AiPD: Autoinhibited Protein Database

Q8TDF6

Gene name	RASGRP4
Protein name	RAS guanyl-releasing protein 4
Names
Species	Homo sapiens (Human)
KEGG Pathway	hsa:115727
EC number
Protein Class

Descriptions

Ras regulation in B cells involves a Ras-guanyl nucleotide exchange factor. RasGRP, a member of the cdc25 family of Ras guanyl nucleotide exchange factors (Ras-GEFs), has a DAG-binding C1 domain, DAG generated upon antigen receptor stimulation contributes to recruiting RasGRP to the membrane, where it interacts with Ras. PKC, after being activated by diacylglycerol, phosphorylates RasGRP3, thereby contributing to the full activation of RasGRP3. Mutation of Thr-133 in the Cdc25 domain of RasGRP3 alone severely impairs its ability to activate Ras in B cell signaling, which represents an autoinhibition mechanism in RasGRP3. The Thr-133 site is conserved in human, mouse, and chicken. <br> In other RasGRP proteins, the phosphorylation of the Cdc25 domain could aid in removal of the inhibitory linker between Cdc25 and EF domain. Briefly, inactive RasGRP is stabilized by the C1-dimer interface, which sequesters the membrane-interacting surface of the C1 domain, and the active-site blocking RasGEF catalytic domain (Cdc25)-EF domain linker. The C-terminal coiled-coil stabilizes the dimer, thereby preventing inappropriate Ras activation. The autoinhibited form is activated by multiple signaling inputs that enhance nucleotide exchange activity. Diacylglycerol binding disrupts C1 dimerization, while Ca2+ binding to EF1 causes a conformational change that contributes to C1 reorientation, and the release of the inhibitory segment from the Ras-binding surface. Phosphorylation of the Cdc25 domain could aid in removal of the inhibitory linker.

Autoinhibitory domains (AIDs)

433-465 (RasGEF catalytic domain-EF domain linker) SS

Target domain	197-433 (Ras guanine-nucleotide exchange factors catalytic domain)
Relief mechanism	Ligand binding, PTM
Assay

AID

433-465 (RasGEF catalytic domain-EF domain linker)

Target domain

197-433 (Ras guanine-nucleotide exchange factors catalytic domain)

Relief mechanism

Ligand binding (Ca2+ binding to EF domain and diacylglycerol binding to C1 domain), PTM (Phosphorylation of the RasGEF catalytic domain)

Assay

540-590 (C1 domain) SS

Target domain	466-501 (EF domain)
Relief mechanism	Ligand binding, PTM
Assay

AID

540-590 (C1 domain)

Target domain

466-501 (EF domain)

Relief mechanism

Ligand binding (Ca2+ binding to EF domain and diacylglycerol binding to C1 domain), PTM (Phosphorylation of the RasGEF catalytic domain)

Assay

Accessory elements

No accessory elements

References

Czikora A et al. (2016) "Structural Basis for the Failure of the C1 Domain of Ras Guanine Nucleotide Releasing Protein 2 (RasGRP2) to Bind Phorbol Ester with High Affinity", The Journal of biological chemistry, 291, 11133-47

Canault M et al. (2020) "RasGRP2 Structure, Function and Genetic Variants in Platelet Pathophysiology", International journal of molecular sciences, 21,

Aiba Y et al. (2004) "Activation of RasGRP3 by phosphorylation of Thr-133 is required for B cell receptor-mediated Ras activation", Proceedings of the National Academy of Sciences of the United States of America, 101, 16612-7

Autoinhibited structure

Activated structure

2 structures for Q8TDF6

Entry ID	Method	Resolution	Chain	Position	Source
6AXG	X-ray	330 A	A/C/E/G/I/K	46-460	PDB
AF-Q8TDF6-F1	Predicted				AlphaFoldDB

499 variants for Q8TDF6

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA308095090 rs542070808	3	R>G		No	ClinGen 1000Genomes TOPMed
CA9415761 rs777738099	4	K>E		No	ClinGen ExAC gnomAD
CA9415760 rs758325708	5	D>V		No	ClinGen ExAC gnomAD
rs1441205160 CA405666784	7	K>E		No	ClinGen TOPMed
rs1000100969 CA308089630	9	K>*		No	ClinGen Ensembl
rs1407440842 CA405665306	9	K>N		No	ClinGen TOPMed gnomAD
rs1414728350 CA405665278	11	H>Y		No	ClinGen gnomAD
rs187355849 CA9415740	13	E>D		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs749329021 CA308089616	14	C>W		No	ClinGen ExAC TOPMed gnomAD
CA308089585 rs1043968214	15	T>I		No	ClinGen Ensembl
CA308089593 rs903505143	15	T>S		No	ClinGen TOPMed
CA9415736 rs750881682	16	G>R		No	ClinGen ExAC TOPMed gnomAD
CA9415735 rs892055 VAR_038144	18	I>T		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs1316681554 CA405665096	19	G>E		No	ClinGen gnomAD
CA308089563 rs894836402	19	G>R		No	ClinGen gnomAD
CA9415734 rs757500988	20	G>R		No	ClinGen ExAC TOPMed gnomAD
CA405665083 rs757500988	20	G>W		No	ClinGen ExAC TOPMed gnomAD
CA9415733 rs766578361	21	R>*		No	ClinGen ExAC
COSM711635 CA9415732 rs376854073	21	R>Q	lung [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA405665024 rs1220382436	23	R>Q		No	ClinGen gnomAD
CA9415731 rs759135742	23	R>W		No	ClinGen ExAC gnomAD
CA405665004 rs1568415635	24	P>L		No	ClinGen Ensembl
rs776089203 CA9415730	25	R>C		No	ClinGen ExAC gnomAD
rs1297627862 CA405665000	25	R>H		No	ClinGen gnomAD
CA405664985 rs1433749796	26	Q>H		No	ClinGen gnomAD
CA405664973 rs1600577159	27	V>G		No	ClinGen Ensembl
rs766087172 CA9415729	28	R>C		No	ClinGen ExAC TOPMed gnomAD
CA9415728 rs374569775	28	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
CA405664963 rs374569775	28	R>P		No	ClinGen ESP ExAC TOPMed gnomAD
rs1350828171 CA405664957	29	R>C		No	ClinGen TOPMed gnomAD
rs938183308 CA405664956	29	R>H		No	ClinGen TOPMed gnomAD
CA308089520 rs938183308	29	R>L		No	ClinGen TOPMed gnomAD
CA9415726 rs771905697	33	C>S		No	ClinGen ExAC gnomAD
CA405664878 rs1389799102	35	S>R		No	ClinGen TOPMed
rs1448957866 CA405664871	36	P>L		No	ClinGen gnomAD
rs375650709 CA405664869	37	R>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA9415724 rs375650709	37	R>P		No	ClinGen ESP ExAC TOPMed gnomAD
CA9415723 rs375650709	37	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA9415725 rs747855727	37	R>W		No	ClinGen ExAC TOPMed gnomAD
CA9415722 rs749417200	38	E>V		No	ClinGen ExAC gnomAD
rs780272913 CA9415721	40	S>G		No	ClinGen ExAC gnomAD
rs1600576878 CA405664848	40	S>R		No	ClinGen Ensembl
rs1219133538 CA405664832	43	M>V		No	ClinGen gnomAD
rs1600576835 CA405664792	46	M>T		No	ClinGen Ensembl
rs1226950330 CA405664755	49	G>C		No	ClinGen gnomAD
CA9415718 rs372634426	49	G>D		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA308089467 rs866823900	53	E>D		No	ClinGen Ensembl
CA405664721 rs1221404707	53	E>K		No	ClinGen gnomAD
CA405664703 rs1228859254	54	G>D		No	ClinGen TOPMed
CA9415716 rs751849188	54	G>S		No	ClinGen ExAC gnomAD
rs369267928 CA9415714	55	G>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
COSM1612180 CA405664665 rs1308852837	58	E>K	liver [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1429433468 CA405664658	58	E>V		No	ClinGen gnomAD
CA9415711 rs760111810	61	L>M		No	ClinGen ExAC gnomAD
rs767027762 CA405664581	65	C>G		No	ClinGen ExAC gnomAD
rs767027762 CA9415709	65	C>R		No	ClinGen ExAC gnomAD
CA405664569 rs1241833915	66	I>F		No	ClinGen TOPMed
rs1252343812 CA405664545	67	Q>L		No	ClinGen TOPMed gnomAD
rs1252343812 CA405664546	67	Q>R		No	ClinGen TOPMed gnomAD
rs183422897 CA405664513	70	D>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA9415706 rs183422897	70	D>N		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1315122495 CA405663523	73	G>S		No	ClinGen TOPMed gnomAD
CA9415689 rs544684240	74	S>N		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA9415687 rs199697303	77	H>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs180932169 CA9415686	78	E>K		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs762800780 CA9415685	79	D>E		No	ClinGen ExAC gnomAD
CA405663337 rs1490060372	81	M>V		No	ClinGen TOPMed
CA9415683 rs769834860	83	N>S		No	ClinGen ExAC gnomAD
rs1568414771 CA405663290	83	N>Y		No	ClinGen Ensembl
CA405663255 rs1466605086	87	A>G		No	ClinGen gnomAD
CA405663258 rs1189969069	87	A>P		No	ClinGen gnomAD
rs747210244 CA9415679	88	M>T		No	ClinGen ExAC gnomAD
CA405663241 rs1348963464	89	H>P		No	ClinGen TOPMed gnomAD
CA405663242 rs1348963464	89	H>R		No	ClinGen TOPMed gnomAD
rs1040075580 CA308089079	90	S>G		No	ClinGen TOPMed
CA9415678 rs777983419	93	L>V		No	ClinGen ExAC gnomAD
CA405663207 rs1245755729	94	P>L		No	ClinGen TOPMed gnomAD
CA9415676 rs190970921	96	A>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA9415675 rs190970921	96	A>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA9415673 rs200230486	97	D>N		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1205542753 CA405663187	98	L>V		No	ClinGen TOPMed
CA9415672 rs374755676	99	A>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1052296186 CA308089046	100	A>V		No	ClinGen TOPMed
rs572991560 COSM439400 CA9415671	101	R>C	large_intestine breast [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
CA405663172 rs572991560	101	R>G		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs751204980 COSM1636801 CA9415670	101	R>H	bone [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA308089032 rs990878286	103	L>P		No	ClinGen Ensembl
CA9415669 rs763795610	104	T>I		No	ClinGen ExAC gnomAD
rs904511761 CA308088944	106	Y>C		No	ClinGen TOPMed
rs757910257 CA308088935	107	Q>E		No	ClinGen Ensembl
rs368774668 CA308088930	109	A>V		No	ClinGen ESP TOPMed gnomAD
rs760717073 CA9415644	116	L>R		No	ClinGen ExAC gnomAD
rs752669756 CA9415642	118	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA9415643 rs773243909	118	R>W		No	ClinGen ExAC TOPMed gnomAD
rs1600573616 CA405663004	119	L>V		No	ClinGen Ensembl
rs1568414401 CA405662990	120	Q>*		No	ClinGen Ensembl
rs760133721 CA9415618	128	W>*		No	ClinGen ExAC gnomAD
CA405662786 rs1407784119	128	W>S		No	ClinGen gnomAD
rs777212070 CA308088637	129	L>M		No	ClinGen ExAC TOPMed gnomAD
CA405662745 rs1238100505	131	R>*		No	ClinGen TOPMed gnomAD
rs771740857 CA9415616	131	R>P		No	ClinGen ExAC TOPMed gnomAD
rs771740857 CA405662743	131	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA9415615 rs369177036	132	H>Y		No	ClinGen ESP ExAC gnomAD
CA405662671 rs1600571711	135	V>G		No	ClinGen Ensembl
rs778756186 CA9415614	137	H>Q		No	ClinGen ExAC gnomAD
rs1568413853 CA405662621	138	Q>E		No	ClinGen Ensembl
CA405662530 rs1446209662	140	P>L		No	ClinGen TOPMed gnomAD
CA405662533 rs1446209662	140	P>R		No	ClinGen TOPMed gnomAD
CA405662551 rs1340026468	140	P>S		No	ClinGen TOPMed
rs755802919 CA9415610	146	I>T		No	ClinGen ExAC gnomAD
rs201449950 CA9415611	146	I>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs750362289 CA9415609	148	R>C		No	ClinGen ExAC TOPMed gnomAD
CA9415608 rs781065392	148	R>H		No	ClinGen ExAC TOPMed gnomAD
CA308088600 rs781065392	148	R>L		No	ClinGen ExAC TOPMed gnomAD
CA9415607 rs757379439	153	V>M		No	ClinGen ExAC gnomAD
CA9415606 rs777144681	155	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA308088594 rs888318910	155	R>W		No	ClinGen TOPMed gnomAD
rs1386125635 CA405661999	158	N>S		No	ClinGen TOPMed gnomAD
CA405661925 rs1442870500	160	A>D		No	ClinGen gnomAD
CA405661959 rs1162936224	160	A>T		No	ClinGen gnomAD
rs1442870500 CA405661921	160	A>V		No	ClinGen gnomAD
rs1039909424 CA308088584	165	G>E		No	ClinGen Ensembl
CA9415604 rs41465445	165	G>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs752806146 CA9415602	166	D>G		No	ClinGen ExAC gnomAD
rs765639885 CA9415601	170	L>P		No	ClinGen ExAC TOPMed gnomAD
rs765330338 CA9415584	172	S>G		No	ClinGen ExAC TOPMed gnomAD
rs958501657 CA308088434	174	G>D		No	ClinGen Ensembl
rs1307358618 CA405661529	174	G>S		No	ClinGen gnomAD
CA405661508 rs1271519848	175	G>D		No	ClinGen gnomAD
CA308088429 rs1034288951	176	P>L		No	ClinGen TOPMed gnomAD
CA9415582 rs754222225	177	G>A		No	ClinGen ExAC TOPMed gnomAD
rs761249940 CA9415581	179	P>L		No	ClinGen ExAC TOPMed gnomAD
rs761249940 CA405661454	179	P>Q		No	ClinGen ExAC TOPMed gnomAD
rs761249940 CA9415580	179	P>R		No	ClinGen ExAC TOPMed gnomAD
CA308088413 rs773531170	180	L>I		No	ClinGen ExAC TOPMed gnomAD
CA9415578 rs773531170	180	L>V		No	ClinGen ExAC TOPMed gnomAD
rs775226635 CA9415575	182	M>I		No	ClinGen ExAC TOPMed gnomAD
rs762326895 CA9415576	182	M>V		No	ClinGen ExAC TOPMed gnomAD
rs769408645 CA9415574	186	G>S		No	ClinGen ExAC TOPMed gnomAD
rs1329520124 CA405661321	189	K>E		No	ClinGen TOPMed
CA405661291 COSM284488 rs1428306763	191	R>C	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1174018700 CA405661287	191	R>H		No	ClinGen TOPMed gnomAD
CA9415572 rs776401639	196	L>P		No	ClinGen ExAC gnomAD
rs746970869 CA9415570	198	D>N		No	ClinGen ExAC gnomAD
CA9415569 COSM241364 rs368484426	202	T>M	prostate [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC gnomAD
CA9415567 rs748156494	203	G>R		No	ClinGen ExAC gnomAD
CA405661098 rs1331419043	206	A>T		No	ClinGen gnomAD
CA405661035 rs1371229313	211	Y>N		No	ClinGen gnomAD
CA405661026 rs1304708172	212	L>V		No	ClinGen gnomAD
CA9415564 rs754312220	215	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs1173902608 CA405661005 COSM3378932	215	R>W	pancreas [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA9415563 rs766863261	217	F>L		No	ClinGen ExAC gnomAD
rs756477194 CA9415562	220	I>V		No	ClinGen ExAC TOPMed gnomAD
CA9415561 rs201189052	221	T>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs1303379209 CA405660255	222	P>L		No	ClinGen TOPMed gnomAD
CA308087673 rs897804007	222	P>S		No	ClinGen TOPMed
CA405660249 rs1235871831	223	Q>*		No	ClinGen TOPMed
CA405660245 rs1472501695	223	Q>R		No	ClinGen TOPMed
rs749521711 CA9415546	224	D>N		No	ClinGen ExAC gnomAD
rs780379476 CA9415545	226	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA405660222 rs1169965214	226	R>W		No	ClinGen gnomAD
CA9415544 rs756520734	227	S>N		No	ClinGen ExAC TOPMed gnomAD
CA405660208 rs1192852556	228	Y>C		No	ClinGen gnomAD
rs1600567368 CA405660204	229	V>I		No	ClinGen Ensembl
CA405660192 rs1402577528	230	L>W		No	ClinGen TOPMed
CA405660179 rs1331783519	231	Q>R		No	ClinGen TOPMed
CA405660163 rs1200371680	232	G>D		No	ClinGen gnomAD
rs1050537038 CA308087653	233	S>L		No	ClinGen TOPMed
CA308087647 rs778001765	235	R>Q		No	ClinGen TOPMed gnomAD
rs943282834 CA308087636	237	C>R		No	ClinGen Ensembl
rs911244181 CA308087631	239	A>S		No	ClinGen Ensembl
rs1225233747 CA405660091	240	L>M		No	ClinGen gnomAD
CA9415539 rs373960414	242	G>C		No	ClinGen ESP ExAC TOPMed gnomAD
CA9415538 rs369986884	244	V>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA9415536 rs765995207	245	G>S		No	ClinGen ExAC gnomAD
CA405659936 rs1460955016	247	S>R		No	ClinGen gnomAD
rs1431876433 CA405659893	250	V>L		No	ClinGen gnomAD
rs1485409944 CA405659873	252	R>C		No	ClinGen TOPMed
rs1480193658 CA405659867	252	R>L		No	ClinGen TOPMed gnomAD
CA9415534 rs772877163	255	Q>*		No	ClinGen ExAC gnomAD
rs1249954618 CA405659812	255	Q>H		No	ClinGen gnomAD
CA405659819 rs1476810474	255	Q>R		No	ClinGen TOPMed
CA405659806 rs1193978893	256	V>M		No	ClinGen gnomAD
rs372706430 CA9415533	258	V>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs988989823 CA308087604	260	S>N		No	ClinGen Ensembl
CA9415531 rs369224194	261	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs1280915926 CA405659714	263	G>R		No	ClinGen gnomAD
rs200429403 CA9415529	264	P>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs200429403 CA9415528	264	P>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA9415527 rs769872818	265	L>P		No	ClinGen ExAC TOPMed gnomAD
rs769872818 CA308087589	265	L>Q		No	ClinGen ExAC TOPMed gnomAD
CA308087578 rs971083401	267	R>G		No	ClinGen TOPMed
rs746303879 CA9415526	269	Q>H		No	ClinGen ExAC TOPMed gnomAD
CA405659612 rs746303879	269	Q>H		No	ClinGen ExAC TOPMed gnomAD
rs1469598203 CA405659589	271	L>V		No	ClinGen gnomAD
CA9415525 rs371808287	272	D>G		No	ClinGen ESP ExAC TOPMed gnomAD
CA405659501 rs1470661277	276	H>D		No	ClinGen gnomAD
CA405659503 rs1470661277	276	H>N		No	ClinGen gnomAD
rs1363245638 CA405659473	278	A>T		No	ClinGen gnomAD
CA9415504 rs781440593	280	R>S		No	ClinGen ExAC TOPMed gnomAD
CA308086685 rs781440593	280	R>S		No	ClinGen ExAC TOPMed gnomAD
rs771222724 CA9415503	281	L>I		No	ClinGen ExAC gnomAD
CA405658456 rs1600562453	282	H>P		No	ClinGen Ensembl
rs747352606 CA9415502	282	H>Q		No	ClinGen ExAC gnomAD
rs1426836692 CA405658432	283	Q>*		No	ClinGen gnomAD
rs987986399 CA308086650	292	A>V		No	ClinGen Ensembl
CA405658073 rs1403497256	294	T>I		No	ClinGen gnomAD
CA405658030 rs1474956839	297	L>P		No	ClinGen TOPMed gnomAD
CA9415499 rs748853031	298	C>Y		No	ClinGen ExAC gnomAD
CA308086634 rs865920131	301	A>V		No	ClinGen Ensembl
rs1291657382 CA405657851	305	L>F		No	ClinGen gnomAD
rs1313574694 CA405657836	306	K>E		No	ClinGen TOPMed
rs868226724 CA308086612	306	K>N		No	ClinGen Ensembl
CA405657805 rs1290340621	309	H>Y		No	ClinGen gnomAD
CA405657769 rs1320386174	310	A>D		No	ClinGen gnomAD
rs1215741324 CA405657724	312	L>V		No	ClinGen gnomAD
CA405657705 rs1339108409	313	S>T		No	ClinGen gnomAD
rs755584074 CA9415496	315	D>E		No	ClinGen ExAC TOPMed gnomAD
rs979372404 CA308086593	315	D>N		No	ClinGen TOPMed gnomAD
CA405657177 rs1430521683	320	L>R		No	ClinGen TOPMed
CA405657157 rs1420557836	322	E>A		No	ClinGen gnomAD
rs147903500 CA405657120	324	T>I		No	ClinGen 1000Genomes ExAC gnomAD
rs147903500 CA9415484	324	T>S		No	ClinGen 1000Genomes ExAC gnomAD
CA9415483 rs773554915	327	L>P		No	ClinGen ExAC TOPMed gnomAD
CA405657057 rs1206195058	328	A>V		No	ClinGen gnomAD
rs931987800 CA308085556	330	H>R		No	ClinGen Ensembl
rs1208221586 CA405657032	330	H>Y		No	ClinGen gnomAD
CA405656947 rs1374844480	334	A>G		No	ClinGen gnomAD
rs762299166 CA9415481	334	A>T		No	ClinGen ExAC gnomAD
CA405656945 rs1374844480	334	A>V		No	ClinGen gnomAD
rs202008979 CA9415479	335	R>C		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA9415478 VAR_038148 rs202008979 RCV000954316	335	R>G		No	ClinGen ClinVar UniProt 1000Genomes ExAC TOPMed dbSNP gnomAD
CA405656933 rs1208570686	335	R>H		No	ClinGen gnomAD
rs1600556532 CA405656915	336	Y>S		No	ClinGen Ensembl
rs756963580 CA9415476	337	R>C		No	ClinGen ExAC TOPMed gnomAD
CA308085540 rs373989881	337	R>H		No	ClinGen TOPMed
rs756963580 CA308085543	337	R>S		No	ClinGen ExAC TOPMed gnomAD
CA9415475 rs751201302	338	R>C		No	ClinGen ExAC gnomAD
rs763988472 CA9415474	338	R>H		No	ClinGen ExAC gnomAD
rs758230627 CA9415473	339	T>N		No	ClinGen ExAC gnomAD
CA9415471 rs765199836	342	G>V		No	ClinGen ExAC gnomAD
CA9415469 rs762397665	344	A>T		No	ClinGen ExAC TOPMed gnomAD
rs74780073 CA9415468	344	A>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA9415466 rs773354653	345	G>D		No	ClinGen ExAC gnomAD
CA9415464 rs748462834	346	F>V		No	ClinGen ExAC gnomAD
rs371482212 CA9415463	347	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs745433120 CA9415461	350	V>A		No	ClinGen ExAC gnomAD
rs777522736 CA9415457	353	V>M		No	ClinGen ExAC gnomAD
CA405656445 rs1366838703	358	L>P		No	ClinGen gnomAD
rs754932964 CA9415453	361	L>P		No	ClinGen ExAC TOPMed gnomAD
CA405656378 rs754932964	361	L>R		No	ClinGen ExAC TOPMed gnomAD
rs1294838131 CA405656365	362	H>R		No	ClinGen TOPMed
rs1186116641 CA405656328	364	A>T		No	ClinGen gnomAD
CA9415450 rs760702740	367	D>N		No	ClinGen ExAC TOPMed gnomAD
CA9415449 rs372390867	368	R>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs1487445264 CA405656244	369	L>S		No	ClinGen gnomAD
CA405656230 rs767704869	370	P>S		No	ClinGen ExAC gnomAD
CA9415448 rs767704869	370	P>T		No	ClinGen ExAC gnomAD
rs368971000 CA9415446	372	G>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA9415445 rs375873487	373	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs776102602 CA9415443	373	R>H		No	ClinGen ExAC gnomAD
rs776102602 CA9415444	373	R>L		No	ClinGen ExAC gnomAD
rs1600555905 CA405656107	375	H>Y		No	ClinGen Ensembl
rs527416058 CA405655997	379	L>V		No	ClinGen 1000Genomes TOPMed gnomAD
CA405655941 rs1403783453	380	N>K		No	ClinGen TOPMed gnomAD
CA405655914 rs1600555802	381	N>T		No	ClinGen Ensembl
CA405655894 rs1427194313	382	L>P		No	ClinGen TOPMed
rs1600555762 CA405655864	383	Y>S		No	ClinGen Ensembl
rs1161947557 CA405655818	385	R>Q		No	ClinGen gnomAD
rs1388028960 CA405655821	385	R>W		No	ClinGen TOPMed gnomAD
CA405655785 rs1600555716	386	L>R		No	ClinGen Ensembl
CA405655704 rs1600555662	390	V>G		No	ClinGen Ensembl
rs747954385 CA405655708	390	V>L		No	ClinGen ExAC TOPMed gnomAD
CA9415438 rs747954385	390	V>M		No	ClinGen ExAC TOPMed gnomAD
CA9415437 rs769701535	391	A>D		No	ClinGen ExAC TOPMed gnomAD
CA405655646 rs1476926463	393	Q>R		No	ClinGen gnomAD
rs753842105 CA9415435	396	H>N		No	ClinGen ExAC gnomAD
rs779914355 CA9415434	400	S>G		No	ClinGen ExAC gnomAD
CA9415433 rs756231469	401	A>T		No	ClinGen ExAC TOPMed gnomAD
rs569953333 CA9415432	401	A>V		No	ClinGen 1000Genomes ExAC gnomAD
CA405655421 rs1600555500	402	N>S		No	ClinGen Ensembl
rs767792931 CA9415431	404	D>V		No	ClinGen ExAC gnomAD
rs372910379 CA405655347	406	L>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA308085351 rs900511442	407	H>D		No	ClinGen TOPMed
CA9415429 rs751673157	408	L>M		No	ClinGen ExAC gnomAD
rs1040363352 CA308085341	409	L>R		No	ClinGen TOPMed
rs536745461 CA308085340	410	T>M		No	ClinGen TOPMed gnomAD
CA308084378 rs376332266	416	F>Y		No	ClinGen Ensembl
CA9415404 rs372116904	418	T>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs1400890346 CA405653763	419	E>K		No	ClinGen gnomAD
CA405653678 rs1426402455	421	E>D		No	ClinGen TOPMed gnomAD
rs761175979 CA9415401	421	E>K		No	ClinGen ExAC gnomAD
rs774098889 CA9415400	422	I>N		No	ClinGen ExAC gnomAD
CA405653616 rs1162650696	424	E>K		No	ClinGen gnomAD
CA9415397 rs775252271	429	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA9415398 rs551041567	429	R>W		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs769519232 CA9415396	431	P>L		No	ClinGen ExAC gnomAD
CA405653355 rs1387286074	432	R>C		No	ClinGen TOPMed gnomAD
rs757409206 CA9415393	432	R>H		No	ClinGen ExAC TOPMed gnomAD
CA405653282 rs1291208010	434	P>L		No	ClinGen gnomAD
CA405653287 rs1359605342	434	P>S		No	ClinGen gnomAD
CA9415392 rs747030338	435	K>Q		No	ClinGen ExAC gnomAD
rs778124312 CA9415391	436	S>R		No	ClinGen ExAC gnomAD
rs1272309550 CA405653203	437	L>P		No	ClinGen gnomAD
CA9415367 rs779226326	439	P>L		No	ClinGen ExAC gnomAD
rs754220315 CA9415365	440	S>A		No	ClinGen ExAC gnomAD
CA9415364 rs769743830	440	S>F		No	ClinGen ExAC TOPMed gnomAD
CA9415361 rs763515377	441	P>H		No	ClinGen ExAC TOPMed gnomAD
CA9415362 rs763515377	441	P>R		No	ClinGen ExAC TOPMed gnomAD
rs561844658 CA9415360	442	F>L		No	ClinGen 1000Genomes ExAC gnomAD
CA9415359 rs752398396	443	N>S		No	ClinGen ExAC TOPMed gnomAD
rs1446008015 CA405652904	444	A>E		No	ClinGen gnomAD
CA405652894 rs1374316286	445	P>S		No	ClinGen gnomAD
rs1374316286 CA405652898	445	P>T		No	ClinGen gnomAD
rs1338490125 CA405652846	447	V>A		No	ClinGen gnomAD
CA405652857 rs1278571684	447	V>M		No	ClinGen gnomAD
CA308084209 rs541863413	450	W>*		No	ClinGen Ensembl
CA405652731 rs1466174041	452	P>S		No	ClinGen gnomAD
rs1160081899 CA405652710	453	G>S		No	ClinGen TOPMed
CA405652649 rs1328446642	455	T>I		No	ClinGen gnomAD
CA308084203 rs980735670	456	P>L		No	ClinGen Ensembl
rs759394488 CA9415357	456	P>S		No	ClinGen ExAC gnomAD
rs1380421516 CA405652552	458	P>A		No	ClinGen TOPMed gnomAD
rs760538598 CA9415354	458	P>L		No	ClinGen ExAC TOPMed gnomAD
rs760538598 CA9415355	458	P>Q		No	ClinGen ExAC TOPMed gnomAD
rs1380421516 CA405652530	458	P>T		No	ClinGen TOPMed gnomAD
rs1236690299 CA405652512	459	D>H		No	ClinGen gnomAD
CA405652426 rs1183976804	462	T>A		No	ClinGen gnomAD
CA9415350 rs779316201	464	G>C		No	ClinGen ExAC TOPMed gnomAD
rs768991158 CA9415349	464	G>V		No	ClinGen ExAC TOPMed gnomAD
CA9415348 rs377433325	465	R>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs374568572 CA9415346	465	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA9415347 rs377433325	465	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs1225258857 CA405652306	466	H>Y		No	ClinGen TOPMed
CA405652153 rs1600550211	471	V>G		No	ClinGen Ensembl
rs757945897 CA9415343	471	V>M		No	ClinGen ExAC gnomAD
rs755898806 CA9415320	473	S>P		No	ClinGen ExAC TOPMed gnomAD
rs750236036 CA9415319	476	K>E		No	ClinGen ExAC
CA405651966 rs1433051807	477	N>D		No	ClinGen Ensembl
CA405651944 rs1462309757	478	Y>H		No	ClinGen TOPMed
rs767617354 CA9415318	479	D>N		No	ClinGen ExAC gnomAD
CA9415317 rs201088850	483	R>*		No	ClinGen ExAC TOPMed gnomAD
rs774362903 CA9415316	483	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA308083911 rs367590774	485	T>A		No	ClinGen Ensembl
CA405651792 rs1210309739	486	I>M		No	ClinGen gnomAD
rs763037710 CA9415314	487	S>A		No	ClinGen ExAC gnomAD
CA405651686 rs1200287744	492	E>G		No	ClinGen gnomAD
rs931114411 CA308083907	493	R>*		No	ClinGen TOPMed gnomAD
rs775615920 CA9415313	493	R>Q		No	ClinGen ExAC gnomAD
CA9415312 rs376620042	495	S>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA9415310 rs776994464	496	G>S		No	ClinGen ExAC gnomAD
rs186928850 CA405651628	497	N>I		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs186928850 CA9415309	497	N>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs972614489 CA308083868	499	P>A		No	ClinGen TOPMed
CA405651592 rs1353912161	499	P>R		No	ClinGen gnomAD
rs1292354546 CA405651586	500	F>L		No	ClinGen gnomAD
CA9415308 rs747549298	500	F>S		No	ClinGen ExAC gnomAD
CA9415304 rs748797528	501	A>P		No	ClinGen ExAC TOPMed gnomAD
CA9415305 rs748797528	501	A>T		No	ClinGen ExAC TOPMed gnomAD
CA405651526 rs1476979674	503	H>L		No	ClinGen TOPMed gnomAD
rs1476979674 CA405651527	503	H>R		No	ClinGen TOPMed gnomAD
CA308083834 rs917890267	504	G>R		No	ClinGen Ensembl
CA9415300 rs750035492	506	H>L		No	ClinGen ExAC
CA9415301 rs755773710	506	H>Y		No	ClinGen ExAC gnomAD
rs1195424690 CA405651458	509	P>L		No	ClinGen TOPMed
CA9415298 rs181501556	510	R>C		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs751562921 CA9415297	510	R>H		No	ClinGen ExAC TOPMed gnomAD
rs1188177664 CA405651380	513	R>S		No	ClinGen TOPMed
rs1395691038 CA405651332	518	R>G		No	ClinGen gnomAD
CA308083654 rs1010403125	520	E>*		No	ClinGen TOPMed gnomAD
CA405651307 rs1010403125	520	E>K		No	ClinGen TOPMed gnomAD
rs892882499 CA308083646	520	E>V		No	ClinGen TOPMed gnomAD
rs1420168515 CA405651295	521	L>M		No	ClinGen TOPMed gnomAD
CA405651271 rs1430989655	523	G>A		No	ClinGen TOPMed
rs367859380 CA9415275	525	L>P		No	ClinGen ESP ExAC TOPMed gnomAD
rs937175533 CA308083589	527	R>Q		No	ClinGen TOPMed gnomAD
rs375300341 CA9415274	527	R>W		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1291181219 CA405651230	528	A>S		No	ClinGen TOPMed
rs1186341606 CA405651218	529	S>N		No	ClinGen gnomAD
CA9415272 rs766560217	530	A>T		No	ClinGen ExAC TOPMed gnomAD
rs1238716189 CA405651142	535	L>V		No	ClinGen gnomAD
CA405651094 rs1285888892	538	A>D		No	ClinGen TOPMed gnomAD
rs1285888892 CA405651092	538	A>V		No	ClinGen TOPMed gnomAD
CA405651078 rs1282781385	539	F>C		No	ClinGen TOPMed
CA405651041 rs1600548186	542	T>P		No	ClinGen Ensembl
rs1285186182 CA405651022	543	F>Y		No	ClinGen gnomAD
CA405650999 rs1317614845	544	H>R		No	ClinGen TOPMed
rs1353812602 CA405650928	547	T>S		No	ClinGen gnomAD
rs1300344441 CA405650901	549	R>*		No	ClinGen gnomAD
CA9415268 rs762382897	549	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA9415267 rs774679294	550	K>T		No	ClinGen ExAC gnomAD
rs1414201030 CA405650797	554	C>R		No	ClinGen gnomAD
rs1471574695 CA405650776	555	D>N		No	ClinGen TOPMed gnomAD
rs1425313371 CA405650755	556	S>G		No	ClinGen TOPMed gnomAD
rs770696140 CA9415263	558	S>I		No	ClinGen ExAC gnomAD
CA9415264 rs770696140	558	S>N		No	ClinGen ExAC gnomAD
rs1568407602 CA405650681	558	S>R		No	ClinGen Ensembl
rs920776227 CA308082734	562	W>R		No	ClinGen TOPMed
CA405649218 rs1368485120	563	G>S		No	ClinGen gnomAD
CA9415249 rs370977740	565	T>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA405649201 rs370977740	565	T>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA9415248 rs202093358	570	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs764664951 CA9415247	570	R>H		No	ClinGen ExAC TOPMed gnomAD
CA405649151 rs202093358	570	R>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs776295355 CA9415245	572	R>L		No	ClinGen ExAC TOPMed gnomAD
rs776295355 CA308082709	572	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA9415246 rs759183398	572	R>W		No	ClinGen ExAC TOPMed gnomAD
CA9415227 rs535167551	573	E>G		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1208797598 CA405648636	574	C>R		No	ClinGen gnomAD
rs1239395830 CA405648606	575	G>E		No	ClinGen TOPMed gnomAD
rs1286610037 CA405648613	575	G>R		No	ClinGen gnomAD
rs1220387828 CA405648464	580	K>R		No	ClinGen TOPMed
CA9415222 rs552954609	581	H>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1568406525 CA405648279	583	R>T		No	ClinGen Ensembl
rs768369603 CA9415221	585	Q>H		No	ClinGen ExAC TOPMed gnomAD
CA9415219 rs200303204	588	V>A		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs769909775 CA9415218	590	C>Y		No	ClinGen ExAC gnomAD
rs1299325021 CA405647711	593	R>S		No	ClinGen gnomAD
CA405647684 rs1343729491	594	P>Q		No	ClinGen gnomAD
CA405647681 rs1343729491	594	P>R		No	ClinGen gnomAD
CA405647688 rs1453705883	594	P>S		No	ClinGen gnomAD
rs377244167 CA9415216	595	G>E		No	ClinGen ESP ExAC TOPMed gnomAD
rs1167363041 CA405647663	595	G>R		No	ClinGen TOPMed gnomAD
rs757406841 CA9415214	596	A>D		No	ClinGen ExAC gnomAD
rs1186127553 CA405647646	596	A>T		No	ClinGen gnomAD
rs570499971 CA308082543	597	K>Q		No	ClinGen 1000Genomes gnomAD
CA405647619 rs1264023302	598	G>S		No	ClinGen TOPMed gnomAD
rs142842646 CA9415212	599	D>N		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs758788130 CA9415211	600	A>S		No	ClinGen ExAC gnomAD
CA9415209 rs765811092	601	G>E		No	ClinGen ExAC gnomAD
rs1220144982 CA405647487	602	P>A		No	ClinGen gnomAD
rs760304432 CA9415208	602	P>H		No	ClinGen ExAC TOPMed gnomAD
rs760304432 CA9415207	602	P>L		No	ClinGen ExAC TOPMed gnomAD
CA9415205 rs749891880	603	P>S		No	ClinGen ExAC TOPMed gnomAD
CA308082510 rs370210961	604	G>R		No	ClinGen TOPMed gnomAD
rs761372184 CA9415202	605	A>V		No	ClinGen ExAC TOPMed gnomAD
rs773949642 CA9415201	608	P>A		No	ClinGen ExAC gnomAD
CA308082503 rs933305299	610	T>R		No	ClinGen TOPMed
rs1467408880 CA405647005	615	A>D		No	ClinGen TOPMed gnomAD
CA405647004 rs1467408880	615	A>G		No	ClinGen TOPMed gnomAD
CA405647011 rs1162993259	615	A>S		No	ClinGen gnomAD
rs1467408880 CA405647003	615	A>V		No	ClinGen TOPMed gnomAD
rs1424343640 CA405646939	617	C>Y		No	ClinGen gnomAD
rs370282627 CA308082399	618	G>A		No	ClinGen ESP TOPMed
rs370282627 CA405646769	618	G>D		No	ClinGen ESP TOPMed
CA405646927 rs1296025421	618	G>S		No	ClinGen gnomAD
rs776582292 CA9415177	619	S>F		No	ClinGen ExAC gnomAD
rs1242764418 CA405646753	619	S>T		No	ClinGen gnomAD
VAR_057172 rs34377632 CA9415175	620	E>K		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs1404397590 CA405646687	621	E>K		No	ClinGen gnomAD
CA308082386 rs1034024144	622	N>S		No	ClinGen TOPMed
rs1326161341 CA405646624	623	H>P		No	ClinGen TOPMed gnomAD
CA405646582 rs1303507194	625	Y>D		No	ClinGen gnomAD
CA9415173 rs772414329	626	T>M		No	ClinGen ExAC TOPMed gnomAD
rs755325515 CA9415171	628	S>C		No	ClinGen ExAC TOPMed gnomAD
rs755325515 CA9415170	628	S>F		No	ClinGen ExAC TOPMed gnomAD
CA9415172 rs748326713	628	S>P		No	ClinGen ExAC gnomAD
CA9415168 rs780584876	629	L>R		No	ClinGen ExAC TOPMed gnomAD
CA405646445 rs1484443791	631	P>S		No	ClinGen gnomAD
CA9415167 rs756755908	632	E>D		No	ClinGen ExAC gnomAD
rs1600542399 CA405646366	633	T>N		No	ClinGen Ensembl
CA9415165 rs763793418	635	C>*		No	ClinGen ExAC TOPMed gnomAD
CA9415166 rs751062755	635	C>S		No	ClinGen ExAC gnomAD
rs758058477 CA9415164	638	R>C		No	ClinGen ExAC TOPMed gnomAD
rs117355762 CA9415162	638	R>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs117355762 CA9415163	638	R>P		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs923168477 CA308082335	639	H>Y		No	ClinGen Ensembl
rs759354719 CA9415161	640	A>S		No	ClinGen ExAC gnomAD
CA405646154 rs1414209810	640	A>V		No	ClinGen TOPMed gnomAD
rs766338486 CA9415159	641	W>R		No	ClinGen ExAC gnomAD
rs760898144 CA9415158	643	Q>*		No	ClinGen ExAC TOPMed gnomAD
rs370483513 CA9415157	644	T>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA405646024 rs1568405939	646	S>A		No	ClinGen Ensembl
CA405645995 rs886638990	648	H>N		No	ClinGen TOPMed gnomAD
rs1169720483 CA405645985	648	H>P		No	ClinGen gnomAD
rs886638990 CA308082308	648	H>Y		No	ClinGen TOPMed gnomAD
rs1473927492 CA405645961	649	P>S		No	ClinGen gnomAD
rs748408538 CA9415155	650	S>F		No	ClinGen ExAC gnomAD
CA405645892 rs1219386963	652	E>K		No	ClinGen TOPMed gnomAD
CA308082305 rs1000693191	654	D>A		No	ClinGen Ensembl
CA405645851 rs1260039971	654	D>H		No	ClinGen TOPMed
rs200790875 CA9415154	655	T>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA405645605 rs1600538939	656	V>A		No	ClinGen Ensembl
CA405645609 rs1240229371	656	V>I		No	ClinGen gnomAD
CA405645591 rs768916629	657	P>L		No	ClinGen ExAC TOPMed gnomAD
CA9415136 rs768916629	657	P>R		No	ClinGen ExAC TOPMed gnomAD
rs141622048 CA9415135	658	C>W		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs377701983 CA9415134	659	P>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA405645573 rs1271011751	659	P>T		No	ClinGen gnomAD
rs746396484 CA9415132	661	M>I		No	ClinGen ExAC gnomAD
CA308081781 rs552244915	662	D>G		No	ClinGen 1000Genomes
rs771612485 CA9415130	664	P>L		No	ClinGen ExAC TOPMed gnomAD
CA9415128 rs370177675	666	T>P		No	ClinGen ESP ExAC TOPMed gnomAD
CA405645442 rs778489895	670	K>M		No	ClinGen ExAC TOPMed gnomAD
rs778489895 CA9415127	670	K>R		No	ClinGen ExAC TOPMed gnomAD
CA405645432 rs1332648729	671	L>M		No	ClinGen TOPMed
rs530924409 CA9415125	672	D>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs530924409 CA405645421	672	D>N		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs374894240 CA9415124	673	S>F		No	ClinGen ESP ExAC TOPMed

No associated diseases with Q8TDF6

5 regional properties for Q8TDF6

Type	Name	Position	InterPro Accession
domain	Dbl homology (DH) domain	264 - 448	IPR000219
domain	SH3 domain	603 - 664	IPR001452
domain	Pleckstrin homology domain	480 - 594	IPR001849
domain	Ephexin-1, SH3 domain	607 - 661	IPR035635
domain	Ephexin-like, PH domain	468 - 594	IPR047270

Functions

		Description
EC Number
Subcellular Localization	Cytoplasm Cell membrane	Recruited to membranes upon activation by DAG
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

4 GO annotations of cellular component

Name	Definition
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
membrane	A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.
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.

4 GO annotations of molecular function

Name	Definition
calcium ion binding	Binding to a calcium ion (Ca2+).
diacylglycerol binding	Binding to a diacylglycerol, a diester of glycerol and two fatty acids.
GTP-dependent protein binding	Binding to a protein or protein complex when at least one of the interacting partners is in the GTP-bound state.
guanyl-nucleotide exchange factor activity	Stimulates the exchange of GDP to GTP on a signaling GTPase, changing its conformation to its active form. Guanine nucleotide exchange factors (GEFs) act by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP), which is more abundant in the cell under normal cellular physiological conditions.

8 GO annotations of biological process

Name	Definition
activation of phospholipase C activity	The initiation of the activity of the inactive enzyme phospolipase C as the result of The series of molecular signals generated as a consequence of a G protein-coupled receptor binding to its physiological ligand.
cell population proliferation	The multiplication or reproduction of cells, resulting in the expansion of a cell population.
myeloid cell differentiation	The process in which a relatively unspecialized myeloid precursor cell acquires the specialized features of any cell of the myeloid leukocyte, megakaryocyte, thrombocyte, or erythrocyte lineages.
positive regulation of Ras protein signal transduction	Any process that activates or increases the frequency, rate or extent of Ras protein signal transduction.
regulation of G protein-coupled receptor signaling pathway	Any process that modulates the frequency, rate or extent of G protein-coupled receptor signaling pathway.
response to extracellular stimulus	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an extracellular stimulus.
small GTPase mediated signal transduction	The series of molecular signals in which a small monomeric GTPase relays a signal.
transmembrane receptor protein tyrosine kinase signaling pathway	The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses tyrosine kinase activity, and ending with the regulation of a downstream cellular process, e.g. transcription.

30 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
A6N9I4	RASGRP2	RAS guanyl-releasing protein 2	Bos taurus (Bovine)	SS
Q1LZ97	RASGRP4	RAS guanyl-releasing protein 4	Bos taurus (Bovine)	SS
A0A3S5ZPR1	RASGRP3	RAS guanyl releasing protein 3	Gallus gallus (Chicken)	SS
P26675	Sos	Protein son of sevenless	Drosophila melanogaster (Fruit fly)	SS
Q07890	SOS2	Son of sevenless homolog 2	Homo sapiens (Human)	SS
Q07889	SOS1	Son of sevenless homolog 1	Homo sapiens (Human)	EV
Q13905	RAPGEF1	Rap guanine nucleotide exchange factor 1	Homo sapiens (Human)	PR
O95398	RAPGEF3	Rap guanine nucleotide exchange factor 3	Homo sapiens (Human)	EV
Q8WZA2	RAPGEF4	Rap guanine nucleotide exchange factor 4	Homo sapiens (Human)	SS
Q8N431	RASGEF1C	Ras-GEF domain-containing family member 1C	Homo sapiens (Human)	PR
Q8N9B8	RASGEF1A	Ras-GEF domain-containing family member 1A	Homo sapiens (Human)	PR
Q8IZJ4	RGL4	Ral-GDS-related protein	Homo sapiens (Human)	PR
Q12967	RALGDS	Ral guanine nucleotide dissociation stimulator	Homo sapiens (Human)	PR
O95267	RASGRP1	RAS guanyl-releasing protein 1	Homo sapiens (Human)	EV
Q7LDG7	RASGRP2	RAS guanyl-releasing protein 2	Homo sapiens (Human)	EV SS
Q8IV61	RASGRP3	Ras guanyl-releasing protein 3	Homo sapiens (Human)	SS
Q86X27	RALGPS2	Ras-specific guanine nucleotide-releasing factor RalGPS2	Homo sapiens (Human)	PR
Q5JS13	RALGPS1	Ras-specific guanine nucleotide-releasing factor RalGPS1	Homo sapiens (Human)	PR
Q62245	Sos1	Son of sevenless homolog 1	Mus musculus (Mouse)	SS
A2AR50	Ralgps1	Ras-specific guanine nucleotide-releasing factor RalGPS1	Mus musculus (Mouse)	PR
Q9Z1S3	Rasgrp1	RAS guanyl-releasing protein 1	Mus musculus (Mouse)	SS
Q9QUG9	Rasgrp2	RAS guanyl-releasing protein 2	Mus musculus (Mouse)	SS
Q9ERD6	Ralgps2	Ras-specific guanine nucleotide-releasing factor RalGPS2	Mus musculus (Mouse)	PR
Q02384	Sos2	Son of sevenless homolog 2	Mus musculus (Mouse)	SS
Q8BTM9	Rasgrp4	RAS guanyl-releasing protein 4	Mus musculus (Mouse)	SS
Q9R1K8	Rasgrp1	RAS guanyl-releasing protein 1	Rattus norvegicus (Rat)	SS
P0C643	Rasgrp2	RAS guanyl-releasing protein 2	Rattus norvegicus (Rat)	SS
Q8R5I4	Rasgrp4	RAS guanyl-releasing protein 4	Rattus norvegicus (Rat)	SS
Q9N5D3	sos-1	Son of sevenless homolog	Caenorhabditis elegans	EV
A4IJ06	rasgrp1	RAS guanyl-releasing protein 1	Xenopus tropicalis (Western clawed frog) (Silurana tropicalis)	SS

10	20	30	40	50	60
MNRKDSKRKS	HQECTGKIGG	RGRPRQVRRH	KTCPSPREIS	KVMASMNLGL	LSEGGCSEDE
70	80	90	100	110	120
LLEKCIQSFD	SAGSLCHEDH	MLNMVLAMHS	WVLPSADLAA	RLLTSYQKAT	GDTQELRRLQ
130	140	150	160	170	180
ICHLVRYWLM	RHPEVMHQDP	QLEEVIGRFW	ATVAREGNSA	QRRLGDSSDL	LSPGGPGPPL
190	200	210	220	230	240
PMSSPGLGKK	RKVSLLFDHL	ETGELAQHLT	YLEFRSFQAI	TPQDLRSYVL	QGSVRGCPAL
250	260	270	280	290	300
EGSVGLSNSV	SRWVQVMVLS	RPGPLQRAQV	LDKFIHVAQR	LHQLQNFNTL	MAVTGGLCHS
310	320	330	340	350	360
AISRLKDSHA	HLSPDSTKAL	LELTELLASH	NNYARYRRTW	AGCAGFRLPV	LGVHLKDLVS
370	380	390	400	410	420
LHEAQPDRLP	DGRLHLPKLN	NLYLRLQELV	ALQGQHPPCS	ANEDLLHLLT	LSLDLFYTED
430	440	450	460	470	480
EIYELSYARE	PRCPKSLPPS	PFNAPLVVEW	APGVTPKPDR	VTLGRHVEQL	VESVFKNYDP
490	500	510	520	530	540
EGRGTISQED	FERLSGNFPF	ACHGLHPPPR	QGRGSFSREE	LTGYLLRASA	ICSKLGLAFL
550	560	570	580	590	600
HTFHEVTFRK	PTFCDSCSGF	LWGVTKQGYR	CRECGLCCHK	HCRDQVKVEC	KKRPGAKGDA
610	620	630	640	650	660
GPPGAPVPST	PAPHASCGSE	ENHSYTLSLE	PETGCQLRHA	WTQTESPHPS	WETDTVPCPV
670
MDPPSTASSK	LDS