AiPD: Autoinhibited Protein Database

P08754

Gene name	GNAI3
Protein name	Guanine nucleotide-binding protein G
Names	i subunit alpha-3 , G, i alpha-3
Species	Homo sapiens (Human)
KEGG Pathway	hsa:2773
EC number
Protein Class

Descriptions

Gαi1 is a G-protein alpha subunit that plays a crucial role in signal transduction pathway initiated by G-protein-coupled receptor (GPCR) activation. G proteins function as transducers downstream of GPCRs in numerous signaling cascades. The alpha subunit contains the guanine nucleotide binding site and alternates between an active (GTP-bound state) and an inactive (GDP-bound state). Activated GPCR induces conformational change in Gαi1, which allows for GDP-to-GTP exchange by binding to the GPCR-binding site within a Ras-like domain, leading to dissociation of the Gαi1 subunit and initiation of downstream signaling.

Autoinhibitory domains (AIDs)

62-177 (α-H domain) SS

Target domain	184-348 (Ras-like domain)
Relief mechanism	Ligand binding, Partner binding
Assay

AID

62-177 (α-H domain)

Target domain

184-348 (Ras-like domain)

Relief mechanism

Ligand binding (GTP binding), Partner binding(Binding of activated GPCR)

Assay

Accessory elements

No accessory elements

References

Goricanec D et al. (2016) "Conformational dynamics of a G-protein α subunit is tightly regulated by nucleotide binding", Proceedings of the National Academy of Sciences of the United States of America, 113, E3629-38

Coleman DE et al. (1999) "Structure of Gialpha1.GppNHp, autoinhibition in a galpha protein-substrate complex", The Journal of biological chemistry, 274, 16669-72

Lutz S et al. (2007) "Structure of Galphaq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs", Science (New York, N.Y.), 318, 1923-7

Autoinhibited structure

Activated structure

18 structures for P08754

Entry ID	Method	Resolution	Chain	Position	Source
2IHB	X-ray	271 A	A	32-354	PDB
2ODE	X-ray	190 A	A/C	4-350	PDB
2V4Z	X-ray	280 A	A	4-350	PDB
4G5O	X-ray	290 A	A/B/C/D	25-354	PDB
4G5R	X-ray	348 A	A/B/C/D	25-354	PDB
4G5S	X-ray	362 A	A/B/C/D	25-354	PDB
7E9H	EM	400 A	A	1-354	PDB
7KH0	EM	280 A	A	2-19	PDB
7RA3	EM	324 A	A	1-19	PDB
7RGP	EM	290 A	A	4-19	PDB
7T10	EM	250 A	A	1-354	PDB
7T11	EM	270 A	A	1-354	PDB
7X6I	EM	393 A	E/F/G/H	1-354	PDB
8GVX	EM	391 A	E/F/G/H	1-354	PDB
8JD6	EM	340 A	A	1-354	PDB
8SZH	EM	310 A	C	1-354	PDB
8SZI	EM	350 A	C	1-354	PDB
AF-P08754-F1	Predicted				AlphaFoldDB

296 variants for P08754

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
RCV000024332 CA129857 rs387907178 VAR_068558	40	G>R	Auriculocondylar syndrome 1 Auriculocondylar syndrome 1 (arcnd1) ARCND1; likely pathogenic [ClinVar, Ensembl, UniProt]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
VAR_088775	45	G>S	ARCND1; likely pathogenic [UniProt]	Yes	UniProt
VAR_088776 RCV003486856 rs1553223897 RCV000522627 CA341537789	47	S>N	Auriculocondylar syndrome 1 ARCND1; likely pathogenic [ClinVar, UniProt]	Yes	ClinGen ClinVar Ensembl dbSNP UniProt
CA144738 rs397514768 RCV000054837 VAR_088777	47	S>R	Auriculocondylar syndrome 1 Auriculocondylar syndrome 1 (arcnd1) ARCND1; likely pathogenic [ClinVar, Ensembl, UniProt]	Yes	ClinGen ClinVar Ensembl dbSNP UniProt
rs1553223899 RCV000661971	49	I>T	Auriculocondylar syndrome 1 [ClinVar]	Yes	ClinVar Ensembl dbSNP
RCV002552676 rs142294586 RCV001395809	134	G>S	Inborn genetic diseases [ClinVar]	Yes	ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs1647894530	6	S>R		No	TOPMed
rs759308989	7	A>T		No	ExAC TOPMed gnomAD
TCGA novel rs1647894763	8	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Ensembl
COSM4892771	9	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
COSM893535	9	D>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1377976855	10	K>N		No	TOPMed
rs1364731927	10	K>R		No	TOPMed gnomAD
rs765061923	12	A>S		No	ExAC gnomAD
rs1470319513	13	V>L		No	TOPMed gnomAD
rs1304624945	14	E>Q		No	gnomAD
rs998068034	15	R>G		No	Ensembl
rs1157917891	15	R>Q		No	TOPMed
rs532356820	17	K>R		No	1000Genomes
rs532356820	17	K>T		No	1000Genomes
rs1395654665	18	M>T		No	gnomAD
rs758232853	21	R>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs1185211300	22	N>H		No	TOPMed gnomAD
rs1571143525	22	N>S		No	Ensembl
rs1407780609	24	R>Q		No	gnomAD
rs552016998	27	G>E		No	1000Genomes ExAC gnomAD
rs1647897205	27	G>W		No	TOPMed
COSM4020381	28	E>G	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1647897698	31	A>G		No	TOPMed
rs1647897632	31	A>S		No	Ensembl
rs1484210996	32	K>R		No	TOPMed gnomAD
rs1571143550	34	V>G		No	Ensembl
rs2101084857	34	V>M		No	Ensembl
rs1647898120	36	L>P		No	TOPMed
rs772399470	39	L>V		No	ExAC gnomAD
rs387907178	40	G>S	Auriculocondylar syndrome 1 (arcnd1) [Ensembl]	No	gnomAD
TCGA novel	42	G>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	43	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1648666212	44	S>C		No	Ensembl
rs1264163466	48	T>A		No	TOPMed gnomAD
rs1648666311	48	T>I		No	TOPMed
rs1648666311 RCV001269856	48	T>N		No	ClinVar TOPMed dbSNP
rs1264163466	48	T>P		No	TOPMed gnomAD
rs1648666750	49	I>M		No	gnomAD
rs762653380	49	I>V		No	ExAC TOPMed gnomAD
rs1209959386	52	Q>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA TOPMed gnomAD
rs1447808309	53	M>T		No	gnomAD
rs981945258	53	M>V		No	TOPMed gnomAD
rs1445343635	56	I>M		No	gnomAD
rs1360442445	56	I>T		No	gnomAD
rs749573857	56	I>V		No	ExAC
rs768305730	57	H>R		No	ExAC gnomAD
rs1206379975	58	E>K		No	TOPMed
rs377596642	60	G>S		No	ESP ExAC TOPMed gnomAD
rs1350784536	60	G>V		No	TOPMed
TCGA novel	62	S>I	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1648672452	63	E>A		No	Ensembl
COSM4020382	65	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1327656457	67	K>N		No	TOPMed gnomAD
rs142991217	68	Q>R		No	1000Genomes ExAC gnomAD
rs760245898	70	K>E		No	ExAC TOPMed gnomAD
rs766032672	72	V>L		No	ExAC gnomAD
rs1394246744	73	V>A		No	gnomAD
rs1571155890 COSM4020383	74	Y>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic Ensembl
rs1282184445	75	S>G		No	TOPMed
rs754615263	77	T>A		No	ExAC TOPMed gnomAD
rs764823071	77	T>I		No	ExAC gnomAD
rs764823071	77	T>S		No	ExAC gnomAD
rs754615263	77	T>S		No	ExAC TOPMed gnomAD
COSM123392 rs1648674036	78	I>V	upper_aerodigestive_tract [Cosmic]	No	cosmic curated Ensembl
rs751897781	82	I>T		No	ExAC TOPMed gnomAD
rs757625106	83	A>V		No	ExAC gnomAD
rs1648674729	84	I>S		No	TOPMed
rs146129509	84	I>V		No	ESP TOPMed
rs944930491	85	I>L		No	TOPMed
rs944930491	85	I>V		No	TOPMed
rs756166163	86	R>K		No	ExAC gnomAD
TCGA novel rs1370816061	86	R>S	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs1040602339	87	A>P		No	Ensembl
rs767886358	89	G>R		No	Ensembl
RCV000916581 rs138850957	90	R>Q		No	ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs145097404	90	R>W		No	1000Genomes ESP ExAC TOPMed gnomAD
rs768865385	91	L>V		No	ExAC TOPMed gnomAD
rs1648676016	94	D>E		No	Ensembl
rs1278137311	96	G>E		No	gnomAD
rs1648676157	96	G>R		No	Ensembl
rs2101101010	97	E>G		No	1000Genomes
rs773259816	98	A>G		No	ExAC gnomAD
rs760730490	99	A>T		No	ExAC gnomAD
rs770801709	101	A>T		No	ExAC gnomAD
rs1375149399	101	A>V		No	TOPMed
rs1416473519	102	D>G		No	gnomAD
rs1648829421	103	D>E		No	TOPMed
rs759084420	103	D>Y		No	ExAC TOPMed gnomAD
rs1648829475	104	A>S		No	TOPMed
rs371540739	105	R>Q		No	ESP ExAC TOPMed gnomAD
rs1414758829	105	R>W		No	TOPMed
rs538498659	108	F>L		No	1000Genomes ExAC TOPMed gnomAD
rs1238456421	109	V>F		No	TOPMed
rs762635947	111	A>V		No	ExAC TOPMed gnomAD
rs1326040014	114	A>T		No	TOPMed gnomAD
rs2101104973	116	E>G		No	Ensembl
TCGA novel	118	V>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs901759563	121	P>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA TOPMed gnomAD
rs760950766	121	P>L		No	ExAC gnomAD
rs766902855	123	L>I		No	ExAC TOPMed gnomAD
rs766902855	123	L>V		No	ExAC TOPMed gnomAD
rs1648830637	124	A>G		No	Ensembl
rs1648830581	124	A>P		No	TOPMed
rs1648830695	125	G>E		No	Ensembl
rs779171377	126	V>A		No	ExAC gnomAD
TCGA novel	126	V>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1648830969	129	R>Q		No	TOPMed
rs1206316589	129	R>W	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs752850874	132	R>*		No	ExAC TOPMed gnomAD
rs758640921 COSM4020384	132	R>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ExAC NCI-TCGA TOPMed gnomAD
rs746738567	134	G>D		No	ExAC gnomAD
rs770701318	135	G>R		No	ExAC gnomAD
TCGA novel	136	V>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs745843348	138	A>T		No	ExAC gnomAD
rs769318984	141	S>G		No	ExAC TOPMed gnomAD
rs554102264	143	S>C		No	1000Genomes ExAC gnomAD
rs1336402307	145	E>K		No	gnomAD
COSM1332468	146	Y>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs768230604	148	L>F		No	1000Genomes ExAC TOPMed gnomAD
rs768230604	148	L>V		No	1000Genomes ExAC TOPMed gnomAD
rs774057080	150	D>A		No	ExAC TOPMed gnomAD
rs1226552555	151	S>C		No	gnomAD
rs1259614863	152	A>P		No	TOPMed gnomAD
rs1259614863	152	A>T		No	TOPMed gnomAD
rs1345195559	153	S>L		No	gnomAD
rs2025523728	154	Y>S		No	Ensembl
rs1437244383	155	Y>N		No	TOPMed
rs747792423	160	D>E		No	ExAC TOPMed gnomAD
rs773969643	160	D>G		No	ExAC TOPMed gnomAD
rs773969643	160	D>V		No	ExAC TOPMed gnomAD
COSM4829021	161	R>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1648919760	162	I>L		No	TOPMed
rs771785264	162	I>T		No	ExAC gnomAD
rs1648919760	162	I>V		No	TOPMed
COSM3984065	163	S>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
COSM225438 rs1037845211	163	S>F	NS [Cosmic]	No	cosmic curated TOPMed gnomAD
COSM1320161	164	Q>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
COSM893537	164	Q>P	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1184071666	164	Q>R		No	TOPMed
rs1443939349	165	S>F		No	TOPMed
rs1648920324	166	N>D		No	TOPMed gnomAD
rs1199652974	166	N>K		No	Ensembl
rs1205497380	170	T>A		No	TOPMed gnomAD
RCV000900074 rs61754626	170	T>I		No	ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs1205497380	170	T>P		No	TOPMed gnomAD
rs1648920863	171	Q>E		No	TOPMed
rs1238102675	173	D>E		No	TOPMed gnomAD
rs993932612	173	D>N		No	Ensembl
rs1194522820	175	L>F		No	gnomAD
rs765776409	176	R>Q		No	ExAC TOPMed gnomAD
rs1005271218	176	R>W		No	TOPMed gnomAD
rs763113801	177	T>M		No	ExAC TOPMed gnomAD
rs1648921858	179	V>M		No	gnomAD
rs1312243694	182	T>A		No	gnomAD
rs1169540779	187	T>I		No	gnomAD
rs536687404	190	T>I		No	1000Genomes ExAC gnomAD
rs767803865	193	D>N		No	ExAC gnomAD
rs1388492799	194	L>Q		No	gnomAD
rs1298539052	195	Y>C		No	TOPMed gnomAD
rs199684276	196	F>L		No	1000Genomes ExAC TOPMed gnomAD
rs1369689853	196	F>L		No	gnomAD
rs761968376 COSM239985	197	K>N	prostate [Cosmic]	No	cosmic curated ExAC gnomAD
rs369731340	197	K>R		No	ESP TOPMed
rs767569679	198	M>L		No	ExAC gnomAD
rs1649029320	199	F>L		No	gnomAD
rs750713417	199	F>V		No	ExAC TOPMed gnomAD
rs1649029440	201	V>I		No	Ensembl
rs935291032 COSM4850210	204	Q>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic NCI-TCGA TOPMed
COSM3417834	205	R>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1271844147	206	S>*		No	TOPMed gnomAD
rs1649029734	206	S>T		No	TOPMed gnomAD
rs1173982138	207	E>D		No	gnomAD
rs766202043 COSM4020385	208	R>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ExAC NCI-TCGA TOPMed gnomAD
COSM893538	213	H>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1320143144	214	C>S		No	TOPMed gnomAD
rs1320143144	214	C>Y		No	TOPMed gnomAD
COSM4844206	216	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs754856898	219	T>I		No	ExAC gnomAD
rs1256508029	221	I>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs1392269617	222	I>L		No	gnomAD
rs755852446	223	F>L		No	gnomAD
rs778921356	224	C>S		No	ExAC TOPMed gnomAD
rs1417117553	226	A>S		No	gnomAD
COSM3470938	226	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1649030737	227	L>V		No	gnomAD
rs1457740085	228	S>I		No	TOPMed gnomAD
rs1160711205	229	D>G		No	gnomAD
rs1429587639	232	L>F		No	gnomAD
rs1303070459	233	V>I		No	gnomAD
rs1398180623 COSM3788397	238	E>K	Variant assessed as Somatic; MODERATE impact. urinary_tract [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA TOPMed gnomAD
rs1649031408	239	E>K		No	TOPMed gnomAD
TCGA novel	242	R>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs766607222	242	R>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA gnomAD
rs1286625983	244	H>P		No	Ensembl
rs1409297134	247	M>V		No	TOPMed gnomAD
rs1649040868	249	L>V		No	TOPMed
rs1343938370	251	D>E		No	TOPMed gnomAD
rs753568476	251	D>N		No	ExAC gnomAD
rs753568476	251	D>Y		No	ExAC gnomAD
rs1649041558	253	I>L		No	TOPMed
rs759328943	255	N>S		No	ExAC gnomAD
TCGA novel	255	N>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1223320569	256	N>T		No	gnomAD
COSM4020386	260	T>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1314141047	261	E>G		No	gnomAD
rs370566993	263	S>*		No	ESP ExAC
rs61758986	264	I>V		No	ESP ExAC TOPMed gnomAD
rs777387686	265	I>V		No	ExAC gnomAD
rs1557911980	268	L>F		No	Ensembl
TCGA novel	270	K>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs751150020	271	K>I		No	ExAC gnomAD
rs1469148447	272	D>E		No	TOPMed gnomAD
rs1446527399	272	D>H		No	TOPMed
rs1649043080	273	L>F		No	TOPMed
rs781004958	273	L>H		No	ExAC gnomAD
rs749599403	274	F>L		No	ExAC gnomAD
rs1649043291	274	F>S		No	TOPMed
TCGA novel	274	F>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1649043345	275	E>D		No	TOPMed
rs1452176374	277	K>E		No	TOPMed gnomAD
TCGA novel	278	I>N	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
COSM1294690	279	K>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1649043603	280	R>G		No	Ensembl
rs975415905	281	S>N		No	Ensembl
rs755438174	282	P>L		No	ExAC TOPMed gnomAD
rs984351571	284	T>I		No	gnomAD
rs1331410451	285	I>L		No	gnomAD
rs1331410451	285	I>V		No	gnomAD
rs538155138	286	C>S		No	1000Genomes
rs1247237265	287	Y>D		No	gnomAD
rs1353233613	287	Y>F		No	gnomAD
rs1649044487	290	Y>*		No	TOPMed
rs1488083940	292	G>C		No	TOPMed gnomAD
rs1488083940	292	G>S		No	TOPMed gnomAD
rs1649186242	292	G>V		No	gnomAD
TCGA novel	293	S>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	293	S>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs750147979	294	N>S		No	ExAC TOPMed gnomAD
rs112547520 RCV002274534	295	T>A		No	ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs1285631581	296	Y>C		No	TOPMed gnomAD
rs1285631581	296	Y>F		No	TOPMed gnomAD
rs1649186784	297	E>*		No	Ensembl
rs1649186724	297	E>K		No	TOPMed gnomAD
rs1349826959	299	A>V		No	TOPMed gnomAD
rs1571165287	300	A>P		No	Ensembl
rs758878530	302	Y>C		No	ExAC TOPMed gnomAD
rs1571165295	302	Y>H		No	Ensembl
rs1649187311	303	I>T		No	gnomAD
rs778253859	303	I>V		No	ExAC TOPMed gnomAD
rs747084694	304	Q>*		No	ExAC gnomAD
rs771054388	305	C>*		No	ExAC gnomAD
rs1212484942	306	Q>P		No	TOPMed gnomAD
rs1212484942	306	Q>R		No	TOPMed gnomAD
rs1649187631	309	D>N		No	TOPMed gnomAD
rs746144403 COSM674455	311	N>S	lung Variant assessed as Somatic; MODERATE impact. [Cosmic, NCI-TCGA]	No	NCI-TCGA Cosmic cosmic curated ExAC NCI-TCGA gnomAD
rs1649187705	313	R>K		No	TOPMed gnomAD
rs769944767	314	K>R		No	ExAC gnomAD
rs1649187901	315	D>Y		No	TOPMed gnomAD
rs775310579	316	T>I		No	ExAC TOPMed gnomAD
rs1571165323	316	T>P		No	Ensembl
rs1475299470	317	K>*		No	gnomAD
rs1010572885	317	K>R		No	TOPMed gnomAD
rs1649188398	318	E>K		No	TOPMed
rs1456833751	321	T>S		No	gnomAD
rs764057747	321	T>S		No	ExAC TOPMed gnomAD
rs1649188815	324	T>I		No	TOPMed
rs1649188870	325	C>G		No	TOPMed
COSM893540	328	D>G	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1360252169	328	D>H		No	TOPMed gnomAD
rs1402664631	329	T>A		No	gnomAD
RCV001174948 rs1316507687	329	T>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinVar NCI-TCGA TOPMed dbSNP gnomAD
rs1448517515	330	K>N		No	TOPMed gnomAD
rs1369725282	331	N>H		No	TOPMed gnomAD
rs767175862	331	N>K		No	ExAC gnomAD
rs1353457033	332	V>M		No	gnomAD
rs1008562705	334	F>I		No	TOPMed gnomAD
rs1162004404	339	V>I		No	TOPMed gnomAD
TCGA novel	340	T>R	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs749982513	342	V>A		No	ExAC gnomAD
rs1649190029	342	V>I		No	Ensembl
rs138513964	343	I>N		No	ESP
rs138513964	343	I>T		No	ESP
rs755742994	344	I>V		No	ExAC TOPMed gnomAD
rs1283147244	345	K>I		No	gnomAD
RCV001763791 rs2101113277	346	N>I		No	ClinVar Ensembl dbSNP
TCGA novel	346	N>T	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1649190568	347	N>S		No	gnomAD
rs1649190866	351	C>R		No	Ensembl
rs1187959410	354	Y>C		No	gnomAD
rs1187959410	354	Y>F		No	gnomAD

1 associated diseases with P08754

[MIM: 602483]: Auriculocondylar syndrome 1 (ARCND1)

An autosomal dominant form of auriculocondylar syndrome, a craniofacial malformation syndrome characterized by variable mandibular anomalies, including mild to severe micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark (question-mark ear). Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia. Glossoptosis, masticatory abnormalities, orthodontic problems, and malocclusion occur in a majority of affected subjects. . Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

An autosomal dominant form of auriculocondylar syndrome, a craniofacial malformation syndrome characterized by variable mandibular anomalies, including mild to severe micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark (question-mark ear). Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia. Glossoptosis, masticatory abnormalities, orthodontic problems, and malocclusion occur in a majority of affected subjects. . Note=The disease is caused by variants affecting the gene represented in this entry.

1 regional properties for P08754

Type	Name	Position	InterPro Accession
domain	Formin, FH2 domain	68 - 464	IPR015425

Functions

		Description
EC Number
Subcellular Localization	Cytoplasm Cell membrane ; Lipid-anchor Cytoplasm, cytoskeleton, microtubule organizing center, centrosome	Localizes in the centrosomes of interphase and mitotic cells Detected at the cleavage furrow and/or the midbody
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

11 GO annotations of cellular component

Name	Definition
centrosome	A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle.
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
extracellular exosome	A vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane. Extracellular exosomes, also simply called exosomes, have a diameter of about 40-100 nm.
Golgi apparatus	A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways.
heterotrimeric G-protein complex	Any of a family of heterotrimeric GTP-binding and hydrolyzing proteins; they belong to a superfamily of GTPases that includes monomeric proteins such as EF-Tu and RAS. Heterotrimeric G-proteins consist of three subunits; the alpha subunit contains the guanine nucleotide binding site and possesses GTPase activity; the beta and gamma subunits are tightly associated and function as a beta-gamma heterodimer; extrinsic plasma membrane proteins (cytoplasmic face) that function as a complex to transduce signals from G protein-coupled receptors to an effector protein.
lysosomal membrane	The lipid bilayer surrounding the lysosome and separating its contents from the cell cytoplasm.
membrane	A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it.
midbody	A thin cytoplasmic bridge formed between daughter cells at the end of cytokinesis. The midbody forms where the contractile ring constricts, and may persist for some time before finally breaking to complete cytokinesis.
nucleolus	A small, dense body one or more of which are present in the nucleus of eukaryotic cells. It is rich in RNA and protein, is not bounded by a limiting membrane, and is not seen during mitosis. Its prime function is the transcription of the nucleolar DNA into 45S ribosomal-precursor RNA, the processing of this RNA into 5.8S, 18S, and 28S components of ribosomal RNA, and the association of these components with 5S RNA and proteins synthesized outside the nucleolus. This association results in the formation of ribonucleoprotein precursors; these pass into the cytoplasm and mature into the 40S and 60S subunits of the ribosome.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

6 GO annotations of molecular function

Name	Definition
G protein-coupled receptor binding	Binding to a G protein-coupled receptor.
G-protein beta/gamma-subunit complex binding	Binding to a complex of G-protein beta/gamma subunits.
GDP binding	Binding to GDP, guanosine 5'-diphosphate.
GTP binding	Binding to GTP, guanosine triphosphate.
GTPase activity	Catalysis of the reaction
metal ion binding	Binding to a metal ion.

8 GO annotations of biological process

Name	Definition
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	A G protein-coupled receptor signaling pathway in which the signal is transmitted via the inhibition of adenylyl cyclase activity and a subsequent decrease in the intracellular concentration of cyclic AMP (cAMP).
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	A G protein-coupled receptor signaling pathway in which the signal is transmitted via the activation or inhibition of adenylyl cyclase activity and a subsequent change in the intracellular concentration of cyclic AMP (cAMP).
cell cycle	The progression of biochemical and morphological phases and events that occur in a cell during successive cell replication or nuclear replication events. Canonically, the cell cycle comprises the replication and segregation of genetic material followed by the division of the cell, but in endocycles or syncytial cells nuclear replication or nuclear division may not be followed by cell division.
cell division	The process resulting in division and partitioning of components of a cell to form more cells; may or may not be accompanied by the physical separation of a cell into distinct, individually membrane-bounded daughter cells.
dopamine receptor signaling pathway	The series of molecular signals generated as a consequence of a dopamine receptor binding to one of its physiological ligands.
GTP metabolic process	The chemical reactions and pathways involving GTP, guanosine triphosphate.
negative regulation of adenylate cyclase activity	Any process that stops, prevents, or reduces the frequency, rate or extent of adenylate cyclase activity.
positive regulation of macroautophagy	Any process, such as recognition of nutrient depletion, that activates or increases the rate of macroautophagy to bring cytosolic macromolecules to the vacuole/lysosome for degradation.

61 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P63097	GNAI1	Guanine nucleotide-binding protein G	Bos taurus (Bovine)	SS
P0C7Q4	GNAT3	Guanine nucleotide-binding protein G	Bos taurus (Bovine)	SS
P04696	GNAT2	Guanine nucleotide-binding protein G	Bos taurus (Bovine)	SS
P04695	GNAT1	Guanine nucleotide-binding protein G	Bos taurus (Bovine)	SS
P08239	GNAO1	Guanine nucleotide-binding protein G	Bos taurus (Bovine)	SS
P50147	GNAI2	Guanine nucleotide-binding protein G	Gallus gallus (Chicken)	SS
P50146	GNAI1	Guanine nucleotide-binding protein G	Gallus gallus (Chicken)	SS
P16378	Galphao	G protein alpha o subunit	Drosophila melanogaster (Fruit fly)	SS
P25157	cta	Guanine nucleotide-binding protein subunit alpha homolog	Drosophila melanogaster (Fruit fly)	SS
P20353	Galphai	G protein alpha i subunit	Drosophila melanogaster (Fruit fly)	SS
A8MTJ3	GNAT3	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
P11488	GNAT1	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
P19086	GNAZ	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
P19087	GNAT2	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
P29992	GNA11	Guanine nucleotide-binding protein subunit alpha-11	Homo sapiens (Human)	SS
P30679	GNA15	Guanine nucleotide-binding protein subunit alpha-15	Homo sapiens (Human)	SS
P50148	GNAQ	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
O95837	GNA14	Guanine nucleotide-binding protein subunit alpha-14	Homo sapiens (Human)	SS
Q14344	GNA13	Guanine nucleotide-binding protein subunit alpha-13	Homo sapiens (Human)	SS
Q03113	GNA12	Guanine nucleotide-binding protein subunit alpha-12	Homo sapiens (Human)	SS
P38405	GNAL	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
P04899	GNAI2	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
P63096	GNAI1	Guanine nucleotide-binding protein G	Homo sapiens (Human)	EV
P09471	GNAO1	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
P27600	Gna12	Guanine nucleotide-binding protein subunit alpha-12	Mus musculus (Mouse)	SS
P20612	Gnat1	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
P27601	Gna13	Guanine nucleotide-binding protein subunit alpha-13	Mus musculus (Mouse)	SS
Q3V3I2	Gnat3	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
O70443	Gnaz	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
P50149	Gnat2	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
P08752	Gnai2	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
B2RSH2	Gnai1	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
P18872	Gnao1	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
Q9DC51	Gnai3	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
P93564	GPA1	Guanine nucleotide-binding protein alpha-1 subunit	Solanum tuberosum (Potato)	SS
Q63210	Gna12	Guanine nucleotide-binding protein subunit alpha-12	Rattus norvegicus (Rat)	SS
P19627	Gnaz	Guanine nucleotide-binding protein G	Rattus norvegicus (Rat)	SS
P29348	Gnat3	Guanine nucleotide-binding protein G	Rattus norvegicus (Rat)	SS
P04897	Gnai2	Guanine nucleotide-binding protein G	Rattus norvegicus (Rat)	SS
P59215	Gnao1	Guanine nucleotide-binding protein G	Rattus norvegicus (Rat)	SS
Q6Q7Y5	Gna13	Guanine nucleotide-binding protein subunit alpha-13	Rattus norvegicus (Rat)	SS
P08753	Gnai3	Guanine nucleotide-binding protein G	Rattus norvegicus (Rat)	SS
Q0DJ33	GPA1	Guanine nucleotide-binding protein alpha-1 subunit	Oryza sativa subsp. japonica (Rice)	SS
P51875	goa-1	Guanine nucleotide-binding protein G	Caenorhabditis elegans	SS
Q18434	odr-3	Guanine nucleotide-binding protein alpha-17 subunit	Caenorhabditis elegans	SS
Q9BIG4	gpa-10	Guanine nucleotide-binding protein alpha-10 subunit	Caenorhabditis elegans	PR
P28052	gpa-3	Guanine nucleotide-binding protein alpha-3 subunit	Caenorhabditis elegans	SS
Q9XTB2	gpa-13	Guanine nucleotide-binding protein alpha-13 subunit	Caenorhabditis elegans	SS
Q9BIG5	gpa-4	Guanine nucleotide-binding protein alpha-4 subunit	Caenorhabditis elegans	SS
P28051	gpa-1	Guanine nucleotide-binding protein alpha-1 subunit	Caenorhabditis elegans	SS
P91907	gpa-15	Guanine nucleotide-binding protein alpha-15 subunit	Caenorhabditis elegans	SS
Q20907	gpa-8	Guanine nucleotide-binding protein alpha-8 subunit	Caenorhabditis elegans	PR
Q21917	gpa-7	Guanine nucleotide-binding protein alpha-7 subunit	Caenorhabditis elegans	SS
Q93743	gpa-6	Guanine nucleotide-binding protein alpha-6 subunit	Caenorhabditis elegans	SS
Q9N2V6	gpa-16	Guanine nucleotide-binding protein alpha-16 subunit	Caenorhabditis elegans	SS
O76584	gpa-11	Guanine nucleotide-binding protein alpha-11 subunit	Caenorhabditis elegans	SS
P49084	GPA1	Guanine nucleotide-binding protein alpha-1 subunit	Glycine max (Soybean) (Glycine hispida)	SS
P93163	GPA2	Guanine nucleotide-binding protein alpha-2 subunit	Glycine max (Soybean) (Glycine hispida)	SS
O80462	XLG1	Extra-large guanine nucleotide-binding protein 1	Arabidopsis thaliana (Mouse-ear cress)	PR
P18064	GPA1	Guanine nucleotide-binding protein alpha-1 subunit	Arabidopsis thaliana (Mouse-ear cress)	SS
P26981	GPA1	Guanine nucleotide-binding protein alpha-1 subunit	Solanum lycopersicum (Tomato) (Lycopersicon esculentum)	SS

10	20	30	40	50	60
MGCTLSAEDK	AAVERSKMID	RNLREDGEKA	AKEVKLLLLG	AGESGKSTIV	KQMKIIHEDG
70	80	90	100	110	120
YSEDECKQYK	VVVYSNTIQS	IIAIIRAMGR	LKIDFGEAAR	ADDARQLFVL	AGSAEEGVMT
130	140	150	160	170	180
PELAGVIKRL	WRDGGVQACF	SRSREYQLND	SASYYLNDLD	RISQSNYIPT	QQDVLRTRVK
190	200	210	220	230	240
TTGIVETHFT	FKDLYFKMFD	VGGQRSERKK	WIHCFEGVTA	IIFCVALSDY	DLVLAEDEEM
250	260	270	280	290	300
NRMHESMKLF	DSICNNKWFT	ETSIILFLNK	KDLFEEKIKR	SPLTICYPEY	TGSNTYEEAA
310	320	330	340	350
AYIQCQFEDL	NRRKDTKEIY	THFTCATDTK	NVQFVFDAVT	DVIIKNNLKE	CGLY