ID PTPRE_RAT Reviewed; 699 AA.
AC B2GV87; Q63476; Q63477;
DT 15-DEC-2009, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 24-JAN-2024, entry version 96.
DE RecName: Full=Receptor-type tyrosine-protein phosphatase epsilon;
DE Short=Protein-tyrosine phosphatase epsilon;
DE Short=R-PTP-epsilon;
DE EC=3.1.3.48;
DE Flags: Precursor;
GN Name=Ptpre; Synonyms=Ptpe;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-297 (ISOFORM 1).
RC TISSUE=Spleen;
RX PubMed=8579581; DOI=10.1006/bbrc.1996.0129;
RA Nakamura K., Mizuno Y., Kikuchi K.;
RT "Molecular cloning of a novel cytoplasmic protein tyrosine phosphatase PTP
RT epsilon.";
RL Biochem. Biophys. Res. Commun. 218:726-732(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE PROMOTER USAGE, AND TISSUE
RP SPECIFICITY.
RX PubMed=9914474; DOI=10.1046/j.1432-1327.1999.00004.x;
RA Tanuma N., Nakamura K., Kikuchi K.;
RT "Distinct promoters control transmembrane and cytosolic protein tyrosine
RT phosphatase epsilon expression during macrophage differentiation.";
RL Eur. J. Biochem. 259:46-54(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-131 (ISOFORM 3).
RC TISSUE=Placenta;
RA Strausberg R.L.;
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=15738637; DOI=10.2108/zsj.22.169;
RA Nakagawa Y., Aoki N., Aoyama K., Shimizu H., Shimano H., Yamada N.,
RA Miyazaki H.;
RT "Receptor-type protein tyrosine phosphatase epsilon (PTPepsilonM) is a
RT negative regulator of insulin signaling in primary hepatocytes and liver.";
RL Zool. Sci. 22:169-175(2005).
CC -!- FUNCTION: Isoform 1 plays a critical role in signaling transduction
CC pathways and phosphoprotein network topology in red blood cells. May
CC play a role in osteoclast formation and function (By similarity). Acts
CC as a negative regulator of insulin receptor (IR) signaling and is
CC involved in insulin-induced glucose metabolism mainly through direct
CC dephosphorylation and inactivation of IR in hepatocytes and liver.
CC {ECO:0000250}.
CC -!- FUNCTION: Isoform 2 acts as a negative regulator of insulin receptor
CC (IR) signaling in skeletal muscle. Regulates insulin-induced tyrosine
CC phosphorylation of insulin receptor (IR) and insulin receptor substrate
CC 1 (IRS-1), phosphorylation of protein kinase B and glycogen synthase
CC kinase-3 and insulin induced stimulation of glucose uptake (By
CC similarity). {ECO:0000250}.
CC -!- FUNCTION: Isoform 1 and isoform 2 act as a negative regulator of FceRI-
CC mediated signal transduction leading to cytokine production and
CC degranulation, most likely by acting at the level of SYK to affect
CC downstream events such as phosphorylation of SLP76 and LAT and
CC mobilization of Ca(2+). {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: Monomer. Isoform 2: Homodimer. Can form oligomers.
CC Dimerization is increased by oxidative stress and decreased by EGFR.
CC Isoform 2 interacts with GRB2 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000250}; Single-
CC pass type I membrane protein {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000250}.
CC Note=Predominantly cytoplasmic. A small fraction is also associated
CC with nucleus and membrane. Insulin can induce translocation to the
CC membrane (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative initiation; Named isoforms=3;
CC Name=1; Synonyms=PTPeM, RPTPe, tm-PTPe;
CC IsoId=B2GV87-1; Sequence=Displayed;
CC Name=2; Synonyms=PTPeC, cyt-PTPe;
CC IsoId=B2GV87-2; Sequence=VSP_038489;
CC Name=3; Synonyms=p67;
CC IsoId=B2GV87-3; Sequence=VSP_038488;
CC -!- TISSUE SPECIFICITY: Isoform 1 is highly expressed in the brain, lung,
CC spleen and testis. Isoform 2 is highly expressed in thymus, spleen and
CC lung. Isoform 1 and isoform 2 are expressed in primary hepatocytes.
CC {ECO:0000269|PubMed:15738637, ECO:0000269|PubMed:9914474}.
CC -!- DOMAIN: The tyrosine-protein phosphatase 2 domain (D2) mediates
CC dimerization. The extreme N- and C- termini of the D2 domain act to
CC inhibit dimerization and removal of these sequences increases
CC dimerization and inhibits enzyme activity (By similarity).
CC {ECO:0000250}.
CC -!- PTM: A catalytically active cytoplasmic form (p65) is produced by
CC proteolytic cleavage of either isoform 1, isoform 2 or isoform 3.
CC {ECO:0000250}.
CC -!- PTM: Isoform 1 and isoform 2 are phosphorylated on tyrosine residues by
CC tyrosine kinase Neu. {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 1]: Produced by alternative promoter usage.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative promoter usage.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative initiation at Met-
CC 85 of isoform 1. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family.
CC Receptor class 4 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI66573.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; D78610; BAA20333.1; -; mRNA.
DR EMBL; D78613; BAA11433.1; -; mRNA.
DR EMBL; CH473953; EDM11793.1; -; Genomic_DNA.
DR EMBL; CH473953; EDM11794.1; -; Genomic_DNA.
DR EMBL; BC166573; AAI66573.1; ALT_INIT; mRNA.
DR EMBL; CV110063; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_446219.1; NM_053767.1. [B2GV87-1]
DR RefSeq; XP_006230511.1; XM_006230449.3. [B2GV87-1]
DR RefSeq; XP_008758193.1; XM_008759971.2.
DR RefSeq; XP_008758194.1; XM_008759972.2.
DR AlphaFoldDB; B2GV87; -.
DR SMR; B2GV87; -.
DR IntAct; B2GV87; 1.
DR MINT; B2GV87; -.
DR STRING; 10116.ENSRNOP00000021359; -.
DR GlyCosmos; B2GV87; 2 sites, No reported glycans.
DR GlyGen; B2GV87; 2 sites.
DR iPTMnet; B2GV87; -.
DR PhosphoSitePlus; B2GV87; -.
DR PaxDb; 10116-ENSRNOP00000021359; -.
DR Ensembl; ENSRNOT00000110825.1; ENSRNOP00000078012.1; ENSRNOG00000015717.9. [B2GV87-2]
DR GeneID; 114767; -.
DR KEGG; rno:114767; -.
DR UCSC; RGD:620771; rat. [B2GV87-1]
DR AGR; RGD:620771; -.
DR CTD; 5791; -.
DR RGD; 620771; Ptpre.
DR VEuPathDB; HostDB:ENSRNOG00000015717; -.
DR eggNOG; KOG4228; Eukaryota.
DR GeneTree; ENSGT00940000156570; -.
DR HOGENOM; CLU_001645_8_2_1; -.
DR InParanoid; B2GV87; -.
DR OrthoDB; 2875525at2759; -.
DR PhylomeDB; B2GV87; -.
DR PRO; PR:B2GV87; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Proteomes; UP000234681; Chromosome 1.
DR Bgee; ENSRNOG00000015717; Expressed in lung and 19 other cell types or tissues.
DR Genevisible; B2GV87; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; ISO:RGD.
DR GO; GO:0016311; P:dephosphorylation; IEA:InterPro.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0033003; P:regulation of mast cell activation; ISO:RGD.
DR GO; GO:0007185; P:transmembrane receptor protein tyrosine phosphatase signaling pathway; ISO:RGD.
DR CDD; cd14620; R-PTPc-E-1; 1.
DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 2.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000242; PTP_cat.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR016336; Tyr_Pase_rcpt_a/e-type.
DR PANTHER; PTHR19134; RECEPTOR-TYPE TYROSINE-PROTEIN PHOSPHATASE; 1.
DR PANTHER; PTHR19134:SF499; RECEPTOR-TYPE TYROSINE-PROTEIN PHOSPHATASE EPSILON; 1.
DR Pfam; PF00102; Y_phosphatase; 2.
DR PIRSF; PIRSF002006; PTPR_alpha_epsilon; 1.
DR PRINTS; PR00700; PRTYPHPHTASE.
DR SMART; SM00194; PTPc; 2.
DR SMART; SM00404; PTPc_motif; 2.
DR SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 2.
DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 2.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 2.
DR PROSITE; PS50055; TYR_PHOSPHATASE_PTP; 2.
PE 2: Evidence at transcript level;
KW Alternative initiation; Alternative promoter usage; Cell membrane;
KW Cytoplasm; Glycoprotein; Hydrolase; Membrane; Phosphoprotein;
KW Protein phosphatase; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..699
FT /note="Receptor-type tyrosine-protein phosphatase epsilon"
FT /id="PRO_0000389638"
FT TOPO_DOM 23..47
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 48..68
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 69..699
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 134..393
FT /note="Tyrosine-protein phosphatase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT DOMAIN 425..688
FT /note="Tyrosine-protein phosphatase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 20..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 334
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000250"
FT ACT_SITE 629
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000250"
FT BINDING 302
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 334..340
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 378
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 695
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P23469"
FT CARBOHYD 23
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 31
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..84
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_038488"
FT VAR_SEQ 1..69
FT /note="MEPFCPLLLASFSLSLATAGQGNDTTPTESNWTSTTAGPPDPGTSQPLLTWL
FT LLPLLLLLFLLAAYFFR -> MSSRKNFSRLTW (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8579581"
FT /id="VSP_038489"
FT CONFLICT 4
FT /note="F -> L (in Ref. 1; BAA11433)"
FT /evidence="ECO:0000305"
FT CONFLICT 573
FT /note="K -> T (in Ref. 1; BAA20333)"
FT /evidence="ECO:0000305"
FT CONFLICT 593
FT /note="G -> A (in Ref. 1; BAA20333)"
FT /evidence="ECO:0000305"
FT CONFLICT 610..611
FT /note="IA -> LS (in Ref. 1; BAA20333)"
FT /evidence="ECO:0000305"
FT CONFLICT 621
FT /note="G -> D (in Ref. 1; BAA20333)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 699 AA; 80734 MW; 799F63B840FF7C67 CRC64;
MEPFCPLLLA SFSLSLATAG QGNDTTPTES NWTSTTAGPP DPGTSQPLLT WLLLPLLLLL
FLLAAYFFRF RKQRKAVVNS NDKKMPNGIL EEQEQQRVML LSRSPSGPKK YFPIPVEHLE
EEIRVRSADD CKRFREEFNS LPSGHIQGTF ELANKEENRE KNRYPNILPN DHCRVILSQL
DGIPCSDYIN ASYIDGYKEK NKFIAAQGPK QETVNDFWRM VWEQRSATIV MLTNLKERKE
EKCYQYWPDQ GCWTYGNIRV CVEDCVVLVD YTIRKFCIHP QLPDSCKAPR LVSQLHFTSW
PDFGVPFTPI GMLKFLKKVK TLNPSHAGPI VVHCSAGVGR TGTFIVIDAM MDMIHSEQKV
DVFEFVSRIR NQRPQMVQTD VQYTFIYQAL LEYYLYGDTE LDVSSLERHL QTLHGTATHF
DKIGLEEEFR KLTNVRIMKE NMRTGNLPAN MKKARVIQII PYDFNRVILS MKRGQEFTDY
INASFIDGYR QKDYFMATQG PLAHTVEDFW RMVWEWKSHT IVMLTEVQER EQDKCYQYWP
TEGSVTHGDI TIEIKSDTLS EAISIRDFLV TFKQPLARQE EQVRMVRQFH FHGWPEVGIP
TEGKGMIDLI AAVQKQQQQT GNHPITVHCS AGAGRTGTFI ALSNILERVK AEGLLDVFQA
VKSLRLQRPH MVQTLEQYEF CYKVVQDFID IFSDYANFK
//
