ID   PTN4_MOUSE              Reviewed;         926 AA.
AC   Q9WU22; G5E8E7;
DT   26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT   18-SEP-2013, sequence version 2.
DT   24-JAN-2024, entry version 157.
DE   RecName: Full=Tyrosine-protein phosphatase non-receptor type 4;
DE            EC=3.1.3.48;
DE   AltName: Full=Testis-enriched protein tyrosine phosphatase;
GN   Name=Ptpn4;
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], AND TISSUE SPECIFICITY.
RC   TISSUE=Testis;
RX   PubMed=11054567; DOI=10.1016/s0378-1119(00)00351-6;
RA   Park K.-W., Lee E.-J., Lee S.-H., Lee J.-E., Choi E.-Y., Kim B.J.,
RA   Hwang R., Park K.A., Baik J.-H.;
RT   "Molecular cloning and characterization of a protein tyrosine phosphatase
RT   enriched in testis, a putative murine homologue of human PTPMEG.";
RL   Gene 257:45-55(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=17953619; DOI=10.1111/j.1460-9568.2007.05829.x;
RA   Kina S., Tezuka T., Kusakawa S., Kishimoto Y., Kakizawa S., Hashimoto K.,
RA   Ohsugi M., Kiyama Y., Horai R., Sudo K., Kakuta S., Iwakura Y., Iino M.,
RA   Kano M., Manabe T., Yamamoto T.;
RT   "Involvement of protein-tyrosine phosphatase PTPMEG in motor learning and
RT   cerebellar long-term depression.";
RL   Eur. J. Neurosci. 26:2269-2278(2007).
RN   [5]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=18614237; DOI=10.1016/j.molimm.2008.05.023;
RA   Young J.A., Becker A.M., Medeiros J.J., Shapiro V.S., Wang A., Farrar J.D.,
RA   Quill T.A., Hooft van Huijsduijnen R., van Oers N.S.;
RT   "The protein tyrosine phosphatase PTPN4/PTP-MEG1, an enzyme capable of
RT   dephosphorylating the TCR ITAMs and regulating NF-kappaB, is dispensable
RT   for T cell development and/or T cell effector functions.";
RL   Mol. Immunol. 45:3756-3766(2008).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-474, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue;
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).
RN   [7]
RP   FUNCTION.
RX   PubMed=25825441; DOI=10.4049/jimmunol.1402183;
RA   Huai W., Song H., Wang L., Li B., Zhao J., Han L., Gao C., Jiang G.,
RA   Zhang L., Zhao W.;
RT   "Phosphatase PTPN4 preferentially inhibits TRIF-dependent TLR4 pathway by
RT   dephosphorylating TRAM.";
RL   J. Immunol. 194:4458-4465(2015).
CC   -!- FUNCTION: Phosphatase that plays a role in immunity, learning, synaptic
CC       plasticity or cell homeostasis (PubMed:17953619, PubMed:25825441).
CC       Regulates neuronal cell homeostasis by protecting neurons against
CC       apoptosis (By similarity). Negatively regulates TLR4-induced interferon
CC       beta production by dephosphorylating adapter TICAM2 and inhibiting
CC       subsequent TRAM-TRIF interaction (PubMed:25825441). Dephosphorylates
CC       also the immunoreceptor tyrosine-based activation motifs/ITAMs of the
CC       TCR zeta subunit and thereby negatively regulates TCR-mediated
CC       signaling pathway (PubMed:18614237). May act at junctions between the
CC       membrane and the cytoskeleton. {ECO:0000250,
CC       ECO:0000250|UniProtKB:P29074, ECO:0000269|PubMed:17953619,
CC       ECO:0000269|PubMed:18614237, ECO:0000269|PubMed:25825441}.
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   -!- INTERACTION:
CC       Q9WU22; P24161: Cd247; NbExp=3; IntAct=EBI-7249866, EBI-7803400;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Peripheral membrane
CC       protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Cytoplasm,
CC       cytoskeleton {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in testis. Specifically expressed
CC       in spermatocytes and spermatids within seminiferous tubules (at protein
CC       level). {ECO:0000269|PubMed:11054567}.
CC   -!- DISRUPTION PHENOTYPE: PTPN4-deficient mice are born at normal Mendelian
CC       ratio with no apparent developmental or phenotypic defects. They
CC       display normal cytokine production and T-cell effector functions
CC       (PubMed:18614237). However, they show impairment in motor learning and
CC       cerebellar long-term depression (PubMed:17953619).
CC       {ECO:0000269|PubMed:17953619, ECO:0000269|PubMed:18614237}.
CC   -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC       receptor class subfamily. {ECO:0000305}.
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DR   EMBL; AF106702; AAD22773.1; -; mRNA.
DR   EMBL; AC123955; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC124760; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH466520; EDL39812.1; -; Genomic_DNA.
DR   CCDS; CCDS15227.1; -.
DR   RefSeq; NP_064317.2; NM_019933.2.
DR   AlphaFoldDB; Q9WU22; -.
DR   SMR; Q9WU22; -.
DR   BioGRID; 202487; 4.
DR   IntAct; Q9WU22; 1.
DR   MINT; Q9WU22; -.
DR   STRING; 10090.ENSMUSP00000067614; -.
DR   iPTMnet; Q9WU22; -.
DR   PhosphoSitePlus; Q9WU22; -.
DR   SwissPalm; Q9WU22; -.
DR   EPD; Q9WU22; -.
DR   MaxQB; Q9WU22; -.
DR   PaxDb; 10090-ENSMUSP00000067614; -.
DR   PeptideAtlas; Q9WU22; -.
DR   ProteomicsDB; 301941; -.
DR   Antibodypedia; 18333; 159 antibodies from 22 providers.
DR   DNASU; 19258; -.
DR   Ensembl; ENSMUST00000064091.12; ENSMUSP00000067614.6; ENSMUSG00000026384.14.
DR   GeneID; 19258; -.
DR   KEGG; mmu:19258; -.
DR   UCSC; uc007ciz.1; mouse.
DR   AGR; MGI:1099792; -.
DR   CTD; 5775; -.
DR   MGI; MGI:1099792; Ptpn4.
DR   VEuPathDB; HostDB:ENSMUSG00000026384; -.
DR   eggNOG; KOG0792; Eukaryota.
DR   GeneTree; ENSGT00940000157211; -.
DR   HOGENOM; CLU_001645_7_0_1; -.
DR   InParanoid; Q9WU22; -.
DR   OMA; MRWLDPS; -.
DR   OrthoDB; 5345383at2759; -.
DR   PhylomeDB; Q9WU22; -.
DR   TreeFam; TF315900; -.
DR   Reactome; R-MMU-166016; Toll Like Receptor 4 (TLR4) Cascade.
DR   BioGRID-ORCS; 19258; 3 hits in 77 CRISPR screens.
DR   ChiTaRS; Ptpn4; mouse.
DR   PRO; PR:Q9WU22; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; Q9WU22; Protein.
DR   Bgee; ENSMUSG00000026384; Expressed in lateral geniculate body and 223 other cell types or tissues.
DR   ExpressionAtlas; Q9WU22; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISO:MGI.
DR   GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0008092; F:cytoskeletal protein binding; IEA:InterPro.
DR   GO; GO:0035254; F:glutamate receptor binding; IPI:MGI.
DR   GO; GO:0004726; F:non-membrane spanning protein tyrosine phosphatase activity; IDA:MGI.
DR   GO; GO:0004725; F:protein tyrosine phosphatase activity; IBA:GO_Central.
DR   GO; GO:0016311; P:dephosphorylation; IEA:InterPro.
DR   CDD; cd14473; FERM_B-lobe; 1.
DR   CDD; cd13189; FERM_C_PTPN4_PTPN3_like; 1.
DR   CDD; cd17194; FERM_F1_PTPN4; 1.
DR   CDD; cd00992; PDZ_signaling; 1.
DR   Gene3D; 1.20.80.10; -; 1.
DR   Gene3D; 2.30.42.10; -; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR   Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1.
DR   InterPro; IPR019749; Band_41_domain.
DR   InterPro; IPR014847; FA.
DR   InterPro; IPR014352; FERM/acyl-CoA-bd_prot_sf.
DR   InterPro; IPR035963; FERM_2.
DR   InterPro; IPR019748; FERM_central.
DR   InterPro; IPR019747; FERM_CS.
DR   InterPro; IPR000299; FERM_domain.
DR   InterPro; IPR018979; FERM_N.
DR   InterPro; IPR018980; FERM_PH-like_C.
DR   InterPro; IPR001478; PDZ.
DR   InterPro; IPR036034; PDZ_sf.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR   InterPro; IPR000242; PTP_cat.
DR   InterPro; IPR041783; PTPN3/4_FERM_C.
DR   InterPro; IPR016130; Tyr_Pase_AS.
DR   InterPro; IPR003595; Tyr_Pase_cat.
DR   InterPro; IPR000387; Tyr_Pase_dom.
DR   InterPro; IPR012151; Tyr_Pase_non-rcpt_typ-3/4.
DR   InterPro; IPR029071; Ubiquitin-like_domsf.
DR   PANTHER; PTHR45706; TYROSINE-PROTEIN PHOSPHATASE; 1.
DR   PANTHER; PTHR45706:SF7; TYROSINE-PROTEIN PHOSPHATASE NON-RECEPTOR TYPE 4; 1.
DR   Pfam; PF08736; FA; 1.
DR   Pfam; PF09380; FERM_C; 1.
DR   Pfam; PF00373; FERM_M; 1.
DR   Pfam; PF09379; FERM_N; 1.
DR   Pfam; PF00595; PDZ; 1.
DR   Pfam; PF00102; Y_phosphatase; 1.
DR   PIRSF; PIRSF000927; Tyr-Ptase_nr3; 1.
DR   PRINTS; PR00935; BAND41.
DR   PRINTS; PR00700; PRTYPHPHTASE.
DR   SMART; SM00295; B41; 1.
DR   SMART; SM01195; FA; 1.
DR   SMART; SM01196; FERM_C; 1.
DR   SMART; SM00228; PDZ; 1.
DR   SMART; SM00194; PTPc; 1.
DR   SMART; SM00404; PTPc_motif; 1.
DR   SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1.
DR   SUPFAM; SSF50156; PDZ domain-like; 1.
DR   SUPFAM; SSF50729; PH domain-like; 1.
DR   SUPFAM; SSF47031; Second domain of FERM; 1.
DR   SUPFAM; SSF54236; Ubiquitin-like; 1.
DR   PROSITE; PS00660; FERM_1; 1.
DR   PROSITE; PS00661; FERM_2; 1.
DR   PROSITE; PS50057; FERM_3; 1.
DR   PROSITE; PS50106; PDZ; 1.
DR   PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
DR   PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR   PROSITE; PS50055; TYR_PHOSPHATASE_PTP; 1.
DR   Genevisible; Q9WU22; MM.
PE   1: Evidence at protein level;
KW   Cell membrane; Cytoplasm; Cytoskeleton; Hydrolase; Membrane;
KW   Phosphoprotein; Protein phosphatase; Reference proteome.
FT   CHAIN           1..926
FT                   /note="Tyrosine-protein phosphatase non-receptor type 4"
FT                   /id="PRO_0000320075"
FT   DOMAIN          29..312
FT                   /note="FERM"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT   DOMAIN          517..589
FT                   /note="PDZ"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT   DOMAIN          655..911
FT                   /note="Tyrosine-protein phosphatase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT   REGION          379..412
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          429..474
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          492..511
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        430..458
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        492..507
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        852
FT                   /note="Phosphocysteine intermediate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00160,
FT                   ECO:0000255|PROSITE-ProRule:PRU10044"
FT   BINDING         820
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         852..858
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         896
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         474
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   CONFLICT        311
FT                   /note="D -> G (in Ref. 1; AAD22773)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        359
FT                   /note="P -> S (in Ref. 1; AAD22773)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        741
FT                   /note="T -> I (in Ref. 1; AAD22773)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        781
FT                   /note="V -> A (in Ref. 1; AAD22773)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        800
FT                   /note="F -> I (in Ref. 1; AAD22773)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   926 AA;  105832 MW;  73E465D804C9C5FB CRC64;
     MTARFRLPAG RTYNVRASEL ARDRQHTEVV CNILLLDNTV QAFRVNKHDQ GQVLLDIVFK
     HLDLTERDYF GLQLADDSTD NPRWLDPNKP IRKQLKRGSP YNLNFRVKFF VSDPNKLQEE
     YTRYQYFLQI KQDILTGRLS CPCNTAALLA SFAVQSELGD YNQSENLAGY LSDYSFIPNQ
     PQDFEKEIAK LHQQHVGLSP AEAEFNYLNA ARTLELYGVE FHYARDQSNN EILIGVMSGG
     ILIYKNRVRM NTFLWLKIVK ISFKCKQFFI QLRKELHESR ETLLGFNMVN YRACKTLWKA
     CVEHHTFFRL DRPLPPQKNF FAHYFTLGSK FRYCGRTEVQ SVQYGKEKAN KDRVFARSPS
     KPLARKLMDW EVVSRNSLSD DRLETQSLPS RSPPGTPNHR NSSFTQEATR VRPSSVGHLV
     DHVVHMSPSE DFVSQRSPSS TQANSIVLES SPSQETPEDG QPPALPPKQS KKNSWNQIHF
     SNSQQDLVTH TNESFDVPSS PEKSTPNGGI PHDNLVLIKM KPDENGRFGF NVKGGYDQKM
     PVIVSRVAPG TPADLCVPRL NEGDQVVLIN GRDIAEHTHD QVVLFIKASC EKHSGELVLL
     VRPNAVYDVV EEKLESEPDF QYIPEKAPLD SVHQDDHSLR ESMIQLAEGL ITGTVLAQFD
     QLYRKKPGMT MSCAKLPQNI SKNRYRDISP YDATRVLLKG NEDYINANYI NMEIPSSSII
     NQYIACQGPL PHTCKDFWQM TWEQGSSMVV MLTTQVERGR VKCHQYWPEP SESSSYGCYQ
     VTCHSEEGNP AYIFRKMTLF NQEKNESRQL TQIQYTAWPD HGVPDDSSDF LDFVCHVRDQ
     RAGKEEPIIV HCSAGIGRTG VLITMETAMC LIECNQPVYP LDIVRTMRDQ RAMMIQTPSQ
     YRFVCEAILK VYEEGFVKPL TTSSNK
//