{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P29350","secondaryAccessions":["A8K306","G3V0F8","Q969V8","Q9UK67"],"uniProtkbId":"PTN6_HUMAN","entryAudit":{"firstPublicDate":"1992-12-01","lastAnnotationUpdateDate":"2026-11-04","lastSequenceUpdateDate":"1992-12-01","entryVersion":261,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Tyrosine-protein phosphatase non-receptor type 6"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29925997"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38532423"}],"value":"3.1.3.48"}]},"alternativeNames":[{"fullName":{"value":"Hematopoietic cell protein-tyrosine phosphatase"}},{"fullName":{"value":"Protein-tyrosine phosphatase 1C"},"shortNames":[{"value":"PTP-1C"}]},{"fullName":{"value":"Protein-tyrosine phosphatase SHP-1"}},{"fullName":{"value":"SH-PTP1"}}]},"genes":[{"geneName":{"value":"PTPN6"},"synonyms":[{"value":"HCP"},{"value":"PTP1C"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10574931"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11266449"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11907092"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14739280"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21258366"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29925997"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34811497"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37595871"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37932456"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38166031"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38532423"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9065461"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9733788"}],"value":"Tyrosine phosphatase enzyme that plays important roles in controlling immune signaling pathways and fundamental physiological processes such as hematopoiesis (PubMed:14739280, PubMed:29925997). Dephosphorylates and negatively regulate several receptor tyrosine kinases (RTKs) such as EGFR, PDGFR and FGFR, thereby modulating their signaling activities (PubMed:21258366, PubMed:9733788). When recruited to immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors such as immunoglobulin-like transcript 2/LILRB1, programmed cell death protein 1/PDCD1, CD3D, CD22, CLEC12A and other receptors involved in immune regulation, initiates their dephosphorylation and subsequently inhibits downstream signaling events (PubMed:11907092, PubMed:14739280, PubMed:37932456, PubMed:38166031). Modulates the signaling of several cytokine receptors including IL-4 receptor (PubMed:9065461). Additionally, targets multiple cytoplasmic signaling molecules including STING1, LCK or STAT1 among others involved in diverse cellular processes including modulation of T-cell activation or cGAS-STING signaling (PubMed:34811497, PubMed:38532423). Within the nucleus, negatively regulates the activity of some transcription factors such as NFAT5 via direct dephosphorylation. Also acts as a key transcriptional regulator of hepatic gluconeogenesis by controlling recruitment of RNA polymerase II to the PCK1 promoter together with STAT5A (PubMed:37595871)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:10684"},{"database":"Rhea","id":"RHEA-COMP:10136"},{"database":"Rhea","id":"RHEA-COMP:20101"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:43474"},{"database":"ChEBI","id":"CHEBI:46858"},{"database":"ChEBI","id":"CHEBI:61978"}],"ecNumber":"3.1.3.48","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU10044"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29925997"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38532423"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P29351"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P81718"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11162587"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11266449"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11414741"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14597715"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15184070"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16493035"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17562706"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18604210"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19591923"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19843936"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20933011"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21258366"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21262353"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23112346"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37595871"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38532423"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9151699"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9285411"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9712903"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9842885"}],"value":"Monomer. Interacts with MTUS1 (By similarity). Interacts with MILR1 (tyrosine-phosphorylated) (By similarity). Interacts with KIT (By similarity). Interacts with SIRPA/PTPNS1 (PubMed:9712903). Interacts with LILRB1 and LILRB2 (PubMed:9285411, PubMed:9842885). Interacts with LILRB4 (PubMed:16493035, PubMed:9151699). Interacts with FCRL2 and FCRL4 (PubMed:11162587, PubMed:14597715). Interacts with FCRL3 and FCRL6 (tyrosine phosphorylated form) (PubMed:11162587, PubMed:19843936, PubMed:20933011). Interacts with CD84 (PubMed:11414741). Interacts with CD300LF (PubMed:15184070). Interacts with CDK2 (PubMed:21262353). Interacts with KIR2DL1; the interaction is enhanced by ARRB2 (PubMed:18604210). Interacts (via SH2 1 domain) with ROS1; the interaction is direct and promotes ROS1 dephosphorylation (PubMed:11266449). Interacts with EGFR; inhibits EGFR-dependent activation of MAPK/ERK (PubMed:21258366). Interacts with the tyrosine phosphorylated form of PDPK1 (PubMed:19591923). Interacts with CEACAM1 (via cytoplasmic domain); this interaction depends on the monomer/dimer equilibrium and is phosphorylation-dependent (By similarity). Interacts with MPIG6B (via ITIM motif) (PubMed:23112346). Interacts with KLRI1 and KLRI2 (By similarity). Interacts with moesin/MSN. Interacts with CLEC12B (via ITIM motif). Interacts with polymerase II components POLR2C and POLR2J; these interactions recruit RNA polymerase II to the PCK1 promoter (PubMed:37595871). Interacts with TNFRSF10A; this interaction enables the inhibition of T-cell receptor signaling via LCK (PubMed:38532423)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34811497"}],"value":"(Microbial infection) Interacts with HIV-1 Vif; this interaction promotes the suppression of cytokine 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Shuttles between the cytoplasm and nucleus via its association with PDPK1"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34811497"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9065461"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37595871"}],"value":"Nucleus","id":"SL-0191"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"synonyms":[{"value":"Long"}],"isoformIds":["P29350-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["P29350-3"],"sequenceIds":["VSP_007775"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"synonyms":[{"value":"Short"}],"isoformIds":["P29350-2"],"sequenceIds":["VSP_005129","VSP_005130"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"synonyms":[{"value":"70-kDa"},{"value":"SHP-1L"}],"isoformIds":["P29350-4"],"sequenceIds":["VSP_044447"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1732748"}],"value":"Isoform 1 is expressed in hematopoietic cells. Isoform 2 is expressed in non-hematopoietic cells"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12482860"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21465528"}],"value":"The N-terminal SH2 domain functions as an auto-inhibitory domain, blocking the catalytic domain in the ligand-free close conformation"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P29351"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10574931"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38166031"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38532423"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7781604"}],"value":"Phosphorylated on tyrosine residues. Binding of KITLG/SCF to KIT increases tyrosine phosphorylation (By similarity). Phosphorylation at Tyr-564 by LYN enhances phosphatase activity. Phosphorylation at Thr-394 by TAOK3 leads to polyubiquitination and subsequent proteasomal degradation (PubMed:38166031)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29925997"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38166031"}],"value":"Ubiquitinated after phosphorylation by TAOK3 (PubMed:38166031). Ubiquitinated by a cooperation between ITCH and WWP2 via 'Lys-27'-mediated polyubiquitin chains resulting in the reduction of its association with LCK (PubMed:29925997)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily"}],"commentType":"SIMILARITY"},{"commentType":"WEB RESOURCE","resourceName":"Atlas of Genetics and Cytogenetics in Oncology and Haematology","resourceUrl":"https://atlasgeneticsoncology.org/gene/41920/PTPN6","ftp":false}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":595,"modifier":"EXACT"}},"description":"Tyrosine-protein phosphatase non-receptor type 6","featureId":"PRO_0000094758"},{"type":"Domain","location":{"start":{"value":4,"modifier":"EXACT"},"end":{"value":100,"modifier":"EXACT"}},"description":"SH2 1","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00191"}]},{"type":"Domain","location":{"start":{"value":110,"modifier":"EXACT"},"end":{"value":213,"modifier":"EXACT"}},"description":"SH2 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12"}]}],"sequence":{"value":"MVRWFHRDLSGLDAETLLKGRGVHGSFLARPSRKNQGDFSLSVRVGDQVTHIRIQNSGDFYDLYGGEKFATLTELVEYYTQQQGVLQDRDGTIIHLKYPLNCSDPTSERWYHGHMSGGQAETLLQAKGEPWTFLVRESLSQPGDFVLSVLSDQPKAGPGSPLRVTHIKVMCEGGRYTVGGLETFDSLTDLVEHFKKTGIEEASGAFVYLRQPYYATRVNAADIENRVLELNKKQESEDTAKAGFWEEFESLQKQEVKNLHQRLEGQRPENKGKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYIKNQLLGPDENAKTYIASQGCLEATVNDFWQMAWQENSRVIVMTTREVEKGRNKCVPYWPEVGMQRAYGPYSVTNCGEHDTTEYKLRTLQVSPLDNGDLIREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMENISTKGLDCDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFIETTKKKLEVLQSQKGQESEYGNITYPPAMKNAHAKASRTSSKHKEDVYENLHTKNKREEKVKKQRSADKEKSKGSLKRNLSPDPVEAFRDGQTHNLNLGVPHSFVI","length":622,"molWeight":70489,"crc64":"2C64BDF681E89317","md5":"95122EF96367DBB328751AD41A2A44C4"},"extraAttributes":{"uniParcId":"UPI004931D566"}}]}