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Protein

Receptor-type tyrosine-protein phosphatase epsilon

Gene

Ptpre

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Isoform 1 plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells. May play a role in osteoclast formation and function (By similarity). Acts as a negative regulator of insulin receptor (IR) signaling and is involved in insulin-induced glucose metabolism mainly through direct dephosphorylation and inactivation of IR in hepatocytes and liver.By similarity
Isoform 2 acts as a negative regulator of insulin receptor (IR) signaling in skeletal muscle. Regulates insulin-induced tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate 1 (IRS-1), phosphorylation of protein kinase B and glycogen synthase kinase-3 and insulin induced stimulation of glucose uptake (By similarity).By similarity
Isoform 1 and isoform 2 act as a negative regulator of FceRI-mediated signal transduction leading to cytokine production and degranulation, most likely by acting at the level of SYK to affect downstream events such as phosphorylation of SLP76 and LAT and mobilization of Ca2+.By similarity

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei302SubstrateBy similarity1
Active sitei334Phosphocysteine intermediateBy similarity1
Binding sitei378SubstrateBy similarity1
Active sitei629Phosphocysteine intermediateBy similarity1

GO - Molecular functioni

  • protein tyrosine phosphatase activity Source: RGD

GO - Biological processi

  • negative regulation of insulin receptor signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Names & Taxonomyi

Protein namesi
Recommended name:
Receptor-type tyrosine-protein phosphatase epsilon (EC:3.1.3.48)
Short name:
Protein-tyrosine phosphatase epsilon
Short name:
R-PTP-epsilon
Gene namesi
Name:Ptpre
Synonyms:Ptpe
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi620771. Ptpre.

Subcellular locationi

Isoform 2 :
  • Cytoplasm By similarity

  • Note: Predominantly cytoplasmic. A small fraction is also associated with nucleus and membrane. Insulin can induce translocation to the membrane (By similarity).By similarity
Isoform 3 :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 47ExtracellularSequence analysisAdd BLAST25
Transmembranei48 – 68HelicalSequence analysisAdd BLAST21
Topological domaini69 – 699CytoplasmicSequence analysisAdd BLAST631

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000038963823 – 699Receptor-type tyrosine-protein phosphatase epsilonAdd BLAST677

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi23N-linked (GlcNAc...)Sequence analysis1
Glycosylationi31N-linked (GlcNAc...)Sequence analysis1
Modified residuei695PhosphotyrosineBy similarity1

Post-translational modificationi

A catalytically active cytoplasmic form (p65) is produced by proteolytic cleavage of either isoform 1, isoform 2 or isoform 3.By similarity
Isoform 1 and isoform 2 are phosphorylated on tyrosine residues by tyrosine kinase Neu.By similarity
N-glycosylated.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiB2GV87.
PRIDEiB2GV87.

PTM databases

iPTMnetiB2GV87.
PhosphoSitePlusiB2GV87.

Expressioni

Tissue specificityi

Isoform 1 is highly expressed in the brain, lung, spleen and testis. Isoform 2 is highly expressed in thymus, spleen and lung. Isoform 1 and isoform 2 are expressed in primary hepatocytes.2 Publications

Gene expression databases

BgeeiENSRNOG00000015717.
GenevisibleiB2GV87. RN.

Interactioni

Subunit structurei

Monomer. Isoform 2: Homodimer. Can form oligomers. Dimerization is increased by oxidative stress and decreased by EGFR. Isoform 2 interacts with GRB2 (By similarity).By similarity

Protein-protein interaction databases

IntActiB2GV87. 1 interactor.
STRINGi10116.ENSRNOP00000021359.

Structurei

3D structure databases

ProteinModelPortaliB2GV87.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini134 – 393Tyrosine-protein phosphatase 1PROSITE-ProRule annotationAdd BLAST260
Domaini425 – 688Tyrosine-protein phosphatase 2PROSITE-ProRule annotationAdd BLAST264

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni334 – 340Substrate bindingBy similarity7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi52 – 63Poly-LeuAdd BLAST12

Domaini

The tyrosine-protein phosphatase 2 domain (D2) mediates dimerization. The extreme N- and C- termini of the D2 domain act to inhibit dimerization and removal of these sequences increases dimerization and inhibits enzyme activity (By similarity).By similarity

Sequence similaritiesi

Contains 2 tyrosine-protein phosphatase domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4228. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00760000118900.
HOGENOMiHOG000231465.
HOVERGENiHBG053758.
InParanoidiB2GV87.
KOiK18033.
OMAiANDKKMP.
OrthoDBiEOG091G02ID.
PhylomeDBiB2GV87.

Family and domain databases

Gene3Di3.90.190.10. 2 hits.
InterProiIPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR016336. Tyr_Pase_rcpt_a/e-type.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
PfamiPF00102. Y_phosphatase. 2 hits.
[Graphical view]
PIRSFiPIRSF002006. PTPR_alpha_epsilon. 1 hit.
PRINTSiPR00700. PRTYPHPHTASE.
SMARTiSM00194. PTPc. 2 hits.
SM00404. PTPc_motif. 2 hits.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 2 hits.
PROSITEiPS00383. TYR_PHOSPHATASE_1. 2 hits.
PS50056. TYR_PHOSPHATASE_2. 2 hits.
PS50055. TYR_PHOSPHATASE_PTP. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative promoter usage and alternative initiation. AlignAdd to basket

Isoform 1 (identifier: B2GV87-1) [UniParc]FASTAAdd to basket
Also known as: PTPeM, RPTPe, tm-PTPe

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEPFCPLLLA SFSLSLATAG QGNDTTPTES NWTSTTAGPP DPGTSQPLLT
60 70 80 90 100
WLLLPLLLLL FLLAAYFFRF RKQRKAVVNS NDKKMPNGIL EEQEQQRVML
110 120 130 140 150
LSRSPSGPKK YFPIPVEHLE EEIRVRSADD CKRFREEFNS LPSGHIQGTF
160 170 180 190 200
ELANKEENRE KNRYPNILPN DHCRVILSQL DGIPCSDYIN ASYIDGYKEK
210 220 230 240 250
NKFIAAQGPK QETVNDFWRM VWEQRSATIV MLTNLKERKE EKCYQYWPDQ
260 270 280 290 300
GCWTYGNIRV CVEDCVVLVD YTIRKFCIHP QLPDSCKAPR LVSQLHFTSW
310 320 330 340 350
PDFGVPFTPI GMLKFLKKVK TLNPSHAGPI VVHCSAGVGR TGTFIVIDAM
360 370 380 390 400
MDMIHSEQKV DVFEFVSRIR NQRPQMVQTD VQYTFIYQAL LEYYLYGDTE
410 420 430 440 450
LDVSSLERHL QTLHGTATHF DKIGLEEEFR KLTNVRIMKE NMRTGNLPAN
460 470 480 490 500
MKKARVIQII PYDFNRVILS MKRGQEFTDY INASFIDGYR QKDYFMATQG
510 520 530 540 550
PLAHTVEDFW RMVWEWKSHT IVMLTEVQER EQDKCYQYWP TEGSVTHGDI
560 570 580 590 600
TIEIKSDTLS EAISIRDFLV TFKQPLARQE EQVRMVRQFH FHGWPEVGIP
610 620 630 640 650
TEGKGMIDLI AAVQKQQQQT GNHPITVHCS AGAGRTGTFI ALSNILERVK
660 670 680 690
AEGLLDVFQA VKSLRLQRPH MVQTLEQYEF CYKVVQDFID IFSDYANFK
Note: Produced by alternative promoter usage.
Length:699
Mass (Da):80,734
Last modified:June 10, 2008 - v1
Checksum:i799F63B840FF7C67
GO
Isoform 2 (identifier: B2GV87-2) [UniParc]FASTAAdd to basket
Also known as: PTPeC, cyt-PTPe

The sequence of this isoform differs from the canonical sequence as follows:
     1-69: MEPFCPLLLA...LFLLAAYFFR → MSSRKNFSRLTW

Note: Produced by alternative promoter usage.
Show »
Length:642
Mass (Da):74,806
Checksum:i8D2C47A09BAFE304
GO
Isoform 3 (identifier: B2GV87-3) [UniParc]FASTAAdd to basket
Also known as: p67

The sequence of this isoform differs from the canonical sequence as follows:
     1-84: Missing.

Note: Produced by alternative initiation at Met-85 of isoform 1.
Show »
Length:615
Mass (Da):71,511
Checksum:iD258D7FD1F75638E
GO

Sequence cautioni

The sequence AAI66573 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti4F → L in BAA11433 (PubMed:8579581).Curated1
Sequence conflicti573K → T in BAA20333 (PubMed:8579581).Curated1
Sequence conflicti593G → A in BAA20333 (PubMed:8579581).Curated1
Sequence conflicti610 – 611IA → LS in BAA20333 (PubMed:8579581).Curated2
Sequence conflicti621G → D in BAA20333 (PubMed:8579581).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0384881 – 84Missing in isoform 3. 1 PublicationAdd BLAST84
Alternative sequenceiVSP_0384891 – 69MEPFC…AYFFR → MSSRKNFSRLTW in isoform 2. 1 PublicationAdd BLAST69

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D78610 mRNA. Translation: BAA20333.1.
D78613 mRNA. Translation: BAA11433.1.
CH473953 Genomic DNA. Translation: EDM11793.1.
CH473953 Genomic DNA. Translation: EDM11794.1.
BC166573 mRNA. Translation: AAI66573.1. Different initiation.
CV110063 mRNA. No translation available.
RefSeqiNP_446219.1. NM_053767.1. [B2GV87-1]
XP_006230511.1. XM_006230449.3. [B2GV87-1]
XP_008758193.1. XM_008759971.2. [B2GV87-1]
XP_008758194.1. XM_008759972.2. [B2GV87-1]
UniGeneiRn.107819.

Genome annotation databases

EnsembliENSRNOT00000021359; ENSRNOP00000021359; ENSRNOG00000015717. [B2GV87-1]
GeneIDi114767.
KEGGirno:114767.
UCSCiRGD:620771. rat. [B2GV87-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative promoter usage

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D78610 mRNA. Translation: BAA20333.1.
D78613 mRNA. Translation: BAA11433.1.
CH473953 Genomic DNA. Translation: EDM11793.1.
CH473953 Genomic DNA. Translation: EDM11794.1.
BC166573 mRNA. Translation: AAI66573.1. Different initiation.
CV110063 mRNA. No translation available.
RefSeqiNP_446219.1. NM_053767.1. [B2GV87-1]
XP_006230511.1. XM_006230449.3. [B2GV87-1]
XP_008758193.1. XM_008759971.2. [B2GV87-1]
XP_008758194.1. XM_008759972.2. [B2GV87-1]
UniGeneiRn.107819.

3D structure databases

ProteinModelPortaliB2GV87.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiB2GV87. 1 interactor.
STRINGi10116.ENSRNOP00000021359.

PTM databases

iPTMnetiB2GV87.
PhosphoSitePlusiB2GV87.

Proteomic databases

PaxDbiB2GV87.
PRIDEiB2GV87.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000021359; ENSRNOP00000021359; ENSRNOG00000015717. [B2GV87-1]
GeneIDi114767.
KEGGirno:114767.
UCSCiRGD:620771. rat. [B2GV87-1]

Organism-specific databases

CTDi5791.
RGDi620771. Ptpre.

Phylogenomic databases

eggNOGiKOG4228. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00760000118900.
HOGENOMiHOG000231465.
HOVERGENiHBG053758.
InParanoidiB2GV87.
KOiK18033.
OMAiANDKKMP.
OrthoDBiEOG091G02ID.
PhylomeDBiB2GV87.

Miscellaneous databases

PROiB2GV87.

Gene expression databases

BgeeiENSRNOG00000015717.
GenevisibleiB2GV87. RN.

Family and domain databases

Gene3Di3.90.190.10. 2 hits.
InterProiIPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR016336. Tyr_Pase_rcpt_a/e-type.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
PfamiPF00102. Y_phosphatase. 2 hits.
[Graphical view]
PIRSFiPIRSF002006. PTPR_alpha_epsilon. 1 hit.
PRINTSiPR00700. PRTYPHPHTASE.
SMARTiSM00194. PTPc. 2 hits.
SM00404. PTPc_motif. 2 hits.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 2 hits.
PROSITEiPS00383. TYR_PHOSPHATASE_1. 2 hits.
PS50056. TYR_PHOSPHATASE_2. 2 hits.
PS50055. TYR_PHOSPHATASE_PTP. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPTPRE_RAT
AccessioniPrimary (citable) accession number: B2GV87
Secondary accession number(s): Q63476, Q63477
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 2009
Last sequence update: June 10, 2008
Last modified: November 2, 2016
This is version 64 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.