PTN2_RAT
ID PTN2_RAT Reviewed; 416 AA.
AC P35233;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Tyrosine-protein phosphatase non-receptor type 2;
DE EC=3.1.3.48;
DE AltName: Full=Protein-tyrosine phosphatase PTP-S;
GN Name=Ptpn2;
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]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC TISSUE=Spleen;
RX PubMed=1849097; DOI=10.1016/0014-5793(91)80205-h;
RA Swarup G., Kamatkar S., Radha V., Rema V.;
RT "Molecular cloning and expression of a protein-tyrosine phosphatase showing
RT homology with transcription factors Fos and Jun.";
RL FEBS Lett. 280:65-69(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP DNA-BINDING.
RX PubMed=8443161; DOI=10.1021/bi00060a010;
RA Radha V., Kamatkar S., Swarup G.;
RT "Binding of a protein-tyrosine phosphatase to DNA through its carboxy-
RT terminal noncatalytic domain.";
RL Biochemistry 32:2194-2201(1993).
RN [4]
RP ALTERNATIVE SPLICING.
RX PubMed=8534367; DOI=10.1089/dna.1995.14.1007;
RA Reddy R.S., Swarup G.;
RT "Alternative splicing generates four different forms of a non-transmembrane
RT protein tyrosine phosphatase mRNA.";
RL DNA Cell Biol. 14:1007-1015(1995).
RN [5]
RP SUBCELLULAR LOCATION (ISOFORMS 1 AND 2).
RX PubMed=8900155; DOI=10.1074/jbc.271.43.26755;
RA Kamatkar S., Radha V., Nambirajan S., Reddy R.S., Swarup G.;
RT "Two splice variants of a tyrosine phosphatase differ in substrate
RT specificity, DNA binding, and subcellular location.";
RL J. Biol. Chem. 271:26755-26761(1996).
CC -!- FUNCTION: Non-receptor type tyrosine-specific phosphatase that
CC dephosphorylates receptor protein tyrosine kinases including INSR,
CC EGFR, CSF1R, PDGFR. Also dephosphorylates non-receptor protein tyrosine
CC kinases like JAK1, JAK2, JAK3, Src family kinases, STAT1, STAT3 and
CC STAT6 either in the nucleus or the cytoplasm. Negatively regulates
CC numerous signaling pathways and biological processes like
CC hematopoiesis, inflammatory response, cell proliferation and
CC differentiation, and glucose homeostasis. Plays a multifaceted and
CC important role in the development of the immune system. Functions in T-
CC cell receptor signaling through dephosphorylation of FYN and LCK to
CC control T-cells differentiation and activation. Dephosphorylates CSF1R,
CC negatively regulating its downstream signaling and macrophage
CC differentiation. Negatively regulates cytokine (IL2/interleukin-2 and
CC interferon)-mediated signaling through dephosphorylation of the
CC cytoplasmic kinases JAK1, JAK3 and their substrate STAT1, that
CC propagate signaling downstream of the cytokine receptors. Also
CC regulates the IL6/interleukin-6 and IL4/interleukin-4 cytokine
CC signaling through dephosphorylation of STAT3 and STAT6 respectively. In
CC addition to the immune system, it is involved in anchorage-dependent,
CC negative regulation of EGF-stimulated cell growth. Activated by the
CC integrin ITGA1/ITGB1, it dephosphorylates EGFR and negatively regulates
CC EGF signaling. Dephosphorylates PDGFRB and negatively regulates
CC platelet-derived growth factor receptor-beta signaling pathway and
CC therefore cell proliferation. Negatively regulates tumor necrosis
CC factor-mediated signaling downstream via MAPK through SRC
CC dephosphorylation. May also regulate the hepatocyte growth factor
CC receptor signaling pathway through dephosphorylation of the hepatocyte
CC growth factor receptor MET. Also plays an important role in glucose
CC homeostasis. For instance, negatively regulates the insulin receptor
CC signaling pathway through the dephosphorylation of INSR and control
CC gluconeogenesis and liver glucose production through negative
CC regulation of the IL6 signaling pathways. May also bind DNA (By
CC similarity). {ECO:0000250|UniProtKB:P17706}.
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; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10044};
CC -!- SUBUNIT: Interacts with RMDN3. Interacts with TMED9. Interacts with
CC STX17; dephosphorylates STX17. Interacts with ITGA1 (via cytoplasmic
CC domain); activates the phosphatase activity towards EGFR. Interacts
CC with TRAF2; probably involved in tumor necrosis factor-mediated
CC signaling. Interacts with MET (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Endoplasmic reticulum-Golgi
CC intermediate compartment {ECO:0000250}. Note=Targeted to the
CC endoplasmic reticulum by its C-terminal hydrophobic region.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum
CC {ECO:0000269|PubMed:8900155}. Nucleus membrane
CC {ECO:0000269|PubMed:8900155}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000250}. Cytoplasm
CC {ECO:0000250}. Cell membrane {ECO:0000250}. Note=Predominantly
CC localizes to chromatin. Able to shuttle between the nucleus and the
CC cytoplasm and to dephosphorylate plasma membrane receptors. Recruited
CC by activated ITGA1 at the plasma membrane (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=PTP-S4;
CC IsoId=P35233-1; Sequence=Displayed;
CC Name=2; Synonyms=PTP-S2;
CC IsoId=P35233-2; Sequence=VSP_042002;
CC Name=3; Synonyms=PTP-S3;
CC IsoId=P35233-3; Sequence=VSP_042001;
CC Name=4; Synonyms=PTP-S1;
CC IsoId=P35233-4; Sequence=VSP_042001, VSP_042002;
CC -!- TISSUE SPECIFICITY: Does not show tissue- or cell-type specificity
CC although levels of transcription show variability. Macrophages showed
CC higher levels of expression than lymphocytes.
CC -!- PTM: [Isoform 2]: Specifically phosphorylated in a cell cycle-dependent
CC manner by cyclin-dependent kinases CDK1 and CDK2. Probably activated
CC through phosphorylation by PKR. {ECO:0000250|UniProtKB:P17706}.
CC -!- MISCELLANEOUS: [Isoform 3]: Minor. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Minor. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class 1 subfamily. {ECO:0000305}.
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DR EMBL; X58828; CAA41633.1; -; mRNA.
DR EMBL; BC078758; AAH78758.1; -; mRNA.
DR PIR; S14294; S14294.
DR RefSeq; NP_446442.1; NM_053990.1. [P35233-4]
DR AlphaFoldDB; P35233; -.
DR SMR; P35233; -.
DR IntAct; P35233; 1.
DR STRING; 10116.ENSRNOP00000063665; -.
DR PhosphoSitePlus; P35233; -.
DR jPOST; P35233; -.
DR PaxDb; P35233; -.
DR PRIDE; P35233; -.
DR GeneID; 117063; -.
DR KEGG; rno:117063; -.
DR UCSC; RGD:620710; rat. [P35233-1]
DR CTD; 5771; -.
DR RGD; 620710; Ptpn2.
DR VEuPathDB; HostDB:ENSRNOG00000017453; -.
DR eggNOG; KOG0789; Eukaryota.
DR InParanoid; P35233; -.
DR OMA; NTAQMVQ; -.
DR OrthoDB; 411281at2759; -.
DR Reactome; R-RNO-6807004; Negative regulation of MET activity.
DR Reactome; R-RNO-877312; Regulation of IFNG signaling.
DR PRO; PR:P35233; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Bgee; ENSRNOG00000017453; Expressed in thymus and 20 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISS:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; TAS:RGD.
DR GO; GO:0005178; F:integrin binding; ISO:RGD.
DR GO; GO:0004726; F:non-membrane spanning protein tyrosine phosphatase activity; IDA:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; ISS:UniProtKB.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:RGD.
DR GO; GO:0097677; F:STAT family protein binding; ISO:RGD.
DR GO; GO:0019905; F:syntaxin binding; ISO:RGD.
DR GO; GO:0030183; P:B cell differentiation; ISS:UniProtKB.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0050922; P:negative regulation of chemotaxis; ISS:UniProtKB.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0060336; P:negative regulation of interferon-gamma-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:1902206; P:negative regulation of interleukin-2-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:1902215; P:negative regulation of interleukin-4-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0070104; P:negative regulation of interleukin-6-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0010888; P:negative regulation of lipid storage; ISS:UniProtKB.
DR GO; GO:1902227; P:negative regulation of macrophage colony-stimulating factor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045650; P:negative regulation of macrophage differentiation; ISS:UniProtKB.
DR GO; GO:2000587; P:negative regulation of platelet-derived growth factor receptor-beta signaling pathway; ISS:UniProtKB.
DR GO; GO:1902233; P:negative regulation of positive thymic T cell selection; ISS:UniProtKB.
DR GO; GO:0061099; P:negative regulation of protein tyrosine kinase activity; ISO:RGD.
DR GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; IBA:GO_Central.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; ISS:UniProtKB.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; ISS:UniProtKB.
DR GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; ISS:UniProtKB.
DR GO; GO:1903899; P:positive regulation of PERK-mediated unfolded protein response; ISO:RGD.
DR GO; GO:0006470; P:protein dephosphorylation; ISO:RGD.
DR GO; GO:1902202; P:regulation of hepatocyte growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0030217; P:T cell differentiation; ISS:UniProtKB.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000242; PTP_cat.
DR InterPro; IPR012265; Ptpn1/Ptpn2.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR Pfam; PF00102; Y_phosphatase; 1.
DR PIRSF; PIRSF000926; Tyr-Ptase_nr1; 1.
DR PRINTS; PR00700; PRTYPHPHTASE.
DR SMART; SM00194; PTPc; 1.
DR SMART; SM00404; PTPc_motif; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
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 Alternative splicing; Cell membrane; Cytoplasm; Endoplasmic reticulum;
KW Hydrolase; Membrane; Nucleus; Phosphoprotein; Protein phosphatase;
KW Reference proteome; S-nitrosylation.
FT CHAIN 1..416
FT /note="Tyrosine-protein phosphatase non-receptor type 2"
FT /id="PRO_0000094754"
FT DOMAIN 5..275
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 341..410
FT /note="Endoplasmic reticulum location"
FT /evidence="ECO:0000250"
FT REGION 371..410
FT /note="May mediate interaction with STX17"
FT /evidence="ECO:0000250"
FT ACT_SITE 216
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160,
FT ECO:0000255|PROSITE-ProRule:PRU10044"
FT BINDING 182
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 216..222
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 260
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 22
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 68
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 216
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 293
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17706"
FT MOD_RES 298
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17706"
FT MOD_RES 304
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17706"
FT MOD_RES 320
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06180"
FT MOD_RES 339
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT VAR_SEQ 287..305
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1849097"
FT /id="VSP_042001"
FT VAR_SEQ 377..410
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1849097"
FT /id="VSP_042002"
FT MOD_RES P35233-2:304
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17706"
SQ SEQUENCE 416 AA; 48446 MW; E8FB1E670FFC5308 CRC64;
MSATIEREFE ELDAQCRWQP LYLEIRNESH DYPHRVAKFP ENRNRNRYRD VSPYDHSRVK
LQSAENDYIN ASLVDIEEAQ RSYILTQGPL PNTCCHFWLM VWQQKTRAVV MLNRTVEKES
VKCAQYWPTD DREMVFKETG FSVKLLSEDV KSYYTVHLLQ LENINSGETR TISHFHYTTW
PDFGVPESPA SFLNFLFKVR ESGSLNPDHG PAVIHCSAGI GRSGTFSLVD TCLVLMEKGE
DVNVKQILLS MRKYRMGLIQ TPDQLRFSYM AIIEGAKYTK GDSNIQKRWK ELSKEDLSPV
CRHSQNRTMT EKYNGKRIGS EDEKLTGLSS KVPDTVEESS ESILRKRIRE DRKATTAQKV
QQMRQRLNET ERKRKRWLYW QPILTKMGFV SVILVGALVG WTLLFQLNVL PRLTDT
