PTN4_MOUSE
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 03-AUG-2022, entry version 150.
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 EPD; Q9WU22; -.
DR MaxQB; Q9WU22; -.
DR PaxDb; Q9WU22; -.
DR PeptideAtlas; Q9WU22; -.
DR PRIDE; Q9WU22; -.
DR ProteomicsDB; 301941; -.
DR Antibodypedia; 18333; 143 antibodies from 22 providers.
DR DNASU; 19258; -.
DR Ensembl; ENSMUST00000064091; ENSMUSP00000067614; ENSMUSG00000026384.
DR GeneID; 19258; -.
DR KEGG; mmu:19258; -.
DR UCSC; uc007ciz.1; mouse.
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; 96595at2759; -.
DR PhylomeDB; Q9WU22; -.
DR TreeFam; TF315900; -.
DR BioGRID-ORCS; 19258; 3 hits in 72 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 220 other tissues.
DR ExpressionAtlas; Q9WU22; baseline and differential.
DR Genevisible; Q9WU22; MM.
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:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:InterPro.
DR CDD; cd14473; FERM_B-lobe; 1.
DR CDD; cd13189; FERM_C_PTPN4_PTPN3_like; 1.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.30.42.10; -; 1.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR014847; FERM-adjacent.
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 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; SSF47031; SSF47031; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR SUPFAM; SSF54236; SSF54236; 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.
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
