AiPD: Autoinhibited Protein Database

O95267

Gene name	RASGRP1 (RASGRP)
Protein name	RAS guanyl-releasing protein 1
Names	Calcium and DAG-regulated guanine nucleotide exchange factor II, CalDAG-GEFII, Ras guanyl-releasing protein
Species	Homo sapiens (Human)
KEGG Pathway	hsa:10125
EC number
Protein Class	GUANINE NUCLEOTIDE EXCHANGE FACTOR (PTHR23113)

Descriptions

RAS guanyl-releasing protein 1 (RasGRP1) is a nucleotide exchange factor that controls the development of immune cells, and leukemia and lupus can result if RasGRP1 is not regulated correctly. Inactive RasGRP1 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)

Target domain	201-437 (Ras guanine-nucleotide exchange factors catalytic domain)
Relief mechanism	Ligand binding, PTM
Assay	Structural analysis, Mutagenesis experiment

AID

436-462 (RasGEF catalytic domain-EF domain linker)

Target domain

201-437 (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

Structural analysis, Mutagenesis experiment

Target domain	463-505 (EF domain)
Relief mechanism	Ligand binding, PTM
Assay	Structural analysis, Mutagenesis experiment

AID

541-591 (C1 domain)

Target domain

463-505 (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

Structural analysis, Mutagenesis experiment

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,

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 O95267

Entry ID	Method	Resolution	Chain	Position	Source
4L9M	X-ray	300 A	A	50-607	PDB
4L9U	X-ray	160 A	A/B	739-793	PDB
AF-O95267-F1	Predicted				AlphaFoldDB

436 variants for O95267

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs1595848141 CA391653085 VAR_083338 RCV000824712	214	T>I	Immunodeficiency 64 IMD64; no effect on protein expression; decreased T cell activation [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs1408683294 RCV000824710 CA391651770	246	R>*	Immunodeficiency 64 [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
RCV000824711 CA391651569 rs1595843113	257	W>*	Immunodeficiency 64 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000824713 CA391650818 rs779560450	322	K>*	Immunodeficiency 64 [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
rs1891006332 RCV001262170	531	S>*	Immunodeficiency 64 [ClinVar]	Yes	ClinVar dbSNP
rs1595816926 RCV000824714	638	A>missing	Immunodeficiency 64 [ClinVar]	Yes	ClinVar dbSNP
CA391663823 rs1180553068	3	T>I		No	ClinGen TOPMed
rs1302951133 CA391663772	9	E>K		No	ClinGen gnomAD
CA7471238 rs777064884	12	R>G		No	ClinGen ExAC TOPMed gnomAD
rs1372955652 CA391663736	12	R>Q		No	ClinGen gnomAD
CA391663276 rs1595887574	13	K>N		No	ClinGen Ensembl
CA391663274 rs1206625365	14	P>A		No	ClinGen gnomAD
CA268716816 rs955391750	14	P>L		No	ClinGen Ensembl
rs1429824421 CA391663269	15	S>T		No	ClinGen TOPMed
CA268716813 rs374319829	16	H>R		No	ClinGen ESP TOPMed gnomAD
rs1390497343 CA391663249	18	C>R		No	ClinGen gnomAD
rs774411490 CA7471214	18	C>Y		No	ClinGen ExAC gnomAD
CA391663238 rs1595887542	19	R>S		No	ClinGen Ensembl
CA391663235 rs1595887540	20	A>P		No	ClinGen Ensembl
CA268716807 rs370615853	22	S>A		No	ClinGen ESP TOPMed
CA391663223 rs370615853	22	S>P		No	ClinGen ESP TOPMed
rs770742443 CA7471213	25	R>T		No	ClinGen ExAC gnomAD
rs772727617 CA7471209	27	E>K		No	ClinGen ExAC gnomAD
rs769249413 CA7471208	30	P>R		No	ClinGen ExAC gnomAD
CA391663159 rs1466440887	32	N>S		No	ClinGen gnomAD
CA7471206 rs780647755	33	S>I		No	ClinGen ExAC TOPMed gnomAD
CA7471205 rs772557493	33	S>R		No	ClinGen ExAC TOPMed gnomAD
CA7471203 rs779526645 COSM50761	34	P>L	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA7471204 rs746190168	34	P>S		No	ClinGen ExAC gnomAD
rs1243244698 CA391663131	36	P>L		No	ClinGen TOPMed gnomAD
rs757864721 CA7471201	37	S>C		No	ClinGen ExAC gnomAD
CA391663121 rs1566940584	38	H>R		No	ClinGen Ensembl
rs377526732 CA7471198	45	T>N		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA268716757 rs912036186	46	Q>R		No	ClinGen TOPMed gnomAD
CA7471196 rs767627019	48	R>*		No	ClinGen ExAC gnomAD
rs202243185 CA7471195	48	R>Q		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1373844622 CA391663012	50	M>V		No	ClinGen TOPMed gnomAD
CA391662990 rs370888491	51	V>L		No	ClinGen ESP ExAC TOPMed
rs370888491 CA7471194	51	V>M		No	ClinGen ESP ExAC TOPMed
CA7471193 rs766147987	54	G>R		No	ClinGen ExAC gnomAD
CA7471192 rs762906072	56	L>V		No	ClinGen ExAC gnomAD
CA7471190 rs769304356	57	A>S		No	ClinGen ExAC TOPMed gnomAD
rs1490332709 CA391662869	60	A>V		No	ClinGen gnomAD
CA7471189 rs761311759	61	S>R		No	ClinGen ExAC gnomAD
rs1343753169 CA391662835	63	D>A		No	ClinGen gnomAD
CA391662841 rs1243136189	63	D>N		No	ClinGen TOPMed gnomAD
CA7471187 rs768175330	64	D>N		No	ClinGen ExAC gnomAD
rs746626961 CA7471186	65	L>F		No	ClinGen ExAC gnomAD
rs779177028 CA7471185	66	I>T		No	ClinGen ExAC gnomAD
CA7471184 rs771354774	67	D>A		No	ClinGen ExAC gnomAD
CA7471182 rs577541812	71	Q>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA7471183 rs749829007	71	Q>K		No	ClinGen ExAC gnomAD
CA391658266 rs1566926306	74	D>A		No	ClinGen Ensembl
CA268701587 rs887934618	74	D>E		No	ClinGen Ensembl
CA391658244 rs1281264657	76	D>H		No	ClinGen TOPMed gnomAD
rs776032506 CA7471171	76	D>V		No	ClinGen ExAC TOPMed gnomAD
rs1328285884 CA391658231	77	G>R		No	ClinGen gnomAD
CA391658212 rs925433591	78	N>K		No	ClinGen TOPMed gnomAD
rs369162228 CA7471169	80	C>Y		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs775150830 CA7471168	81	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA7471167 rs771483161	82	S>N		No	ClinGen ExAC TOPMed gnomAD
CA7471165 rs773894680	94	R>Q		No	ClinGen ExAC gnomAD
rs1180477660 CA391658081	95	I>T		No	ClinGen gnomAD
CA391658076 rs1165012732	96	V>F		No	ClinGen TOPMed
rs1253891737 CA391658068	97	I>T		No	ClinGen gnomAD
CA391658060 rs1394420446	98	S>F		No	ClinGen TOPMed
CA7471164 rs544477730	101	E>G		No	ClinGen 1000Genomes ExAC gnomAD
CA391658040 rs1409501768	102	L>V		No	ClinGen TOPMed
rs1308828556 CA391658013	106	V>I		No	ClinGen TOPMed
CA391658007 rs1261043638 RCV000995292	107	I>F		No	ClinGen ClinVar TOPMed dbSNP gnomAD
rs755014871 CA7471161	108	T>N		No	ClinGen ExAC gnomAD
CA7471160 rs747206032	109	L>V		No	ClinGen ExAC TOPMed gnomAD
rs1316800069 CA391656312	114	L>V		No	ClinGen gnomAD
CA391656298 rs1407594457	115	A>T		No	ClinGen gnomAD
rs143250519 CA7471138	116	K>N		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA391656241 rs1440597576	118	S>A		No	ClinGen TOPMed
rs757018691 CA7471137	118	S>L		No	ClinGen ExAC gnomAD
rs1440597576 CA391656245	118	S>T		No	ClinGen TOPMed
rs1291591106 CA391656170	123	L>R		No	ClinGen TOPMed
CA391656175 rs1230291577	123	L>V		No	ClinGen TOPMed
rs1214577279 CA391656156	124	K>N		No	ClinGen TOPMed
rs779094402 CA7471120	130	R>S		No	ClinGen ExAC gnomAD
CA391656020 rs1283168387	131	Y>C		No	ClinGen gnomAD
CA7471118 rs749080633	133	I>T		No	ClinGen ExAC TOPMed gnomAD
CA7471117 rs777619685	134	T>I		No	ClinGen ExAC gnomAD
CA391655958 rs1462120177	136	F>I		No	ClinGen gnomAD
CA391655926 rs1449862602	137	W>C		No	ClinGen TOPMed
rs1595850746 CA391655907	139	M>I		No	ClinGen Ensembl
CA391655914 rs1353561130	139	M>V		No	ClinGen gnomAD
rs866633256 CA268696409	142	M>I		No	ClinGen Ensembl
rs373625187 CA7471115	144	A>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs1429772639 CA391655841	144	A>V		No	ClinGen TOPMed gnomAD
rs1255024718 CA391655831	145	S>T		No	ClinGen gnomAD
CA7471114 rs780853641	147	T>R		No	ClinGen ExAC TOPMed gnomAD
rs1252672673 CA391655795	148	D>V		No	ClinGen gnomAD
CA7471112 rs201283825	149	T>I		No	ClinGen ExAC TOPMed gnomAD
rs201283825 CA391655785	149	T>N		No	ClinGen ExAC TOPMed gnomAD
rs766047781 CA7471111	150	M>V		No	ClinGen ExAC TOPMed gnomAD
rs1231372563 CA391655755	151	E>D		No	ClinGen gnomAD
rs762122305 CA7471110	155	E>G		No	ClinGen ExAC gnomAD
rs992837178 CA268696382	155	E>K		No	ClinGen TOPMed gnomAD
CA7471109 rs371219345	157	V>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs764328797 CA7471108	159	A>T		No	ClinGen ExAC TOPMed gnomAD
rs761178833 CA7471107	159	A>V		No	ClinGen ExAC TOPMed gnomAD
rs1391454027 CA391655570	162	E>K		No	ClinGen gnomAD
CA7471105 rs75646785	164	L>I		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA268696345 rs148766586	165	H>Q		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA7471104 rs192394608	165	H>Y		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs368861027 CA7471102	166	C>Y		No	ClinGen ESP ExAC TOPMed gnomAD
CA7471101 rs749420646	167	R>C		No	ClinGen ExAC gnomAD
rs773089795 CA7471100	167	R>H		No	ClinGen ExAC gnomAD
rs1210329186 CA391655443	168	L>Q		No	ClinGen TOPMed
rs1030168911 CA268696304	169	I>T		No	ClinGen TOPMed gnomAD
rs188455450 CA7471082	176	A>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA391654153 rs769765288	177	R>C		No	ClinGen ExAC gnomAD
CA7471081 rs769765288	177	R>G		No	ClinGen ExAC gnomAD
CA7471079 rs201247088	177	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs201247088 CA7471080	177	R>P		No	ClinGen ESP ExAC TOPMed gnomAD
rs1566920861 CA391654079	179	W>*		No	ClinGen Ensembl
CA7471078 rs377660704	180	S>C		No	ClinGen ExAC TOPMed gnomAD
rs1294667498 CA391654004	182	K>R		No	ClinGen gnomAD
CA268695078 rs1049136387	188	K>T		No	ClinGen TOPMed
rs1327928660 CA391653732	191	T>N		No	ClinGen gnomAD
rs1304943483 CA391653455	198	S>C		No	ClinGen gnomAD
rs1425359262 CA391653254	205	E>D		No	ClinGen gnomAD
rs1365085041 CA391653231	206	P>L		No	ClinGen gnomAD
rs1161641679 CA391653208	207	E>D		No	ClinGen gnomAD
CA391653165 rs1158997965	211	E>K		No	ClinGen TOPMed
rs1403546553 CA391653098	213	L>P		No	ClinGen TOPMed
rs753040113 CA7471071	215	Y>C		No	ClinGen ExAC gnomAD
CA268695018 rs894960876	219	K>R		No	ClinGen TOPMed
CA391653014 rs1477077711	220	S>P		No	ClinGen gnomAD
CA391652995 rs1271654333	221	F>L		No	ClinGen gnomAD
CA391652989 rs1200829567	222	R>L		No	ClinGen gnomAD
rs1200829567 CA391652991	222	R>Q		No	ClinGen gnomAD
CA391652993 rs1595848108	222	R>W		No	ClinGen Ensembl
rs1406337456 CA391652988	223	R>G		No	ClinGen TOPMed
CA268695012 rs932803820	224	I>T		No	ClinGen Ensembl
CA391652000 rs1344208503	230	Q>H		No	ClinGen gnomAD
rs267604163 CA268692828	233	L>F		No	ClinGen Ensembl
rs1273062347 CA391651950	234	V>A		No	ClinGen TOPMed gnomAD
CA391651860 rs1336469702	241	N>S		No	ClinGen TOPMed gnomAD
rs771679174 CA7471050	243	T>I		No	ClinGen ExAC gnomAD
rs1464022694 CA391651795	245	E>K		No	ClinGen TOPMed
CA391651768 COSM215604 rs1330653682	246	R>Q	central_nervous_system [Cosmic]	No	ClinGen cosmic curated TOPMed
rs1328783722 CA391651726	248	I>M		No	ClinGen TOPMed gnomAD
CA391651739 rs1315790508	248	I>V		No	ClinGen Ensembl
rs1300701741 CA391651661	252	N>S		No	ClinGen TOPMed
rs867704540 CA268692819	253	G>D		No	ClinGen Ensembl
CA7471047 rs770594654	253	G>S		No	ClinGen ExAC gnomAD
CA391651632 rs1228040548	254	I>V		No	ClinGen TOPMed
CA391651531 rs1470863423	259	Q>L		No	ClinGen gnomAD
rs1363911918 CA391651515	260	L>R		No	ClinGen gnomAD
rs781539471 CA7471045	262	V>G		No	ClinGen ExAC gnomAD
rs752166771 COSM294743 CA7471043	265	R>C	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs766659143 CA7471042	265	R>H		No	ClinGen ExAC TOPMed gnomAD
CA268692783 rs888821403	267	T>M		No	ClinGen TOPMed gnomAD
rs750445245 CA7471040	267	T>S		No	ClinGen ExAC gnomAD
CA391651406 rs1308640716	268	P>L		No	ClinGen gnomAD
CA268692778 rs930641482	271	R>*		No	ClinGen TOPMed
CA268692777 rs200520227	271	R>Q		No	ClinGen Ensembl
CA7471036 rs764039536	273	E>Q		No	ClinGen ExAC gnomAD
CA7471035 rs760383338	275	F>S		No	ClinGen ExAC gnomAD
CA7471034 rs761190592	277	K>R		No	ClinGen ExAC TOPMed gnomAD
CA7471033 rs771885093	281	V>M		No	ClinGen ExAC gnomAD
CA391651099 rs1429382586	286	H>Q		No	ClinGen TOPMed gnomAD
COSM1223229 rs1191470869 CA391651105	286	H>R	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1030776991 CA268691968	291	F>L		No	ClinGen Ensembl
CA7471013 rs752460747	293	T>K		No	ClinGen ExAC gnomAD
CA7471011 rs759394125	298	I>T		No	ClinGen ExAC gnomAD
CA391650941 rs1317732776	303	H>Q		No	ClinGen gnomAD
CA391650925 rs1212828880	306	I>V		No	ClinGen TOPMed
rs1407319895 CA391650914	307	S>L		No	ClinGen gnomAD
rs1486826067 CA391650881	312	T>A		No	ClinGen gnomAD
rs762442488 CA7471008	313	S>N		No	ClinGen ExAC TOPMed gnomAD
rs369326621 CA7471007 COSM76175	314	S>L	ovary large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
rs369326621 CA391650866	314	S>W		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA7471005 rs373200131	315	H>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs1200453306 CA391650842	318	H>Q		No	ClinGen TOPMed gnomAD
rs772425297 CA7471003	318	H>R		No	ClinGen ExAC gnomAD
CA7471004 rs775746697	318	H>Y		No	ClinGen ExAC gnomAD
CA268691873 rs1053788655	320	I>M		No	ClinGen gnomAD
rs746436340 CA7471002	321	N>S		No	ClinGen ExAC TOPMed gnomAD
CA7471001 rs779560450	322	K>E		No	ClinGen ExAC gnomAD
rs1255891312 CA391666800	323	V>I		No	ClinGen gnomAD
CA391666790 rs775047562	324	L>F		No	ClinGen ExAC gnomAD
CA7470984 rs775047562	324	L>V		No	ClinGen ExAC gnomAD
COSM961008 rs372568458 CA7470983	325	G>S	endometrium [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA7470982 rs749775996	328	T>I		No	ClinGen ExAC gnomAD
CA391666737 rs1375694917	329	E>K		No	ClinGen gnomAD
rs1402678800 CA391666696	333	S>C		No	ClinGen gnomAD
CA391666700 rs1595835640	333	S>P		No	ClinGen Ensembl
CA391666692 rs1595835625	334	S>P		No	ClinGen Ensembl
CA391666647 rs1346968600	338	D>N		No	ClinGen TOPMed gnomAD
rs1439636466 CA391666628	339	N>S		No	ClinGen TOPMed
rs1595835537 CA391666617	340	Y>S		No	ClinGen Ensembl
CA7470975 rs539860819	341	R>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs750292508 CA7470974	342	R>*		No	ClinGen ExAC gnomAD
rs750292508 CA7470973	342	R>G		No	ClinGen ExAC gnomAD
rs764712824 CA7470972 COSM173494	342	R>Q	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs761383737 CA7470971	346	E>G		No	ClinGen ExAC gnomAD
rs1185165990 CA391666535	348	T>N		No	ClinGen TOPMed
rs565898524 CA7470968 COSM225905	349	D>N	skin [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs1352408861 CA391666454	356	G>S		No	ClinGen gnomAD
CA391666362 rs1283384373	364	S>C		No	ClinGen TOPMed gnomAD
rs1247742652 CA391666357	365	L>M		No	ClinGen gnomAD
CA7470963 rs376682602	366	Y>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs769827900 CA7470962	367	E>*		No	ClinGen ExAC
rs1406316386 CA391666309	369	M>I		No	ClinGen TOPMed
CA268738014 rs751118810	369	M>T		No	ClinGen Ensembl
CA7470960 rs1454294069	372	Y>C		No	ClinGen TOPMed
CA7470959 rs748225035	374	E>K		No	ClinGen ExAC gnomAD
CA7470958 rs199706420	375	D>E		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs747191064 CA7470956	376	G>R		No	ClinGen ExAC TOPMed gnomAD
CA391666189 rs1368192890	380	V>G		No	ClinGen gnomAD
rs1458618688 CA391666196	380	V>I		No	ClinGen gnomAD
rs1423199679 CA391666154	384	L>V		No	ClinGen gnomAD
CA391666142 rs1271300282	385	A>G		No	ClinGen TOPMed
CA7470951 rs750396457	387	Y>H		No	ClinGen ExAC TOPMed gnomAD
rs368147450 CA7470950	388	N>H		No	ClinGen ESP ExAC gnomAD
CA268737972 rs374625898	389	H>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs374625898 CA7470949	389	H>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA7470948 rs753411664	391	S>T		No	ClinGen ExAC gnomAD
CA391666027 rs1260423984	396	L>P		No	ClinGen TOPMed gnomAD
CA391665985 rs1356606150	399	V>A		No	ClinGen gnomAD
rs372045194 CA7470945	400	A>D		No	ClinGen ESP ExAC TOPMed gnomAD
CA391665978 rs1595835222	400	A>T		No	ClinGen Ensembl
rs372045194 CA7470944	400	A>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA391665965 rs1595835194	401	P>L		No	ClinGen Ensembl
CA391665958 rs1595835187	402	P>R		No	ClinGen Ensembl
rs773629287 CA7470942	405	A>D		No	ClinGen ExAC gnomAD
rs1399351748 CA391665931	405	A>T		No	ClinGen gnomAD
rs1305040987 CA391665902	407	K>R		No	ClinGen gnomAD
rs770307729 CA7470941	409	L>S		No	ClinGen ExAC gnomAD
CA391665858 rs1161733169	411	H>R		No	ClinGen gnomAD
rs776803150 CA7470939	412	L>W		No	ClinGen ExAC
rs1463827499 CA391665826	414	T>M		No	ClinGen TOPMed gnomAD
CA391665741 rs1376605076	423	E>D		No	ClinGen gnomAD
CA391665740 rs1196224594	424	D>N		No	ClinGen gnomAD
rs1197772194 CA391665703	428	E>D		No	ClinGen gnomAD
CA391665673 rs1200982458	433	R>Q		No	ClinGen gnomAD
CA391665674 rs1280617107	433	R>W		No	ClinGen gnomAD
rs774203566 CA7470915	442	P>S		No	ClinGen ExAC gnomAD
CA391665585 rs1285519567	444	T>I		No	ClinGen gnomAD
CA391665559 rs1238286956	448	P>L		No	ClinGen gnomAD
rs1285169444 CA391665544	451	V>L		No	ClinGen gnomAD
CA391665536 rs1447835279	452	V>A		No	ClinGen gnomAD
CA7470914 rs770578649	453	D>E		No	ClinGen ExAC TOPMed gnomAD
rs1339221618 CA391665532	453	D>H		No	ClinGen gnomAD
CA7470913 rs749308955	459	S>A		No	ClinGen ExAC gnomAD
CA391665436 rs1360628756	464	P>T		No	ClinGen gnomAD
CA7470912 rs777845828	467	I>T		No	ClinGen ExAC gnomAD
rs1417503597 CA391665390	468	S>T		No	ClinGen gnomAD
rs200227355 CA7470910	471	V>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1283414213 CA391665335	473	R>T		No	ClinGen TOPMed
CA391665302 rs1595828680	475	V>G		No	ClinGen Ensembl
CA7470909 rs780796375	476	D>E		No	ClinGen ExAC gnomAD
CA391665299 rs1595828671	476	D>H		No	ClinGen Ensembl
CA7470894 rs774426499	480	K>R		No	ClinGen ExAC gnomAD
rs749002764 CA7470892	483	D>N		No	ClinGen ExAC gnomAD
CA7470890 rs200353501	485	D>N		No	ClinGen 1000Genomes ExAC gnomAD
CA391665139 rs1235114092	486	Q>R		No	ClinGen gnomAD
CA7470889 rs62621817	487	D>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA7470886 rs779567751	495	F>C		No	ClinGen ExAC gnomAD
rs779567751 CA7470885	495	F>S		No	ClinGen ExAC gnomAD
CA7470883 rs754225038	496	E>*		No	ClinGen ExAC TOPMed
rs754225038 CA391665030	496	E>K		No	ClinGen ExAC TOPMed
rs1212276960 CA391665013	497	K>R		No	ClinGen TOPMed gnomAD
rs778072138 CA7470882 COSM1290371	498	I>T	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs1391942530 CA391664950	503	P>L		No	ClinGen gnomAD
CA7470878 rs563079518	509	M>I		No	ClinGen 1000Genomes ExAC gnomAD
CA7470879 rs767697975	509	M>L		No	ClinGen ExAC TOPMed gnomAD
rs751844628 CA7470877	510	D>V		No	ClinGen ExAC TOPMed gnomAD
CA391664859 rs1168503574	511	K>R		No	ClinGen TOPMed gnomAD
rs1479094001 CA391664604	515	G>D		No	ClinGen gnomAD
rs770588727 CA7470825	520	D>N		No	ClinGen ExAC gnomAD
CA391664430 rs1211302006	524	A>G		No	ClinGen TOPMed gnomAD
CA7470824 rs748926334	527	M>I		No	ClinGen ExAC gnomAD
rs1211649979 CA391664276	533	Y>C		No	ClinGen gnomAD
rs776862042 CA7470823	534	S>C		No	ClinGen ExAC gnomAD
rs769004371 CA7470822	537	G>S		No	ClinGen ExAC gnomAD
CA7470821 rs368060712	543	N>D		No	ClinGen ESP ExAC TOPMed gnomAD
CA7470819 rs758591562	545	Q>*		No	ClinGen ExAC gnomAD
rs745919993 CA7470818	547	T>A		No	ClinGen ExAC gnomAD
CA391664016 rs1467571513	549	Y>F		No	ClinGen TOPMed gnomAD
CA391664002 rs1401637524	550	L>M		No	ClinGen gnomAD
CA7470817 rs779097574	551	K>Q		No	ClinGen ExAC gnomAD
rs757557977 CA7470816	551	K>R		No	ClinGen ExAC gnomAD
rs1370852076 CA391663960	552	P>L		No	ClinGen gnomAD
CA391663881 rs1566911051	559	A>T		No	ClinGen Ensembl
rs951327072 CA268733660	560	G>E		No	ClinGen gnomAD
rs1305470479 CA391663872	560	G>R		No	ClinGen TOPMed gnomAD
rs1480603641 CA391663524	563	W>*		No	ClinGen TOPMed
CA268732937 rs1049857089	570	Y>C		No	ClinGen TOPMed gnomAD
rs1354798579 CA391663469	571	R>*		No	ClinGen gnomAD
rs1279324286 CA391663468	571	R>Q		No	ClinGen gnomAD
rs776826375 CA7470749	576	G>R		No	ClinGen ExAC TOPMed gnomAD
CA7470748 rs768478247	587	V>A		No	ClinGen ExAC gnomAD
CA391662849 rs1450235680	589	F>S		No	ClinGen gnomAD
rs746782650 CA7470747	592	K>N		No	ClinGen ExAC gnomAD
rs779664541 CA7470746	593	K>T		No	ClinGen ExAC gnomAD
CA7470745 rs758391429	594	R>G		No	ClinGen ExAC gnomAD
rs370892389 CA7470744	594	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA7470743 rs778543433	595	A>G		No	ClinGen ExAC TOPMed gnomAD
CA391662714 rs1268240035	600	A>T		No	ClinGen TOPMed
rs1443310307 CA391662679	603	E>A		No	ClinGen TOPMed
CA391662631 rs1315324954	609	G>R		No	ClinGen TOPMed gnomAD
rs753586174 CA391662619	611	V>L		No	ClinGen ExAC gnomAD
CA7470740 rs753586174	611	V>M		No	ClinGen ExAC gnomAD
CA391662612 rs1483909448	612	S>F		No	ClinGen gnomAD
CA7470739 rs763819006	612	S>T		No	ClinGen ExAC gnomAD
CA268731933 rs957499000	613	N>S		No	ClinGen Ensembl
CA7470735 rs763526840	620	K>E		No	ClinGen ExAC gnomAD
CA268731891 rs998869758	621	D>H		No	ClinGen gnomAD
rs773574536 CA391662549	622	L>M		No	ClinGen ExAC gnomAD
CA7470734 rs773574536	622	L>V		No	ClinGen ExAC gnomAD
rs200878936 CA268731867	623	L>F		No	ClinGen Ensembl
CA391662532 rs1566909591	625	A>T		No	ClinGen Ensembl
CA391662512 rs1462331575	626	P>S		No	ClinGen gnomAD
CA268729604 rs1018024227	628	E>K		No	ClinGen TOPMed
rs780367030 CA268729597	629	G>R		No	ClinGen Ensembl
rs762256928 CA391662487	630	P>S		No	ClinGen ExAC gnomAD
CA7470713 rs762256928	630	P>T		No	ClinGen ExAC gnomAD
CA268729594 rs1007014655	633	F>L		No	ClinGen TOPMed
rs889315254 CA268729589	634	P>S		No	ClinGen TOPMed
rs764093796 CA7470711	636	G>A		No	ClinGen ExAC gnomAD
rs975447814 CA268729582	636	G>R		No	ClinGen Ensembl
CA7470710 rs760945936	638	A>T		No	ClinGen ExAC gnomAD
rs775570996 CA7470709	638	A>V		No	ClinGen ExAC gnomAD
rs1468768278 CA391662432	639	V>M		No	ClinGen gnomAD
CA268729543 rs1051874596	641	H>R		No	ClinGen TOPMed gnomAD
CA7470708 rs147833189	641	H>Y		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1320021891 CA391662412	642	G>R		No	ClinGen gnomAD
rs1226872711 CA391662377	646	K>N		No	ClinGen gnomAD
CA391662365 rs374321340	648	R>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA7470706 rs374321340	648	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs759232410 CA7470707	648	R>W		No	ClinGen ExAC gnomAD
rs771027287 CA7470705	650	I>V		No	ClinGen ExAC TOPMed gnomAD
rs749173806 CA7470704	653	M>T		No	ClinGen ExAC gnomAD
rs777443051 CA7470703	655	V>M		No	ClinGen ExAC TOPMed gnomAD
rs369010965 CA7470702	657	S>P		No	ClinGen ESP ExAC TOPMed gnomAD
CA391662306 rs1167961605	658	Q>*		No	ClinGen gnomAD
CA391662304 rs1461089442	658	Q>R		No	ClinGen TOPMed gnomAD
rs747897701 CA7470701	659	K>N		No	ClinGen ExAC gnomAD
CA7470700 rs780674236	660	I>V		No	ClinGen ExAC
CA7470699 rs201076575	661	S>A		No	ClinGen ExAC TOPMed gnomAD
rs144303289 CA7470698	663	R>P		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs144303289 CA7470697	663	R>Q		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA391662275 rs1454503887	663	R>W		No	ClinGen gnomAD
rs754330937 CA7470695	669	A>D		No	ClinGen ExAC gnomAD
rs1439484414 CA391662241	669	A>T		No	ClinGen gnomAD
CA391662217 rs1195277516	672	A>S		No	ClinGen gnomAD
CA391662219 rs1195277516	672	A>T		No	ClinGen gnomAD
CA391662210 rs1337553249	673	T>I		No	ClinGen gnomAD
rs1267404012 CA391662171	679	P>T		No	ClinGen TOPMed gnomAD
CA391662162 rs1282688116	680	W>*		No	ClinGen gnomAD
rs1235302997 CA391662157	680	W>*		No	ClinGen gnomAD
CA391662156 rs1595816731	681	I>L		No	ClinGen Ensembl
rs576367702 CA7470694	681	I>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA7470693 rs372593199	682	G>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA7470692 rs753015158	682	G>V		No	ClinGen ExAC TOPMed gnomAD
CA7470691 rs767657623	683	S>N		No	ClinGen ExAC gnomAD
CA7470690 rs759767160	685	G>D		No	ClinGen ExAC TOPMed gnomAD
CA391662117 rs1393702963	687	S>L		No	ClinGen gnomAD
rs1566907499 CA391662119	687	S>P		No	ClinGen Ensembl
CA268729379 rs763001228	690	F>S		No	ClinGen gnomAD
rs1595816643 CA391662093	691	V>A		No	ClinGen Ensembl
CA268729374 rs951944562	691	V>L		No	ClinGen TOPMed
rs1394169459 CA391662087	692	L>P		No	ClinGen gnomAD
CA391662082 rs1171486056	693	S>Y		No	ClinGen gnomAD
CA391662076 rs1595816629	694	S>C		No	ClinGen Ensembl
CA268729366 rs1026168933	695	P>S		No	ClinGen gnomAD
CA7470689 rs369533261	698	T>A		No	ClinGen ESP ExAC gnomAD
CA7470688 rs770796496	698	T>I		No	ClinGen ExAC gnomAD
CA391662026 rs1177137600	702	T>A		No	ClinGen TOPMed
rs1259715929 CA391662022	702	T>I		No	ClinGen gnomAD
rs1485450892 CA391662016 COSM1608298	704	Y>H	liver [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1243020007 CA391662006	705	V>E		No	ClinGen TOPMed gnomAD
CA268729338 rs896269994	705	V>L		No	ClinGen TOPMed
rs769465594 CA7470685	706	L>F		No	ClinGen ExAC gnomAD
CA391662002 rs769465594	706	L>I		No	ClinGen ExAC gnomAD
rs1279422154 CA391662000	706	L>P		No	ClinGen gnomAD
CA391661994 rs1163029524	707	P>R		No	ClinGen TOPMed
rs1342846122 CA391661996	707	P>S		No	ClinGen gnomAD
CA7470684 rs747586541	709	P>H		No	ClinGen ExAC gnomAD
rs747586541 CA268729285	709	P>R		No	ClinGen ExAC gnomAD
CA391661980 rs1414909003	710	T>P		No	ClinGen gnomAD
CA7470683 rs780701439	711	S>F		No	ClinGen ExAC gnomAD
rs765212266 CA391661962	713	C>G		No	ClinGen ExAC TOPMed gnomAD
rs765212266 CA7470682	713	C>R		No	ClinGen ExAC TOPMed gnomAD
rs1385406934 CA391661951	714	P>L		No	ClinGen TOPMed gnomAD
rs757614705 CA7470679	719	V>F		No	ClinGen ExAC gnomAD
CA391661904 rs1188721687	721	K>N		No	ClinGen gnomAD
CA391661900 rs1255621589	722	R>Q		No	ClinGen gnomAD
CA391661902 rs1045163521	722	R>W		No	ClinGen TOPMed gnomAD
CA7470677 rs778231793	729	N>T		No	ClinGen ExAC gnomAD
rs756596594 CA7470676	730	K>E		No	ClinGen ExAC gnomAD
CA391661826 rs1230966093	732	S>F		No	ClinGen TOPMed
CA391661819 rs1566907311	734	I>L		No	ClinGen Ensembl
CA268729228 rs946990679	737	K>E		No	ClinGen gnomAD
rs201585269 COSM960999 CA7470672	741	R>H	endometrium [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
CA391661758 rs766339971	742	H>Q		No	ClinGen ExAC TOPMed gnomAD
CA7470671 rs766339971	742	H>Q		No	ClinGen ExAC TOPMed gnomAD
rs1432473809 CA391661732	747	T>A		No	ClinGen gnomAD
rs374885075 CA268729197	753	Q>E		No	ClinGen ESP
rs745459574 CA7470642	757	T>S		No	ClinGen ExAC gnomAD
CA268726467 rs536145017	758	L>V		No	ClinGen 1000Genomes TOPMed gnomAD
rs1379982433 CA391661027	761	D>G		No	ClinGen TOPMed
rs1299835406 CA391661029	761	D>Y		No	ClinGen TOPMed gnomAD
CA268726441 rs750535294	769	L>M		No	ClinGen TOPMed gnomAD
CA7470639 rs569090890	771	Y>S		No	ClinGen 1000Genomes ExAC gnomAD
CA7470638 rs781699506	772	A>T		No	ClinGen ExAC gnomAD
CA7470636 rs747104731	773	Q>K		No	ClinGen ExAC gnomAD
CA7470634 rs758700161	774	K>R		No	ClinGen ExAC gnomAD
rs750616287 CA7470633	776	I>T		No	ClinGen ExAC TOPMed gnomAD
rs1486432181 CA391660867	777	E>G		No	ClinGen TOPMed gnomAD
rs1355081514 CA391660854	778	S>Y		No	ClinGen gnomAD
CA391660837 rs1264256668	780	Q>E		No	ClinGen TOPMed
rs375426529 CA7470630	780	Q>H		No	ClinGen ESP ExAC TOPMed
rs1310249723 CA391660791	782	E>D		No	ClinGen gnomAD
rs935683618 CA268726341	782	E>Q		No	ClinGen TOPMed gnomAD
CA391660755 rs1429331839	785	N>H		No	ClinGen TOPMed
rs1196167299 CA391660737	786	H>R		No	ClinGen TOPMed
rs1595811429 CA391660731	787	V>L		No	ClinGen Ensembl
CA391660695 rs1595811410	789	A>P		No	ClinGen Ensembl
rs868410294 CA268726331	790	Q>*		No	ClinGen Ensembl
rs1041781496 CA268726322	791	M>T		No	ClinGen TOPMed gnomAD
CA391660667 rs1376266516	792	E>Q		No	ClinGen gnomAD
CA7470625 rs752206174	793	Q>*		No	ClinGen ExAC gnomAD
rs752206174 CA7470626	793	Q>E		No	ClinGen ExAC gnomAD
rs759241268 CA7470623	794	G>D		No	ClinGen ExAC gnomAD
CA7470624 rs766952859	794	G>S		No	ClinGen ExAC gnomAD
rs770100472 CA7470621	797	S>C		No	ClinGen ExAC gnomAD
CA7470619 rs776814722	798	S>K		No	ClinGen ExAC gnomAD
CA391660577 rs769320375	798	S>Y		No	ClinGen ExAC TOPMed gnomAD
CA617205597 rs1237333061	798	S>Y		No	ClinGen TOPMed gnomAD

2 associated diseases with O95267

[MIM: 152700]: Systemic lupus erythematosus (SLE)

A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269|PubMed:17878389}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. Aberrantly spliced isoforms and/or diminished levels of RASGRP1 are found in a cohort of SLE patients raising the possibility that dysregulation of this signaling protein contributes to the development of autoimmunity in a subset of SLE patients.

[MIM: 618534]: Immunodeficiency 64 (IMD64)

An autosomal recessive primary immunodeficiency characterized by recurrent bacterial, viral and fungal infections, variably decreased numbers of T cells, deficiencies of B and NK cells, and increased susceptibility to Epstein-Barr virus (EBV) infection. Patients may develop lymphoproliferation or EBV-associated lymphoma. Some patients may develop features of autoimmunity. {ECO:0000269|PubMed:27776107, ECO:0000269|PubMed:28822832, ECO:0000269|PubMed:29155103}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269|PubMed:17878389}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. Aberrantly spliced isoforms and/or diminished levels of RASGRP1 are found in a cohort of SLE patients raising the possibility that dysregulation of this signaling protein contributes to the development of autoimmunity in a subset of SLE patients.
An autosomal recessive primary immunodeficiency characterized by recurrent bacterial, viral and fungal infections, variably decreased numbers of T cells, deficiencies of B and NK cells, and increased susceptibility to Epstein-Barr virus (EBV) infection. Patients may develop lymphoproliferation or EBV-associated lymphoma. Some patients may develop features of autoimmunity. {ECO:0000269|PubMed:27776107, ECO:0000269|PubMed:28822832, ECO:0000269|PubMed:29155103}. Note=The disease is caused by variants affecting the gene represented in this entry.

7 regional properties for O95267

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	494 - 779	IPR000719
domain	S-locus glycoprotein domain	205 - 311	IPR000858
domain	Serine-threonine/tyrosine-protein kinase, catalytic domain	496 - 763	IPR001245
domain	Bulb-type lectin domain	23 - 173	IPR001480
domain	PAN/Apple domain	333 - 413	IPR003609
active_site	Serine/threonine-protein kinase, active site	615 - 627	IPR008271
domain	S-locus receptor kinase, C-terminal	766 - 807	IPR021820

Functions

		Description
EC Number
Subcellular Localization	Cytoplasm, cytosol Cell membrane; Peripheral membrane protein Golgi apparatus membrane; Peripheral membrane protein Endoplasmic reticulum membrane; Peripheral membrane protein	Found both in the cytosol and associated with membranes Relocalization to the cell membrane upon activation is F-actin-dependent Translocates to the Golgi in response to phorbol ester or nerve growth factor Localizes to somata and dendrites but not to axons of hippocampal pyramidal cells (By similarity)
PANTHER Family	PTHR23113	GUANINE NUCLEOTIDE EXCHANGE FACTOR
PANTHER Subfamily	PTHR23113:SF174	RAS GUANYL-RELEASING PROTEIN 1
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

6 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.
endoplasmic reticulum membrane	The lipid bilayer surrounding the endoplasmic reticulum.
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.
Golgi membrane	The lipid bilayer surrounding any of the compartments of the Golgi apparatus.
membrane	A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

7 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.
identical protein binding	Binding to an identical protein or proteins.
lipid binding	Binding to a lipid.
phosphatidylcholine binding	Binding to a phosphatidylcholine, a glycophospholipid in which a phosphatidyl group is esterified to the hydroxyl group of choline.
zinc ion binding	Binding to a zinc ion (Zn).

27 GO annotations of biological process

Name	Definition
activation of GTPase activity	Any process that initiates the activity of an inactive GTPase through the replacement of GDP by GTP.
B cell activation	The change in morphology and behavior of a mature or immature B cell resulting from exposure to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific.
B cell proliferation	The expansion of a B cell population by cell division. Follows B cell activation.
cell differentiation	The process in which relatively unspecialized cells, e.g. embryonic or regenerative cells, acquire specialized structural and/or functional features that characterize the cells, tissues, or organs of the mature organism or some other relatively stable phase of the organism's life history. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state.
inflammatory response to antigenic stimulus	An inflammatory response to an antigenic stimulus, which can be include any number of T cell or B cell epitopes.
mast cell degranulation	The regulated exocytosis of secretory granules containing preformed mediators such as histamine, serotonin, and neutral proteases by a mast cell.
natural killer cell activation	The change in morphology and behavior of a natural killer cell in response to a cytokine, chemokine, cellular ligand, or soluble factor.
positive regulation of ERK1 and ERK2 cascade	Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade.
positive regulation of granulocyte macrophage colony-stimulating factor production	Any process that activates or increases the frequency, rate, or extent of granulocyte macrophage colony-stimulating factor production.
positive regulation of GTPase activity	Any process that activates or increases the activity of a GTPase.
positive regulation of interferon-gamma production	Any process that activates or increases the frequency, rate, or extent of interferon-gamma production. Interferon-gamma is also known as type II interferon.
positive regulation of JNK cascade	Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the JNK cascade.
positive regulation of MAP kinase activity	Any process that activates or increases the frequency, rate or extent of MAP kinase activity.
positive regulation of natural killer cell differentiation	Any process that activates or increases the frequency, rate or extent of natural killer cell differentiation.
positive regulation of natural killer cell mediated cytotoxicity	Any process that activates or increases the frequency, rate or extent of natural killer cell mediated cytotoxicity.
positive regulation of protein phosphorylation	Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein.
positive regulation of Ras protein signal transduction	Any process that activates or increases the frequency, rate or extent of Ras protein signal transduction.
positive regulation of T cell differentiation in thymus	Any process that activates or increases the frequency, rate or extent of T cell differentiation in the thymus.
positive regulation of tumor necrosis factor production	Any process that activates or increases the frequency, rate or extent of tumor necrosis factor production.
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 ERK1 and ERK2 cascade	Any process that modulates the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade.
regulation of phosphatidylinositol 3-kinase signaling	Any process that modulates the frequency, rate or extent of signal transduction mediated by the phosphatidylinositol 3-kinase cascade.
secretory granule localization	Any process in which a secretory granule is transported to, and/or maintained in, a specific location within the cell.
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.
T cell activation	The change in morphology and behavior of a mature or immature T cell resulting from exposure to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific.
T cell proliferation	The expansion of a T cell population by cell division. Follows T cell activation.
vesicle transport along microtubule	The directed movement of a vesicle along a microtubule, mediated by motor proteins. This process begins with the attachment of a vesicle to a microtubule, and ends when the vesicle reaches its final destination.

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
Q8TDF6	RASGRP4	RAS guanyl-releasing protein 4	Homo sapiens (Human)	SS
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
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
Q9QUG9	Rasgrp2	RAS guanyl-releasing protein 2	Mus musculus (Mouse)	SS
Q9Z1S3	Rasgrp1	RAS guanyl-releasing protein 1	Mus musculus (Mouse)	SS
P0C643	Rasgrp2	RAS guanyl-releasing protein 2	Rattus norvegicus (Rat)	SS
Q8R5I4	Rasgrp4	RAS guanyl-releasing protein 4	Rattus norvegicus (Rat)	SS
Q9R1K8	Rasgrp1	RAS guanyl-releasing protein 1	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
MGTLGKAREA	PRKPSHGCRA	ASKARLEAKP	ANSPFPSHPS	LAHITQFRMM	VSLGHLAKGA
70	80	90	100	110	120
SLDDLIDSCI	QSFDADGNLC	RSNQLLQVML	TMHRIVISSA	ELLQKVITLY	KDALAKNSPG
130	140	150	160	170	180
LCLKICYFVR	YWITEFWVMF	KMDASLTDTM	EEFQELVKAK	GEELHCRLID	TTQINARDWS
190	200	210	220	230	240
RKLTQRIKSN	TSKKRKVSLL	FDHLEPEELS	EHLTYLEFKS	FRRISFSDYQ	NYLVNSCVKE
250	260	270	280	290	300
NPTMERSIAL	CNGISQWVQL	MVLSRPTPQL	RAEVFIKFIQ	VAQKLHQLQN	FNTLMAVIGG
310	320	330	340	350	360
LCHSSISRLK	ETSSHVPHEI	NKVLGEMTEL	LSSSRNYDNY	RRAYGECTDF	KIPILGVHLK
370	380	390	400	410	420
DLISLYEAMP	DYLEDGKVNV	HKLLALYNHI	SELVQLQEVA	PPLEANKDLV	HLLTLSLDLY
430	440	450	460	470	480
YTEDEIYELS	YAREPRNHRA	PPLTPSKPPV	VVDWASGVSP	KPDPKTISKH	VQRMVDSVFK
490	500	510	520	530	540
NYDHDQDGYI	SQEEFEKIAA	SFPFSFCVMD	KDREGLISRD	EITAYFMRAS	SIYSKLGLGF
550	560	570	580	590	600
PHNFQETTYL	KPTFCDNCAG	FLWGVIKQGY	RCKDCGMNCH	KQCKDLVVFE	CKKRAKNPVA
610	620	630	640	650	660
PTENNTSVGP	VSNLCSLGAK	DLLHAPEEGP	FTFPNGEAVE	HGEESKDRTI	MLMGVSSQKI
670	680	690	700	710	720
SLRLKRAVAH	KATQTESQPW	IGSEGPSGPF	VLSSPRKTAQ	DTLYVLPSPT	SPCPSPVLVR
730	740	750	760	770	780
KRAFVKWENK	DSLIKSKEEL	RHLRLPTYQE	LEQEINTLKA	DNDALKIQLK	YAQKKIESLQ
790
LEKSNHVLAQ	MEQGDCS