AiPD: Autoinhibited Protein Database

P41240

Gene name	CSK
Protein name	Tyrosine-protein kinase CSK
Names	EC 2.7.10.2 , C-Src kinase , Protein-tyrosine kinase CYL
Species	Homo sapiens (Human)
KEGG Pathway	hsa:1445
EC number	2.7.10.2: Protein-tyrosine kinases
Protein Class

Descriptions

The kinase Csk is the primary negative regulator of the Src‐family kinases (SFKs, e.g., Lck, Fyn, Lyn, Hck, Fgr, Blk, Yes). Csk phosphorylates a tyrosine on the SFK C‐terminal tail that mediates autoinhibition. Csk is recruited to membrane-anchored SFKs and activated allosterically via its SH2 domain, which binds SFK- phosphorylated motifs in CBP/PAG1 (Csk binding protein/phosphoprotein associated with glycosphingolipid- enriched microdomains), Paxillin, Fak, the Dok family, and other tyrosine-phosphorylated proteins. Csk also binds phosphatases, including PTPN12 (PTP‐PEST) and immune‐cell PTPN22 (LYP/Pep), which dephosphorylate SFK activation loop to promote autoinhibition. <br> Purified Csk homodimerizes in competition with PTPN22 binding through an interface that is mediated by symmetrical SH3-SH3 interactions and that overlaps the phosphatase binding footprint. Mutation in SH3 impairing homodimerization enhances PTPN22 binding.

Autoinhibitory domains (AIDs)

9-70 (SH3 domain) SS

Target domain	9-70 (SH3 domain)
Relief mechanism	Partner binding
Assay

AID

9-70 (SH3 domain)

Target domain

9-70 (SH3 domain)

Relief mechanism

Partner binding (Binding of SFKs to SH2 domain)

Assay

80-171 (SH2 domain) SS

Target domain	195-444 (Protein kinase domain)
Relief mechanism	Ligand binding
Assay

AID

80-171 (SH2 domain)

Target domain

195-444 (Protein kinase domain)

Relief mechanism

Ligand binding (Phosphotyrosine-containing peptide binding)

Assay

Accessory elements

331-351 (Activation loop from InterPro)

Target domain	195-449 (Protein kinase domain)
Relief mechanism
Assay

References

Brian BF 4th et al. (2022) "SH3-domain mutations selectively disrupt Csk homodimerization or PTPN22 binding", Scientific reports, 12, 5875

Ghose R et al. (2001) "A novel, specific interaction involving the Csk SH3 domain and its natural ligand", Nature structural biology, 8, 998-1004

Hong E et al. (2004) "Solution structure and backbone dynamics of the non-receptor protein-tyrosine kinase-6 Src homology 2 domain", The Journal of biological chemistry, 279, 29700-8

Ko S et al. (2009) "Structural basis of the auto-inhibition mechanism of nonreceptor tyrosine kinase PTK6", Biochemical and biophysical research communications, 384, 236-42

Qiu H et al. (2002) "Regulation of the nonreceptor tyrosine kinase Brk by autophosphorylation and by autoinhibition", The Journal of biological chemistry, 277, 34634-41

Autoinhibited structure

Activated structure

7 structures for P41240

Entry ID	Method	Resolution	Chain	Position	Source
1BYG	X-ray	240 A	A	173-450	PDB
1CSK	X-ray	250 A	A/B/C/D	1-71	PDB
3D7T	X-ray	290 A	A	188-450	PDB
3D7U	X-ray	411 A	A/C	188-450	PDB
3EAC	X-ray	137 A	A	73-178	PDB
3EAZ	X-ray	131 A	A	73-178	PDB
AF-P41240-F1	Predicted				AlphaFoldDB

272 variants for P41240

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
TCGA novel	1	M>?	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1477359685	2	S>T		No	gnomAD
rs2063736526	3	A>V		No	TOPMed
rs1409275533	4	I>V		No	TOPMed gnomAD
rs758951634	7	A>S		No	ExAC TOPMed gnomAD
rs758951634	7	A>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs749997068	7	A>V		No	ExAC TOPMed gnomAD
rs1158879587	9	P>L		No	gnomAD
rs779667521	9	P>S		No	ExAC gnomAD
rs2063742694	10	S>P		No	TOPMed
rs2063742782	11	G>S		No	TOPMed
rs2063742827	12	T>I		No	TOPMed gnomAD
rs1222737325	13	E>*		No	TOPMed gnomAD
rs1222737325	13	E>K		No	TOPMed gnomAD
TCGA novel	14	C>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	14	C>missing	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs2063742985	19	N>D		No	Ensembl
rs2063743024	19	N>S		No	TOPMed
rs747892475	22	G>S		No	ExAC TOPMed gnomAD
rs572429345	25	E>K		No	1000Genomes ExAC TOPMed gnomAD
rs572429345	25	E>Q		No	1000Genomes ExAC TOPMed gnomAD
COSM1678589	26	Q>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1429627492	31	C>R		No	Ensembl
rs945128501	31	C>W		No	TOPMed
rs776646592	32	K>Q		No	ExAC
rs2063743547	32	K>R		No	gnomAD
COSM4056917	34	D>G	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1262834900	35	V>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
TCGA novel	39	V>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs775978864	41	V>I		No	ExAC TOPMed gnomAD
COSM1493511	44	D>E	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs2063745965 VAR_041678	45	P>L		No	TOPMed UniProt
rs1481958129	53	K>N		No	TOPMed gnomAD
rs745947125	54	V>L		No	ExAC gnomAD
TCGA novel	55	G>D	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1313037569	55	G>S		No	gnomAD
COSM4056918 rs144688425	56	R>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ESP ExAC NCI-TCGA TOPMed gnomAD
rs200009296	56	R>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs1176856084	57	E>K		No	TOPMed
rs1367369609	58	G>A		No	gnomAD
COSM3503992	61	P>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1266338668	62	A>T		No	TOPMed gnomAD
rs1369181420	63	N>S		No	gnomAD
rs11553759	65	V>F		No	Ensembl
rs562760763	71	V>L		No	1000Genomes ExAC TOPMed gnomAD
rs1312171186	74	G>D		No	gnomAD
rs759095664	79	L>F		No	ExAC TOPMed gnomAD
rs2063747272	80	M>T		No	TOPMed
rs1247514280	80	M>V		No	TOPMed
rs1413143879	85	G>S		No	gnomAD
rs2063753016	86	K>R		No	Ensembl
rs1338069794	87	I>V		No	TOPMed gnomAD
rs2063753222	89	R>W		No	TOPMed gnomAD
rs2063753413	92	A>G		No	gnomAD
rs1318690448	92	A>T		No	gnomAD
rs763802749	93	E>G		No	ExAC gnomAD
COSM3794402	93	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs751418156	94	R>L		No	ExAC TOPMed gnomAD
COSM1189066 rs751418156	94	R>Q	lung [Cosmic]	No	cosmic curated ExAC TOPMed gnomAD
rs2063753547	94	R>W		No	TOPMed gnomAD
rs750380440	97	Y>C		No	ExAC gnomAD
rs750380440	97	Y>F		No	ExAC gnomAD
rs767255442	97	Y>H		No	ExAC TOPMed gnomAD
rs750380440	97	Y>S		No	ExAC gnomAD
rs780001574	99	P>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs780001574	99	P>R		No	ExAC TOPMed gnomAD
rs1328560214 COSM5054487	107	R>W	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic NCI-TCGA TOPMed gnomAD
TCGA novel	108	E>G	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1177463069	109	S>R		No	TOPMed
rs150653589	111	N>S		No	ESP TOPMed
rs1477309088	113	P>S		No	gnomAD
rs2063754317	114	G>R		No	Ensembl
TCGA novel	114	G>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs2063754367	115	D>H		No	Ensembl
rs2063754415	117	T>M		No	Ensembl
rs2063754610	120	V>M		No	TOPMed
rs979623672	123	D>E		No	TOPMed gnomAD
rs1325558907	123	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA TOPMed gnomAD
rs771405153	124	G>S		No	ExAC TOPMed gnomAD
rs2063754933	125	K>R		No	gnomAD
rs2063754973	128	H>L		No	Ensembl
COSM964902	128	H>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
COSM4056919	129	Y>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1033335420	130	R>H		No	TOPMed gnomAD
rs1286085887	132	M>R		No	gnomAD
rs762515591	133	Y>C		No	ExAC gnomAD
rs2063755187	134	H>R		No	gnomAD
rs987781536	136	S>N		No	TOPMed gnomAD
rs763772785	136	S>R		No	ExAC gnomAD
COSM471062	138	L>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1374677580	140	I>L		No	TOPMed
rs1567218733	141	D>N		No	TOPMed
rs1340149747	142	E>K		No	TOPMed gnomAD
rs767310391	143	E>D		No	ExAC TOPMed gnomAD
rs1484250970	144	V>L		No	gnomAD
rs1220491616	145	Y>C		No	TOPMed gnomAD
rs2063755701	145	Y>H		No	gnomAD
rs1220491616	145	Y>S		No	TOPMed gnomAD
TCGA novel	146	F>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1180413663	147	E>Q		No	gnomAD
rs1411541330	150	M>L		No	gnomAD
rs750164772	151	Q>H		No	ExAC gnomAD
rs2063771917	158	S>T		No	TOPMed
rs2063772052	160	A>S		No	TOPMed
COSM471063	162	G>E	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs770536054	165	T>M		No	Ensembl
rs1451324956	166	R>C		No	gnomAD
rs1451324956	166	R>G		No	gnomAD
rs1186597974	166	R>H		No	gnomAD
rs2063772508	168	I>N		No	TOPMed
rs1466377939	170	P>S		No	gnomAD
rs770216524	172	V>I		No	ExAC gnomAD
rs778460459	173	M>L		No	ExAC gnomAD
COSM1301422	174	E>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1297530307	178	A>T		No	gnomAD
rs760205672	178	A>V		No	ExAC
COSM3401918	181	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs2063773281	184	Y>C		No	gnomAD
rs2063773220	184	Y>H		No	gnomAD
rs2063773220	184	Y>N		No	gnomAD
rs759552485	185	R>H		No	ExAC gnomAD
rs1310202149	187	G>D		No	gnomAD
rs1348912854	189	A>S		No	gnomAD
rs1348912854	189	A>T		No	gnomAD
rs866908578	192	M>I		No	Ensembl
rs549434240	192	M>L		No	1000Genomes ExAC TOPMed gnomAD
rs1242628158	192	M>T		No	TOPMed gnomAD
rs549434240	192	M>V		No	1000Genomes ExAC TOPMed gnomAD
rs1051823960	194	E>*		No	TOPMed
rs890109964	194	E>V		No	TOPMed
rs372947242	200	T>I		No	ESP ExAC TOPMed gnomAD
rs1481906626	202	G>R		No	TOPMed gnomAD
rs1483193519	204	G>W		No	TOPMed gnomAD
rs1567219233	207	G>R		No	Ensembl
rs780972244	209	V>M		No	ExAC gnomAD
rs745701299	210	M>L		No	ExAC gnomAD
rs1359726754	210	M>T		No	gnomAD
rs775362844	213	D>E		No	ExAC gnomAD
rs566346664	213	D>N		No	1000Genomes TOPMed gnomAD
rs1201384880	215	R>*		No	TOPMed gnomAD
rs997937990	215	R>Q		No	TOPMed gnomAD
rs768469694	218	K>E		No	ExAC gnomAD
rs774545610	218	K>R		No	ExAC TOPMed gnomAD
rs767820258 COSM3387055	220	A>T	Variant assessed as Somatic; MODERATE impact. pancreas [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated ExAC NCI-TCGA gnomAD
rs971393786	221	V>I		No	TOPMed gnomAD
rs971393786	221	V>L		No	TOPMed gnomAD
rs1412911111	225	K>R		No	TOPMed gnomAD
rs536570468	226	N>K		No	1000Genomes ExAC TOPMed gnomAD
rs1361275369	226	N>S		No	TOPMed gnomAD
rs2141826180	227	D>H		No	Ensembl
rs754136671 COSM1374569	228	A>T	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated ExAC NCI-TCGA gnomAD
TCGA novel	230	A>G	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs990229117	230	A>S		No	Ensembl
rs2063781168	231	Q>R		No	Ensembl
rs967190286	238	S>L		No	TOPMed gnomAD
COSM4056920	240	M>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1484195423	242	Q>K		No	gnomAD
rs1179929961	243	L>P		No	gnomAD
rs766840083	244	R>G		No	TOPMed gnomAD
rs765816002	244	R>Q		No	ExAC TOPMed gnomAD
rs766840083	244	R>W		No	TOPMed gnomAD
rs2063783990	245	H>R		No	Ensembl
rs2063784096	248	L>M		No	Ensembl
COSM195775 rs749945630	254	V>M	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	cosmic curated ExAC NCI-TCGA gnomAD
rs766534464	256	V>L		No	ExAC TOPMed gnomAD
rs766534464	256	V>M		No	ExAC TOPMed gnomAD
rs1448172830	260	G>S		No	gnomAD
COSM4056921 rs754759286	261	G>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ExAC NCI-TCGA gnomAD
rs2063784941	264	I>V		No	TOPMed
rs771931241	265	V>I		No	ExAC TOPMed gnomAD
rs777897715	266	T>A		No	ExAC TOPMed gnomAD
rs747080333	266	T>S		No	ExAC gnomAD
rs1443188273	269	M>L		No	gnomAD
rs771193750	269	M>R		No	ExAC
rs1235811612	272	G>=	Variant assessed as Somatic; LOW impact. [NCI-TCGA]	No	NCI-TCGA
rs1281649576	276	D>N		No	gnomAD
rs1352830580	279	R>L		No	gnomAD
rs1376088793	280	S>T		No	gnomAD
rs2063793113	283	R>Q		No	Ensembl
rs545332946	283	R>W		No	TOPMed
VAR_025203 rs34866753 RCV000885289	287	G>D		No	ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs749474606	288	G>E		No	ExAC gnomAD
rs780302906	288	G>R		No	ExAC TOPMed gnomAD
rs1242745809	290	C>S		No	TOPMed
rs1365027158	293	K>M		No	gnomAD
rs1450915839	295	S>L		No	gnomAD
rs756242690	298	V>I		No	ExAC
rs981252185	300	E>G		No	TOPMed gnomAD
COSM5434397 rs754118184	300	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ExAC NCI-TCGA TOPMed gnomAD
rs2063795991	307	G>D		No	Ensembl
rs2063796095	308	N>S		No	TOPMed
rs375481603	309	N>Y		No	ESP TOPMed gnomAD
rs779478770	311	V>L		No	ExAC TOPMed gnomAD
rs779478770	311	V>M		No	ExAC TOPMed gnomAD
rs1383516475	316	A>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs1312749029 COSM169366	318	R>C	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	cosmic curated NCI-TCGA gnomAD
rs1567219689 COSM1195509	318	R>H	lung [Cosmic]	No	cosmic curated Ensembl
COSM1374570	319	N>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
TCGA novel	321	L>P	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	321	L>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1194789965	326	N>S		No	gnomAD
rs1272128188	326	N>Y		No	TOPMed
rs774910976	327	V>M		No	ExAC TOPMed gnomAD
TCGA novel	329	K>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1385100717	332	D>N		No	gnomAD
rs2063797148	333	F>S		No	Ensembl
rs768298004	337	K>E		No	ExAC
rs1050199703	338	E>D		No	Ensembl
rs1450511331	339	A>V		No	gnomAD
rs2063797335	341	S>G		No	gnomAD
rs906627853	341	S>N		No	TOPMed gnomAD
rs767170810	345	T>M		No	ExAC TOPMed gnomAD
rs760464941	347	K>N		No	ExAC gnomAD
rs2141102593	349	P>S		No	Ensembl
rs1596373768	352	W>C		No	Ensembl
rs2063797723	353	T>A		No	Ensembl
rs2063797772	353	T>I		No	TOPMed
rs1596373772	354	A>D		No	Ensembl
TCGA novel	354	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1596373775	355	P>L		No	Ensembl
TCGA novel	361	K>E	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs759665126	369	V>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs1479570035	373	G>R		No	gnomAD
rs2063800661	375	L>F		No	TOPMed
rs2063800837	380	Y>C		No	Ensembl
rs1377869916	384	R>*		No	TOPMed
rs2063800924	390	I>T		No	TOPMed gnomAD
rs374867799 COSM332663	394	D>E	lung [Cosmic]	No	cosmic curated ESP ExAC TOPMed gnomAD
rs2063805934 TCGA novel	395	V>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA TOPMed
rs775372400	396	V>I		No	ExAC TOPMed gnomAD
COSM3672114 rs34616395	398	R>L	prostate [Cosmic]	No	cosmic curated 1000Genomes ExAC TOPMed gnomAD
COSM1640345 VAR_025204 rs34616395	398	R>Q	stomach [Cosmic]	No	cosmic curated UniProt 1000Genomes ExAC TOPMed dbSNP gnomAD
rs1247351581	398	R>W		No	TOPMed gnomAD
rs757645378	400	E>G		No	ExAC gnomAD
rs2063806328	400	E>Q		No	TOPMed
rs202236681	403	Y>C		No	ESP ExAC TOPMed gnomAD
rs202236681	403	Y>F		No	ESP ExAC TOPMed gnomAD
rs756556608	407	A>T		No	ExAC TOPMed gnomAD
rs778545309	407	A>V		No	ExAC TOPMed gnomAD
rs139316383	409	D>N		No	ESP TOPMed gnomAD
rs777268682	410	G>S		No	ExAC TOPMed gnomAD
rs746622803	412	P>L		No	ExAC gnomAD
rs775701272	414	A>S		No	ExAC TOPMed gnomAD
rs775701272	414	A>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs1048533928	416	Y>C		No	TOPMed gnomAD
rs1398367358	416	Y>D		No	TOPMed
rs1461438187	417	E>D		No	TOPMed
rs2063807315	417	E>K		No	TOPMed
rs1567219941	420	K>N		No	Ensembl
rs2141103933	424	H>Q		No	Ensembl
rs576918025	426	D>E		No	1000Genomes ExAC TOPMed gnomAD
rs149114083	427	A>T		No	1000Genomes ESP ExAC TOPMed gnomAD
rs1012429693	427	A>V		No	TOPMed gnomAD
rs147023686	428	A>T		No	1000Genomes ESP ExAC TOPMed gnomAD
rs761238167	429	M>I		No	ExAC gnomAD
rs1461844771	429	M>T		No	gnomAD
rs906788163	429	M>V		No	Ensembl
rs1596374084	430	R>W		No	Ensembl
COSM4056924	437	R>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1755941198	437	R>G		No	TOPMed
rs372255756	437	R>L		No	ESP TOPMed gnomAD
rs372255756	437	R>Q		No	ESP TOPMed gnomAD
rs1242489251	441	E>K		No	TOPMed gnomAD
VAR_025205 rs35556162	442	H>R		No	UniProt ExAC TOPMed dbSNP gnomAD
rs752299945	445	T>A		No	ExAC TOPMed gnomAD
rs752299945	445	T>P		No	ExAC TOPMed gnomAD
rs777296284	447	E>K		No	ExAC gnomAD
rs1567219983	447	E>V		No	Ensembl
rs1395950932	448	L>P		No	gnomAD
rs2063808793	449	H>P		No	Ensembl
TCGA novel	449	H>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs2063808900	450	L>P		No	Ensembl

No associated diseases with P41240

8 regional properties for P41240

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	195 - 449	IPR000719
domain	SH2 domain	80 - 171	IPR000980
domain	Serine-threonine/tyrosine-protein kinase, catalytic domain	195 - 440	IPR001245
domain	SH3 domain	9 - 70	IPR001452
active_site	Tyrosine-protein kinase, active site	310 - 322	IPR008266
binding_site	Protein kinase, ATP binding site	201 - 222	IPR017441
domain	Tyrosine-protein kinase, catalytic domain	195 - 440	IPR020635
domain	CSK-like, SH2 domain	78 - 175	IPR035027

Functions

		Description
EC Number	2.7.10.2	Protein-tyrosine kinases
Subcellular Localization	Cytoplasm Cell membrane	Mainly cytoplasmic, also present in lipid rafts
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

5 GO annotations of cellular component

Name	Definition
cell-cell junction	A cell junction that forms a connection between two or more cells of an organism; excludes direct cytoplasmic intercellular bridges, such as ring canals in insects.
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.
extracellular exosome	A vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane. Extracellular exosomes, also simply called exosomes, have a diameter of about 40-100 nm.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

9 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
identical protein binding	Binding to an identical protein or proteins.
metal ion binding	Binding to a metal ion.
non-membrane spanning protein tyrosine kinase activity	Catalysis of the reaction
proline-rich region binding	Binding to a proline-rich region, i.e. a region that contains a high proportion of proline residues, in a protein.
protein kinase A catalytic subunit binding	Binding to one or both of the catalytic subunits of protein kinase A.
protein phosphatase binding	Binding to a protein phosphatase.
protein tyrosine kinase activity	Catalysis of the reaction
protein tyrosine kinase binding	Binding to protein tyrosine kinase.

15 GO annotations of biological process

Name	Definition
adaptive immune response	An immune response mediated by cells expressing specific receptors for antigens produced through a somatic diversification process, and allowing for an enhanced secondary response to subsequent exposures to the same antigen (immunological memory).
adherens junction organization	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of an adherens junction. An adherens junction is a cell-cell junction composed of the epithelial cadherin-catenin complex at which the cytoplasmic face of the plasma membrane is attached to actin filaments.
cellular response to peptide hormone stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a peptide hormone stimulus. A peptide hormone is any of a class of peptides that are secreted into the blood stream and have endocrine functions in living animals.
negative regulation of bone resorption	Any process that stops, prevents, or reduces the frequency, rate or extent of bone resorption.
negative regulation of cell population proliferation	Any process that stops, prevents or reduces the rate or extent of cell proliferation.
negative regulation of ERK1 and ERK2 cascade	Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade.
negative regulation of Golgi to plasma membrane protein transport	Any process that stops, prevents, or reduces the frequency, rate or extent of the transport of proteins from the Golgi to the plasma membrane.
negative regulation of interleukin-6 production	Any process that stops, prevents, or reduces the frequency, rate, or extent of interleukin-6 production.
negative regulation of low-density lipoprotein particle clearance	Any process that decreases the rate, frequency or extent of low-density lipoprotein particle clearance. Low-density lipoprotein particle clearance is the process in which a low-density lipoprotein particle is removed from the blood via receptor-mediated endocytosis and its constituent parts degraded.
negative regulation of phagocytosis	Any process that stops, prevents, or reduces the frequency, rate or extent of phagocytosis.
oligodendrocyte differentiation	The process in which a relatively unspecialized cell acquires the specialized features of an oligodendrocyte. An oligodendrocyte is a type of glial cell involved in myelinating the axons of neurons in the central nervous system.
protein phosphorylation	The process of introducing a phosphate group on to a protein.
regulation of Fc receptor mediated stimulatory signaling pathway	Any process that modulates the rate, frequency or extent of the Fc receptor mediated stimulatory signaling pathway..
T cell costimulation	The process of providing, via surface-bound receptor-ligand pairs, a second, antigen-independent, signal in addition to that provided by the T cell receptor to augment T cell activation.
T cell receptor signaling pathway	The series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell.

88 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
A0JNB0	FYN	Tyrosine-protein kinase Fyn	Bos taurus (Bovine)	SS
Q3ZC95	BTK	Tyrosine-protein kinase	Bos taurus (Bovine)	EV SS
Q0VBZ0	CSK	Tyrosine-protein kinase CSK	Bos taurus (Bovine)	SS
P42683	LCK	Proto-oncogene tyrosine-protein kinase LCK	Gallus gallus (Chicken)	SS
P00523	SRC	Proto-oncogene tyrosine-protein kinase Src	Gallus gallus (Chicken)	EV
Q02977	YRK	Proto-oncogene tyrosine-protein kinase Yrk	Gallus gallus (Chicken)	SS
Q8JH64	BTK	Tyrosine-protein kinase BTK	Gallus gallus (Chicken)	SS
P09324	YES1	Tyrosine-protein kinase Yes	Gallus gallus (Chicken)	SS
Q05876	FYN	Tyrosine-protein kinase Fyn	Gallus gallus (Chicken)	SS
Q75R65	JAK2	Tyrosine-protein kinase JAK2	Gallus gallus (Chicken)	SS
P41239	CSK	Tyrosine-protein kinase CSK	Gallus gallus (Chicken)	SS
Q24592	hop	Tyrosine-protein kinase hopscotch	Drosophila melanogaster (Fruit fly)	PR
Q9V9J3	Src42A	Tyrosine-protein kinase Src42A	Drosophila melanogaster (Fruit fly)	SS
P00528	Src64B	Tyrosine-protein kinase Src64B	Drosophila melanogaster (Fruit fly)	SS
P08630	Btk	Tyrosine-protein kinase Btk	Drosophila melanogaster (Fruit fly)	SS
P23458	JAK1	Tyrosine-protein kinase JAK1	Homo sapiens (Human)	SS
O60674	JAK2	Tyrosine-protein kinase JAK2	Homo sapiens (Human)	EV
P52333	JAK3	Tyrosine-protein kinase JAK3	Homo sapiens (Human)	SS
P29597	TYK2	Non-receptor tyrosine-protein kinase TYK2	Homo sapiens (Human)	EV
P07947	YES1	Tyrosine-protein kinase Yes	Homo sapiens (Human)	SS
P09769	FGR	Tyrosine-protein kinase Fgr	Homo sapiens (Human)	SS
P42680	TEC	Tyrosine-protein kinase Tec	Homo sapiens (Human)	SS
P51451	BLK	Tyrosine-protein kinase Blk	Homo sapiens (Human)	SS
P51813	BMX	Cytoplasmic tyrosine-protein kinase BMX	Homo sapiens (Human)	SS
Q08881	ITK	Tyrosine-protein kinase ITK/TSK	Homo sapiens (Human)	EV
P43405	SYK	Tyrosine-protein kinase SYK	Homo sapiens (Human)	EV
P43403	ZAP70	Tyrosine-protein kinase ZAP-70	Homo sapiens (Human)	EV
Q13882	PTK6	Protein-tyrosine kinase 6	Homo sapiens (Human)	EV
P07948	LYN	Tyrosine-protein kinase Lyn	Homo sapiens (Human)	SS
P06241	FYN	Tyrosine-protein kinase Fyn	Homo sapiens (Human)	SS
P12931	SRC	Proto-oncogene tyrosine-protein kinase Src	Homo sapiens (Human)	EV
P06239	LCK	Tyrosine-protein kinase Lck	Homo sapiens (Human)	EV
P08631	HCK	Tyrosine-protein kinase HCK	Homo sapiens (Human)	EV
P42685	FRK	Tyrosine-protein kinase FRK	Homo sapiens (Human)	EV
Q06187	BTK	Tyrosine-protein kinase BTK	Homo sapiens (Human)	EV
P42679	MATK	Megakaryocyte-associated tyrosine-protein kinase	Homo sapiens (Human)	SS
Q14289	PTK2B	Protein-tyrosine kinase 2-beta	Homo sapiens (Human)	PR
Q05397	PTK2	Focal adhesion kinase 1	Homo sapiens (Human)	EV
Q13470	TNK1	Non-receptor tyrosine-protein kinase TNK1	Homo sapiens (Human)	PR
Q07912	TNK2	Activated CDC42 kinase 1	Homo sapiens (Human)	EV
P16591	FER	Tyrosine-protein kinase Fer	Homo sapiens (Human)	PR
Q6J9G0	STYK1	Tyrosine-protein kinase STYK1	Homo sapiens (Human)	PR
P42684	ABL2	Tyrosine-protein kinase ABL2	Homo sapiens (Human)	SS
P00519	ABL1	Tyrosine-protein kinase ABL1	Homo sapiens (Human)	EV
Q9R117	Tyk2	Non-receptor tyrosine-protein kinase TYK2	Mus musculus (Mouse)	SS
P08103	Hck	Tyrosine-protein kinase HCK	Mus musculus (Mouse)	SS
P16277	Blk	Tyrosine-protein kinase Blk	Mus musculus (Mouse)	SS
Q62270	Srms	Tyrosine-protein kinase Srms	Mus musculus (Mouse)	SS
Q64434	Ptk6	Protein-tyrosine kinase 6	Mus musculus (Mouse)	SS
P05480	Src	Proto-oncogene tyrosine-protein kinase Src	Mus musculus (Mouse)	EV
P14234	Fgr	Tyrosine-protein kinase Fgr	Mus musculus (Mouse)	SS
P35991	Btk	Tyrosine-protein kinase BTK	Mus musculus (Mouse)	EV
P25911	Lyn	Tyrosine-protein kinase Lyn	Mus musculus (Mouse)	EV
Q62137	Jak3	Tyrosine-protein kinase JAK3	Mus musculus (Mouse)	SS
Q62120	Jak2	Tyrosine-protein kinase JAK2	Mus musculus (Mouse)	EV
P06240	Lck	Proto-oncogene tyrosine-protein kinase LCK	Mus musculus (Mouse)	SS
P24604	Tec	Tyrosine-protein kinase Tec	Mus musculus (Mouse)	SS
Q04736	Yes1	Tyrosine-protein kinase Yes	Mus musculus (Mouse)	SS
P39688	Fyn	Tyrosine-protein kinase Fyn	Mus musculus (Mouse)	SS
P52332	Jak1	Tyrosine-protein kinase JAK1	Mus musculus (Mouse)	SS
Q03526	Itk	Tyrosine-protein kinase ITK/TSK	Mus musculus (Mouse)	SS
P41242	Matk	Megakaryocyte-associated tyrosine-protein kinase	Mus musculus (Mouse)	SS
Q922K9	Frk	Tyrosine-protein kinase FRK	Mus musculus (Mouse)	SS
P41241	Csk	Tyrosine-protein kinase CSK	Mus musculus (Mouse)	EV
A1Y2K1	FYN	Tyrosine-protein kinase Fyn	Sus scrofa (Pig)	SS
O19064	JAK2	Tyrosine-protein kinase JAK2	Sus scrofa (Pig)	SS
Q62662	Frk	Tyrosine-protein kinase FRK	Rattus norvegicus (Rat)	SS
Q62844	Fyn	Tyrosine-protein kinase Fyn	Rattus norvegicus (Rat)	SS
Q07014	Lyn	Tyrosine-protein kinase Lyn	Rattus norvegicus (Rat)	SS
P50545	Hck	Tyrosine-protein kinase HCK	Rattus norvegicus (Rat)	SS
Q9WUD9	Src	Proto-oncogene tyrosine-protein kinase Src	Rattus norvegicus (Rat)	SS
Q01621	Lck	Proto-oncogene tyrosine-protein kinase LCK	Rattus norvegicus (Rat)	SS
Q6P6U0	Fgr	Tyrosine-protein kinase Fgr	Rattus norvegicus (Rat)	SS
Q62689	Jak2	Tyrosine-protein kinase JAK2	Rattus norvegicus (Rat)	SS
Q63272	Jak3	Tyrosine-protein kinase JAK3	Rattus norvegicus (Rat)	SS
P41243	Matk	Megakaryocyte-associated tyrosine-protein kinase	Rattus norvegicus (Rat)	SS
F1LM93	Yes1	Tyrosine-protein kinase Yes	Rattus norvegicus (Rat)	SS
P32577	Csk	Tyrosine-protein kinase CSK	Rattus norvegicus (Rat)	SS
O45539	src-2	Tyrosine protein-kinase src-2	Caenorhabditis elegans	SS
G5EE56	src-1	Tyrosine protein-kinase src-1	Caenorhabditis elegans	SS
Q8I7I5	rol-3	Protein roller-3	Caenorhabditis elegans	PR
O16262	nipi-4	Protein nipi-4	Caenorhabditis elegans	PR
G5ECJ6	csk-1	Tyrosine-protein kinase csk-1	Caenorhabditis elegans	SS
A1A5H8	yes1	Tyrosine-protein kinase yes	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
F1RDG9	fynb	Tyrosine-protein kinase fynb	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
O12990	jak1	Tyrosine-protein kinase JAK1	Danio rerio (Zebrafish) (Brachydanio rerio)	PR
Q1JPZ3	src	Proto-oncogene tyrosine-protein kinase Src	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
Q6EWH2	fyna	Tyrosine-protein kinase fyna	Danio rerio (Zebrafish) (Brachydanio rerio)	SS

10	20	30	40	50	60
MSAIQAAWPS	GTECIAKYNF	HGTAEQDLPF	CKGDVLTIVA	VTKDPNWYKA	KNKVGREGII
70	80	90	100	110	120
PANYVQKREG	VKAGTKLSLM	PWFHGKITRE	QAERLLYPPE	TGLFLVREST	NYPGDYTLCV
130	140	150	160	170	180
SCDGKVEHYR	IMYHASKLSI	DEEVYFENLM	QLVEHYTSDA	DGLCTRLIKP	KVMEGTVAAQ
190	200	210	220	230	240
DEFYRSGWAL	NMKELKLLQT	IGKGEFGDVM	LGDYRGNKVA	VKCIKNDATA	QAFLAEASVM
250	260	270	280	290	300
TQLRHSNLVQ	LLGVIVEEKG	GLYIVTEYMA	KGSLVDYLRS	RGRSVLGGDC	LLKFSLDVCE
310	320	330	340	350	360
AMEYLEGNNF	VHRDLAARNV	LVSEDNVAKV	SDFGLTKEAS	STQDTGKLPV	KWTAPEALRE
370	380	390	400	410	420
KKFSTKSDVW	SFGILLWEIY	SFGRVPYPRI	PLKDVVPRVE	KGYKMDAPDG	CPPAVYEVMK
430	440
NCWHLDAAMR	PSFLQLREQL	EHIKTHELHL