PTN1_MOUSE
ID PTN1_MOUSE Reviewed; 432 AA.
AC P35821; Q60840; Q62131; Q64498; Q99JS1;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Tyrosine-protein phosphatase non-receptor type 1;
DE EC=3.1.3.48;
DE AltName: Full=Protein-tyrosine phosphatase 1B;
DE Short=PTP-1B;
DE AltName: Full=Protein-tyrosine phosphatase HA2;
DE Short=PTP-HA2;
GN Name=Ptpn1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1932742;
RA Yi T., Cleveland J.L., Ihle J.N.;
RT "Identification of novel protein tyrosine phosphatases of hematopoietic
RT cells by polymerase chain reaction amplification.";
RL Blood 78:2222-2228(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=1378268; DOI=10.1016/0006-291x(92)91700-z;
RA Miyasaka H., Li S.S.L.;
RT "The cDNA cloning, nucleotide sequence and expression of an intracellular
RT protein tyrosine phosphatase from mouse testis.";
RL Biochem. Biophys. Res. Commun. 185:818-825(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Liao K., Lane M.D.;
RL Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Park K., Byun S.;
RL Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 102-213.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=7832766; DOI=10.1042/bj3050499;
RA Hendriks W., Schepens J., Brugman C., Zeeuwen P., Wieringa B.;
RT "A novel receptor-type protein tyrosine phosphatase with a single catalytic
RT domain is specifically expressed in mouse brain.";
RL Biochem. J. 305:499-504(1995).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-335, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Tyrosine-protein phosphatase which acts as a regulator of
CC endoplasmic reticulum unfolded protein response. Mediates
CC dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase
CC activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-
CC src-induced signal transduction cascades. May regulate the EFNA5-EPHA3
CC signaling pathway which modulates cell reorganization and cell-cell
CC repulsion. May also regulate the hepatocyte growth factor receptor
CC signaling pathway through dephosphorylation of MET (By similarity).
CC {ECO:0000250}.
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 EPHA3 (phosphorylated); dephosphorylates EPHA3
CC and may regulate its trafficking and function. Interacts with MET.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}; Cytoplasmic side
CC {ECO:0000250}. Note=Interacts with EPHA3 at the cell membrane.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Most abundant in testis. Also found in kidney,
CC spleen, muscle, liver, heart and brain.
CC -!- PTM: Ser-50 is the major site of phosphorylation as compared to Ser-242
CC and Ser-243. Activated by phosphorylation at Ser-50 (By similarity).
CC {ECO:0000250}.
CC -!- PTM: S-nitrosylation of Cys-215 inactivates the enzyme activity.
CC {ECO:0000250}.
CC -!- PTM: Sulfhydration at Cys-215 following endoplasmic reticulum stress
CC inactivates the enzyme activity, promoting EIF2AK3/PERK activity.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class 1 subfamily. {ECO:0000305}.
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DR EMBL; M97590; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; L40595; AAA64615.1; -; mRNA.
DR EMBL; U24700; AAA98605.1; -; mRNA.
DR EMBL; Z23057; CAA80592.1; -; mRNA.
DR EMBL; BC005729; AAH05729.1; -; mRNA.
DR EMBL; BC010191; AAH10191.1; -; mRNA.
DR CCDS; CCDS17107.1; -.
DR PIR; JN0317; JN0317.
DR RefSeq; NP_035331.3; NM_011201.3.
DR AlphaFoldDB; P35821; -.
DR SMR; P35821; -.
DR BioGRID; 202476; 3.
DR STRING; 10090.ENSMUSP00000029053; -.
DR ChEMBL; CHEMBL3336; -.
DR iPTMnet; P35821; -.
DR PhosphoSitePlus; P35821; -.
DR SwissPalm; P35821; -.
DR EPD; P35821; -.
DR jPOST; P35821; -.
DR PaxDb; P35821; -.
DR PeptideAtlas; P35821; -.
DR PRIDE; P35821; -.
DR ProteomicsDB; 291629; -.
DR Antibodypedia; 2724; 788 antibodies from 43 providers.
DR DNASU; 19246; -.
DR Ensembl; ENSMUST00000029053; ENSMUSP00000029053; ENSMUSG00000027540.
DR GeneID; 19246; -.
DR KEGG; mmu:19246; -.
DR UCSC; uc008oaj.1; mouse.
DR CTD; 5770; -.
DR MGI; MGI:97805; Ptpn1.
DR VEuPathDB; HostDB:ENSMUSG00000027540; -.
DR eggNOG; KOG0789; Eukaryota.
DR GeneTree; ENSGT00940000158041; -.
DR HOGENOM; CLU_001645_9_0_1; -.
DR InParanoid; P35821; -.
DR OMA; WSPLLAN; -.
DR OrthoDB; 411281at2759; -.
DR PhylomeDB; P35821; -.
DR TreeFam; TF315897; -.
DR BRENDA; 3.1.3.48; 3474.
DR Reactome; R-MMU-354192; Integrin signaling.
DR Reactome; R-MMU-6807004; Negative regulation of MET activity.
DR Reactome; R-MMU-8849472; PTK6 Down-Regulation.
DR Reactome; R-MMU-912694; Regulation of IFNA/IFNB signaling.
DR Reactome; R-MMU-982772; Growth hormone receptor signaling.
DR BioGRID-ORCS; 19246; 8 hits in 74 CRISPR screens.
DR ChiTaRS; Ptpn1; mouse.
DR PRO; PR:P35821; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P35821; protein.
DR Bgee; ENSMUSG00000027540; Expressed in femorotibial joint and 260 other tissues.
DR ExpressionAtlas; P35821; baseline and differential.
DR Genevisible; P35821; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:ParkinsonsUK-UCL.
DR GO; GO:0098554; C:cytoplasmic side of endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005769; C:early endosome; IDA:BHF-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0030061; C:mitochondrial crista; ISO:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0097443; C:sorting endosome; IDA:BHF-UCL.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0046875; F:ephrin receptor binding; ISO:MGI.
DR GO; GO:0005158; F:insulin receptor binding; ISO:MGI.
DR GO; GO:0004726; F:non-membrane spanning protein tyrosine phosphatase activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0051721; F:protein phosphatase 2A binding; ISO:MGI.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; ISS:UniProtKB.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP:MGI.
DR GO; GO:0036498; P:IRE1-mediated unfolded protein response; IMP:ParkinsonsUK-UCL.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IGI:BHF-UCL.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISO:MGI.
DR GO; GO:1903898; P:negative regulation of PERK-mediated unfolded protein response; IMP:ParkinsonsUK-UCL.
DR GO; GO:0030948; P:negative regulation of vascular endothelial growth factor receptor signaling pathway; IGI:BHF-UCL.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; IMP:UniProtKB.
DR GO; GO:1990264; P:peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity; IGI:BHF-UCL.
DR GO; GO:0035791; P:platelet-derived growth factor receptor-beta signaling pathway; IMP:UniProtKB.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:2000646; P:positive regulation of receptor catabolic process; ISO:MGI.
DR GO; GO:0006470; P:protein dephosphorylation; IMP:MGI.
DR GO; GO:0030100; P:regulation of endocytosis; ISS:UniProtKB.
DR GO; GO:1902202; P:regulation of hepatocyte growth factor receptor signaling pathway; ISO:MGI.
DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; ISO:MGI.
DR GO; GO:0033157; P:regulation of intracellular protein transport; ISO:MGI.
DR GO; GO:0009966; P:regulation of signal transduction; ISS:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:ParkinsonsUK-UCL.
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 Acetylation; Endoplasmic reticulum; Hydrolase; Membrane; Phosphoprotein;
KW Protein phosphatase; Reference proteome; S-nitrosylation.
FT CHAIN 1..432
FT /note="Tyrosine-protein phosphatase non-receptor type 1"
FT /id="PRO_0000094749"
FT DOMAIN 3..277
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 297..322
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 335..399
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 215
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160,
FT ECO:0000255|PROSITE-ProRule:PRU10044"
FT BINDING 181
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 215..221
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 262
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 20
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 50
FT /note="Phosphoserine; by CLK1, CLK2 and PKB/AKT1 or
FT PKB/AKT2"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 66
FT /note="Phosphotyrosine; by EGFR"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 215
FT /note="Cysteine persulfide"
FT /evidence="ECO:0000250"
FT MOD_RES 215
FT /note="S-nitrosocysteine; in reversibly inhibited form"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 242
FT /note="Phosphoserine; by CLK1 and CLK2"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 243
FT /note="Phosphoserine; by CLK1 and CLK2"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 335
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 362
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 364
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT MOD_RES 367
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P18031"
FT CONFLICT 48
FT /note="D -> Y (in Ref. 2; M97590)"
FT /evidence="ECO:0000305"
FT CONFLICT 173
FT /note="H -> P (in Ref. 3; AAA64615)"
FT /evidence="ECO:0000305"
FT CONFLICT 266..267
FT /note="QL -> HV (in Ref. 3; AAA64615)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 432 AA; 49593 MW; 4843D2DD4C288C48 CRC64;
MEMEKEFEEI DKAGNWAAIY QDIRHEASDF PCKVAKLPKN KNRNRYRDVS PFDHSRIKLH
QEDNDYINAS LIKMEEAQRS YILTQGPLPN TCGHFWEMVW EQKSRGVVML NRIMEKGSLK
CAQYWPQQEE KEMVFDDTGL KLTLISEDVK SYYTVRQLEL ENLTTKETRE ILHFHYTTWP
DFGVPESPAS FLNFLFKVRE SGSLSLEHGP IVVHCSAGIG RSGTFCLADT CLLLMDKRKD
PSSVDIKKVL LEMRRFRMGL IQTADQLRFS YLAVIEGAKF IMGDSSVQDQ WKELSREDLD
LPPEHVPPPP RPPKRTLEPH NGKCKELFSS HQWVSEETCG DEDSLAREEG RAQSSAMHSV
SSMSPDTEVR RRMVGGGLQS AQASVPTEEE LSSTEEEHKA HWPSHWKPFL VNVCMATLLA
TGAYLCYRVC FH
