PTN6_RAT
ID PTN6_RAT Reviewed; 613 AA.
AC P81718;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Tyrosine-protein phosphatase non-receptor type 6;
DE EC=3.1.3.48;
DE AltName: Full=Protein-tyrosine phosphatase SHP-1;
GN Name=Ptpn6; Synonyms=Ptph6;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Aoki N., Yamaguchi-Aoki Y., Ullrich A.;
RT "The rat SH2-containing protein-tyrosine phosphatase SHP-1 is a positive
RT regulator of NGF-induced neuronal differentiation of PC12 cells.";
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP MTUS1.
RX PubMed=17068200; DOI=10.1210/me.2006-0005;
RA Li J.-M., Mogi M., Tsukuda K., Tomochika H., Iwanami J., Min L.-J.,
RA Nahmias C., Iwai M., Horiuchi M.;
RT "Angiotensin II-induced neural differentiation via angiotensin II type 2
RT (AT2) receptor-MMS2 cascade involving interaction between AT2 receptor-
RT interacting protein and Src homology 2 domain-containing protein-tyrosine
RT phosphatase 1.";
RL Mol. Endocrinol. 21:499-511(2007).
RN [3]
RP INTERACTION WITH KLRI1 AND KLRI2.
RX PubMed=18713988; DOI=10.4049/jimmunol.181.5.3177;
RA Saether P.C., Westgaard I.H., Hoelsbrekken S.E., Benjamin J., Lanier L.L.,
RA Fossum S., Dissen E.;
RT "KLRE/I1 and KLRE/I2: a novel pair of heterodimeric receptors that
RT inversely regulate NK cell cytotoxicity.";
RL J. Immunol. 181:3177-3182(2008).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Modulates signaling by tyrosine phosphorylated cell surface
CC receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may
CC interact with other cellular components to modulate its own phosphatase
CC activity against interacting substrates. Together with MTUS1, induces
CC UBE2V2 expression upon angiotensin II stimulation. Plays a key role in
CC hematopoiesis. {ECO:0000269|PubMed:17068200}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620; EC=3.1.3.48;
CC Evidence={ECO:0000250|UniProtKB:P29351, ECO:0000255|PROSITE-
CC ProRule:PRU10044};
CC -!- SUBUNIT: Monomer. Interacts with MTUS1 (PubMed:17068200). Interacts
CC with MILR1 (tyrosine-phosphorylated) (By similarity). Interacts with
CC KIT (By similarity). Interacts with SIRPA/PTPNS1 (By similarity).
CC Interacts with FCRL2 and FCRL4 (By similarity). Interacts with CD84 (By
CC similarity). Interacts with CD300LF (By similarity). Interacts with
CC CDK2 (By similarity). Interacts with KIR2DL1; the interaction is
CC enhanced by ARRB2 (By similarity). Interacts (via SH2 1 domain) with
CC ROS1; the interaction is direct and promotes ROS1 dephosphorylation (By
CC similarity). Interacts with EGFR; inhibits EGFR-dependent activation of
CC MAPK/ERK (By similarity). Interacts with LYN (By similarity). Interacts
CC with the tyrosine phosphorylated form of PDPK1 (By similarity).
CC Interacts with CEACAM1 (via cytoplasmic domain); this interaction
CC depends on the monomer/dimer equilibrium and is phosphorylation-
CC dependent (By similarity). Interacts with MPIG6B (via ITIM motif) (By
CC similarity). Interacts with KLRI1 and KLRI2 (PubMed:18713988).
CC Interacts with moesin/MSN. Interacts with CLEC12B (via ITIM motif).
CC {ECO:0000250|UniProtKB:P29350, ECO:0000250|UniProtKB:P29351,
CC ECO:0000269|PubMed:17068200, ECO:0000269|PubMed:18713988}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17068200}. Nucleus
CC {ECO:0000269|PubMed:17068200}. Note=In neurons, translocates into the
CC nucleus after treatment with angiotensin II. Shuttles between the
CC cytoplasm and nucleus via its association with PDPK (By similarity).
CC {ECO:0000250}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in embryonic cerebral cortex
CC between day 18 and up to birth. Expression levels decrease after birth
CC (at protein level). {ECO:0000269|PubMed:17068200}.
CC -!- DOMAIN: The N-terminal SH2 domain functions as an auto-inhibitory
CC domain, blocking the catalytic domain in the ligand-free close
CC conformation. {ECO:0000250}.
CC -!- PTM: Phosphorylated on tyrosine residues. Binding of KITLG/SCF to KIT
CC increases tyrosine phosphorylation (By similarity). Phosphorylation at
CC Tyr-566 enhances phosphatase activity (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class 2 subfamily. {ECO:0000305}.
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DR EMBL; U77038; AAD00262.1; -; mRNA.
DR RefSeq; NP_446360.1; NM_053908.1.
DR AlphaFoldDB; P81718; -.
DR SMR; P81718; -.
DR BioGRID; 250571; 3.
DR DIP; DIP-47802N; -.
DR IntAct; P81718; 5.
DR STRING; 10116.ENSRNOP00000059867; -.
DR iPTMnet; P81718; -.
DR PhosphoSitePlus; P81718; -.
DR jPOST; P81718; -.
DR PaxDb; P81718; -.
DR GeneID; 116689; -.
DR KEGG; rno:116689; -.
DR UCSC; RGD:620660; rat.
DR CTD; 5777; -.
DR RGD; 620660; Ptpn6.
DR eggNOG; KOG0790; Eukaryota.
DR InParanoid; P81718; -.
DR OrthoDB; 411281at2759; -.
DR PhylomeDB; P81718; -.
DR Reactome; R-RNO-114604; GPVI-mediated activation cascade.
DR Reactome; R-RNO-1433559; Regulation of KIT signaling.
DR Reactome; R-RNO-201556; Signaling by ALK.
DR Reactome; R-RNO-210990; PECAM1 interactions.
DR Reactome; R-RNO-388841; Costimulation by the CD28 family.
DR Reactome; R-RNO-389948; PD-1 signaling.
DR Reactome; R-RNO-432142; Platelet sensitization by LDL.
DR Reactome; R-RNO-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-RNO-5690714; CD22 mediated BCR regulation.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-877300; Interferon gamma signaling.
DR Reactome; R-RNO-912526; Interleukin receptor SHC signaling.
DR Reactome; R-RNO-912694; Regulation of IFNA/IFNB signaling.
DR Reactome; R-RNO-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR PRO; PR:P81718; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0042105; C:alpha-beta T cell receptor complex; ISO:RGD.
DR GO; GO:0005911; C:cell-cell junction; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0050839; F:cell adhesion molecule binding; ISO:RGD.
DR GO; GO:0046703; F:natural killer cell lectin-like receptor binding; IPI:RGD.
DR GO; GO:0004726; F:non-membrane spanning protein tyrosine phosphatase activity; IBA:GO_Central.
DR GO; GO:0140031; F:phosphorylation-dependent protein binding; ISO:RGD.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; ISO:RGD.
DR GO; GO:0042169; F:SH2 domain binding; ISO:RGD.
DR GO; GO:0017124; F:SH3 domain binding; ISO:RGD.
DR GO; GO:0005001; F:transmembrane receptor protein tyrosine phosphatase activity; ISS:UniProtKB.
DR GO; GO:0033277; P:abortive mitotic cell cycle; ISO:RGD.
DR GO; GO:0050853; P:B cell receptor signaling pathway; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; ISS:UniProtKB.
DR GO; GO:1905867; P:epididymis development; ISO:RGD.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:RGD.
DR GO; GO:0035855; P:megakaryocyte development; ISO:RGD.
DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; ISO:RGD.
DR GO; GO:0002924; P:negative regulation of humoral immune response mediated by circulating immunoglobulin; ISO:RGD.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISO:RGD.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISO:RGD.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0033007; P:negative regulation of mast cell activation involved in immune response; ISO:RGD.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; ISO:RGD.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; ISO:RGD.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; ISO:RGD.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0070527; P:platelet aggregation; ISO:RGD.
DR GO; GO:0030220; P:platelet formation; ISO:RGD.
DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:RGD.
DR GO; GO:0006470; P:protein dephosphorylation; ISS:UniProtKB.
DR GO; GO:0045577; P:regulation of B cell differentiation; ISO:RGD.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; ISO:RGD.
DR GO; GO:0009611; P:response to wounding; IEP:RGD.
DR Gene3D; 3.30.505.10; -; 2.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000242; PTP_cat.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR012152; Tyr_Pase_non-rcpt_typ-6/11.
DR Pfam; PF00017; SH2; 2.
DR Pfam; PF00102; Y_phosphatase; 1.
DR PIRSF; PIRSF000929; Tyr-Ptase_nr_6; 1.
DR PRINTS; PR00700; PRTYPHPHTASE.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00194; PTPc; 1.
DR SMART; SM00404; PTPc_motif; 1.
DR SMART; SM00252; SH2; 2.
DR SUPFAM; SSF52799; SSF52799; 1.
DR SUPFAM; SSF55550; SSF55550; 2.
DR PROSITE; PS50001; SH2; 2.
DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR PROSITE; PS50055; TYR_PHOSPHATASE_PTP; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Hydrolase; Nucleus; Phosphoprotein; Protein phosphatase;
KW Reference proteome; Repeat; SH2 domain.
FT CHAIN 1..613
FT /note="Tyrosine-protein phosphatase non-receptor type 6"
FT /id="PRO_0000094760"
FT DOMAIN 6..102
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191,
FT ECO:0000305"
FT DOMAIN 112..215
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191,
FT ECO:0000305"
FT DOMAIN 246..517
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 549..598
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 556..594
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 455
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160,
FT ECO:0000255|PROSITE-ProRule:PRU10044"
FT BINDING 421
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 455..461
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 502
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 12
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 59
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29351"
FT MOD_RES 66
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P29350"
FT MOD_RES 379
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P29351"
FT MOD_RES 538
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P29351"
FT MOD_RES 566
FT /note="Phosphotyrosine; by LYN"
FT /evidence="ECO:0000250|UniProtKB:P29350"
SQ SEQUENCE 613 AA; 69578 MW; 29364B22E8F45C87 CRC64;
MLSRGWFHRD LSGPDAETLL KGRGVPGSFL ARPSRKNQGD FSLSVRVDDQ VTHIRIQNSG
DFYDLYGGEK FATSTELVEY YTQQQGILQD RDGTIIHLKY PLNCSDPTSE RWYHGHMSGG
QAESLLQAKG EPWTFLVRES LSQPGDFVLS VLNDQPKAAP GSPLRVTHIK VMCEGGRYTV
GGSETFDSLT DLVEHFKKTG IEEASGAFVY LRQPYYATRV NAADIENRVL ELNKKQESED
TAKAGFWEEF ESLQKQEAKN LHQRLEGQRP ENKSKNRYKN ILPFDHSRVI LQGRDSNIPG
SDYINANYVK NQLLGPDENS KTYIASQGCL DATVNDFWQM AWQENTRVIV MTTREVEKGR
NKCVPYWPEV GTQRVYGLYS VTNCKEHDTA EYKLRTLQIS PLDNGDLVRE IWHYQYLSWP
DHGVPSEPGG VLSFLDQINQ RQESLPHAGP IIVHCSAGIG RTGTIIVIDM LMESVSTKGL
DCDIDIQKTI QMVRAQRSGM VQTEAQYKFI YVAIAQFIET TKKKLEIIQS QRGQESEYGN
ITYPPALRSA HAKASRTSSK HKEEVYENVH SKNKKEEKVK KQRSADKEKN KGSLKRNISL
TPCRGLRWAD RDL
