AiPD: Autoinhibited Protein Database

Q7LDG7

EV SS

Gene name	RASGRP2 (CDC25L, MCG7)
Protein name	RAS guanyl-releasing protein 2
Names	Calcium and DAG-regulated guanine nucleotide exchange factor I, CalDAG-GEFI, Cdc25-like protein, hCDC25L, F25B3.3 kinase-like protein
Species	Homo sapiens (Human)
KEGG Pathway	hsa:10235
EC number
Protein Class	GUANINE NUCLEOTIDE EXCHANGE FACTOR (PTHR23113)

Descriptions

RasGRP2 is a calcium and diacylglycerol-regulated guanine exchange factor I, which is required for proper αIIbβ3 integrin activation and fibrinogen binding. Regulation of RasGRP2 depends on the level of cytoplasmic Ca2+ concentration onto two EF-hand domains. Calcium binding to EF hands induces conformational changes in the structure of RasGRP2, most prominently in an autoinhibitory linker region located between the CDC25 and the first EF-hand domains, that blocks the catalytic surface of the CDC25 domain and prevents Rap1 engagement.
Both RasGRP1 and RasGRP2 contain C1 domain, a binding site of DAG. In RasGRP1, the C1 domain is involved in autoinhibition. Thus, the C1 domain in RasGRP2 could be also involved in autoinhibition.

Autoinhibitory domains (AIDs)

Target domain	150-388 (Ras guanine-nucleotide exchange factors catalytic domain)
Relief mechanism	Ligand binding
Assay	Mutagenesis experiment, Structural analysis

AID

388-430 (CDC25-EF linker)

Target domain

150-388 (Ras guanine-nucleotide exchange factors catalytic domain)

Relief mechanism

Ligand binding (Calcium binding)

Assay

Mutagenesis experiment, Structural analysis

498-548 (C1 domain) SS

Target domain	426-490 (EF domain)
Relief mechanism	Ligand binding, PTM
Assay

AID

498-548 (C1 domain)

Target domain

426-490 (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,

Ren J et al. (2016) "A negative-feedback loop regulating ERK1/2 activation and mediated by RasGPR2 phosphorylation", Biochemical and biophysical research communications, 474, 193-198

Iwig JS et al. (2013) "Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1", eLife, 2, e00813

Autoinhibited structure

Activated structure

3 structures for Q7LDG7

Entry ID	Method	Resolution	Chain	Position	Source
2MA2	NMR	-	A	417-497	PDB
6AXF	X-ray	310 A	A/C/E/G/I/K/M/O	1-394	PDB
AF-Q7LDG7-F1	Predicted				AlphaFoldDB

482 variants for Q7LDG7

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA16616920 RCV000477885 rs1060499609	181	F>S	Platelet-type bleeding disorder 18 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs587777529 VAR_071474 CA215007 RCV000128611	248	G>W	BDPLT18; prevents Rap1 activation upon calcium stimulation; reduces platelet adhesion and spreading Platelet-type bleeding disorder 18 [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt ExAC dbSNP gnomAD
RCV001003528 rs200434813 CA381140628	345	A>P	Platelet-type bleeding disorder 18 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
rs767965347 CA6079011 VAR_079618	381	S>F	BDPLT18; loss of guanyl-nucleotide exchange factor activity [UniProt]	Yes	ClinGen UniProt ExAC dbSNP
rs1555122100 RCV000477816	494	R>missing	Platelet-type bleeding disorder 18 [ClinVar]	Yes	ClinVar dbSNP
rs774996406 RCV001003527	494	R>missing	Platelet-type bleeding disorder 18 [ClinVar]	Yes	ClinVar dbSNP
RCV001003526 rs752492512 RCV000851699	497	F>missing	Platelet-type bleeding disorder 18 [ClinVar]	Yes	ClinVar dbSNP
CA381159705 rs1188838456	2	A>S		No	ClinGen gnomAD
CA6079409 rs562383121	5	L>P		No	ClinGen ExAC gnomAD
rs142746069 RCV000264218 CA6079408	6	D>G		No	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
CA381159469 rs1335442289	7	L>Q		No	ClinGen TOPMed gnomAD
CA381159434 rs1215424081	8	D>A		No	ClinGen gnomAD
rs1471019810 CA381159429	8	D>E		No	ClinGen TOPMed gnomAD
CA381159421 rs1398171453	9	K>E		No	ClinGen TOPMed gnomAD
rs1344009449 CA381159370	10	G>C		No	ClinGen gnomAD
CA6079405 rs759488586	11	C>S		No	ClinGen ExAC gnomAD
rs759488586 CA381159336	11	C>Y		No	ClinGen ExAC gnomAD
CA6079404 rs776144756	12	T>A		No	ClinGen ExAC gnomAD
rs1345997961 CA381159287	12	T>M		No	ClinGen gnomAD
rs1345997961 CA381159298	12	T>R		No	ClinGen gnomAD
CA381159284 rs1264040086	13	V>M		No	ClinGen TOPMed
CA381159160 rs1266432844	18	R>C		No	ClinGen Ensembl
rs1170679601 CA381159088	20	C>F		No	ClinGen gnomAD
CA381159033 rs1424894341	22	E>*		No	ClinGen gnomAD
CA6079379 rs760079672	25	D>E		No	ClinGen ExAC gnomAD
rs1479214239 CA381158944	25	D>N		No	ClinGen gnomAD
CA381157774 rs1592389023	26	D>E		No	ClinGen Ensembl
rs1028636428 CA223893560	26	D>V		No	ClinGen Ensembl
rs1247644888 CA381157736	28	G>E		No	ClinGen gnomAD
CA223893556 rs865832274	31	R>L		No	ClinGen gnomAD
CA381157677 rs865832274	31	R>Q		No	ClinGen gnomAD
rs777850328 CA6079375	32	D>E		No	ClinGen ExAC TOPMed gnomAD
rs1309241170 CA381157629	33	P>R		No	ClinGen TOPMed
rs748370784 CA6079373	35	L>V		No	ClinGen ExAC gnomAD
rs1263888906 CA381157513	37	R>C		No	ClinGen TOPMed
rs1355931209 CA381157470	39	F>C		No	ClinGen TOPMed
CA381157424 rs1294965992	41	M>I		No	ClinGen gnomAD
CA381157346 rs1364563110	42	M>I		No	ClinGen gnomAD
rs1433287503 CA381157388	42	M>T		No	ClinGen gnomAD
CA381157334 rs1592388739	43	H>P		No	ClinGen Ensembl
CA381157312 rs1289941754	44	P>A		No	ClinGen gnomAD
CA381157288 rs1165475409	45	W>*		No	ClinGen gnomAD
rs754787747 CA381157297	45	W>*		No	ClinGen ExAC gnomAD
CA381157302 rs1199280575	45	W>R		No	ClinGen TOPMed
rs754787747 CA6079371	45	W>S		No	ClinGen ExAC gnomAD
rs1285351081 CA381157260	47	I>L		No	ClinGen gnomAD
CA223893555 rs1038937851	48	P>S		No	ClinGen TOPMed gnomAD
rs1038937851 CA381157234	48	P>T		No	ClinGen TOPMed gnomAD
CA381157101 rs1262231265	53	A>E		No	ClinGen gnomAD
CA381157068 rs1487505117	54	A>V		No	ClinGen gnomAD
rs749896674 CA6079367	55	K>M		No	ClinGen ExAC TOPMed gnomAD
CA6079368 rs749896674	55	K>R		No	ClinGen ExAC TOPMed gnomAD
CA381157028 rs1340873848	56	L>V		No	ClinGen gnomAD
CA381156933 rs1330765025	58	H>R		No	ClinGen gnomAD
rs1456519920 CA381156309	61	Q>*		No	ClinGen gnomAD
rs1386302381 CA381156273	62	Q>*		No	ClinGen gnomAD
rs1453808928 CA381156228	64	R>P		No	ClinGen TOPMed gnomAD
rs1453808928 CA381156238	64	R>Q		No	ClinGen TOPMed gnomAD
CA6079343 rs754090867	64	R>W		No	ClinGen ExAC gnomAD
rs371364266 CA6079341	66	D>E		No	ClinGen ESP ExAC TOPMed gnomAD
rs973463306 CA223893479	68	S>C		No	ClinGen TOPMed gnomAD
rs1437764504 CA381156041	69	N>K		No	ClinGen TOPMed
CA6079340 rs773765522	69	N>S		No	ClinGen ExAC TOPMed gnomAD
CA381156026 rs1282723020	70	S>F		No	ClinGen gnomAD
rs1207452585 CA381155953	72	Q>*		No	ClinGen gnomAD
CA381155956 rs1207452585	72	Q>K		No	ClinGen gnomAD
rs904622381 CA381155917	73	V>L		No	ClinGen gnomAD
rs904622381 CA223893477	73	V>M		No	ClinGen gnomAD
rs866807663 CA223893474	76	C>*		No	ClinGen Ensembl
CA223893475 rs1033819901	76	C>Y		No	ClinGen TOPMed
rs1024424979 CA223893473	79	V>I		No	ClinGen TOPMed gnomAD
rs866294671 CA223893471	80	R>M		No	ClinGen gnomAD
CA6079321 rs774230462	81	Y>F		No	ClinGen ExAC gnomAD
CA223893415 rs373984261	83	I>L		No	ClinGen gnomAD
CA6079317 rs145541826	85	A>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs759368276 CA6079316	88	A>V		No	ClinGen ExAC gnomAD
rs1460525185 CA381154728	90	F>L		No	ClinGen TOPMed
rs370769462 CA6079315	93	N>K		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6079313 RCV001270609 rs186484036	94	P>L		No	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
CA381154625 rs186484036	94	P>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA223893408 rs969839723	98	E>K		No	ClinGen TOPMed gnomAD
CA6079311 rs771666847	102	E>D		No	ClinGen ExAC TOPMed gnomAD
CA381154314 rs1410849917	104	K>M		No	ClinGen gnomAD
rs1334255712 CA381154287	105	A>P		No	ClinGen TOPMed
rs1401997605 CA381154281	105	A>V		No	ClinGen gnomAD
CA6079310 rs556398819	107	L>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA381154150 rs1181480395	109	Q>R		No	ClinGen gnomAD
rs866790849 CA223893402	112	N>H		No	ClinGen Ensembl
rs1592384832 CA381154007	113	R>*		No	ClinGen Ensembl
CA6079307 rs750735438	114	R>L		No	ClinGen ExAC TOPMed gnomAD
rs750735438 CA6079308	114	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs535901850 CA6079309	114	R>W		No	ClinGen 1000Genomes ExAC gnomAD
rs781543360 CA6079306	117	S>N		No	ClinGen ExAC gnomAD
CA6079305 rs757759731	118	L>V		No	ClinGen ExAC gnomAD
rs1261087127 CA381153723	119	I>M		No	ClinGen gnomAD
CA6079303 rs764060342	121	I>T		No	ClinGen ExAC gnomAD
CA6079304 rs752166979	121	I>V		No	ClinGen ExAC gnomAD
CA6079302 rs752755233	122	D>E		No	ClinGen ExAC TOPMed gnomAD
rs1000200549 CA223893395	123	S>G		No	ClinGen TOPMed gnomAD
rs1000200549 CA381153584	123	S>R		No	ClinGen TOPMed gnomAD
rs375059620 CA6079300	124	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs375059620 CA381153541	124	V>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA6079237 rs749330853	131	R>Q		No	ClinGen ExAC gnomAD
CA6079238 rs368390509	131	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs756291981 CA6079235	133	V>G		No	ClinGen ExAC gnomAD
rs750670678 CA6079234	134	T>I		No	ClinGen ExAC gnomAD
rs767321876 CA6079233	135	Q>P		No	ClinGen ExAC gnomAD
rs751387962 CA6079231	136	R>Q		No	ClinGen ExAC gnomAD
rs757044187 CA6079232	136	R>W		No	ClinGen ExAC TOPMed
rs1450139017 CA381151772	138	P>L		No	ClinGen gnomAD
rs1279260532 CA381151769	139	V>M		No	ClinGen TOPMed
CA6079230 rs560187757	140	G>V		No	ClinGen 1000Genomes ExAC gnomAD
CA6079229 rs762893963	142	K>I		No	ClinGen ExAC TOPMed gnomAD
rs752140782 CA6079228	143	K>N		No	ClinGen ExAC gnomAD
rs764724759 CA6079227	144	R>C		No	ClinGen ExAC TOPMed gnomAD
CA6079226 rs759209716	144	R>H		No	ClinGen ExAC TOPMed gnomAD
CA6079225 rs776190886	145	K>N		No	ClinGen ExAC TOPMed gnomAD
CA381151611 rs1565516537	145	K>Q		No	ClinGen Ensembl
CA6079224 rs377027979	147	S>A		No	ClinGen ESP ExAC TOPMed gnomAD
rs1161324506 CA381151456	149	L>F		No	ClinGen TOPMed gnomAD
CA381151457 rs1161324506	149	L>F		No	ClinGen TOPMed gnomAD
CA6079223 rs774876012	151	D>G		No	ClinGen ExAC gnomAD
CA6079222 rs774876012	151	D>V		No	ClinGen ExAC gnomAD
CA6079221 rs769228103	152	H>Q		No	ClinGen ExAC TOPMed gnomAD
CA381150007 rs1254773056	156	M>V		No	ClinGen gnomAD
rs749816858 CA6079220	159	A>V		No	ClinGen ExAC TOPMed gnomAD
CA381149807 rs1416261864	160	E>D		No	ClinGen TOPMed
CA381149511 rs1284498873	167	Y>C		No	ClinGen gnomAD
CA6079217 rs746074180	167	Y>H		No	ClinGen ExAC gnomAD
CA6079216 rs199706727	168	R>C		No	ClinGen ExAC TOPMed gnomAD
CA6079214 rs146725264	168	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs146725264 CA6079215	168	R>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs144822791 CA6079212	171	C>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA381149294 rs1196753465	173	I>N		No	ClinGen TOPMed gnomAD
CA381149016 rs1396040131	176	Q>E		No	ClinGen TOPMed
rs1171997172 CA381148879	178	Y>C		No	ClinGen TOPMed
rs1592380294 CA381148639	182	V>L		No	ClinGen Ensembl
CA223891900 rs571451227	184	H>R		No	ClinGen Ensembl
CA6079187 rs753229128	186	C>Y		No	ClinGen ExAC gnomAD
CA6079186 rs765918312	187	T>S		No	ClinGen ExAC gnomAD
rs940936208 CA223891899	188	V>A		No	ClinGen TOPMed
CA223891898 rs1047079433	190	N>S		No	ClinGen TOPMed gnomAD
rs1382936558 CA381148173	191	P>A		No	ClinGen TOPMed
CA6079184 rs750150071	191	P>L		No	ClinGen ExAC gnomAD
rs763370908 CA6079182	192	V>D		No	ClinGen ExAC gnomAD
CA381148133 rs1278570656	192	V>I		No	ClinGen TOPMed gnomAD
rs1049036601 CA223891897	194	E>Q		No	ClinGen TOPMed gnomAD
rs775948285 CA6079181	195	R>W		No	ClinGen ExAC gnomAD
CA381147920 rs1445769227	196	F>S		No	ClinGen gnomAD
CA381147949 rs1592380064	196	F>V		No	ClinGen Ensembl
rs765607002 CA381147825	199	L>F		No	ClinGen ExAC gnomAD
rs765607002 CA6079180	199	L>I		No	ClinGen ExAC gnomAD
CA223891893 rs920000457	200	F>L		No	ClinGen Ensembl
rs760096205 CA381147683	202	S>R		No	ClinGen ExAC gnomAD
CA6079178 rs776573272	203	V>I		No	ClinGen ExAC TOPMed gnomAD
rs771060735 CA6079177	207	V>A		No	ClinGen ExAC gnomAD
rs747205429 CA6079176	213	S>R		No	ClinGen ExAC gnomAD
CA381147114 rs1205539807	215	P>L		No	ClinGen gnomAD
rs1565515407 CA381147082	217	A>V		No	ClinGen Ensembl
rs376286649 CA6079174	218	P>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs773459054 CA6079175	218	P>S		No	ClinGen ExAC TOPMed gnomAD
CA6079172 rs778780409	220	R>P		No	ClinGen ExAC gnomAD
CA381146939 rs778780409	220	R>Q		No	ClinGen ExAC gnomAD
rs1352326694 CA381146958	220	R>W		No	ClinGen gnomAD
rs1254249039 CA381146737	225	T>I		No	ClinGen TOPMed
CA381146729 rs1360257142	226	H>Y		No	ClinGen gnomAD
CA6079169 rs373088872	228	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA6079166 rs767231242	230	V>L		No	ClinGen ExAC TOPMed gnomAD
CA6079167 rs767231242	230	V>M		No	ClinGen ExAC TOPMed gnomAD
CA381146557 rs1159523444	231	A>G		No	ClinGen gnomAD
rs1592379633 CA381146567	231	A>S		No	ClinGen Ensembl
CA381146556 rs1159523444	231	A>V		No	ClinGen gnomAD
RCV000852192 rs1592379014 CA381146157	235	L>P		No	ClinGen ClinVar Ensembl dbSNP
rs766819833 CA6079143	240	F>L		No	ClinGen ExAC gnomAD
CA381146009 rs1342449891	240	F>V		No	ClinGen gnomAD
CA223891881 rs373891470	242	T>M		No	ClinGen ESP TOPMed gnomAD
CA381145894 rs1458200018	243	L>P		No	ClinGen gnomAD
CA381145684 rs1207082414	247	V>A		No	ClinGen TOPMed
rs767701927 CA6079139	247	V>F		No	ClinGen ExAC gnomAD
CA6079136 rs587777529	248	G>R		No	ClinGen ExAC gnomAD
rs762761145 CA6079135	249	G>V		No	ClinGen ExAC gnomAD
rs760934443 CA223891878	253	S>R		No	ClinGen Ensembl
CA381145488 rs1479188900	255	I>V		No	ClinGen gnomAD
CA6079134 rs369137458	256	S>C		No	ClinGen ESP ExAC TOPMed gnomAD
CA6079133 rs769789900	257	R>C		No	ClinGen ExAC gnomAD
CA6079132 rs745870814	257	R>H		No	ClinGen ExAC TOPMed gnomAD
CA381145369 rs1592378730 RCV000852213	258	L>P		No	ClinGen ClinVar Ensembl dbSNP
CA381145351 rs1202874110	259	K>R		No	ClinGen gnomAD
CA6079131 rs780839242	262	H>N		No	ClinGen ExAC gnomAD
CA381145221 rs1389480196	262	H>R		No	ClinGen TOPMed gnomAD
rs1412979588 CA381145204	263	S>C		No	ClinGen TOPMed
rs542524220 CA6079128	265	V>I		No	ClinGen ExAC TOPMed gnomAD
CA381145039 rs1303658509	266	S>C		No	ClinGen gnomAD
CA223891869 rs267603104	267	P>L		No	ClinGen ExAC gnomAD
CA6079127 rs267603104	267	P>R		No	ClinGen ExAC gnomAD
CA6079124 rs756607534	269	T>A		No	ClinGen ExAC gnomAD
rs750985978 CA6079123	271	K>M		No	ClinGen ExAC TOPMed gnomAD
CA6079105 rs780382741	272	L>F		No	ClinGen ExAC TOPMed gnomAD
rs780382741 CA381143223	272	L>I		No	ClinGen ExAC TOPMed gnomAD
rs1381389618 CA381143211	272	L>P		No	ClinGen gnomAD
rs756519568 CA6079104	275	G>D		No	ClinGen ExAC gnomAD
rs868625458 CA223891493	276	L>F		No	ClinGen Ensembl
CA6079101 rs757719823	277	T>M		No	ClinGen ExAC TOPMed gnomAD
rs200799017 CA6079102	277	T>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA381143072 rs1284122937	278	E>*		No	ClinGen gnomAD
rs764148903 CA6079099	280	V>A		No	ClinGen ExAC gnomAD
rs1219145027 CA381143030	280	V>L		No	ClinGen gnomAD
rs1243522728 CA381143001	281	T>A		No	ClinGen gnomAD
rs367847638 CA6079097	281	T>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA381142904 rs1382210829	283	T>I		No	ClinGen gnomAD
CA381142828 rs1299646809	286	Y>C		No	ClinGen TOPMed gnomAD
rs1299646809 CA381142835	286	Y>S		No	ClinGen TOPMed gnomAD
CA6079094 rs776317269	287	G>D		No	ClinGen ExAC gnomAD
rs201361347 CA6079095	287	G>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA381142695 rs1163282747	289	Y>*		No	ClinGen gnomAD
CA381142698 rs1592372097 RCV000851906	289	Y>C		No	ClinGen ClinVar Ensembl dbSNP
rs1592372097 CA381142702	289	Y>S		No	ClinGen Ensembl
CA381142683 rs1489642473	290	R>Q		No	ClinGen TOPMed
CA381142692 rs1472032952	290	R>W		No	ClinGen gnomAD
rs1370671981 CA381142653	291	R>C		No	ClinGen gnomAD
rs919782236 CA223891475	291	R>H		No	ClinGen TOPMed gnomAD
rs760536759 CA381142633	292	R>L		No	ClinGen ExAC TOPMed gnomAD
CA6079092 rs760536759	292	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA6079093 rs766285452	292	R>W		No	ClinGen ExAC TOPMed gnomAD
CA381142542 rs1157156687	294	A>G		No	ClinGen TOPMed
rs550854298 CA6079091	294	A>T		No	ClinGen 1000Genomes ExAC gnomAD
rs973852010 CA223891472	295	A>G		No	ClinGen TOPMed
rs142770924 CA6079088	297	V>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA6079087 rs202159133	300	R>C		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs568335357 CA6079086	300	R>H		No	ClinGen 1000Genomes ExAC gnomAD
rs1338340813 CA381142216	302	P>L		No	ClinGen TOPMed gnomAD
rs746173380 CA6079085	304	L>M		No	ClinGen ExAC gnomAD
RCV000851953 CA381142098 RCV000852247 rs1592371840	305	G>D		No	ClinGen ClinVar Ensembl dbSNP
CA223891460 rs1034193387	307	H>Y		No	ClinGen TOPMed gnomAD
rs1592371802 CA381141963	308	L>F		No	ClinGen Ensembl
CA381141869 rs1592371792	310	D>A		No	ClinGen Ensembl
CA6079084 rs781413213	310	D>E		No	ClinGen ExAC gnomAD
rs1405975564 CA381141819	312	V>M		No	ClinGen gnomAD
CA6079082 rs547924942	313	A>S		No	ClinGen 1000Genomes ExAC gnomAD
rs192530379 CA223891454	313	A>V		No	ClinGen 1000Genomes gnomAD
CA381141651 rs1350999347	315	Q>H		No	ClinGen TOPMed
CA223891452 rs200958131	319	P>S		No	ClinGen Ensembl
rs753605072 CA6079076	320	D>E		No	ClinGen ExAC gnomAD
CA6079074 rs367926669	322	L>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs773073274 CA381141359	323	D>E		No	ClinGen ExAC TOPMed gnomAD
rs768230608 CA6079069	326	R>L		No	ClinGen ExAC TOPMed gnomAD
rs768230608 CA381141280	326	R>P		No	ClinGen ExAC TOPMed gnomAD
rs768230608 CA6079070	326	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA6079071 rs761273034	326	R>W		No	ClinGen ExAC TOPMed gnomAD
rs1272705632 CA381141246	327	T>I		No	ClinGen TOPMed gnomAD
rs1272705632 CA381141251	327	T>S		No	ClinGen TOPMed gnomAD
CA6079066 rs771246989	328	R>Q		No	ClinGen ExAC gnomAD
rs147886381 CA6079067	328	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
CA223891429 rs199792530	330	N>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6079063 rs144906532	330	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs141060165 CA381141112	331	G>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6079061 rs141060165	331	G>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
RCV000851925 rs374345558 CA381141015	333	K>N		No	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs1424307374 CA381140945	334	M>I		No	ClinGen TOPMed
CA6079059 rs754068377	336	Q>H		No	ClinGen ExAC gnomAD
CA223891421 rs936544661	337	L>H		No	ClinGen Ensembl
rs779878541 CA6079058	339	S>G		No	ClinGen ExAC gnomAD
CA6079056 rs750264906	341	L>M		No	ClinGen ExAC TOPMed gnomAD
rs200434813 CA6079055	345	A>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs889067305 CA223891405	346	M>T		No	ClinGen gnomAD
CA6079054 rs761743070	347	V>A		No	ClinGen ExAC gnomAD
CA223891385 rs746378275	351	R>Q		No	ClinGen gnomAD
rs541845100 CA6079051	351	R>W		No	ClinGen ExAC TOPMed gnomAD
rs1278628258 CA381140416	352	P>A		No	ClinGen gnomAD
CA381140379 rs1239843087	353	P>A		No	ClinGen gnomAD
rs1050398330 CA223891380	354	V>A		No	ClinGen Ensembl
CA6079047 rs532777492	356	A>D		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6079048 rs532777492	356	A>G		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6079049 rs200768691	356	A>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs563686135 CA6079046	357	N>K		No	ClinGen 1000Genomes ExAC gnomAD
rs748733848 CA6079045	358	P>H		No	ClinGen ExAC TOPMed gnomAD
CA381140149 rs1158261949	359	D>N		No	ClinGen gnomAD
rs1382015882 CA381140080	361	L>V		No	ClinGen gnomAD
rs1179031027 CA381140031	362	S>N		No	ClinGen gnomAD
rs780100580 CA6079041	365	T>M		No	ClinGen ExAC TOPMed gnomAD
CA6079023 rs775653915	367	S>C		No	ClinGen ExAC gnomAD
CA223890962 rs949884432	368	L>V		No	ClinGen TOPMed
CA6079020 rs139499587	373	T>K		No	ClinGen ESP ExAC TOPMed gnomAD
rs139499587 CA6079019	373	T>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA6079021 rs139499587	373	T>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA381138703 rs1245280018	375	D>N		No	ClinGen gnomAD
rs777519573 CA6079017	376	E>G		No	ClinGen ExAC gnomAD
CA381138646 rs1258017601	378	Y>H		No	ClinGen gnomAD
rs754577211 CA6079013	380	L>Q		No	ClinGen ExAC gnomAD
CA223890911 rs61759870	384	R>Q		No	ClinGen TOPMed gnomAD
CA6079009 rs71583719	384	R>W		No	ClinGen ExAC TOPMed gnomAD
rs114654732 CA6079008	386	P>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs746056618 CA6079004 RCV001270546	387	R>C		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs746056618 CA6079006	387	R>G		No	ClinGen ExAC TOPMed gnomAD
CA381138459 rs1431038254	387	R>H		No	ClinGen gnomAD
rs746056618 CA6079005	387	R>S		No	ClinGen ExAC TOPMed gnomAD
CA6079003 rs776791601	390	S>Y		No	ClinGen ExAC TOPMed gnomAD
rs746745684 CA6079001	391	S>L		No	ClinGen ExAC TOPMed gnomAD
CA381138393 rs1469224631	391	S>T		No	ClinGen gnomAD
CA6078980 rs748007505	392	P>Q		No	ClinGen ExAC gnomAD
rs765990424 CA6078979	393	T>A		No	ClinGen ExAC TOPMed gnomAD
rs768737956 CA6078978	396	T>M		No	ClinGen ExAC gnomAD
CA6078977 rs748749998	397	S>N		No	ClinGen ExAC TOPMed gnomAD
rs931674883 CA223890709	399	T>A		No	ClinGen Ensembl
rs931674883 CA381138278	399	T>P		No	ClinGen Ensembl
CA6078975 rs755815297	403	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs779716553 CA6078976	403	R>W		No	ClinGen ExAC TOPMed gnomAD
rs139873299 CA6078974	404	P>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA381138250 rs1218558183	404	P>S		No	ClinGen TOPMed gnomAD
CA6078973 rs141700750	405	P>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1422576471 CA381138197	408	E>G		No	ClinGen TOPMed
rs753022840 CA381138183	409	E>D		No	ClinGen ExAC TOPMed gnomAD
CA6078970 rs765671882	412	S>L		No	ClinGen ExAC TOPMed gnomAD
rs753906875 CA6078968	413	A>V		No	ClinGen ExAC gnomAD
CA6078967 rs766507209	415	K>E		No	ClinGen ExAC TOPMed gnomAD
rs760868395 CA6078966	415	K>I		No	ClinGen ExAC gnomAD
CA381138092 rs1278146808	415	K>N		No	ClinGen TOPMed
rs760868395 CA381138105	415	K>T		No	ClinGen ExAC gnomAD
CA6078965 rs147974963	416	P>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs1370680452 CA381138028	419	D>N		No	ClinGen gnomAD
CA381138004 rs1225703346	420	Q>R		No	ClinGen TOPMed
rs141842144 CA6078962	423	V>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6078960 rs201325045	424	V>L		No	ClinGen 1000Genomes ExAC
rs201703741 CA6078959	425	E>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs769469271 CA6078958	428	E>K		No	ClinGen ExAC TOPMed gnomAD
CA381137869 rs769469271	428	E>Q		No	ClinGen ExAC TOPMed gnomAD
CA6078930 rs138764936	436	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA6078931 rs371237302	436	R>W		No	ClinGen ESP ExAC gnomAD
CA381137551 rs750452972	438	F>L		No	ClinGen ExAC TOPMed gnomAD
CA6078927 rs757489122	440	V>I		No	ClinGen ExAC gnomAD
CA6078925 rs764442265	441	D>N		No	ClinGen ExAC TOPMed gnomAD
rs1177761525 CA381137488	441	D>V		No	ClinGen TOPMed gnomAD
rs149091632 CA223890497	447	S>P		No	ClinGen ESP TOPMed
RCV000591623 CA6078923 rs371857837	455	R>C		No	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs569602568 CA6078922	455	R>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6078921 rs569602568	455	R>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6078920 rs776187625	456	G>E		No	ClinGen ExAC gnomAD
CA381136957 rs1441284269	456	G>R		No	ClinGen gnomAD
CA381136771 rs1201749666	460	Y>H		No	ClinGen gnomAD
CA6078917 rs373654113	463	A>D		No	ClinGen ESP ExAC TOPMed gnomAD
CA6078918 rs746646945	463	A>S		No	ClinGen ExAC TOPMed gnomAD
rs746646945 CA381136714	463	A>T		No	ClinGen ExAC TOPMed gnomAD
CA381136607 rs1446163797	466	D>N		No	ClinGen TOPMed
CA6078914 rs780403372	468	D>E		No	ClinGen ExAC TOPMed gnomAD
rs1281735696 CA381136538	468	D>N		No	ClinGen gnomAD
CA381133960 rs764997166	472	D>H		No	ClinGen ExAC TOPMed gnomAD
CA6078905 rs764997166	472	D>N		No	ClinGen ExAC TOPMed gnomAD
CA381133931 rs1397926075	473	G>S		No	ClinGen gnomAD
CA381133896 rs1160126563	474	C>S		No	ClinGen TOPMed
CA381133800 rs1346673928	478	E>K		No	ClinGen gnomAD
rs1437336367 CA381133697	481	V>F		No	ClinGen gnomAD
rs546496527 CA6078904	482	S>F		No	ClinGen 1000Genomes ExAC gnomAD
rs1414490542 CA381133607	483	Y>C		No	ClinGen TOPMed
CA381133565 rs1455652926	484	F>V		No	ClinGen TOPMed
CA381133540 rs1475223161	485	L>P		No	ClinGen gnomAD
rs760132708 CA6078901	486	R>H		No	ClinGen ExAC gnomAD
CA6078902 rs760132708	486	R>P		No	ClinGen ExAC gnomAD
rs1190973943 CA381133479	488	S>G		No	ClinGen gnomAD
CA381133462 rs1489066343	488	S>R		No	ClinGen gnomAD
CA6078900 rs140514685 RCV001702526 RCV000592702	489	S>C		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA381133438 rs1216927641	490	V>M		No	ClinGen gnomAD
rs1451579237 CA381133392	491	L>F		No	ClinGen gnomAD
rs1050610536 CA223888232	492	G>E		No	ClinGen TOPMed gnomAD
CA381133391 rs771647146	492	G>R		No	ClinGen ExAC TOPMed gnomAD
CA381133388 rs771647146	492	G>R		No	ClinGen ExAC TOPMed gnomAD
CA381133371 rs1050610536	492	G>V		No	ClinGen TOPMed gnomAD
CA6078899 rs771647146	492	G>W		No	ClinGen ExAC TOPMed gnomAD
rs2301562 CA6078898 VAR_038257	493	G>A		No	ClinGen UniProt 1000Genomes ExAC TOPMed dbSNP gnomAD
rs2301562 CA381133346	493	G>E		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA223888231 rs2301562	493	G>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1277810657 CA381133284	494	R>H		No	ClinGen TOPMed gnomAD
rs1217101363 CA381133258	495	M>I		No	ClinGen gnomAD
CA381133280 rs1592352544	495	M>L		No	ClinGen Ensembl
rs1364330001 CA381133203	496	G>S		No	ClinGen gnomAD
CA381133142 rs1435450843	497	F>S		No	ClinGen TOPMed gnomAD
rs866750893 CA223888228	498	V>L		No	ClinGen TOPMed gnomAD
rs866750893 CA381133088	498	V>L		No	ClinGen TOPMed gnomAD
rs1461514749 CA381133016	500	N>S		No	ClinGen gnomAD
rs1422379151 CA381132996	501	F>L		No	ClinGen gnomAD
rs200117326 CA6078895	501	F>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA223888224 rs923442147	501	F>S		No	ClinGen gnomAD
CA381132915 rs1419754045	503	E>K		No	ClinGen gnomAD
rs1219907458 CA381132777	505	N>I		No	ClinGen gnomAD
rs1477876384 CA381132706	507	L>M		No	ClinGen gnomAD
CA6078893 rs781500865	508	R>H		No	ClinGen ExAC TOPMed gnomAD
CA381132629 rs1257566950	510	V>I		No	ClinGen gnomAD
CA381132582 rs1196800507	511	A>T		No	ClinGen gnomAD
rs1296510724 CA381132486	513	R>S		No	ClinGen gnomAD
rs1181529611 CA381132455	514	H>Y		No	ClinGen TOPMed
CA381132404 rs1218446797	515	C>F		No	ClinGen gnomAD
CA223888201 rs962281617	517	A>S		No	ClinGen Ensembl
rs908204032 CA223888199	517	A>V		No	ClinGen Ensembl
CA381131368 rs1258895334	519	I>N		No	ClinGen gnomAD
rs748972342 CA6078867	520	L>V		No	ClinGen ExAC gnomAD
CA381131272 rs1311447983	521	G>D		No	ClinGen gnomAD
CA381131246 rs1404155909	522	I>L		No	ClinGen TOPMed gnomAD
rs756033009 CA6078865	523	Y>N		No	ClinGen ExAC gnomAD
rs1360368234 CA381131146	525	Q>*		No	ClinGen gnomAD
rs1455854532 CA381131045	529	C>*		No	ClinGen gnomAD
rs1364848899 CA381131037	530	R>G		No	ClinGen TOPMed gnomAD
CA6078862 rs766983672	530	R>Q		No	ClinGen ExAC gnomAD
rs904177547 CA223887491	531	A>V		No	ClinGen TOPMed
CA6078839 rs779803983	532	C>W		No	ClinGen ExAC TOPMed gnomAD
rs1402241984 CA381130748	533	G>E		No	ClinGen TOPMed
rs1592348401 CA381130713	535	N>T		No	ClinGen Ensembl
rs1211817274 CA381130652	538	K>E		No	ClinGen TOPMed gnomAD
CA6078837 rs781047335	539	Q>H		No	ClinGen ExAC gnomAD
rs781047335 CA6078836	539	Q>H		No	ClinGen ExAC gnomAD
rs755945140 CA6078838	539	Q>R		No	ClinGen ExAC gnomAD
CA381130523 rs1565497948	542	D>V		No	ClinGen Ensembl
rs1337075855 CA381130532	542	D>Y		No	ClinGen gnomAD
rs144624605 CA6078834	543	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs144624605 CA6078835	543	R>G		No	ClinGen ESP ExAC TOPMed gnomAD
CA381130505 rs1230092189	543	R>H		No	ClinGen gnomAD
rs1230092189 CA381130502	543	R>L		No	ClinGen gnomAD
CA6078833 rs763714882	546	V>F		No	ClinGen ExAC TOPMed gnomAD
CA381130462 rs763714882	546	V>I		No	ClinGen ExAC TOPMed gnomAD
rs765010423 CA6078831	549	R>P		No	ClinGen ExAC gnomAD
CA6078830 rs765010423	549	R>Q		No	ClinGen ExAC gnomAD
CA6078832 rs757961182	549	R>W		No	ClinGen ExAC TOPMed gnomAD
CA381130298 rs1326711154	550	R>C		No	ClinGen gnomAD
rs761076139 CA6078829	550	R>H		No	ClinGen ExAC TOPMed gnomAD
rs534579271 CA6078828	551	R>G		No	ClinGen 1000Genomes ExAC gnomAD
rs1256838050 CA381130268	551	R>K		No	ClinGen TOPMed
rs768075718 CA6078827	552	A>D		No	ClinGen ExAC TOPMed gnomAD
rs1169810423 CA381130209	552	A>T		No	ClinGen gnomAD
CA381130124 rs1191495832	553	Q>*		No	ClinGen gnomAD
rs1241189917 CA381130071	553	Q>H		No	ClinGen TOPMed
rs1004911225 CA223887429	554	S>N		No	ClinGen TOPMed
rs1592348061 CA381130017	554	S>R		No	ClinGen Ensembl
CA381129971 rs1253508130	556	S>N		No	ClinGen gnomAD
CA381129982 rs1455567180	556	S>R		No	ClinGen gnomAD
CA6078825 rs774283374	557	L>P		No	ClinGen ExAC gnomAD
rs911410083 CA223887413	558	E>G		No	ClinGen TOPMed
CA6078824 rs768830591	558	E>Q		No	ClinGen ExAC gnomAD
CA223887412 rs934254009	560	S>A		No	ClinGen TOPMed
CA6078822 rs775651590	562	P>L		No	ClinGen ExAC gnomAD
rs1343835217 CA381129644	564	P>L		No	ClinGen gnomAD
rs1232510150 CA381129561	566	P>L		No	ClinGen gnomAD
rs952154666 CA223887402	567	M>T		No	ClinGen TOPMed
rs373526994 CA6078819	567	M>V		No	ClinGen ESP TOPMed
rs1592347840 CA381129506	568	H>P		No	ClinGen Ensembl
rs1405966429 CA381129478	569	S>I		No	ClinGen TOPMed
rs770760594 CA6078816	573	R>C		No	ClinGen ExAC TOPMed gnomAD
CA381129285 rs202192382	573	R>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6078815 rs202192382	573	R>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs532620789 CA6078813	574	A>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA381129157 rs752280523	577	F>L		No	ClinGen ExAC gnomAD
CA381129109 rs1436301579	578	S>F		No	ClinGen gnomAD
rs200196770 CA6078810	581	R>C		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6078809 rs754686243	581	R>H		No	ClinGen ExAC gnomAD
rs750816463 CA381128982	582	P>L		No	ClinGen ExAC gnomAD
rs750816463 CA6078808	582	P>R		No	ClinGen ExAC gnomAD
CA223887340 rs970101279	583	G>S		No	ClinGen TOPMed
CA6078806 rs201891010	585	R>P		No	ClinGen ExAC TOPMed gnomAD
CA6078805 rs201891010	585	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs1209199753 CA381128882	586	G>D		No	ClinGen gnomAD
CA6078804 rs375889985	587	S>F		No	ClinGen ESP ExAC gnomAD
rs1185717030 CA381128830	588	R>S		No	ClinGen TOPMed
CA381128809 rs1269142383	589	P>S		No	ClinGen TOPMed
rs1223780057 CA381128777	590	P>L		No	ClinGen gnomAD
CA6078803 rs763029558	590	P>S		No	ClinGen ExAC gnomAD
CA223886982 rs895792195	591	E>D		No	ClinGen Ensembl
CA223886979 rs1057183377	592	I>V		No	ClinGen Ensembl
CA6078789 rs144800583	593	R>C		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs149482849 CA6078787 RCV000729768	593	R>H		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs149482849 CA6078788	593	R>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs144800583 CA223886977	593	R>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA223886971 rs866966518	595	E>*		No	ClinGen Ensembl
rs1428336146 CA381127665	595	E>D		No	ClinGen gnomAD
rs866966518 CA223886969	595	E>K		No	ClinGen Ensembl
CA6078785 rs375127966	596	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA381127659 rs375127966	596	E>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs755923107 CA6078782	598	Q>*		No	ClinGen ExAC TOPMed gnomAD
rs1166446934 CA381127614	599	T>A		No	ClinGen gnomAD
rs750279513 CA6078781	599	T>M		No	ClinGen ExAC gnomAD
rs760463983 CA6078779	600	V>M		No	ClinGen ExAC gnomAD
rs1474600859 CA381127571	601	E>D		No	ClinGen TOPMed gnomAD
CA6078778 rs772891437	604	V>L		No	ClinGen ExAC TOPMed gnomAD
CA6078777 rs772046738	607	I>F		No	ClinGen ExAC gnomAD
RCV000597140 CA381127481 rs1555120400	607	I>M		No	ClinGen ClinVar Ensembl dbSNP
rs976040113 CA223886958	609	L>S		No	ClinGen Ensembl

1 associated diseases with Q7LDG7

[MIM: 615888]: Bleeding disorder, platelet-type, 18 (BDPLT18)

A disorder characterized by increased bleeding tendency due to platelet dysfunction. Clinical features include epistaxis, hematomas, bleeding after tooth extraction, and menorrhagia. {ECO:0000269|PubMed:24958846, ECO:0000269|PubMed:27235135, ECO:0000269|PubMed:28726538, ECO:0000269|PubMed:28762304}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

A disorder characterized by increased bleeding tendency due to platelet dysfunction. Clinical features include epistaxis, hematomas, bleeding after tooth extraction, and menorrhagia. {ECO:0000269|PubMed:24958846, ECO:0000269|PubMed:27235135, ECO:0000269|PubMed:28726538, ECO:0000269|PubMed:28762304}. Note=The disease is caused by variants affecting the gene represented in this entry.

4 regional properties for Q7LDG7

Type	Name	Position	InterPro Accession
domain	Ras-like guanine nucleotide exchange factor, N-terminal	3 - 126	IPR000651
domain	Ras guanine-nucleotide exchange factors catalytic domain	150 - 388	IPR001895
domain	EF-hand domain	426 - 487	IPR002048
domain	Protein kinase C-like, phorbol ester/diacylglycerol-binding domain	498 - 550	IPR002219

Functions

		Description
EC Number
Subcellular Localization	Cytoplasm, cytosol Cell membrane; Peripheral membrane protein Synapse, synaptosome Cell projection, ruffle membrane ; Peripheral membrane protein	Found both in the cytosol and associated with membranes Isoform 2 mainly localizes to the cell membrane Enriched at juxtamembrane areas and membrane ruffles through association with F-actin Localizes to the cell bodies and axons of striatal neurons (By similarity)
PANTHER Family	PTHR23113	GUANINE NUCLEOTIDE EXCHANGE FACTOR
PANTHER Subfamily	PTHR23113:SF16	RAS GUANYL-RELEASING PROTEIN 2
PANTHER Protein Class	guanyl-nucleotide exchange factor G-protein modulator protein-binding activity modulator
PANTHER Pathway Category	Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway CalDAG-GEF

5 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.
neuron projection	A prolongation or process extending from a nerve cell, e.g. an axon or dendrite.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
ruffle membrane	The portion of the plasma membrane surrounding a ruffle.
synapse	The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.

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.
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.
lipid binding	Binding to a lipid.

5 GO annotations of biological process

Name	Definition
cellular response to calcium ion	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a calcium ion stimulus.
positive regulation of GTPase activity	Any process that activates or increases the activity of a GTPase.
Ras protein signal transduction	The series of molecular signals within the cell that are mediated by a member of the Ras superfamily of proteins switching to a GTP-bound active state.
regulation of cell growth	Any process that modulates the frequency, rate, extent or direction of cell growth.
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.

30 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q1LZ97	RASGRP4	RAS guanyl-releasing protein 4	Bos taurus (Bovine)	SS
A6N9I4	RASGRP2	RAS guanyl-releasing protein 2	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
Q8TDF6	RASGRP4	RAS guanyl-releasing protein 4	Homo sapiens (Human)	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
Q8BTM9	Rasgrp4	RAS guanyl-releasing protein 4	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
Q9Z1S3	Rasgrp1	RAS guanyl-releasing protein 1	Mus musculus (Mouse)	SS
Q9QUG9	Rasgrp2	RAS guanyl-releasing protein 2	Mus musculus (Mouse)	SS
Q8R5I4	Rasgrp4	RAS guanyl-releasing protein 4	Rattus norvegicus (Rat)	SS
Q9R1K8	Rasgrp1	RAS guanyl-releasing protein 1	Rattus norvegicus (Rat)	SS
P0C643	Rasgrp2	RAS guanyl-releasing protein 2	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
MAGTLDLDKG	CTVEELLRGC	IEAFDDSGKV	RDPQLVRMFL	MMHPWYIPSS	QLAAKLLHIY
70	80	90	100	110	120
QQSRKDNSNS	LQVKTCHLVR	YWISAFPAEF	DLNPELAEQI	KELKALLDQE	GNRRHSSLID
130	140	150	160	170	180
IDSVPTYKWK	RQVTQRNPVG	QKKRKMSLLF	DHLEPMELAE	HLTYLEYRSF	CKILFQDYHS
190	200	210	220	230	240
FVTHGCTVDN	PVLERFISLF	NSVSQWVQLM	ILSKPTAPQR	ALVITHFVHV	AEKLLQLQNF
250	260	270	280	290	300
NTLMAVVGGL	SHSSISRLKE	THSHVSPETI	KLWEGLTELV	TATGNYGNYR	RRLAACVGFR
310	320	330	340	350	360
FPILGVHLKD	LVALQLALPD	WLDPARTRLN	GAKMKQLFSI	LEELAMVTSL	RPPVQANPDL
370	380	390	400	410	420
LSLLTVSLDQ	YQTEDELYQL	SLQREPRSKS	SPTSPTSCTP	PPRPPVLEEW	TSAAKPKLDQ
430	440	450	460	470	480
ALVVEHIEKM	VESVFRNFDV	DGDGHISQEE	FQIIRGNFPY	LSAFGDLDQN	QDGCISREEM
490	500	510	520	530	540
VSYFLRSSSV	LGGRMGFVHN	FQESNSLRPV	ACRHCKALIL	GIYKQGLKCR	ACGVNCHKQC
550	560	570	580	590	600
KDRLSVECRR	RAQSVSLEGS	APSPSPMHSH	HHRAFSFSLP	RPGRRGSRPP	EIREEEVQTV

EDGVFDIHL