC gnomAD
rs775611627 CA1483928	427	T>I		No	ClinGen ExAC gnomAD
rs746036442	430	T>I		No	ExAC gnomAD
rs746036442 CA1483926	430	T>I		No	ClinGen ExAC gnomAD
rs888799070 CA41019243	439	F>L		No	ClinGen Ensembl
rs888799070	439	F>L		No	Ensembl
rs964744343	440	T>I		No	TOPMed
rs964744343 CA41019242	440	T>I		No	ClinGen TOPMed
CA345668638 rs1325571748	441	A>V		No	ClinGen TOPMed
rs1325571748	441	A>V		No	TOPMed
rs1574509510	444	I>V		No	Ensembl
CA1483924 rs757338728	446	I>V		No	ClinGen ExAC TOPMed gnomAD
rs757338728	446	I>V		No	ExAC TOPMed gnomAD
rs368205016	452	Y>C		No	ESP ExAC TOPMed gnomAD
CA1483909 rs368205016	452	Y>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs1442713931 CA345668569	452	Y>H		No	ClinGen gnomAD
rs1442713931	452	Y>H		No	gnomAD
rs375329841 CA1483908	453	D>G		No	ClinGen ESP ExAC gnomAD
rs375329841	453	D>G		No	ESP ExAC gnomAD
rs1270894056 CA345668516	457	M>I		No	ClinGen gnomAD
rs1270894056	457	M>I		No	gnomAD
rs1216439857 CA345668500	459	C>F		No	ClinGen gnomAD
rs1216439857	459	C>F		No	gnomAD
rs1197744936	460	M>T		No	TOPMed
rs1197744936 CA345668495	460	M>T		No	ClinGen TOPMed
rs774657057	460	M>V		No	ExAC gnomAD
rs774657057 CA1483906	460	M>V		No	ClinGen ExAC gnomAD
rs771193056 CA1483905	461	D>E		No	ClinGen ExAC gnomAD
rs771193056	461	D>E		No	ExAC gnomAD
CA1483904 rs749347952	462	N>S		No	ClinGen ExAC gnomAD
rs749347952	462	N>S		No	ExAC gnomAD
rs587776935	465	R>W		No	Ensembl
rs1287560468 CA345668377	477	G>R		No	ClinGen TOPMed
rs1287560468	477	G>R		No	TOPMed
rs751275167	478	R>Q		No	ExAC gnomAD
CA1483898 rs751275167	478	R>Q		No	ClinGen ExAC gnomAD

2 associated diseases with Q9Y243

[MIM: 615937]: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (MPPH2)

A syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome. {ECO:0000269|PubMed:22500628, ECO:0000269|PubMed:22729223, ECO:0000269|PubMed:22729224, ECO:0000269|PubMed:23745724}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

A syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome. {ECO:0000269|PubMed:22500628, ECO:0000269|PubMed:22729223, ECO:0000269|PubMed:22729224, ECO:0000269|PubMed:23745724}. Note=The disease is caused by variants affecting the gene represented in this entry.

7 regional properties for Q9Y243

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	501 - 786	IPR000719
domain	S-locus glycoprotein domain	206 - 316	IPR000858
domain	Serine-threonine/tyrosine-protein kinase, catalytic domain	502 - 770	IPR001245
domain	Bulb-type lectin domain	24 - 174	IPR001480
domain	PAN/Apple domain	337 - 423	IPR003609
active_site	Serine/threonine-protein kinase, active site	622 - 634	IPR008271
domain	S-locus receptor kinase, C-terminal	773 - 814	IPR021820

Functions

		Description
EC Number
Subcellular Localization	Nucleus Cytoplasm Membrane ; Peripheral membrane protein	Membrane-associated after cell stimulation leading to its translocation
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

3 GO annotations of cellular component

Name	Definition
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
membrane	A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.
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.

5 GO annotations of molecular function

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

16 GO annotations of biological process

Name	Definition
brain morphogenesis	The process in which the anatomical structures of the brain are generated and organized. The brain is one of the two components of the central nervous system and is the center of thought and emotion. It is responsible for the coordination and control of bodily activities and the interpretation of information from the senses (sight, hearing, smell, etc.).
homeostasis of number of cells within a tissue	Any biological process involved in the maintenance of the steady-state number of cells within a population of cells in a tissue.
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.
mitochondrial genome maintenance	The maintenance of the structure and integrity of the mitochondrial genome; includes replication and segregation of the mitochondrial chromosome.
negative regulation of cellular senescence	Any process that stops, prevents or reduces the frequency, rate or extent of cellular senescence.
peptidyl-serine phosphorylation	The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
positive regulation of angiogenesis	Any process that activates or increases angiogenesis.
positive regulation of artery morphogenesis	Any process that activates or increases the frequency, rate or extent of artery morphogenesis.
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 migration involved in sprouting angiogenesis	Any process that increases the frequency, rate or extent of cell migration involved in sprouting angiogenesis. Cell migration involved in sprouting angiogenesis is the orderly movement of endothelial cells into the extracellular matrix in order to form new blood vessels contributing to the process of sprouting angiogenesis.
positive regulation of cell size	Any process that increases cell size.
positive regulation of endothelial cell proliferation	Any process that activates or increases the rate or extent of endothelial cell proliferation.
positive regulation of TOR signaling	Any process that activates or increases the frequency, rate or extent of TOR signaling.
positive regulation of vascular endothelial cell proliferation	Any process that activates or increases the frequency, rate or extent of vascular endothelial cell proliferation.
protein phosphorylation	The process of introducing a phosphate group on to a protein.
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
P31751	AKT2	RAC-beta serine/threonine-protein kinase	Homo sapiens (Human)	EV SS
P31749	AKT1	RAC-alpha serine/threonine-protein kinase	Homo sapiens (Human)	EV
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
Q60823	Akt2	RAC-beta serine/threonine-protein kinase	Mus musculus (Mouse)	PR
Q9WUA6	Akt3	RAC-gamma serine/threonine-protein kinase	Mus musculus (Mouse)	PR
P47197	Akt2	RAC-beta serine/threonine-protein kinase	Rattus norvegicus (Rat)	SS
P47196	Akt1	RAC-alpha serine/threonine-protein kinase	Rattus norvegicus (Rat)	PR
Q63484	Akt3	RAC-gamma 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
MSDVTIVKEG	WVQKRGEYIK	NWRPRYFLLK	TDGSFIGYKE	KPQDVDLPYP	LNNFSVAKCQ
70	80	90	100	110	120
LMKTERPKPN	TFIIRCLQWT	TVIERTFHVD	TPEEREEWTE	AIQAVADRLQ	RQEEERMNCS
130	140	150	160	170	180
PTSQIDNIGE	EEMDASTTHH	KRKTMNDFDY	LKLLGKGTFG	KVILVREKAS	GKYYAMKILK
190	200	210	220	230	240
KEVIIAKDEV	AHTLTESRVL	KNTRHPFLTS	LKYSFQTKDR	LCFVMEYVNG	GELFFHLSRE
250	260	270	280	290	300
RVFSEDRTRF	YGAEIVSALD	YLHSGKIVYR	DLKLENLMLD	KDGHIKITDF	GLCKEGITDA
310	320	330	340	350	360
ATMKTFCGTP	EYLAPEVLED	NDYGRAVDWW	GLGVVMYEMM	CGRLPFYNQD	HEKLFELILM
370	380	390	400	410	420
EDIKFPRTLS	SDAKSLLSGL	LIKDPNKRLG	GGPDDAKEIM	RHSFFSGVNW	QDVYDKKLVP
430	440	450	460	470
PFKPQVTSET	DTRYFDEEFT	AQTITITPPE	KYDEDGMDCM	DNERRPHFPQ	FSYSASGRE