ID   PTPRO_MOUSE             Reviewed;        1226 AA.
AC   E9Q612; Q7TSY7;
DT   14-DEC-2011, integrated into UniProtKB/Swiss-Prot.
DT   05-APR-2011, sequence version 1.
DT   24-JAN-2024, entry version 92.
DE   RecName: Full=Receptor-type tyrosine-protein phosphatase O;
DE            Short=R-PTP-O;
DE            EC=3.1.3.48;
DE   AltName: Full=Glomerular epithelial protein 1;
DE   AltName: Full=Protein tyrosine phosphatase U2;
DE            Short=PTP-U2;
DE            Short=PTPase U2;
DE   Flags: Precursor;
GN   Name=Ptpro; Synonyms=GLEPP1, Ptpn15, PTPU2;
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 [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   [2]
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   [3]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=11086029; DOI=10.1172/jci7236;
RA   Wharram B.L., Goyal M., Gillespie P.J., Wiggins J.E., Kershaw D.B.,
RA   Holzman L.B., Dysko R.C., Saunders T.L., Samuelson L.C., Wiggins R.C.;
RT   "Altered podocyte structure in GLEPP1 (Ptpro)-deficient mice associated
RT   with hypertension and low glomerular filtration rate.";
RL   J. Clin. Invest. 106:1281-1290(2000).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-875, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA   Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA   Thibault P.;
RT   "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL   Immunity 30:143-154(2009).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-875, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Kidney;
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   [6]
RP   INTERACTION WITH FYN AND GRB2, PHOSPHORYLATION AT TYR-1220, AND MUTAGENESIS
RP   OF TYR-1220.
RX   PubMed=20398064; DOI=10.1111/j.1365-2443.2010.01398.x;
RA   Murata Y., Mori M., Kotani T., Supriatna Y., Okazawa H., Kusakari S.,
RA   Saito Y., Ohnishi H., Matozaki T.;
RT   "Tyrosine phosphorylation of R3 subtype receptor-type protein tyrosine
RT   phosphatases and their complex formations with Grb2 or Fyn.";
RL   Genes Cells 15:513-524(2010).
CC   -!- FUNCTION: Possesses tyrosine phosphatase activity. Plays a role in
CC       regulating the glomerular pressure/filtration rate relationship through
CC       an effect on podocyte structure and function.
CC       {ECO:0000269|PubMed:11086029}.
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 (phosphorylated form) with FYN and GRB2.
CC       {ECO:0000269|PubMed:20398064}.
CC   -!- INTERACTION:
CC       E9Q612; P27467: Wnt3a; NbExp=2; IntAct=EBI-8183885, EBI-2899665;
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type I
CC       membrane protein {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Modification of podocyte structure such that the
CC       normal octopoid podocyte is simplified to a more amoeboid structure and
CC       that the foot processes are shorter and broader than normal. These
CC       changes are associated with altered distribution of the podocyte
CC       intermediate cytoskeletal protein vimentin/VIM. Mutant animals have a
CC       reduced glomerular filtration rate and reduced glomerular nephrin
CC       (NPHS1) content. However, there is no evidence of proteinuria. After
CC       removal of one or more kidneys, Ptpro-null animals have higher blood
CC       pressure than does their wild-type littermates.
CC       {ECO:0000269|PubMed:11086029}.
CC   -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family.
CC       Receptor class 3 subfamily. {ECO:0000305}.
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DR   EMBL; AC093120; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC144767; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC163627; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC052743; AAH52743.1; -; mRNA.
DR   CCDS; CCDS20664.1; -.
DR   RefSeq; NP_035346.3; NM_011216.3.
DR   AlphaFoldDB; E9Q612; -.
DR   SMR; E9Q612; -.
DR   BioGRID; 202505; 2.
DR   IntAct; E9Q612; 1.
DR   MINT; E9Q612; -.
DR   STRING; 10090.ENSMUSP00000076364; -.
DR   GlyConnect; 2674; 2 N-Linked glycans (1 site).
DR   GlyCosmos; E9Q612; 10 sites, 2 glycans.
DR   GlyGen; E9Q612; 10 sites, 2 N-linked glycans (1 site).
DR   iPTMnet; E9Q612; -.
DR   PhosphoSitePlus; E9Q612; -.
DR   jPOST; E9Q612; -.
DR   MaxQB; E9Q612; -.
DR   PaxDb; 10090-ENSMUSP00000076364; -.
DR   ProteomicsDB; 301949; -.
DR   Antibodypedia; 23718; 116 antibodies from 22 providers.
DR   DNASU; 19277; -.
DR   Ensembl; ENSMUST00000077115.13; ENSMUSP00000076364.7; ENSMUSG00000030223.15.
DR   GeneID; 19277; -.
DR   KEGG; mmu:19277; -.
DR   UCSC; uc009emv.2; mouse.
DR   AGR; MGI:1097152; -.
DR   CTD; 5800; -.
DR   MGI; MGI:1097152; Ptpro.
DR   VEuPathDB; HostDB:ENSMUSG00000030223; -.
DR   eggNOG; KOG0791; Eukaryota.
DR   GeneTree; ENSGT00940000154814; -.
DR   HOGENOM; CLU_007724_0_0_1; -.
DR   InParanoid; E9Q612; -.
DR   OMA; TISFITX; -.
DR   OrthoDB; 5395787at2759; -.
DR   PhylomeDB; E9Q612; -.
DR   TreeFam; TF351926; -.
DR   BioGRID-ORCS; 19277; 2 hits in 72 CRISPR screens.
DR   PRO; PR:E9Q612; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   RNAct; E9Q612; Protein.
DR   Bgee; ENSMUSG00000030223; Expressed in cortical plate and 190 other cell types or tissues.
DR   ExpressionAtlas; E9Q612; baseline and differential.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR   GO; GO:0043197; C:dendritic spine; IDA:UniProtKB.
DR   GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR   GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR   GO; GO:0016328; C:lateral plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0098839; C:postsynaptic density membrane; IDA:SynGO.
DR   GO; GO:0045296; F:cadherin binding; ISO:MGI.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:UniProtKB.
DR   GO; GO:0017147; F:Wnt-protein binding; IDA:UniProtKB.
DR   GO; GO:0007411; P:axon guidance; IMP:UniProtKB.
DR   GO; GO:0000902; P:cell morphogenesis; IMP:UniProtKB.
DR   GO; GO:0032835; P:glomerulus development; ISS:UniProtKB.
DR   GO; GO:0030032; P:lamellipodium assembly; IMP:UniProtKB.
DR   GO; GO:0002548; P:monocyte chemotaxis; ISS:UniProtKB.
DR   GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR   GO; GO:0003105; P:negative regulation of glomerular filtration; ISS:UniProtKB.
DR   GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; IDA:UniProtKB.
DR   GO; GO:1990264; P:peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity; IDA:CACAO.
DR   GO; GO:0072112; P:podocyte differentiation; IMP:UniProtKB.
DR   GO; GO:0003093; P:regulation of glomerular filtration; IMP:UniProtKB.
DR   GO; GO:0050807; P:regulation of synapse organization; IDA:SynGO.
DR   GO; GO:0036060; P:slit diaphragm assembly; IMP:UniProtKB.
DR   CDD; cd00063; FN3; 3.
DR   CDD; cd14614; R-PTPc-O; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 3.
DR   Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1.
DR   InterPro; IPR003961; FN3_dom.
DR   InterPro; IPR036116; FN3_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR   InterPro; IPR000242; PTP_cat.
DR   InterPro; IPR042996; PTPRO.
DR   InterPro; IPR016130; Tyr_Pase_AS.
DR   InterPro; IPR003595; Tyr_Pase_cat.
DR   InterPro; IPR000387; Tyr_Pase_dom.
DR   PANTHER; PTHR47028; RECEPTOR-TYPE TYROSINE-PROTEIN PHOSPHATASE O; 1.
DR   PANTHER; PTHR47028:SF1; RECEPTOR-TYPE TYROSINE-PROTEIN PHOSPHATASE O; 1.
DR   Pfam; PF00041; fn3; 2.
DR   Pfam; PF00102; Y_phosphatase; 1.
DR   PRINTS; PR00700; PRTYPHPHTASE.
DR   SMART; SM00060; FN3; 4.
DR   SMART; SM00194; PTPc; 1.
DR   SMART; SM00404; PTPc_motif; 1.
DR   SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1.
DR   SUPFAM; SSF49265; Fibronectin type III; 3.
DR   PROSITE; PS50853; FN3; 5.
DR   PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
DR   PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR   PROSITE; PS50055; TYR_PHOSPHATASE_PTP; 1.
DR   Genevisible; E9Q612; MM.
PE   1: Evidence at protein level;
KW   Glycoprotein; Hydrolase; Membrane; Phosphoprotein; Protein phosphatase;
KW   Receptor; Reference proteome; Repeat; Signal; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL          1..29
FT                   /evidence="ECO:0000255"
FT   CHAIN           30..1226
FT                   /note="Receptor-type tyrosine-protein phosphatase O"
FT                   /id="PRO_0000414059"
FT   TOPO_DOM        30..832
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        833..853
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        854..1226
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          30..115
FT                   /note="Fibronectin type-III 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          339..435
FT                   /note="Fibronectin type-III 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          445..541
FT                   /note="Fibronectin type-III 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          542..638
FT                   /note="Fibronectin type-III 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          641..734
FT                   /note="Fibronectin type-III 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          735..827
FT                   /note="Fibronectin type-III 6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          948..1205
FT                   /note="Tyrosine-protein phosphatase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT   REGION          242..305
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        256..271
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        274..305
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        1146
FT                   /note="Phosphocysteine intermediate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00160,
FT                   ECO:0000255|PROSITE-ProRule:PRU10044"
FT   BINDING         1112
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         1146..1152
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         1190
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         875
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19144319,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         1220
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000269|PubMed:20398064"
FT   CARBOHYD        75
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        154
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        227
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        279
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        471
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        500
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        710
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        743
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        800
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   MUTAGEN         1220
FT                   /note="Y->F: Loss of tyrosine phosphorylation. Abolishes
FT                   interaction with FYN and GRB2."
FT                   /evidence="ECO:0000269|PubMed:20398064"
FT   CONFLICT        1184
FT                   /note="Y -> H (in Ref. 2; AAH52743)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1226 AA;  138589 MW;  3FF0BE298354BC32 CRC64;
     MGHLPRGTLG GRRLLPLLGL FVLLKIVTTF HVAVQDDNNI VVSLEASDIV SPASVYVVRV
     AGESKNYFFE FEEFNSTLPP PVVFKATYHG LYYIITLVVV NGNVVTKPSR SITVLTKPLP
     VTSVSIYDYK PSPETGVLFE IHYPEKYNVF SRVNISYWEG RDFRTMLYKD FFKGKTVFNH
     WLPGLCYSNI TFQLVSEATF NKSTLVEYSG VSHEPKQHRT APYPPRNISV RFVNLNKNNW
     EEPSGSFPED SFIKPPQDSI GRDRRFHFPE ETPETPPSNV SSGSPPSNVS SAWPDPNSTD
     YESTSQPFWW DSASAAPENE EDFVSALPAD YDTETTLDRT EKPTADPFSA FPVQMTLSWL
     PPKPPTAFDG FNILIEREEN FTDYLTVDEE AHEFVAELKE PGKYKLSVTT FSSSGACETR
     KSQSAKSLSF YISPTGEWIE ELTEKPQHVS VHVLSSTTAL MSWTSSQENY NSTIVSVVSL
     TCQKQKESQR LEKQYCTQVN SSKPVIENLV PGAQYQVVMY LRKGPLIGPP SDPVTFAIVP
     TGIKDLMLYP LGPTAVVLSW TRPILGVFRK YVVEMFYFNP TTMTSEWTTY YEIAATVSLT
     ASVRIASLLP AWYYNFRVTM VTWGDPELSC CDSSTISFIT APVAPEITSV EYFNSLLYIS
     WTYGDATTDL SHSRMLHWMV VAEGRKKIKK SVTRNVMTAI LSLPPGDIYN LSVTACTERG
     SNTSLPRLVK LEPAPPKSLF AVNKTQTSVT LLWVEEGVAD FFEVFCQQLG SGHNGKLQEP
     VAVSSHVVTI SSLLPATAYN CSVTSFSHDT PSVPTFIAVS TMVTEVNPNV VVISVLAILS
     TLLIGLLLVT LVILRKKHLQ MARECGAGTF VNFASLEREG KLPYSWRRSV FALLTLLPSC
     LWTDYLLAFY INPWSKNGLK KRKLTNPVQL DDFDSYIKDM AKDSDYKFSL QFEELKLIGL
     DIPHFAADLP LNRCKNRYTN ILPYDFSRVR LVSMNEEEGA DYINANYIPG YNSPQEYIAT
     QGPLPETRND FWKMVLQQKS HIIVMLTQCN EKRRVKCDHY WPFTEEPIAY GDITVEMVSE
     EEEEDWASRH FRINYADEAQ DVMHFNYTAW PDHGVPPANA AESILQFVFT VRQQAAKSKG
     PMIIHCSAGV GRTGTFIALD RLLQHIRDHE FVDILGLVSE MRSYRMSMVQ TEEQYIFIHQ
     CVQLMWLRKK QQFCISDVIY ENVSKS
//