PTPRO_MOUSE
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 03-AUG-2022, entry version 84.
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 GlyGen; E9Q612; 10 sites, 2 N-linked glycans (1 site).
DR iPTMnet; E9Q612; -.
DR PhosphoSitePlus; E9Q612; -.
DR jPOST; E9Q612; -.
DR MaxQB; E9Q612; -.
DR PaxDb; E9Q612; -.
DR PRIDE; E9Q612; -.
DR ProteomicsDB; 301949; -.
DR Antibodypedia; 23718; 91 antibodies from 22 providers.
DR DNASU; 19277; -.
DR Ensembl; ENSMUST00000077115; ENSMUSP00000076364; ENSMUSG00000030223.
DR GeneID; 19277; -.
DR KEGG; mmu:19277; -.
DR UCSC; uc009emv.2; mouse.
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; KNATTFH; -.
DR OrthoDB; 411281at2759; -.
DR PhylomeDB; E9Q612; -.
DR TreeFam; TF351926; -.
DR BioGRID-ORCS; 19277; 2 hits in 67 CRISPR screens.
DR PRO; PR:E9Q612; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; E9Q612; protein.
DR Bgee; ENSMUSG00000030223; Expressed in cortical plate and 188 other tissues.
DR ExpressionAtlas; E9Q612; baseline and differential.
DR Genevisible; E9Q612; MM.
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:0099061; C:integral component of postsynaptic density membrane; IDA:SynGO.
DR GO; GO:0016328; C:lateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
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 Gene3D; 2.60.40.10; -; 3.
DR Gene3D; 3.90.190.10; -; 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; PTHR47028; 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; SSF49265; SSF49265; 3.
DR SUPFAM; SSF52799; SSF52799; 1.
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.
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
