AiPD: Autoinhibited Protein Database

Q99418

Gene name	CYTH2
Protein name	Cytohesin-2
Names	ARF exchange factor, ARF nucleotide-binding site opener, Protein ARNO, PH, SEC7 and coiled-coil domain-containing protein 2
Species	Homo sapiens (Human)
KEGG Pathway	hsa:9266
EC number
Protein Class

Descriptions

Cytohesin-2 (CYTH2) promotes guanine-nucleotide exchange on ARF1, ARF3, and ARF6. Cytohesins share a modular architecture consisting of heptad repeats, a Sec7 domain with exchange activity for Arf1 and Arf6, a PH domain that binds phosphatidyl inositol (PI) polyphosphates, and a C-terminal helix (CtH) that overlaps with a polybasic region (PBR). In human CYTH3, it is autoinhibited by the Sec7-PH linker and CtH/PBR, which obstruct substrate binding. The autoinhibition can be relieved by Arf6-GTP binding in the presence of the PIP3 head group.

Autoinhibitory domains (AIDs)

247-259 (Sec7-PH linker) SS

Target domain	54-243 (Sec7 domain)
Relief mechanism	Partner binding
Assay

AID

247-259 (Sec7-PH linker)

Target domain

54-243 (Sec7 domain)

Relief mechanism

Partner binding (Arf6-GTP binding to allosteric site including AiEs and PH domain)

Assay

375-394 (C-terminal helix/polybasic region) SS

Target domain	54-243 (Sec7 domain)
Relief mechanism	Partner binding
Assay

AID

375-394 (C-terminal helix/polybasic region)

Target domain

54-243 (Sec7 domain)

Relief mechanism

Partner binding (Arf6-GTP binding to allosteric site including AiEs and PH domain)

Assay

Accessory elements

No accessory elements

References

Malaby AW et al. (2013) "Structural basis for membrane recruitment and allosteric activation of cytohesin family Arf GTPase exchange factors", Proceedings of the National Academy of Sciences of the United States of America, 110, 14213-8

DiNitto JP et al. (2007) "Structural basis and mechanism of autoregulation in 3-phosphoinositide-dependent Grp1 family Arf GTPase exchange factors", Molecular cell, 28, 569-83

Autoinhibited structure

Activated structure

12 structures for Q99418

Entry ID	Method	Resolution	Chain	Position	Source
1PBV	X-ray	200 A	A	52-246	PDB
1R8M	X-ray	170 A	E	50-252	PDB
1R8Q	X-ray	186 A	E/F	50-252	PDB
1R8S	X-ray	146 A	E	50-252	PDB
1S9D	X-ray	180 A	E	50-252	PDB
4JMI	X-ray	150 A	A	56-251	PDB
4JMO	X-ray	180 A	A	56-251	PDB
4JWL	X-ray	195 A	A	56-251	PDB
4JXH	X-ray	147 A	A	56-251	PDB
4L5M	X-ray	180 A	A	56-251	PDB
4Z21	X-ray	205 A	A	51-252	PDB
AF-Q99418-F1	Predicted				AlphaFoldDB

254 variants for Q99418

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs1414415004 CA406696051	2	E>G		No	ClinGen gnomAD
rs937282050 CA309325114	2	E>K		No	ClinGen TOPMed
CA406696059 rs1410406071	3	D>A		No	ClinGen TOPMed
rs1601017803 CA406696070	5	V>I		No	ClinGen Ensembl
CA406696080 rs1214217118	6	Y>C		No	ClinGen Ensembl
rs1601018996 CA406696289	7	E>D		No	ClinGen Ensembl
rs766679604 CA9551661	8	P>L		No	ClinGen ExAC
CA406696293 rs1400001090	8	P>S		No	ClinGen gnomAD
CA309325890 rs923956181	9	P>S		No	ClinGen Ensembl
CA406696310 rs1296085729	11	L>V		No	ClinGen gnomAD
CA406696320 rs1380712600	13	P>T		No	ClinGen gnomAD
CA406696328 rs1292618359	14	E>Q		No	ClinGen gnomAD
rs1332538604 CA406696346	16	R>Q		No	ClinGen gnomAD
rs1251265118 CA406696343	16	R>W		No	ClinGen TOPMed
CA406696348 rs1258520982	17	M>V		No	ClinGen gnomAD
rs370700968 CA309325907	20	E>G		No	ClinGen Ensembl
CA9551665 rs537667244	23	R>G		No	ClinGen 1000Genomes ExAC gnomAD
rs777522359 CA406696396	24	R>W		No	ClinGen ExAC TOPMed gnomAD
rs1569087238 CA406696401	25	R>W		No	ClinGen Ensembl
rs549628587 CA9551668	27	Q>R		No	ClinGen 1000Genomes ExAC gnomAD
rs895195793 CA309325937	28	E>D		No	ClinGen TOPMed
rs1479118181 CA406696420	28	E>K		No	ClinGen gnomAD
rs1601019111 CA406696441	31	V>G		No	ClinGen Ensembl
CA9551669 rs770558991	31	V>L		No	ClinGen ExAC
rs774291420 CA9551670	32	E>D		No	ClinGen ExAC gnomAD
rs1167890225 CA406696460	34	Q>R		No	ClinGen TOPMed gnomAD
rs745652246 CA9551671	35	R>C		No	ClinGen ExAC gnomAD
CA9551672 rs772190797	37	R>Q		No	ClinGen ExAC gnomAD
rs775542794 CA9551673	38	E>D		No	ClinGen ExAC gnomAD
CA406696488 rs1352996879	39	E>A		No	ClinGen gnomAD
rs1361028571 CA406696523	44	M>T		No	ClinGen TOPMed gnomAD
CA9551675 rs765259016	44	M>V		No	ClinGen ExAC gnomAD
rs763101707 CA9551677	46	E>K		No	ClinGen ExAC gnomAD
rs893860978 CA309325995	49	G>E		No	ClinGen Ensembl
rs1228989292 CA406696558	49	G>R		No	ClinGen TOPMed
CA406696563 rs1278364739	50	L>V		No	ClinGen gnomAD
CA406696569 rs1285957981	51	E>*		No	ClinGen TOPMed
CA9551680 rs759883009	52	A>T		No	ClinGen ExAC gnomAD
CA406696580 rs1195036176	52	A>V		No	ClinGen gnomAD
CA9551681 rs141221874	53	N>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA9551682 rs553747052	54	E>K		No	ClinGen 1000Genomes ExAC gnomAD
CA9551683 rs756604483	55	G>S		No	ClinGen ExAC TOPMed gnomAD
CA406696618 rs1350262503	56	S>R		No	ClinGen gnomAD
rs1319137897 CA406696630	58	T>I		No	ClinGen TOPMed
CA309326140 rs374616805	60	Q>E		No	ClinGen Ensembl
CA9551707 COSM998974 rs368161948	61	R>Q	endometrium [Cosmic]	No	ClinGen cosmic curated ESP ExAC gnomAD
CA406696651 rs1379342506	62	N>H		No	ClinGen TOPMed gnomAD
rs750127655 CA9551708	63	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs1230598442 CA406696683	66	A>E		No	ClinGen gnomAD
CA406696680 rs1348611175	66	A>T		No	ClinGen gnomAD
CA9551711 rs746755444	67	M>T		No	ClinGen ExAC gnomAD
rs371276827 CA9551710	67	M>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA406696693 rs1392230758	68	G>S		No	ClinGen TOPMed
CA9551713 rs781178135	70	K>Q		No	ClinGen ExAC gnomAD
rs749378127 CA9551714	73	N>T		No	ClinGen ExAC gnomAD
rs1448674553 CA406696740	74	M>T		No	ClinGen TOPMed
rs1189396315 CA406696737	74	M>V		No	ClinGen TOPMed
CA9551716 rs774375911	75	D>E		No	ClinGen ExAC TOPMed gnomAD
rs770968634 CA9551715	75	D>N		No	ClinGen ExAC gnomAD
rs1468100030 CA406696762	77	K>R		No	ClinGen gnomAD
CA406697066 rs1354888704	83	L>S		No	ClinGen gnomAD
rs374259450 CA9551735	84	V>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs772338149 CA9551736	85	E>G		No	ClinGen ExAC TOPMed gnomAD
CA9551737 rs146970497	86	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA9551739 rs769094268	90	Q>R		No	ClinGen ExAC TOPMed gnomAD
CA9551740 rs776808302	91	N>H		No	ClinGen ExAC TOPMed gnomAD
rs1201792327 CA406697129	93	P>S		No	ClinGen gnomAD
rs549465913 CA9551742	94	E>K		No	ClinGen 1000Genomes ExAC gnomAD
rs772929195 CA9551744	96	I>F		No	ClinGen ExAC gnomAD
rs1428932273 CA406697182	97	A>T		No	ClinGen TOPMed gnomAD
rs201629158 CA9551747	98	R>C		No	ClinGen ExAC TOPMed gnomAD
CA9551748 rs141764075	98	R>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA9551746 rs201629158	98	R>S		No	ClinGen ExAC TOPMed gnomAD
rs1432884261 CA406697243	102	K>Q		No	ClinGen gnomAD
rs756110822 CA9551751	104	E>K		No	ClinGen ExAC gnomAD
CA406697289 rs1382121931	105	G>R		No	ClinGen gnomAD
rs553287257 CA9551753	107	N>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1480456036 CA406697429	114	Y>C		No	ClinGen TOPMed
CA9551755 rs779954718	114	Y>H		No	ClinGen ExAC gnomAD
CA9551756 rs747275121	115	L>R		No	ClinGen ExAC TOPMed gnomAD
rs1569088566 CA406697447	116	G>R		No	ClinGen Ensembl
CA9551798 rs780899553	120	E>V		No	ClinGen ExAC TOPMed gnomAD
rs1421089711 CA406697766	126	L>F		No	ClinGen TOPMed
rs1186621409 CA406697774	126	L>P		No	ClinGen TOPMed
rs1016381083 CA309328081	127	H>R		No	ClinGen TOPMed gnomAD
CA406697819 rs1555898308	128	A>V		No	ClinGen Ensembl
CA9551800 rs745423372	129	F>S		No	ClinGen ExAC gnomAD
CA309328105 rs532302251	130	V>L		No	ClinGen TOPMed gnomAD
rs1348712323 CA406697891	131	D>G		No	ClinGen gnomAD
CA406698027 rs1161361165	137	D>N		No	ClinGen gnomAD
rs1360712455 CA406698502	149	W>*		No	ClinGen TOPMed gnomAD
CA406698526 rs1235658122 COSM1681179	152	R>C	large_intestine [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA9551830 rs760826182	152	R>H		No	ClinGen ExAC gnomAD
rs764450200 CA9551831	153	L>I		No	ClinGen ExAC TOPMed gnomAD
CA406698543 rs1205714149	155	G>E		No	ClinGen gnomAD
CA9551835 rs372308279	155	G>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA406698554 rs1231790937	157	A>S		No	ClinGen TOPMed gnomAD
rs1231790937 CA406698552	157	A>T		No	ClinGen TOPMed gnomAD
CA406698593 rs1471600535	162	R>Q		No	ClinGen gnomAD
rs752389593 CA9551837	163	M>V		No	ClinGen ExAC TOPMed
CA406698608 rs1418317520	164	M>I		No	ClinGen gnomAD
rs746574144 CA9551838	165	E>Q		No	ClinGen ExAC gnomAD
rs1006139156 COSM998976 CA309328638	166	A>V	endometrium [Cosmic]	No	ClinGen cosmic curated TOPMed
CA9551840 rs780717608	169	Q>R		No	ClinGen ExAC gnomAD
rs1328332327 CA406698645	170	R>*		No	ClinGen gnomAD
rs537835463 CA309328652	170	R>Q		No	ClinGen Ensembl
rs1183956130 CA406698659	172	C>Y		No	ClinGen TOPMed
rs1231797365 CA406698682	175	N>I		No	ClinGen gnomAD
CA406698687 rs1272255750	176	P>S		No	ClinGen gnomAD
CA406698705 rs1196002114	179	F>V		No	ClinGen gnomAD
CA9551845 rs749092477	179	F>Y		No	ClinGen ExAC gnomAD
CA9551846 rs771051877	180	Q>R		No	ClinGen ExAC gnomAD
CA406698719 rs1474777348	181	S>A		No	ClinGen TOPMed gnomAD
CA9551874 rs751866749	184	T>A		No	ClinGen ExAC gnomAD
rs538695510 CA9551876	187	V>M		No	ClinGen 1000Genomes ExAC
CA9551880 rs753565456	191	A>S		No	ClinGen ExAC TOPMed gnomAD
CA406698794 rs753565456	191	A>T		No	ClinGen ExAC TOPMed gnomAD
CA406698802 rs1453638328	192	V>A		No	ClinGen gnomAD
rs141113238 COSM119728 CA9551882	192	V>I	ovary [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs368995401 CA9551883	193	I>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs1601023731 CA406698833	197	T>P		No	ClinGen Ensembl
CA9551886 rs748213849	201	N>S		No	ClinGen ExAC gnomAD
CA406698869 rs1384525163	202	P>A		No	ClinGen gnomAD
rs1488862627 CA406698871	202	P>L		No	ClinGen TOPMed
rs1308478747 CA406698878	203	N>S		No	ClinGen TOPMed gnomAD
CA309328927 rs1804728	204	V>F		No	ClinGen Ensembl
CA309328929 rs1047982304	204	V>G		No	ClinGen TOPMed
CA309328922 rs1804728 COSM474985	204	V>I	kidney [Cosmic]	No	ClinGen cosmic curated Ensembl
CA9551887 rs769951654	205	R>Q		No	ClinGen ExAC gnomAD
CA406698886 rs1336327110	205	R>W		No	ClinGen gnomAD
rs1354100517 CA406698902	207	K>R		No	ClinGen TOPMed gnomAD
CA9551888 rs773229556	208	P>L		No	ClinGen ExAC TOPMed gnomAD
CA309328969 rs920251408	211	E>A		No	ClinGen Ensembl
CA9551891 rs774765800	211	E>Q		No	ClinGen ExAC gnomAD
rs373048304 CA9551892	212	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs373048304 CA406698928	212	R>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs202097541 CA9551893	212	R>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA406698945 rs1337549011	215	A>T		No	ClinGen Ensembl
rs763958248 CA309328987	216	M>V		No	ClinGen Ensembl
CA309328991 rs868252335	218	R>W		No	ClinGen TOPMed
rs1180644969 CA406698971	219	G>S		No	ClinGen gnomAD
CA309328999 rs916982857	221	N>S		No	ClinGen gnomAD
rs1041896108 CA309329019	222	E>K		No	ClinGen Ensembl
rs753332499 CA9551898	224	G>R		No	ClinGen ExAC TOPMed gnomAD
rs878937330 CA309329037	225	D>H		No	ClinGen Ensembl
rs201090869 CA9551899	229	E>K		No	ClinGen 1000Genomes ExAC gnomAD
rs540207507 CA9551900	229	E>V		No	ClinGen 1000Genomes ExAC gnomAD
CA406699048 rs1286314090	231	L>F		No	ClinGen gnomAD
rs750230713 CA9551901	231	L>P		No	ClinGen ExAC gnomAD
CA9551903 rs779670761	232	R>G		No	ClinGen ExAC TOPMed gnomAD
rs746993025 CA9551904	232	R>K		No	ClinGen ExAC gnomAD
CA9551926 rs753968766	236	D>N		No	ClinGen ExAC gnomAD
rs757297911 CA9551927	239	R>*		No	ClinGen ExAC gnomAD
rs757297911 CA406699109	239	R>G		No	ClinGen ExAC gnomAD
CA9551928 COSM998982 rs376539291	239	R>Q	endometrium [Cosmic]	No	ClinGen cosmic curated ESP ExAC gnomAD
CA406699119 rs1289197987 COSM4127756	240	N>K	ovary [Cosmic]	No	ClinGen cosmic curated gnomAD
CA9551930 rs772117901	244	K>R		No	ClinGen ExAC gnomAD
rs1408404265 CA406699179	249	D>N		No	ClinGen TOPMed
CA406699194 rs1172978187	251	N>D		No	ClinGen TOPMed
rs887369879 CA309329601	260	P>L		No	ClinGen TOPMed gnomAD
rs769448978 CA9551936	262	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs1230603772 CA406700458	272	G>D		No	ClinGen gnomAD
CA406700451 rs1236427436	272	G>S		No	ClinGen gnomAD
CA406700464 rs1465922638	273	R>W		No	ClinGen TOPMed
CA406700484 rs1601027920	274	V>G		No	ClinGen Ensembl
CA9552001 rs563715406	274	V>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA406700474 rs563715406	274	V>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA406700501 rs1198558580	276	T>M		No	ClinGen gnomAD
CA9552004 rs768354976	277	W>G		No	ClinGen ExAC gnomAD
CA9552005 rs776425963	279	R>Q		No	ClinGen ExAC gnomAD
CA406700519 rs1188088624	279	R>W		No	ClinGen gnomAD
rs1455607403 CA406700524	280	R>C		No	ClinGen gnomAD
CA406700552 rs1329127742	283	I>V		No	ClinGen TOPMed
rs1305491457 CA406700590	285	T>I		No	ClinGen TOPMed
CA406700611 rs1160710289	287	N>D		No	ClinGen gnomAD
rs1389839940 CA406700615	287	N>S		No	ClinGen gnomAD
CA406700648 rs1362435949	289	L>F		No	ClinGen gnomAD
CA406700695 rs1330502200	291	Y>C		No	ClinGen gnomAD
rs1301323019 CA406700684	291	Y>H		No	ClinGen gnomAD
CA406700753 rs1391046865	296	T>A		No	ClinGen TOPMed
CA9552044 rs777666067	300	P>S		No	ClinGen ExAC gnomAD
rs1370643705 CA406700878	301	R>Q		No	ClinGen TOPMed
CA406700917 rs1460175935	305	P>S		No	ClinGen TOPMed
CA9552046 rs17853856	306	L>P		No	ClinGen ExAC gnomAD
CA309332270 rs17853856	306	L>Q		No	ClinGen ExAC gnomAD
CA9552047 rs775487247	309	L>V		No	ClinGen ExAC gnomAD
CA9552049 rs375295429	312	R>*		No	ClinGen ESP ExAC gnomAD
rs367971748 CA406700984	315	D>E		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA9552052 rs765598233 COSM998986	316	D>N	oesophagus endometrium [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA406700993 rs1429029944	317	P>A		No	ClinGen gnomAD
CA406700997 rs1197905418	317	P>L		No	ClinGen TOPMed
CA406700999 rs1166579756	318	R>W		No	ClinGen TOPMed gnomAD
CA309332299 rs887535289	320	P>L		No	ClinGen TOPMed gnomAD
rs1448435620 CA406701011	320	P>T		No	ClinGen gnomAD
rs1388238596 CA406701043	322	C>W		No	ClinGen gnomAD
CA9552092 rs777942701	327	I>N		No	ClinGen ExAC gnomAD
CA406701080 rs1325689164	328	P>A		No	ClinGen gnomAD
CA309332469 rs1042268629	330	N>S		No	ClinGen TOPMed gnomAD
CA309332473 rs765967604	332	G>R		No	ClinGen gnomAD
CA406701116 rs1569092710	333	Q>*		No	ClinGen Ensembl
CA9552093 rs749472978	333	Q>L		No	ClinGen ExAC gnomAD
rs1334168023 CA406701122	334	L>V		No	ClinGen TOPMed
CA9552094 rs771349770	337	A>S		No	ClinGen ExAC gnomAD
rs1170033168 CA406701179	342	A>S		No	ClinGen gnomAD
COSM998990 rs760096318 CA9552096	342	A>V	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1291413971 CA406701191	344	G>S		No	ClinGen gnomAD
CA9552099 rs561416077	345	R>Q		No	ClinGen 1000Genomes ExAC TOPMed
CA406701201 rs1328950704	346	V>L		No	ClinGen gnomAD
rs1220774178 CA406701210	347	V>A		No	ClinGen gnomAD
CA406701208 rs1451624267	347	V>L		No	ClinGen gnomAD
rs1386395738 CA406701230	350	N>S		No	ClinGen TOPMed
rs750179767 CA9552104	352	M>I		No	ClinGen ExAC gnomAD
rs1017803012 CA309332520	352	M>T		No	ClinGen TOPMed gnomAD
rs144064799 CA9552103	352	M>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA406701249 rs1414652551	353	V>L		No	ClinGen gnomAD
rs1370303603 CA406701263	355	R>W		No	ClinGen TOPMed
CA309332539 rs900643788	356	I>M		No	ClinGen TOPMed gnomAD
CA9552107 rs752815514 COSM567166	357	S>L	lung [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs749526139 CA9552110	358	A>S		No	ClinGen ExAC gnomAD
CA406701297 rs1601028918	359	P>A		No	ClinGen Ensembl
rs770995785 CA9552111	360	T>M		No	ClinGen ExAC gnomAD
rs142243059 CA9552114	361	Q>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA406701363 rs1283227689	363	E>*		No	ClinGen TOPMed
rs761211198 CA406701408	365	D>E		No	ClinGen ExAC TOPMed gnomAD
rs768292381 CA9552117	366	E>K		No	ClinGen ExAC TOPMed gnomAD
rs768292381 CA406701418	366	E>Q		No	ClinGen ExAC TOPMed gnomAD
rs761594213 CA9552119	371	I>V		No	ClinGen ExAC gnomAD
rs201559477 CA9552120	372	Q>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA9552145 rs544398866	373	A>E		No	ClinGen 1000Genomes ExAC
rs367679964 CA9552144	373	A>S		No	ClinGen ExAC gnomAD
CA309332958 rs367679964	373	A>T		No	ClinGen ExAC gnomAD
rs139461129 COSM1661359 CA309332990	374	A>T	kidney [Cosmic]	No	ClinGen cosmic curated ESP TOPMed
rs145091024 CA406701696	375	V>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA9552147 rs145091024	375	V>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA406701725 rs1569093546	376	S>N		No	ClinGen Ensembl
rs1390243202 CA406701762	378	D>N		No	ClinGen gnomAD
rs1435236442 CA406701781	379	P>T		No	ClinGen gnomAD
CA9552149 rs766175406	383	M>L		No	ClinGen ExAC gnomAD
rs1324678727 CA406701833	383	M>T		No	ClinGen TOPMed gnomAD
CA406701847 rs1275225378	384	L>R		No	ClinGen gnomAD
rs774067298 CA309333030	384	L>V		No	ClinGen ExAC gnomAD
rs759539903 CA406701873	386	A>G		No	ClinGen ExAC TOPMed gnomAD
rs1443228159 CA406701865	386	A>T		No	ClinGen TOPMed
rs759539903 CA9552151 COSM998992	386	A>V	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA9552153 rs754002279	388	K>R		No	ClinGen ExAC gnomAD
rs1208248831 CA406701937	390	R>Q		No	ClinGen gnomAD
rs757256464 CA9552154 COSM998994	390	R>W	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs750620505 CA9552157	394	K>Q		No	ClinGen ExAC gnomAD
rs373981969 CA9552158	394	K>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA9552160 rs747364275	396	K>Q		No	ClinGen ExAC gnomAD
rs1409555760 CA406702041	397	Q>*		No	ClinGen TOPMed
CA9552161 rs200059386	398	E>D		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs781519260 CA406702084	401	P>C		No	ClinGen ExAC
CA9552162 rs781519260	401	P>W		No	ClinGen ExAC

No associated diseases with Q99418

2 regional properties for Q99418

Type	Name	Position	InterPro Accession
domain	Sec7 domain	54 - 243	IPR000904
domain	Pleckstrin homology domain	259 - 378	IPR001849

Functions

		Description
EC Number
Subcellular Localization	Cell membrane ; Peripheral membrane protein Cytoplasm Cell projection Cell projection, growth cone Cell junction, tight junction Cell junction, adherens junction	Both isoform 1 and isoform 2 are recruited to the cell membrane through its association with ARL4A, ARL4C and ARL4D They require also interaction with phosphoinositides for targeting to plasma membrane (PubMed:17398095) In differentiating neuroblastoma cells, colocalizes with CCDC120 in both neurite shaft and growth cone areas
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

8 GO annotations of cellular component

Name	Definition
adherens junction	A cell-cell junction composed of the epithelial cadherin-catenin complex. The epithelial cadherins, or E-cadherins, of each interacting cell extend through the plasma membrane into the extracellular space and bind to each other. The E-cadherins bind to catenins on the cytoplasmic side of the membrane, where the E-cadherin-catenin complex binds to cytoskeletal components and regulatory and signaling molecules.
bicellular tight junction	An occluding cell-cell junction that is composed of a branching network of sealing strands that completely encircles the apical end of each cell in an epithelial sheet; the outer leaflets of the two interacting plasma membranes are seen to be tightly apposed where sealing strands are present. Each sealing strand is composed of a long row of transmembrane adhesion proteins embedded in each of the two interacting plasma membranes.
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
Golgi membrane	The lipid bilayer surrounding any of the compartments of the Golgi apparatus.
growth cone	The migrating motile tip of a growing neuron projection, where actin accumulates, and the actin cytoskeleton is the most dynamic.
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.

3 GO annotations of molecular function

Name	Definition
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.
inositol 1,4,5 trisphosphate binding	Binding to inositol 1,4,5 trisphosphate.
lipid binding	Binding to a lipid.

3 GO annotations of biological process

Name	Definition
actin cytoskeleton organization	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins.
endocytosis	A vesicle-mediated transport process in which cells take up external materials or membrane constituents by the invagination of a small region of the plasma membrane to form a new membrane-bounded vesicle.
regulation of ARF protein signal transduction	Any process that modulates the frequency, rate or extent of ARF protein signal transduction.

17 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q2KI41	CYTH2	Cytohesin-2	Bos taurus (Bovine)	SS
Q9Y6D5	ARFGEF2	Brefeldin A-inhibited guanine nucleotide-exchange protein 2	Homo sapiens (Human)	PR
Q9Y6D6	ARFGEF1	Brefeldin A-inhibited guanine nucleotide-exchange protein 1	Homo sapiens (Human)	PR
Q5JU85	IQSEC2	IQ motif and SEC7 domain-containing protein 2	Homo sapiens (Human)	EV
Q9UPP2	IQSEC3	IQ motif and SEC7 domain-containing protein 3	Homo sapiens (Human)	SS
Q6DN90	IQSEC1	IQ motif and SEC7 domain-containing protein 1	Homo sapiens (Human)	EV
Q9UIA0	CYTH4	Cytohesin-4	Homo sapiens (Human)	SS
O43739	CYTH3	Cytohesin-3	Homo sapiens (Human)	EV
Q15438	CYTH1	Cytohesin-1	Homo sapiens (Human)	SS
Q92538	GBF1	Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1	Homo sapiens (Human)	PR
O08967	Cyth3	Cytohesin-3	Mus musculus (Mouse)	EV
Q80YW0	Cyth4	Cytohesin-4	Mus musculus (Mouse)	SS
Q9QX11	Cyth1	Cytohesin-1	Mus musculus (Mouse)	SS
P63034	Cyth2	Cytohesin-2	Mus musculus (Mouse)	SS
P97696	Cyth3	Cytohesin-3	Rattus norvegicus (Rat)	SS
P97694	Cyth1	Cytohesin-1	Rattus norvegicus (Rat)	SS
P63035	Cyth2	Cytohesin-2	Rattus norvegicus (Rat)	SS

10	20	30	40	50	60
MEDGVYEPPD	LTPEERMELE	NIRRRKQELL	VEIQRLREEL	SEAMSEVEGL	EANEGSKTLQ
70	80	90	100	110	120
RNRKMAMGRK	KFNMDPKKGI	QFLVENELLQ	NTPEEIARFL	YKGEGLNKTA	IGDYLGEREE
130	140	150	160	170	180
LNLAVLHAFV	DLHEFTDLNL	VQALRQFLWS	FRLPGEAQKI	DRMMEAFAQR	YCLCNPGVFQ
190	200	210	220	230	240
STDTCYVLSF	AVIMLNTSLH	NPNVRDKPGL	ERFVAMNRGI	NEGGDLPEEL	LRNLYDSIRN
250	260	270	280	290	300
EPFKIPEDDG	NDLTHTFFNP	DREGWLLKLG	GGRVKTWKRR	WFILTDNCLY	YFEYTTDKEP
310	320	330	340	350	360
RGIIPLENLS	IREVDDPRKP	NCFELYIPNN	KGQLIKACKT	EADGRVVEGN	HMVYRISAPT
370	380	390
QEEKDEWIKS	IQAAVSVDPF	YEMLAARKKR	ISVKKKQEQP