AiPD: Autoinhibited Protein Database

P29350

Gene name	PTPN6 (HCP, PTP1C)
Protein name	Tyrosine-protein phosphatase non-receptor type 6
Names	Hematopoietic cell protein-tyrosine phosphatase, Protein-tyrosine phosphatase 1C, PTP-1C, Protein-tyrosine phosphatase SHP-1, SH-PTP1
Species	Homo sapiens (Human)
KEGG Pathway	hsa:5777
EC number	3.1.3.48: Phosphoric monoester hydrolases
Protein Class	TYROSINE-PROTEIN PHOSPHATASE CORKSCREW (PTHR46257)

Descriptions

PTPN6 is a Src homology 2 (SH2) domain-containing protein tyrosine phosphatase (PTPase). Its N-terminal SH2 domain autoinhibits the function of the kinase domain via intramolecular interaction. The N-SH2 domain blocks the active site of the PTPase domain (catalytic domain) in the closed conformation. Ligand binding to SH2 domains will cause conformational changes, resulting in the release of the N-SH2 domain from the PTPase domain. This will trigger the rotation of the C-SH2 domain, the repositioning of the N-SH2 domain, and consequent exposure of the active site of the catalytic domain.

Autoinhibitory domains (AIDs)

Target domain	253-518 (catalytic domain of tyrosine-protein phosphatase non-receptor type 6)
Relief mechanism	Ligand binding
Assay	Deletion assay, Structural analysis

AID

2-100 (N-terminal SH2 domain)

Target domain

253-518 (catalytic domain of tyrosine-protein phosphatase non-receptor type 6)

Relief mechanism

Ligand binding (Binding of pY ligands to N-SH2 domain)

Assay

Deletion assay, Structural analysis

Accessory elements

No accessory elements

References

Pei D et al. (1994) "Intramolecular regulation of protein tyrosine phosphatase SH-PTP1: a new function for Src homology 2 domains", Biochemistry, 33, 15483-93

Wang W et al. (2011) "Crystal structure of human protein tyrosine phosphatase SHP-1 in the open conformation", Journal of cellular biochemistry, 112, 2062-71

Autoinhibited structure

Activated structure

14 structures for P29350

Entry ID	Method	Resolution	Chain	Position	Source
1FPR	X-ray	250 A	A	243-526	PDB
1GWZ	X-ray	250 A	A	243-541	PDB
1X6C	NMR	-	A	110-214	PDB
2B3O	X-ray	280 A	A	1-532	PDB
2RMX	NMR	-	A	110-214	PDB
2YU7	NMR	-	A	110-214	PDB
3PS5	X-ray	310 A	A	1-595	PDB
4GRY	X-ray	170 A	A	243-528	PDB
4GRZ	X-ray	137 A	A	243-528	PDB
4GS0	X-ray	180 A	A/B	243-528	PDB
4HJP	X-ray	140 A	A	243-528	PDB
4HJQ	X-ray	180 A	A/B	243-528	PDB
6SM5	X-ray	275 A	A	100-214	PDB
AF-P29350-F1	Predicted				AlphaFoldDB

323 variants for P29350

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs1591683472 CA383747263	2	V>G		No	ClinGen Ensembl
CA383747329 rs1555147752	4	W>C		No	ClinGen gnomAD
COSM3739862 CA232442152 COSM3739863 rs769682837	7	R>Q	liver [Cosmic]	No	ClinGen cosmic curated Ensembl
rs1555147756 CA383747424	12	L>R		No	ClinGen gnomAD
CA6421460 rs782158849	15	E>K		No	ClinGen ExAC
rs782702822 CA6421461	16	T>N		No	ClinGen ExAC gnomAD
CA383747470 rs1555147762	17	L>V		No	ClinGen gnomAD
CA383747487 rs1555147765	19	K>E		No	ClinGen gnomAD
CA6421463 rs377003393	20	G>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs11547853 CA232442165	28	L>P		No	ClinGen Ensembl
CA6421466 rs782523221	33	R>C		No	ClinGen ExAC gnomAD
rs369614203 CA6421467	33	R>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs369614203 CA383747623	33	R>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1555147772 CA383747624	34	K>Q		No	ClinGen gnomAD
rs782452891 CA6421469	38	D>A		No	ClinGen ExAC TOPMed gnomAD
rs782042492 CA6421470	40	S>T		No	ClinGen 1000Genomes ExAC gnomAD
rs267603654 CA232442178	42	S>F		No	ClinGen Ensembl
rs377254990 CA6421472	43	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs1555147854 CA383747789	45	V>M		No	ClinGen gnomAD
rs782712760 CA6421508	46	G>W		No	ClinGen ExAC gnomAD
rs781820797 CA6421509	47	D>N		No	ClinGen ExAC TOPMed gnomAD
rs1555147857 CA383747878	53	R>Q		No	ClinGen gnomAD
rs370939978 COSM179634 CA6421510	53	R>W	large_intestine [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs1555147859 CA383747896	55	Q>*		No	ClinGen gnomAD
CA6421511 rs782618719	59	D>E		No	ClinGen ExAC gnomAD
CA6421513 rs782531361	70	A>E		No	ClinGen ExAC gnomAD
CA6421515 rs782204971	73	T>A		No	ClinGen ExAC gnomAD
rs782242482 CA6421518	80	T>A		No	ClinGen ExAC gnomAD
CA6421519 rs782393921	83	Q>R		No	ClinGen ExAC TOPMed gnomAD
rs1048597 CA232442300	86	L>V		No	ClinGen Ensembl
CA6421522 COSM3384601 COSM3384600 rs782163170	89	R>C	pancreas [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs782308449 CA6421523	89	R>H		No	ClinGen ExAC gnomAD
rs782302155 CA6421524	90	D>N		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
COSM3384603 COSM3384602 rs1555147881 CA383748279	91	G>D	pancreas [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1342222997 CA383748295	93	I>V		No	ClinGen TOPMed gnomAD
CA232442313 rs1028611737	99	P>A		No	ClinGen Ensembl
CA383748370 rs1555147885	99	P>L		No	ClinGen gnomAD
CA383748400 rs1555147887	102	C>S		No	ClinGen gnomAD
rs782804780 CA6421529	107	S>N		No	ClinGen ExAC gnomAD
CA383748669 rs1189982819	115	M>T		No	ClinGen TOPMed gnomAD
CA6421558 rs782645298	118	G>R		No	ClinGen ExAC gnomAD
rs1555148312 CA383748713	122	T>A		No	ClinGen gnomAD
rs201550362 CA6421559	122	T>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6421563 rs782364925	127	K>R		No	ClinGen ExAC TOPMed gnomAD
CA383748748 rs1555148318	128	G>S		No	ClinGen gnomAD
CA6421566 COSM1242731 rs782797143	132	T>M	oesophagus [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs782054048 CA6421568	135	V>G		No	ClinGen ExAC gnomAD
rs782710028 CA6421569	136	R>C		No	ClinGen ExAC gnomAD
rs1228369426 CA383748803	136	R>H		No	ClinGen TOPMed
CA6421570 rs781818617	139	L>P		No	ClinGen ExAC gnomAD
CA232443273 rs1048598	146	V>E		No	ClinGen Ensembl
rs782775329 CA6421572	153	Q>R		No	ClinGen ExAC gnomAD
rs781874476 CA6421573	154	P>H		No	ClinGen ExAC gnomAD
rs782700653 CA6421574	157	G>D		No	ClinGen 1000Genomes ExAC gnomAD
rs782700653 CA6421575	157	G>V		No	ClinGen 1000Genomes ExAC gnomAD
CA6421577 rs373750986	161	P>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1555148329 CA383748973	161	P>S		No	ClinGen gnomAD
CA6421580 rs782394570	163	R>G		No	ClinGen ExAC TOPMed gnomAD
rs369530834 CA6421581	163	R>K		No	ClinGen ESP ExAC TOPMed gnomAD
rs1555148338 CA383749010	166	H>Y		No	ClinGen gnomAD
CA6421582 rs782299688	170	M>T		No	ClinGen ExAC
rs1555148341 CA383749057	171	C>Y		No	ClinGen gnomAD
CA6421584 rs781941174	172	E>K		No	ClinGen ExAC gnomAD
rs1555148370 CA383749081	173	G>S		No	ClinGen gnomAD
CA383749089 rs1555148372	174	G>R		No	ClinGen gnomAD
CA232443452 rs781988918	175	R>C		No	ClinGen TOPMed gnomAD
CA383749102 rs1281119726	175	R>H		No	ClinGen TOPMed
rs970406672 CA232443456	182	E>K		No	ClinGen Ensembl
CA383749167 rs782304451	183	T>P		No	ClinGen ExAC TOPMed gnomAD
CA6421610 rs782304451	183	T>S		No	ClinGen ExAC TOPMed gnomAD
CA383749179 rs1565581803	184	F>S		No	ClinGen Ensembl
CA383749185 rs1591687142	185	D>A		No	ClinGen Ensembl
rs782079530 CA383749184	185	D>H		No	ClinGen ExAC gnomAD
rs782079530 CA6421612 COSM943094	185	D>N	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA383749207 rs368426352	188	T>K		No	ClinGen ESP ExAC TOPMed gnomAD
rs368426352 CA6421613	188	T>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs781875658 CA383749215	189	D>E		No	ClinGen ExAC gnomAD
CA6421614 rs781875658	189	D>E		No	ClinGen ExAC gnomAD
CA383749209 rs1555148380	189	D>N		No	ClinGen Ensembl
rs1555148382 CA383749217	190	L>V		No	ClinGen gnomAD
CA383749237 rs1555148387	193	H>Y		No	ClinGen gnomAD
rs782576858 CA6421616	197	T>M		No	ClinGen 1000Genomes ExAC gnomAD
CA383749294 rs1555148393	201	E>Q		No	ClinGen gnomAD
CA383749316 rs1555148396	204	G>D		No	ClinGen gnomAD
rs1555148401 CA383749320	205	A>D		No	ClinGen gnomAD
CA6421620 rs375296528	205	A>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs375296528 CA6421619	205	A>T		No	ClinGen ESP ExAC TOPMed gnomAD
CA383749322 rs1555148401	205	A>V		No	ClinGen gnomAD
CA383749330 rs1469972531	206	F>L		No	ClinGen TOPMed
CA383749324 rs1555148406	206	F>L		No	ClinGen gnomAD
rs1159545254 CA383749326	206	F>Y		No	ClinGen TOPMed
CA6421622 rs367551491 COSM179638	210	R>Q	large_intestine [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs973281293 CA232443499	210	R>W		No	ClinGen TOPMed gnomAD
CA383749377 rs1555148454	212	P>L		No	ClinGen gnomAD
rs1555148455 CA383749387	214	Y>H		No	ClinGen gnomAD
rs1591687479 CA383749415	218	V>G		No	ClinGen Ensembl
CA6421644 rs782524619	218	V>M		No	ClinGen ExAC gnomAD
CA383749429 rs1212719021	220	A>V		No	ClinGen TOPMed gnomAD
CA6421646 rs782302331	223	I>T		No	ClinGen ExAC gnomAD
CA6421647 rs201345298	225	N>K		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs781935337 CA383749469	226	R>P		No	ClinGen ExAC gnomAD
CA6421648 rs781935337	226	R>Q		No	ClinGen ExAC gnomAD
rs782212727 CA6421649	231	N>D		No	ClinGen ExAC gnomAD
CA383749526 rs1340881647	234	Q>H		No	ClinGen TOPMed gnomAD
CA383749538 rs1270207675	236	S>A		No	ClinGen TOPMed gnomAD
CA6421650 rs782356549	236	S>F		No	ClinGen ExAC gnomAD
rs1315244865 CA383749545	237	E>D		No	ClinGen TOPMed
CA6421652 rs782130684	237	E>K		No	ClinGen ExAC TOPMed gnomAD
CA6421653 rs782130684	237	E>Q		No	ClinGen ExAC TOPMed gnomAD
CA383749549 rs1555148481	238	D>Y		No	ClinGen gnomAD
CA6421655 rs782045447	240	A>V		No	ClinGen ExAC gnomAD
rs1555148485 CA383749570	241	K>R		No	ClinGen gnomAD
rs1555148488 CA383749586	244	F>I		No	ClinGen gnomAD
CA383749600 rs1555148490	245	W>*		No	ClinGen gnomAD
rs781816472 CA6421657	246	E>D		No	ClinGen ExAC gnomAD
CA6421678 rs782819686	259	L>S		No	ClinGen ExAC gnomAD
rs1591687896 CA383749786	260	H>P		No	ClinGen Ensembl
CA383749790 rs1555148535	260	H>Q		No	ClinGen gnomAD
CA383749792 rs1555148535	260	H>Q		No	ClinGen gnomAD
rs1555148529 CA383749785	260	H>Y		No	ClinGen gnomAD
rs761631984 CA232443808	262	R>H		No	ClinGen gnomAD
rs781848123 CA383749863	267	R>L		No	ClinGen ExAC TOPMed gnomAD
rs781848123 CA6421682	267	R>P		No	ClinGen ExAC TOPMed gnomAD
CA383749861 rs781848123	267	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs1555148541 CA383749860	267	R>W		No	ClinGen gnomAD
CA6421684 rs782637799	269	E>Q		No	ClinGen ExAC gnomAD
CA383750071 rs1555148620	283	D>N		No	ClinGen gnomAD
CA383750091 rs1371026118	284	H>R		No	ClinGen TOPMed
rs1555148621 CA383750087	284	H>Y		No	ClinGen gnomAD
rs1323488790 CA383750113	286	R>Q		No	ClinGen TOPMed
CA232443973 rs56111095	287	V>M		No	ClinGen Ensembl
CA383750166 rs1387683991	292	R>Q		No	ClinGen TOPMed gnomAD
rs782600635 CA6421705	292	R>W		No	ClinGen ExAC gnomAD
rs782502543 CA6421707	293	D>G		No	ClinGen ExAC TOPMed gnomAD
rs1378668798 CA383750182	294	S>G		No	ClinGen TOPMed gnomAD
rs782646307 CA6421708	296	I>F		No	ClinGen ExAC gnomAD
CA6421712 rs782595592	298	G>R		No	ClinGen ExAC gnomAD
rs782595592 CA6421711	298	G>W		No	ClinGen ExAC gnomAD
rs754255009 CA232443997	300	D>N		No	ClinGen Ensembl
rs1555148653 CA383750300	305	N>S		No	ClinGen gnomAD
CA383750319 rs1252389772	307	I>V		No	ClinGen TOPMed
rs1555148694 CA383750389	310	Q>K		No	ClinGen gnomAD
rs1555148695 CA383750396	310	Q>R		No	ClinGen gnomAD
rs1555148696 CA383750425	313	G>D		No	ClinGen Ensembl
CA383750433 rs1555148698	314	P>A		No	ClinGen gnomAD
CA383750434 rs1555148698	314	P>S		No	ClinGen gnomAD
CA383750456 rs1198645982	316	E>K		No	ClinGen TOPMed
CA6421736 rs782211008	318	A>T		No	ClinGen 1000Genomes ExAC gnomAD
CA383750485 rs1555148704	318	A>V		No	ClinGen gnomAD
CA383750500 rs1591689003	320	T>P		No	ClinGen Ensembl
rs782127411 CA6421739	322	I>L		No	ClinGen ExAC gnomAD
rs1555148710 CA383750532	323	A>T		No	ClinGen gnomAD
rs781923789 CA6421741	325	Q>H		No	ClinGen ExAC gnomAD
CA6421746 rs199933225	332	V>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs782547213 CA6421748	339	A>T		No	ClinGen ExAC TOPMed gnomAD
rs201976465 CA6421749	339	A>V		No	ClinGen ExAC TOPMed gnomAD
rs782608469 CA383750738	341	Q>P		No	ClinGen ExAC gnomAD
rs782608469 CA6421752	341	Q>R		No	ClinGen ExAC gnomAD
CA383750746 rs1591689121	342	E>G		No	ClinGen Ensembl
rs369337036 CA6421753	345	R>C		No	ClinGen 1000Genomes ESP ExAC gnomAD
rs1470957233 CA383750773	345	R>H		No	ClinGen TOPMed gnomAD
rs879984166 CA383750780	346	V>I		No	ClinGen Ensembl
rs782671210 CA6421755	348	V>A		No	ClinGen ExAC gnomAD
CA383750801 rs1177433416	348	V>I		No	ClinGen TOPMed gnomAD
CA6421756 rs782187261	350	T>N		No	ClinGen ExAC gnomAD
rs923201462 CA232444147	352	R>Q		No	ClinGen TOPMed gnomAD
rs1555148751 CA383750905	358	R>Q		No	ClinGen gnomAD
CA383751190 rs1555148933	359	N>K		No	ClinGen gnomAD
rs1555148930 CA383751186	359	N>S		No	ClinGen gnomAD
CA6421786 rs781941676	360	K>R		No	ClinGen ExAC gnomAD
CA383751199 rs1555148935	361	C>S		No	ClinGen gnomAD
CA6421788 rs782761798	362	V>I		No	ClinGen ExAC TOPMed gnomAD
rs1177506427 CA383751212	363	P>T		No	ClinGen TOPMed
CA383751228 rs1555148944	365	W>R		No	ClinGen gnomAD
CA232444495 rs959921236	367	E>A		No	ClinGen Ensembl
COSM1512879 CA6421790 rs377517197	367	E>K	lung [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs377517197 CA6421791	367	E>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs781806998 CA6421792	368	V>M		No	ClinGen ExAC gnomAD
CA6421795 rs370538000	372	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs370538000 CA6421794	372	R>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs782528840 CA6421796	372	R>H		No	ClinGen ExAC TOPMed gnomAD
rs782674280 CA6421797	377	Y>C		No	ClinGen ExAC gnomAD
CA383751333 rs1484282642	381	N>S		No	ClinGen TOPMed
rs782455819 CA6421799	383	G>R		No	ClinGen ExAC TOPMed gnomAD
rs1555148958 CA383751355	384	E>D		No	ClinGen gnomAD
rs782570503 CA6421800	385	H>R		No	ClinGen ExAC gnomAD
CA383751368 rs1555148961	386	D>G		No	ClinGen gnomAD
rs376886181 CA6421803	389	E>A		No	ClinGen ESP ExAC TOPMed gnomAD
rs782346134 CA6421802	389	E>K		No	ClinGen ExAC TOPMed gnomAD
CA6421804 rs782262226	390	Y>H		No	ClinGen ExAC gnomAD
rs782405424 CA6421805	392	L>V		No	ClinGen ExAC TOPMed gnomAD
CA6421806 COSM549666 rs782031352	393	R>C	lung [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs782044132 CA6421807	393	R>H		No	ClinGen ExAC gnomAD
rs1555148971 CA383751428	396	Q>E		No	ClinGen gnomAD
rs1555148971 CA383751427	396	Q>K		No	ClinGen gnomAD
CA6421808 rs782746802	398	S>C		No	ClinGen ExAC gnomAD
CA6421809 rs781971151	399	P>L		No	ClinGen ExAC TOPMed gnomAD
rs1302893456 CA383751461	401	D>G		No	ClinGen TOPMed
CA383751501 rs1249604029	405	L>P		No	ClinGen TOPMed gnomAD
CA383751500 rs1249604029	405	L>Q		No	ClinGen TOPMed gnomAD
rs782681772 CA6421844	405	L>V		No	ClinGen ExAC gnomAD
rs781934308 CA232444621	406	I>M		No	ClinGen Ensembl
CA383751511 rs1489313099	407	R>Q		No	ClinGen TOPMed
rs1555149024 CA383751623	422	V>A		No	ClinGen gnomAD
rs781949874 CA6421848	424	S>N		No	ClinGen ExAC gnomAD
rs1555149029 CA383751658	427	G>A		No	ClinGen gnomAD
CA6421850 rs782368432	428	G>S		No	ClinGen ExAC gnomAD
CA6421851 rs781994700	428	G>V		No	ClinGen ExAC TOPMed gnomAD
rs782142224 CA6421852	429	V>I		No	ClinGen ExAC gnomAD
rs1356734316 CA383751708	435	Q>R		No	ClinGen TOPMed gnomAD
rs1555149035 CA383751725	437	N>K		No	ClinGen gnomAD
CA6421854 rs374365975	438	Q>H		No	ClinGen ESP ExAC TOPMed gnomAD
CA383751731 rs1555149037	438	Q>R		No	ClinGen gnomAD
CA6421856 rs782749360	439	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA6421855 rs782065208	439	R>W		No	ClinGen ExAC gnomAD
rs200005925 CA6421858	441	E>G		No	ClinGen ExAC TOPMed gnomAD
rs781860095 CA6421857	441	E>K		No	ClinGen ExAC gnomAD
rs1305426435 CA383751751	442	S>C		No	ClinGen TOPMed
rs1591690821 CA383751758	442	S>R		No	ClinGen Ensembl
CA383751762 rs1565583883	443	L>P		No	ClinGen Ensembl
CA6421859 rs368398907	443	L>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA6421861 rs782437067	444	P>S		No	ClinGen ExAC gnomAD
rs782216134 CA383751776	446	A>P		No	ClinGen ExAC TOPMed gnomAD
CA6421864 rs782216134	446	A>S		No	ClinGen ExAC TOPMed gnomAD
rs782216134 CA6421863	446	A>T		No	ClinGen ExAC TOPMed gnomAD
rs782625225 CA6421865	446	A>V		No	ClinGen ExAC gnomAD
CA6421867 rs782404245	448	P>A		No	ClinGen ExAC gnomAD
rs782028376 CA6421868	449	I>T		No	ClinGen ExAC gnomAD
CA383751797 rs1555149058	450	I>V		No	ClinGen gnomAD
rs62621988 CA6421870	451	V>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6421869 rs62621988	451	V>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1363181410 CA383751826	454	S>N		No	ClinGen TOPMed
rs1435682678 CA383751847	455	A>S		No	ClinGen TOPMed
rs1435682678 CA383751849	455	A>T		No	ClinGen TOPMed
rs1555149392 CA383751856	456	G>D		No	ClinGen gnomAD
rs782000132 CA6421888	457	I>V		No	ClinGen ExAC gnomAD
rs1591692944 CA383751875	459	R>P		No	ClinGen Ensembl
rs926689109 CA232447716	466	I>S		No	ClinGen Ensembl
rs376994439 CA6421892	467	D>N		No	ClinGen ESP ExAC TOPMed gnomAD
rs1565584932 CA383751938	469	L>V		No	ClinGen Ensembl
rs1591693004 CA383751976	474	S>P		No	ClinGen Ensembl
CA6421893 rs782729581	475	T>A		No	ClinGen ExAC gnomAD
rs1171574303 CA383751990	476	K>R		No	ClinGen TOPMed gnomAD
CA383752097 rs1555149453	489	Q>L		No	ClinGen gnomAD
rs1555149453 CA383752096	489	Q>R		No	ClinGen gnomAD
rs1272459641 COSM943098 CA383752124	493	A>V	endometrium [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
rs1356852472 CA383752137	495	R>H		No	ClinGen TOPMed gnomAD
CA383752145 rs1283407292	496	S>L		No	ClinGen TOPMed gnomAD
CA232447860 rs782414151	501	T>M		No	ClinGen Ensembl
CA6421932 rs185835888	503	A>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA383752216 rs1555149474	506	K>N		No	ClinGen gnomAD
CA6421933 rs782252503	507	F>L		No	ClinGen ExAC
CA6421936 rs782170877	510	V>M		No	ClinGen ExAC TOPMed gnomAD
rs1471321885 CA383752272	515	F>L		No	ClinGen TOPMed gnomAD
rs1555149485 CA383752283	516	I>T		No	ClinGen gnomAD
CA6421938 rs781952099	519	T>I		No	ClinGen ExAC gnomAD
CA383752342 rs1555149492	525	V>I		No	ClinGen gnomAD
CA383752348 rs1555149495	526	L>M		No	ClinGen gnomAD
COSM1263370 rs200635165 CA6422009	528	S>L	oesophagus [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs200635165 CA383752378	528	S>W		No	ClinGen ExAC TOPMed gnomAD
rs1555149599 CA383752381	529	Q>*		No	ClinGen gnomAD
CA383752394 rs1555149602	530	K>N		No	ClinGen gnomAD
CA383752425 rs1591693786	534	S>A		No	ClinGen Ensembl
rs782688576 CA6422011	534	S>L		No	ClinGen ExAC TOPMed gnomAD
rs1591693786 CA383752429	534	S>P		No	ClinGen Ensembl
CA383752458 rs1555149614	536	Y>C		No	ClinGen gnomAD
rs1009148404 CA232448104	536	Y>H		No	ClinGen gnomAD
CA6422016 rs782494259	540	T>I		No	ClinGen ExAC gnomAD
CA383752505 rs782494259	540	T>S		No	ClinGen ExAC gnomAD
CA383752526 rs1370018915	542	P>S		No	ClinGen TOPMed
CA383752539 rs1307380937	543	P>Q		No	ClinGen TOPMed
rs1555149629 CA383752547	544	A>P		No	ClinGen gnomAD
rs782265270 CA6422018	545	M>R		No	ClinGen ExAC TOPMed gnomAD
rs782265270 CA383752561	545	M>T		No	ClinGen ExAC TOPMed gnomAD
CA383752558 rs1555149633	545	M>V		No	ClinGen gnomAD
rs782487049 CA232448119	546	K>R		No	ClinGen gnomAD
rs1555149641 CA383752606	548	A>V		No	ClinGen gnomAD
CA6422019 rs782555031	551	K>E		No	ClinGen ExAC gnomAD
CA6422020 rs782253557	552	A>P		No	ClinGen ExAC gnomAD
rs782253557 CA383752645	552	A>S		No	ClinGen ExAC gnomAD
CA232448127 rs782253557	552	A>T		No	ClinGen ExAC gnomAD
CA6422021 rs200155138	553	S>F		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
COSM179640 rs782599498 CA6422023	554	R>C	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA6422024 rs782226517	554	R>H		No	ClinGen ExAC TOPMed gnomAD
CA383752669 rs782226517	554	R>P		No	ClinGen ExAC TOPMed gnomAD
rs1591693916 CA383752680	555	T>I		No	ClinGen Ensembl
CA6422025 rs782366247	556	S>L		No	ClinGen ExAC TOPMed gnomAD
rs1555149653 CA383752709	558	K>R		No	ClinGen gnomAD
CA383752708 rs1555149653	558	K>T		No	ClinGen gnomAD
CA383753277 rs1555149806	559	H>R		No	ClinGen gnomAD
rs1270713882 CA383753300	560	K>N		No	ClinGen TOPMed gnomAD
rs781928397 CA6422068	560	K>R		No	ClinGen ExAC TOPMed gnomAD
rs1555149810 CA383753314	561	E>D		No	ClinGen gnomAD
CA383753302 rs1591694546	561	E>K		No	ClinGen Ensembl
CA383753364 rs1555149814	564	Y>*		No	ClinGen gnomAD
rs782332287 CA6422070	567	L>M		No	ClinGen ExAC
CA6422072 rs782106910	568	H>P		No	ClinGen ExAC
rs1555149821 CA383753405	568	H>Q		No	ClinGen gnomAD
rs375291511 CA6422071	568	H>Y		No	ClinGen ESP ExAC TOPMed gnomAD
rs1231052417 CA383753410	569	T>A		No	ClinGen TOPMed gnomAD
CA232448409 rs782460041	571	N>D		No	ClinGen Ensembl
CA232448412 rs978237552	572	K>R		No	ClinGen TOPMed
CA383753437 rs978237552	572	K>T		No	ClinGen TOPMed
rs1555149837 CA383753443	573	R>G		No	ClinGen gnomAD
CA383753458 rs1555149838	574	E>D		No	ClinGen gnomAD
rs1288467058 CA383753469	576	K>E		No	ClinGen TOPMed
CA383753477 rs1555149841	577	V>M		No	ClinGen gnomAD
CA6422073 rs782777814	580	Q>K		No	ClinGen ExAC TOPMed gnomAD
CA6422075 rs782167753	581	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs782020090 CA6422074	581	R>W		No	ClinGen ExAC gnomAD
rs1326097283 CA383753514	582	S>L		No	ClinGen TOPMed gnomAD
CA6422079 rs367563603	585	K>E		No	ClinGen ESP ExAC TOPMed
rs1555149852 CA383753534	585	K>R		No	ClinGen gnomAD
CA383753558 rs1390422023	587	K>E		No	ClinGen TOPMed
rs1163107482 CA383753567	587	K>N		No	ClinGen TOPMed
CA383753573 rs1555149856	588	S>G		No	ClinGen gnomAD
CA383753577 rs1555149857	588	S>N		No	ClinGen gnomAD
CA6422082 rs781866962	590	G>S		No	ClinGen ExAC TOPMed gnomAD
CA383753629 rs1555149861	591	S>F		No	ClinGen gnomAD
CA6422083 rs782532946	592	L>F		No	ClinGen ExAC gnomAD
rs782676287 CA383753652	593	K>N		No	ClinGen ExAC TOPMed gnomAD
rs1468613421 CA383753663	594	R>S		No	ClinGen TOPMed gnomAD
rs1555149866 CA383753668	595	K>E		No	ClinGen gnomAD

No associated diseases with P29350

6 regional properties for P29350

Type	Name	Position	InterPro Accession
domain	Tyrosine-specific protein phosphatase, PTPase domain	243 - 517	IPR000242
domain	Tyrosine-specific protein phosphatases domain	430 - 506	IPR000387
domain	SH2 domain	2 - 100	IPR000980-1
domain	SH2 domain	108 - 213	IPR000980-2
domain	Protein-tyrosine phosphatase, catalytic	408 - 514	IPR003595
active_site	Protein-tyrosine phosphatase, active site	451 - 461	IPR016130

Functions

		Description
EC Number	3.1.3.48	Phosphoric monoester hydrolases
Subcellular Localization	Cytoplasm Nucleus	In neurons, translocates into the nucleus after treatment with angiotensin II (By similarity) Shuttles between the cytoplasm and nucleus via its association with PDPK1
PANTHER Family	PTHR46257	TYROSINE-PROTEIN PHOSPHATASE CORKSCREW
PANTHER Subfamily	PTHR46257:SF4	TYROSINE-PROTEIN PHOSPHATASE NON-RECEPTOR TYPE 6
PANTHER Protein Class	protein phosphatase protein modifying enzyme
PANTHER Pathway Category	B cell activation SHP-1 FGF signaling pathway SHP2 Angiogenesis SHP2 Interferon-gamma signaling pathway PTP

13 GO annotations of cellular component

Name	Definition
alpha-beta T cell receptor complex	A T cell receptor complex in which the TCR heterodimer comprises alpha and beta chains, associated with the CD3 complex; recognizes a complex consisting of an antigen-derived peptide bound to a class I or class II MHC protein.
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.
extracellular region	The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite.
membrane	A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.
nucleolus	A small, dense body one or more of which are present in the nucleus of eukaryotic cells. It is rich in RNA and protein, is not bounded by a limiting membrane, and is not seen during mitosis. Its prime function is the transcription of the nucleolar DNA into 45S ribosomal-precursor RNA, the processing of this RNA into 5.8S, 18S, and 28S components of ribosomal RNA, and the association of these components with 5S RNA and proteins synthesized outside the nucleolus. This association results in the formation of ribonucleoprotein precursors; these pass into the cytoplasm and mature into the 40S and 60S subunits of the ribosome.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
protein-containing complex	A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.
specific granule lumen	The volume enclosed by the membrane of a specific granule, a granule with a membranous, tubular internal structure, found primarily in mature neutrophil cells. Most are released into the extracellular fluid. Specific granules contain lactoferrin, lysozyme, vitamin B12 binding protein and elastase.
tertiary granule lumen	Any membrane-enclosed lumen that is part of a tertiary granule.

8 GO annotations of molecular function

Name	Definition
cell adhesion molecule binding	Binding to a cell adhesion molecule.
phosphorylation-dependent protein binding	Binding to a protein upon phosphorylation of the target protein.
phosphotyrosine residue binding	Binding to a phosphorylated tyrosine residue within a protein.
protein kinase binding	Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
protein tyrosine phosphatase activity	Catalysis of the reaction: protein tyrosine phosphate + H2O = protein tyrosine + phosphate.
SH2 domain binding	Binding to a SH2 domain (Src homology 2) of a protein, a protein domain of about 100 amino-acid residues and belonging to the alpha + beta domain class.
SH3 domain binding	Binding to a SH3 domain (Src homology 3) of a protein, small protein modules containing approximately 50 amino acid residues found in a great variety of intracellular or membrane-associated proteins.
transmembrane receptor protein tyrosine phosphatase activity	Combining with a signal and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity by catalysis of the reaction: protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

34 GO annotations of biological process

Name	Definition
abortive mitotic cell cycle	A cell cycle in which mitosis is begun and progresses normally through the end of anaphase, but not completed, resulting in a cell with increased ploidy.
B cell receptor signaling pathway	The series of molecular signals initiated by the cross-linking of an antigen receptor on a B cell.
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.
cytokine-mediated signaling pathway	The series of molecular signals initiated by the binding of a cytokine to a receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
epididymis development	The process whose specific outcome is the progression of an epididymis over time, from its formation to the mature structure.
G protein-coupled receptor signaling pathway	The series of molecular signals initiated by a ligand binding to its receptor, in which the activated receptor promotes the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The GTP-bound activated alpha-G-protein then dissociates from the beta- and gamma-subunits to further transmit the signal within the cell. The pathway begins with receptor-ligand interaction, and ends with regulation of a downstream cellular process. The pathway can start from the plasma membrane, Golgi or nuclear membrane.
hematopoietic progenitor cell differentiation	The process in which precursor cell type acquires the specialized features of a hematopoietic progenitor cell, a class of cell types including myeloid progenitor cells and lymphoid progenitor cells.
intracellular signal transduction	The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
megakaryocyte development	The process whose specific outcome is the progression of a megakaryocyte cell over time, from its formation to the mature structure. Megakaryocyte development does not include the steps involved in committing a cell to a megakaryocyte fate. A megakaryocyte is a giant cell 50 to 100 micron in diameter, with a greatly lobulated nucleus, found in the bone marrow.
natural killer cell mediated cytotoxicity	The directed killing of a target cell by a natural killer cell through the release of granules containing cytotoxic mediators or through the engagement of death receptors.
negative regulation of cell population proliferation	Any process that stops, prevents or reduces the rate or extent of cell proliferation.
negative regulation of humoral immune response mediated by circulating immunoglobulin	Any process that stops, prevents, or reduces the frequency, rate, or extent of a humoral immune response mediated by circulating immunoglobulin.
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 MAP kinase activity	Any process that stops, prevents, or reduces the frequency, rate or extent of MAP kinase activity.
negative regulation of mast cell activation involved in immune response	Any process that stops, prevents, or reduces the frequency, rate, or extent of mast cell activation as part of an immune response.
negative regulation of peptidyl-tyrosine phosphorylation	Any process that stops, prevents, or reduces the frequency, rate or extent of the phosphorylation of peptidyl-tyrosine.
negative regulation of T cell proliferation	Any process that stops, prevents or reduces the rate or extent of T cell proliferation.
negative regulation of T cell receptor signaling pathway	Any process that stops, prevents, or reduces the frequency, rate or extent of signaling pathways initiated by the cross-linking of an antigen receptor on a T cell.
negative regulation of tumor necrosis factor production	Any process that stops, prevents, or reduces the frequency, rate, or extent of tumor necrosis factor production.
peptidyl-tyrosine dephosphorylation	The removal of phosphoric residues from peptidyl-O-phospho-tyrosine to form peptidyl-tyrosine.
peptidyl-tyrosine phosphorylation	The phosphorylation of peptidyl-tyrosine to form peptidyl-O4'-phospho-L-tyrosine.
platelet aggregation	The adhesion of one platelet to one or more other platelets via adhesion molecules.
platelet formation	The process in which platelets bud from long processes extended by megakaryocytes.
positive regulation of cell adhesion mediated by integrin	Any process that activates or increases the frequency, rate, or extent of cell adhesion mediated by integrin.
positive regulation of cell population proliferation	Any process that activates or increases the rate or extent of cell proliferation.
positive regulation of phosphatidylinositol 3-kinase signaling	Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the phosphatidylinositol 3-kinase cascade.
protein dephosphorylation	The process of removing one or more phosphoric residues from a protein.
regulation of apoptotic process	Any process that modulates the occurrence or rate of cell death by apoptotic process.
regulation of B cell differentiation	Any process that modulates the frequency, rate or extent of B cell differentiation.
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 G1/S transition of mitotic cell cycle	Any signalling pathway that modulates the activity of a cell cycle cyclin-dependent protein kinase to modulate the switch from G1 phase to S phase of the mitotic cell cycle.
regulation of release of sequestered calcium ion into cytosol	Any process that modulates the frequency, rate or extent of the release into the cytosolic compartment of calcium ions sequestered in the endoplasmic reticulum or mitochondria.
regulation of type I interferon-mediated signaling pathway	Any process that modulates the rate, frequency or extent of a type I interferon-mediated 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.

7 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q90687	PTPN11	Tyrosine-protein phosphatase non-receptor type 11	Gallus gallus (Chicken)	SS
Q06124	PTPN11	Tyrosine-protein phosphatase non-receptor type 11	Homo sapiens (Human)	EV
P35235	Ptpn11	Tyrosine-protein phosphatase non-receptor type 11	Mus musculus (Mouse)	SS
P29351	Ptpn6	Tyrosine-protein phosphatase non-receptor type 6	Mus musculus (Mouse)	SS
P41499	Ptpn11	Tyrosine-protein phosphatase non-receptor type 11	Rattus norvegicus (Rat)	SS
P81718	Ptpn6	Tyrosine-protein phosphatase non-receptor type 6	Rattus norvegicus (Rat)	SS
G5EC24	ptp-2	Tyrosine-protein phosphatase non-receptor type ptp-2	Caenorhabditis elegans	SS

10	20	30	40	50	60
MVRWFHRDLS	GLDAETLLKG	RGVHGSFLAR	PSRKNQGDFS	LSVRVGDQVT	HIRIQNSGDF
70	80	90	100	110	120
YDLYGGEKFA	TLTELVEYYT	QQQGVLQDRD	GTIIHLKYPL	NCSDPTSERW	YHGHMSGGQA
130	140	150	160	170	180
ETLLQAKGEP	WTFLVRESLS	QPGDFVLSVL	SDQPKAGPGS	PLRVTHIKVM	CEGGRYTVGG
190	200	210	220	230	240
LETFDSLTDL	VEHFKKTGIE	EASGAFVYLR	QPYYATRVNA	ADIENRVLEL	NKKQESEDTA
250	260	270	280	290	300
KAGFWEEFES	LQKQEVKNLH	QRLEGQRPEN	KGKNRYKNIL	PFDHSRVILQ	GRDSNIPGSD
310	320	330	340	350	360
YINANYIKNQ	LLGPDENAKT	YIASQGCLEA	TVNDFWQMAW	QENSRVIVMT	TREVEKGRNK
370	380	390	400	410	420
CVPYWPEVGM	QRAYGPYSVT	NCGEHDTTEY	KLRTLQVSPL	DNGDLIREIW	HYQYLSWPDH
430	440	450	460	470	480
GVPSEPGGVL	SFLDQINQRQ	ESLPHAGPII	VHCSAGIGRT	GTIIVIDMLM	ENISTKGLDC
490	500	510	520	530	540
DIDIQKTIQM	VRAQRSGMVQ	TEAQYKFIYV	AIAQFIETTK	KKLEVLQSQK	GQESEYGNIT
550	560	570	580	590
YPPAMKNAHA	KASRTSSKHK	EDVYENLHTK	NKREEKVKKQ	RSADKEKSKG	SLKRK