AiPD: Autoinhibited Protein Database

O43639

Gene name	NCK2 (GRB4)
Protein name	Cytoplasmic protein NCK2
Names	Growth factor receptor-bound protein 4, NCK adaptor protein 2, Nck-2, SH2/SH3 adaptor protein NCK-beta
Species	Homo sapiens (Human)
KEGG Pathway	hsa:8440
EC number
Protein Class	SH2-SH3 ADAPTOR PROTEIN-RELATED (PTHR19969)

Descriptions

NCK2 is a cytoplasmic protein participating in the reorganization of the actin cytoskeleton and in the formation of the immunological synapses. The autoinhibitory domain locates at a conserved non-canonical (K/R)x(K/R)RxxS sequence, specifically at residues 60-110 linker between the SH3.1 and SH3.2. The autoinhibitory domain binds to the SH3.2 domain via acidic electrostatic potential on the SH3 domain surface and masks the proline-rich sequence (PRS) binding site of SH3.2 from its ligands. Only high affinity stable interactions can overcome the inhibitory interaction; such as phosphorylation of Ser85 at the interaction site.

Autoinhibitory domains (AIDs)

Target domain	111-170 (SH3.2 domain)
Relief mechanism	PTM
Assay	Deletion assay, Mutagenesis experiment, Structural analysis

AID

60-110 (Autoinhibitory region)

Target domain

111-170 (SH3.2 domain)

Relief mechanism

PTM (Phosphorylation at Ser85)

Assay

Deletion assay, Mutagenesis experiment, Structural analysis

Accessory elements

No accessory elements

References

Takeuchi K et al. (2010) "Autoinhibitory interaction in the multidomain adaptor protein Nck: possible roles in improving specificity and functional diversity", Biochemistry, 49, 5634-41

Autoinhibited structure

Activated structure

10 structures for O43639

Entry ID	Method	Resolution	Chain	Position	Source
1U5S	NMR	-	A	192-262	PDB
1WX6	NMR	-	A	188-265	PDB
1Z3K	NMR	-	A	283-380	PDB
2B86	NMR	-	A	1-59	PDB
2CIA	X-ray	145 A	A	284-380	PDB
2FRW	NMR	-	A	114-170	PDB
2FRY	NMR	-	A	198-256	PDB
2JXB	NMR	-	A	1-59	PDB
4E6R	X-ray	220 A	A/B	114-170	PDB
AF-O43639-F1	Predicted				AlphaFoldDB

284 variants for O43639

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA348103337 rs1195924667	4	E>V		No	ClinGen TOPMed
rs201418674 CA1815020	6	I>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs769339535 CA53754956	7	V>L		No	ClinGen ExAC TOPMed gnomAD
rs769339535 CA1815022	7	V>L		No	ClinGen ExAC TOPMed gnomAD
rs1573207897 CA348103358	8	I>V		No	ClinGen Ensembl
rs774773148 CA1815023	10	K>R		No	ClinGen ExAC gnomAD
rs768027105 CA1815025	15	A>T		No	ClinGen ExAC gnomAD
CA348103423 rs1330679162	17	Q>*		No	ClinGen TOPMed
rs750771445 CA1815026	23	I>V		No	ClinGen ExAC gnomAD
rs1050345687 CA53754988	26	N>D		No	ClinGen Ensembl
CA348103507 rs1175209860	28	R>Q		No	ClinGen gnomAD
rs1573208012 CA348103538	33	D>G		No	ClinGen Ensembl
COSM1004780 COSM1004778 rs752670187 CA1815032	34	D>N	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs1371960767 CA348103561	36	K>N		No	ClinGen TOPMed
rs765463213 CA53755019	37	T>M		No	ClinGen TOPMed
rs368161463 CA1815036	40	R>Q		No	ClinGen ESP ExAC
COSM1004781 CA1815035 rs746745967	40	R>W	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed
rs1573208133 CA348103594	41	V>G		No	ClinGen Ensembl
rs1573208145 CA348103596	42	R>G		No	ClinGen Ensembl
rs902978534 CA348103610	44	A>P		No	ClinGen TOPMed gnomAD
rs902978534 CA53755061	44	A>T		No	ClinGen TOPMed gnomAD
CA1815038 rs745514962	44	A>V		No	ClinGen ExAC gnomAD
CA53755066 rs973694152	45	A>V		No	ClinGen TOPMed
rs1282227137 CA348103635	48	T>A		No	ClinGen gnomAD
rs775028062 CA1815040	48	T>M		No	ClinGen ExAC TOPMed gnomAD
CA348103685 rs571195450	55	Y>*		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs375461757 CA1815042	55	Y>S		No	ClinGen ESP ExAC gnomAD
rs761188698 CA1815044	56	V>M		No	ClinGen ExAC gnomAD
rs766753457 CA1815045	58	R>Q		No	ClinGen ExAC gnomAD
COSM1613254 CA348103700 rs1558871309 COSM1613253	58	R>W	liver [Cosmic]	No	ClinGen cosmic curated Ensembl
CA348103736 rs1478926029	63	K>R		No	ClinGen gnomAD
CA348103751 rs1395888799	65	G>D		No	ClinGen gnomAD
CA348103766 rs1404717219	68	V>M		No	ClinGen gnomAD
rs757054911 CA1815053	72	K>R		No	ClinGen ExAC gnomAD
CA348103809 rs1220116381	74	T>S		No	ClinGen gnomAD
CA348103839 rs751541163	77	L>F		No	ClinGen ExAC TOPMed gnomAD
CA1815071 rs751541163	77	L>I		No	ClinGen ExAC TOPMed gnomAD
rs751541163 CA53770544	77	L>V		No	ClinGen ExAC TOPMed gnomAD
CA1815072 rs757182579	78	G>S		No	ClinGen ExAC TOPMed gnomAD
CA1815073 rs767240597	80	T>M		No	ClinGen ExAC TOPMed gnomAD
rs1468163686 CA348103863	81	R>C		No	ClinGen TOPMed
rs1189638994 CA348103866	81	R>L		No	ClinGen gnomAD
rs755727286 CA1815075	85	S>G		No	ClinGen ExAC gnomAD
CA348103891 rs1162185719	85	S>T		No	ClinGen gnomAD
COSM1564879 CA348103896 COSM1564878 rs1382749200	86	A>T	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
rs913136866 COSM3772386 COSM3772387 CA53770563	86	A>V	pancreas [Cosmic]	No	ClinGen cosmic curated Ensembl
CA348103900 rs1158424197	87	R>G		No	ClinGen gnomAD
rs748935902 CA1815077	87	R>P		No	ClinGen ExAC gnomAD
CA348103901 rs1158424197	87	R>W		No	ClinGen gnomAD
rs1338072592 CA348103904	88	D>N		No	ClinGen gnomAD
CA348103917 rs1382927137	89	A>V		No	ClinGen gnomAD
rs973651345 CA53770568	90	S>P		No	ClinGen Ensembl
rs747500810 CA1815080	92	T>M		No	ClinGen ExAC TOPMed gnomAD
rs771417618 CA1815081	93	P>L		No	ClinGen ExAC gnomAD
rs1263830219 CA348103943	94	S>T		No	ClinGen TOPMed
rs776872198 CA1815082	95	T>M		No	ClinGen ExAC TOPMed gnomAD
rs201406196 CA53770597	96	D>G		No	ClinGen Ensembl
rs770047813 CA1815084	96	D>N		No	ClinGen ExAC gnomAD
rs1360838761 CA348103963	97	A>D		No	ClinGen TOPMed
CA348103967 rs1267981472	98	E>*		No	ClinGen TOPMed
CA348103970 rs1306556692	98	E>G		No	ClinGen TOPMed
CA1815086 rs763135850	99	Y>S		No	ClinGen ExAC gnomAD
rs764192536 CA1815087	101	A>P		No	ClinGen ExAC TOPMed gnomAD
rs764192536 CA348103987	101	A>T		No	ClinGen ExAC TOPMed gnomAD
CA1815088 rs774367973	102	N>S		No	ClinGen ExAC gnomAD
CA348103999 rs761674486	103	G>C		No	ClinGen ExAC gnomAD
CA1815089 rs761674486	103	G>R		No	ClinGen ExAC gnomAD
rs767425900 CA1815090	104	S>R		No	ClinGen ExAC gnomAD
COSM1527008 rs1335454177 CA348104013 COSM1527009	105	G>S	lung [Cosmic]	No	ClinGen cosmic curated TOPMed
rs755994999 CA1815092	106	A>V		No	ClinGen ExAC gnomAD
rs1573244235 CA348104025	107	D>A		No	ClinGen Ensembl
CA348104042 rs1391915772	109	I>M		No	ClinGen gnomAD
rs1398472942 CA348104039	109	I>N		No	ClinGen gnomAD
CA348104045 rs1285252783	110	Y>D		No	ClinGen gnomAD
rs766256305 CA348104052	111	D>H		No	ClinGen ExAC TOPMed gnomAD
CA1815093 rs766256305	111	D>N		No	ClinGen ExAC TOPMed gnomAD
rs753586078 CA1815094	111	D>V		No	ClinGen ExAC gnomAD
rs778588738 CA1815096	113	N>S		No	ClinGen ExAC gnomAD
CA348104072 rs1417113083	114	I>V		No	ClinGen TOPMed
CA1815099 rs781754645	115	P>S		No	ClinGen ExAC TOPMed gnomAD
rs569250884 CA53770661	116	A>G		No	ClinGen TOPMed gnomAD
CA348104086 rs569250884	116	A>V		No	ClinGen TOPMed gnomAD
CA348104090 rs1235034975	117	F>Y		No	ClinGen TOPMed
rs199727155 CA53770667	120	F>L		No	ClinGen ExAC
CA348104117 rs1359678741	121	A>D		No	ClinGen TOPMed
CA1815103 rs749536605	121	A>S		No	ClinGen ExAC TOPMed gnomAD
CA1815104 rs749536605	121	A>T		No	ClinGen ExAC TOPMed gnomAD
rs1200674888 CA348104125	122	Y>F		No	ClinGen gnomAD
CA1815107 rs772032136	123	V>M		No	ClinGen ExAC gnomAD
rs147879012 CA1815110	125	E>*		No	ClinGen ESP ExAC TOPMed gnomAD
CA348104141 rs1298737987	125	E>G		No	ClinGen TOPMed
rs147879012 CA1815109	125	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
rs147879012 CA348104139	125	E>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs375422663 CA1815112	126	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA1815113 rs200636557	127	E>G		No	ClinGen ExAC TOPMed gnomAD
rs1394316248 CA348104150	127	E>Q		No	ClinGen gnomAD
CA348104191 rs1426817880	133	V>L		No	ClinGen TOPMed
rs937139915 CA53770710	136	S>L		No	ClinGen Ensembl
CA1815116 rs777123504	137	R>H		No	ClinGen ExAC TOPMed gnomAD
CA348104220 rs1297768575	138	V>I		No	ClinGen TOPMed gnomAD
rs756566928 CA1815118	140	V>I		No	ClinGen ExAC TOPMed gnomAD
rs892782902 CA348104240	141	M>K		No	ClinGen TOPMed
CA53770742 rs892782902	141	M>R		No	ClinGen TOPMed
rs1225120822 CA348104272	145	S>N		No	ClinGen TOPMed
rs749591659 CA1815120	150	R>Q		No	ClinGen ExAC gnomAD
rs1491003245 CA348104310	150	R>W		No	ClinGen TOPMed gnomAD
CA1815121 rs769007984	153	Y>C		No	ClinGen ExAC gnomAD
CA53770758 rs769007984	153	Y>F		No	ClinGen ExAC gnomAD
CA348104341 rs1196796618	155	G>R		No	ClinGen gnomAD
CA1815123 rs748295860	157	I>N		No	ClinGen ExAC gnomAD
CA348104361 rs1169212495	158	G>S		No	ClinGen gnomAD
rs1371198261 CA348104373	159	W>*		No	ClinGen gnomAD
rs931923616 CA53770766	160	F>V		No	ClinGen Ensembl
rs1426494010 CA348104394	162	S>F		No	ClinGen gnomAD
CA348104411 rs372651078	165	V>F		No	ClinGen ESP ExAC gnomAD
CA1815127 rs372651078	165	V>I		No	ClinGen ESP ExAC gnomAD
rs1223200437 CA348104420	166	L>W		No	ClinGen TOPMed
CA1815128 rs776572130	168	E>G		No	ClinGen ExAC gnomAD
CA348104446 rs1284994943	170	D>N		No	ClinGen TOPMed
CA348104458 rs1405256560	171	E>D		No	ClinGen TOPMed
CA348104463 rs1362156483	172	A>E		No	ClinGen gnomAD
CA1815130 rs765106638	174	A>V		No	ClinGen ExAC gnomAD
CA1815132 rs762479770	175	E>A		No	ClinGen ExAC TOPMed gnomAD
rs11553852 CA53770837	176	S>P		No	ClinGen Ensembl
rs369379486 CA1815133	176	S>Y		No	ClinGen ESP ExAC TOPMed gnomAD
rs1178579083 CA348104490	177	P>A		No	ClinGen TOPMed gnomAD
CA348104493 rs1243481771	177	P>L		No	ClinGen TOPMed gnomAD
CA1815134 rs750977650	178	S>G		No	ClinGen ExAC gnomAD
CA348104500 rs1419024844	178	S>R		No	ClinGen TOPMed
CA1815135 rs756622014	179	F>L		No	ClinGen ExAC gnomAD
rs534727383 CA1815136	180	L>V		No	ClinGen 1000Genomes ExAC gnomAD
CA348104523 rs1573244918	182	L>P		No	ClinGen Ensembl
rs1468183226 CA348104527	183	R>C		No	ClinGen gnomAD
rs754330998 CA1815137	183	R>H		No	ClinGen ExAC TOPMed gnomAD
rs754330998 CA348104528	183	R>L		No	ClinGen ExAC TOPMed gnomAD
rs373413217 CA53770858	185	G>S		No	ClinGen ESP
CA53770859 rs755385208	186	A>S		No	ClinGen ExAC TOPMed gnomAD
rs755385208 CA1815138	186	A>T		No	ClinGen ExAC TOPMed gnomAD
rs779117347 CA1815139	187	S>T		No	ClinGen ExAC TOPMed gnomAD
rs777919935 CA1815142	188	L>P		No	ClinGen ExAC TOPMed gnomAD
rs1479928639 CA348104565	190	N>D		No	ClinGen gnomAD
rs747018579 CA1815143	190	N>S		No	ClinGen ExAC gnomAD
CA1815146 rs201888318	192	Q>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs771183263 CA53770885	192	Q>P		No	ClinGen ExAC gnomAD
rs771183263 CA1815144	192	Q>R		No	ClinGen ExAC gnomAD
rs376669820 CA1815147	193	G>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA348104592 rs1264859840	194	S>F		No	ClinGen TOPMed
rs763589848 CA1815150	196	V>A		No	ClinGen ExAC gnomAD
rs762683461 CA348104600	196	V>L		No	ClinGen ExAC TOPMed gnomAD
rs762683461 COSM2981295 COSM2981294 CA1815149	196	V>M	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA1815151 rs773992501	197	L>P		No	ClinGen ExAC gnomAD
CA1815154 rs754384046	198	H>P		No	ClinGen ExAC gnomAD
CA1815153 COSM1398598 COSM1398599 rs766993432	198	H>Y	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC
CA1815155 rs755440418	202	T>M		No	ClinGen ExAC gnomAD
rs752945323 CA1815157	205	P>S		No	ClinGen ExAC gnomAD
CA1815158 rs758649473	208	S>A		No	ClinGen ExAC gnomAD
CA1815159 rs777924793	208	S>L		No	ClinGen ExAC gnomAD
CA1815161 rs757457379	209	V>F		No	ClinGen ExAC gnomAD
CA348104684 rs1445013870	210	T>N		No	ClinGen TOPMed gnomAD
CA348104692 rs1573245210	211	E>D		No	ClinGen Ensembl
COSM1004788 CA53770991 COSM1004787 rs776751269	211	E>K	endometrium [Cosmic]	No	ClinGen cosmic curated Ensembl
CA348104694 rs1373018176	212	E>K		No	ClinGen gnomAD
rs745828163 CA1815163	213	E>K		No	ClinGen ExAC gnomAD
CA1815165 rs775361933	215	N>S		No	ClinGen ExAC gnomAD
CA348104770 rs761423872	222	M>R		No	ClinGen ExAC gnomAD
CA1815169 rs761423872	222	M>T		No	ClinGen ExAC gnomAD
CA53771015 rs972066107	223	E>K		No	ClinGen TOPMed
CA53771045 rs1005968215	225	I>T		No	ClinGen TOPMed gnomAD
rs1429091158 CA348104797	226	E>G		No	ClinGen TOPMed
CA348104814 rs1179830468	228	P>L		No	ClinGen TOPMed gnomAD
CA348104812 rs1179830468	228	P>Q		No	ClinGen TOPMed gnomAD
rs1197655713 CA348104809	228	P>T		No	ClinGen TOPMed
CA53771046 rs878946953	229	E>K		No	ClinGen Ensembl
rs1175736952 CA348104867	235	W>C		No	ClinGen gnomAD
rs1221973306 CA348104897	239	N>T		No	ClinGen gnomAD
rs765594937 CA1815174	240	A>P		No	ClinGen ExAC TOPMed
rs765594937 CA348104902	240	A>S		No	ClinGen ExAC TOPMed
CA1815175 rs753243958	240	A>V		No	ClinGen ExAC gnomAD
CA348104906 rs1411771322	241	R>G		No	ClinGen TOPMed gnomAD
rs758746326 CA1815176	241	R>Q		No	ClinGen ExAC gnomAD
CA348104907 rs1411771322	241	R>W		No	ClinGen TOPMed gnomAD
rs975509135 CA53771059	242	G>S		No	ClinGen Ensembl
CA348104922 rs1440465020	243	Q>H		No	ClinGen gnomAD
CA348104925 rs1322701308	244	V>L		No	ClinGen TOPMed
rs1305346471 CA348104932	245	G>D		No	ClinGen gnomAD
rs954576405 CA53771063	247	V>I		No	ClinGen gnomAD
rs751867472 CA1815178	249	K>R		No	ClinGen ExAC TOPMed gnomAD
CA348104980 rs1296634496	252	V>G		No	ClinGen TOPMed
rs1573245524 CA348104983	253	V>L		No	ClinGen Ensembl
rs757510743 CA1815179	254	V>I		No	ClinGen ExAC gnomAD
CA53771081 rs371236589	255	L>F		No	ClinGen ESP gnomAD
COSM144110 COSM1669192 COSM1669193 CA1815181 rs750464687	257	D>E	large_intestine skin [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs779917800 CA1815183	258	G>E		No	ClinGen ExAC gnomAD
rs756217972 CA1815182	258	G>R		No	ClinGen ExAC gnomAD
rs137868721 CA1815185	259	P>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA348105027 rs778640285	261	L>V		No	ClinGen ExAC TOPMed gnomAD
rs747822398 CA1815187	262	H>R		No	ClinGen ExAC gnomAD
CA348105034 rs1165809099	262	H>Y		No	ClinGen gnomAD
CA1815189 rs772711255	263	P>S		No	ClinGen ExAC gnomAD
CA348105049 rs1479873527	264	A>V		No	ClinGen gnomAD
CA53771127 rs990070802	265	H>D		No	ClinGen TOPMed
CA1815192 rs377759138	265	H>Q		No	ClinGen ESP ExAC gnomAD
rs770460763 CA1815191	265	H>R		No	ClinGen ExAC TOPMed gnomAD
CA348105055 rs763482146	266	A>P		No	ClinGen ExAC TOPMed gnomAD
CA1815193 rs763482146	266	A>T		No	ClinGen ExAC TOPMed gnomAD
CA1815194 rs764581321	268	Q>H		No	ClinGen ExAC gnomAD
CA348105070 rs1226124084	268	Q>R		No	ClinGen gnomAD
CA1815195 rs751920917	270	S>T		No	ClinGen ExAC gnomAD
CA1815196 rs762133170	271	Y>C		No	ClinGen ExAC gnomAD
rs947129132 CA53771166	272	T>S		No	ClinGen TOPMed
CA53771168 rs750648011	273	G>R		No	ClinGen ExAC TOPMed gnomAD
CA1815198 rs750648011	273	G>R		No	ClinGen ExAC TOPMed gnomAD
rs1573245763 CA348105105	274	P>S		No	ClinGen Ensembl
rs902885784 CA53771172	275	S>W		No	ClinGen TOPMed gnomAD
CA53771177 rs549114543	277	S>T		No	ClinGen Ensembl
rs1480875247 CA348105135	279	R>C		No	ClinGen TOPMed
CA1815200 rs780151498 COSM1004791 COSM1004793	279	R>H	large_intestine endometrium [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs374552067 CA1815201	280	F>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA348105142 rs1386468934	280	F>S		No	ClinGen gnomAD
CA53771191 rs938578667	281	A>G		No	ClinGen TOPMed
rs1382720762 CA348105155	282	G>V		No	ClinGen TOPMed
rs1388052573 CA348105158	283	R>K		No	ClinGen gnomAD
rs1402102793 CA348105164	284	E>Q		No	ClinGen gnomAD
rs1573245898 CA348105173	285	W>G		No	ClinGen Ensembl
CA53771197 rs894285243	286	Y>C		No	ClinGen TOPMed gnomAD
CA348105188 rs1397706082	287	Y>H		No	ClinGen TOPMed
rs1383526320 CA348105207	289	N>K		No	ClinGen TOPMed gnomAD
CA1815205 rs771849479	289	N>S		No	ClinGen ExAC gnomAD
rs199651832 COSM1631232 CA53771202 COSM1631231	290	V>M	liver [Cosmic]	No	ClinGen cosmic curated gnomAD
rs370241867 CA53771207	291	T>M		No	ClinGen ESP TOPMed
CA348105223 rs1205980457	293	H>Y		No	ClinGen TOPMed gnomAD
CA1815208 rs770384522	294	Q>R		No	ClinGen ExAC gnomAD
CA348105250 rs1183954324	296	E>D		No	ClinGen TOPMed
rs769226018 CA348105259	297	C>W		No	ClinGen ExAC TOPMed gnomAD
rs1244215593 CA348105267	299	L>F		No	ClinGen gnomAD
rs1444575856 CA348105279	300	N>K		No	ClinGen gnomAD
CA1815212 rs774996531	301	E>K		No	ClinGen ExAC gnomAD
rs767975664 CA348105298	304	V>L		No	ClinGen ExAC TOPMed gnomAD
rs767975664 CA1815214	304	V>M		No	ClinGen ExAC TOPMed gnomAD
CA348105346 rs1294156140	311	R>G		No	ClinGen TOPMed
rs765223593 CA1815220	312	D>A		No	ClinGen ExAC gnomAD
rs368417738 CA1815219	312	D>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs368417738 CA1815218	312	D>N		No	ClinGen ESP ExAC TOPMed gnomAD
rs950214307 CA53771306	316	S>A		No	ClinGen Ensembl
rs577283510 CA1815246	318	S>N		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs748686837 CA348105412	318	S>R		No	ClinGen ExAC gnomAD
CA348105411 rs748686837	318	S>R		No	ClinGen ExAC gnomAD
CA1815249 rs773455664	319	D>E		No	ClinGen ExAC gnomAD
CA1815248 rs772650775	319	D>N		No	ClinGen ExAC gnomAD
rs904856726 CA53775347	320	F>L		No	ClinGen TOPMed
rs1273249659 CA348105432	321	S>C		No	ClinGen TOPMed
CA1815250 rs200594599	322	V>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA348105469 rs1490052739	326	A>T		No	ClinGen gnomAD
CA348105474 COSM1004795 COSM1004794 rs1332586401	326	A>V	endometrium [Cosmic]	No	ClinGen cosmic curated TOPMed
rs1270571800 CA348105484	328	G>E		No	ClinGen gnomAD
CA1815254 rs765331885	331	K>R		No	ClinGen ExAC gnomAD
CA53775367 rs895059179	335	V>M		No	ClinGen TOPMed
rs775496029 CA1815255	336	Q>K		No	ClinGen ExAC gnomAD
CA1815256 rs147922486	338	V>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA1815257 rs764022792	340	N>D		No	ClinGen ExAC gnomAD
rs751441679 CA1815258	340	N>S		No	ClinGen ExAC TOPMed gnomAD
rs375398048 CA1815259	341	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs1428631760 CA348105581	342	Y>F		No	ClinGen gnomAD
rs749337403 CA53775378	344	I>T		No	ClinGen Ensembl
COSM1398601 CA1815261 COSM1398602 rs750135733	348	R>C	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1476316800 CA348105619	348	R>H		No	ClinGen TOPMed gnomAD
rs750135733 CA348105617	348	R>S		No	ClinGen ExAC gnomAD
CA1815263 rs779724766	350	H>L		No	ClinGen ExAC gnomAD
rs77614409 CA1815264	351	T>S		No	ClinGen 1000Genomes ExAC gnomAD
rs1456606773 CA348105659	354	E>K		No	ClinGen gnomAD
CA1815266 rs542899610	360	K>R		No	ClinGen 1000Genomes ExAC gnomAD
CA1815267 rs747449570	362	A>T		No	ClinGen ExAC TOPMed gnomAD
rs771366302 CA1815268	362	A>V		No	ClinGen ExAC gnomAD
CA348105754 rs1312487716	367	S>R		No	ClinGen gnomAD
rs775551208 CA1815272	368	E>K		No	ClinGen ExAC gnomAD
rs763085878 CA1815273	369	H>L		No	ClinGen ExAC TOPMed gnomAD
CA1815274 rs768598254	370	G>R		No	ClinGen ExAC gnomAD
CA348105770 rs768598254	370	G>W		No	ClinGen ExAC gnomAD
CA1815278 rs144762403	374	Y>C		No	ClinGen ESP ExAC TOPMed gnomAD
CA53775416 rs1026995769	374	Y>H		No	ClinGen TOPMed gnomAD
rs1412845098 CA348105807	375	L>P		No	ClinGen gnomAD
CA348105809 rs1161526080	376	V>I		No	ClinGen TOPMed gnomAD
CA348105817 rs1456773337	377	R>K		No	ClinGen gnomAD
rs1377398900 CA348105833	380	Q>K		No	ClinGen gnomAD

No associated diseases with O43639

No regional properties for O43639

Type	Name	Position	InterPro Accession
No domain, repeats, and functional sites for O43639

Functions

		Description
EC Number
Subcellular Localization	Cytoplasm Endoplasmic reticulum
PANTHER Family	PTHR19969	SH2-SH3 ADAPTOR PROTEIN-RELATED
PANTHER Subfamily	PTHR19969:SF12	CYTOPLASMIC PROTEIN NCK2
PANTHER Protein Class	scaffold/adaptor protein
PANTHER Pathway Category	Angiogenesis Nck PDGF signaling pathway Nck T cell activation nck

5 GO annotations of cellular component

Name	Definition
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.
endoplasmic reticulum	The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached).
postsynaptic density	An electron dense network of proteins within and adjacent to the postsynaptic membrane of an asymmetric, neuron-neuron synapse. Its major components include neurotransmitter receptors and the proteins that spatially and functionally organize them such as anchoring and scaffolding molecules, signaling enzymes and cytoskeletal components.
vesicle membrane	The lipid bilayer surrounding any membrane-bounded vesicle in the cell.

7 GO annotations of molecular function

Name	Definition
cytoskeletal anchor activity	The binding activity of a protein that brings together a cytoskeletal protein (either a microtubule or actin filament, spindle pole body, or protein directly bound to them) and one or more other molecules, permitting them to function in a coordinated way.
phosphotyrosine residue binding	Binding to a phosphorylated tyrosine residue within a protein.
protein-containing complex binding	Binding to a macromolecular complex.
receptor tyrosine kinase binding	Binding to a receptor that possesses protein tyrosine kinase activity.
scaffold protein binding	Binding to a scaffold protein. Scaffold proteins are crucial regulators of many key signaling pathways. Although not strictly defined in function, they are known to interact and/or bind with multiple members of a signaling pathway, tethering them into complexes.
signaling adaptor activity	The binding activity of a molecule that brings together two or more molecules in a signaling pathway, permitting those molecules to function in a coordinated way. Adaptor molecules themselves do not have catalytic activity.
signaling receptor complex adaptor activity	The binding activity of a molecule that provides a physical support for the assembly of a multiprotein receptor signaling complex.

21 GO annotations of biological process

Name	Definition
actin filament 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. Includes processes that control the spatial distribution of actin filaments, such as organizing filaments into meshworks, bundles, or other structures, as by cross-linking.
cell migration	The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. Cell migration is a central process in the development and maintenance of multicellular organisms.
dendritic spine development	The process whose specific outcome is the progression of the dendritic spine over time, from its formation to the mature structure. A dendritic spine is a protrusion from a dendrite and a specialized subcellular compartment involved in synaptic transmission.
ephrin receptor signaling pathway	The series of molecular signals initiated by ephrin binding to its receptor, and ending with the regulation of a downstream cellular process, e.g. transcription.
epidermal growth factor receptor signaling pathway	The series of molecular signals initiated by binding of a ligand to the tyrosine kinase receptor EGFR (ERBB1) on the surface of a cell. The pathway ends with regulation of a downstream cellular process, e.g. transcription.
immunological synapse formation	The formation of an area of close contact between a lymphocyte (T-, B-, or natural killer cell) and a target cell through the clustering of particular signaling and adhesion molecules and their associated membrane rafts on both the lymphocyte and target cell, which facilitates activation of the lymphocyte, transfer of membrane from the target cell to the lymphocyte, and in some situations killing of the target cell through release of secretory granules and/or death-pathway ligand-receptor interaction.
lamellipodium assembly	Formation of a lamellipodium, a thin sheetlike extension of the surface of a migrating cell.
negative regulation of cell population proliferation	Any process that stops, prevents or reduces the rate or extent of cell proliferation.
negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation	Any process that stops, prevents or reduces the frequency, rate or extent of endoplasmic reticulum stress-induced eiF2alpha phosphorylation.
negative regulation of peptidyl-serine phosphorylation	Any process that stops, prevents, or reduces the frequency, rate or extent of the phosphorylation of peptidyl-serine.
negative regulation of PERK-mediated unfolded protein response	Any process that stops, prevents or reduces the frequency, rate or extent of the PERK-mediated unfolded protein response.
negative regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress	Any process that stops, prevents, or reduces the frequency, rate or extent of transcription from an RNA polymerase II promoter as a result of an endoplasmic reticulum stress.
positive regulation of actin filament polymerization	Any process that activates or increases the frequency, rate or extent of actin polymerization.
positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	Any process that activates or increases the frequency, rate or extent of an endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway.
positive regulation of T cell proliferation	Any process that activates or increases the rate or extent of T cell proliferation.
positive regulation of transcription by RNA polymerase II	Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
positive regulation of translation in response to endoplasmic reticulum stress	Any process that activates, or increases the frequency, rate or extent of translation as a result of endoplasmic reticulum stress.
regulation of epidermal growth factor-activated receptor activity	Any process that modulates the frequency, rate or extent of EGF-activated receptor activity.
signal complex assembly	The aggregation, arrangement and bonding together of a set of components to form a complex capable of relaying a signal within a 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.

5 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P16333	NCK1	Cytoplasmic protein NCK1	Homo sapiens (Human)	PR
P46108	CRK	Adapter molecule crk	Homo sapiens (Human)	EV
P46109	CRKL	Crk-like protein	Homo sapiens (Human)	SS
Q99M51	Nck1	Cytoplasmic protein NCK1	Mus musculus (Mouse)	PR
O55033	Nck2	Cytoplasmic protein NCK2	Mus musculus (Mouse)	SS

10	20	30	40	50	60
MTEEVIVIAK	WDYTAQQDQE	LDIKKNERLW	LLDDSKTWWR	VRNAANRTGY	VPSNYVERKN
70	80	90	100	110	120
SLKKGSLVKN	LKDTLGLGKT	RRKTSARDAS	PTPSTDAEYP	ANGSGADRIY	DLNIPAFVKF
130	140	150	160	170	180
AYVAEREDEL	SLVKGSRVTV	MEKCSDGWWR	GSYNGQIGWF	PSNYVLEEVD	EAAAESPSFL
190	200	210	220	230	240
SLRKGASLSN	GQGSRVLHVV	QTLYPFSSVT	EEELNFEKGE	TMEVIEKPEN	DPEWWKCKNA
250	260	270	280	290	300
RGQVGLVPKN	YVVVLSDGPA	LHPAHAPQIS	YTGPSSSGRF	AGREWYYGNV	TRHQAECALN
310	320	330	340	350	360
ERGVEGDFLI	RDSESSPSDF	SVSLKASGKN	KHFKVQLVDN	VYCIGQRRFH	TMDELVEHYK
370
KAPIFTSEHG	EKLYLVRALQ