Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Receptor-type tyrosine-protein phosphatase epsilon

Gene

Ptpre

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Isoform 1 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). 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 similarity2 Publications
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.
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+.

Catalytic activityi

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

Enzyme regulationi

Isoform 1 is inhibited by alendronate (ALN), orthovanadate, and phenylarsine oxide (PAO).1 Publication

Kineticsi

  1. KM=70 µM for fluorescein diphosphate (isoform 1)1 Publication
  1. Vmax=6 µmol/min/mg enzyme for fluorescein diphosphate (isoform 1)1 Publication

Sites

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

GO - Molecular functioni

  • protein homodimerization activity Source: MGI
  • protein tyrosine phosphatase activity Source: MGI

GO - Biological processi

  • negative regulation of insulin receptor signaling pathway Source: UniProtKB
  • regulation of mast cell activation Source: UniProtKB
  • transmembrane receptor protein tyrosine phosphatase signaling pathway Source: MGI
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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:97813. Ptpre.

Subcellular locationi

Isoform 2 :
  • Cytoplasm

  • Note: Predominantly cytoplasmic. A small fraction is also associated with nucleus and membrane. Insulin can induce translocation to the membrane.

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 45ExtracellularSequence analysisAdd BLAST26
Transmembranei46 – 68HelicalSequence analysisAdd BLAST23
Topological domaini69 – 699CytoplasmicSequence analysisAdd BLAST631

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • nucleus Source: MGI
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice show greater insulin-induced tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate 1 (IRS-1) in the skeletal muscle. Antigen- and IgE-mediated passive systemic anaphylactic reactions are enhanced. Erythrocytes exhibit abnormal morphology, increased Ca2+-activated-K+ channel activity and marked perturbation of the erythrocyte membrane tyrosine phosphoproteome.3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000002544020 – 699Receptor-type tyrosine-protein phosphatase epsilonAdd BLAST680

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi23N-linked (GlcNAc...)Sequence analysis1
Glycosylationi31N-linked (GlcNAc...)Sequence analysis1
Modified residuei695PhosphotyrosineCombined sources1

Post-translational modificationi

A catalytically active cytoplasmic form (p65) is produced by proteolytic cleavage of either isoform 1, isoform 2 or isoform 3.1 Publication
Isoform 1 and isoform 2 are phosphorylated on tyrosine residues by tyrosine kinase Neu.By similarity
Isoform 1 is glycosylated.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP49446.
PaxDbiP49446.
PeptideAtlasiP49446.
PRIDEiP49446.

PTM databases

iPTMnetiP49446.
PhosphoSitePlusiP49446.

Expressioni

Tissue specificityi

Isoform 2 is expressed in the spleen and thymus (at protein level). Detected in fibroblasts, myeloid cells, macrophages, and T-cells but not in B-cell lines. Isoform 1 and isoform 2 are expressed predominantly in the brain, testes, and lungs, with lower levels present in lymph nodes, thymus, spleen, heart and mammary glands. Isoform 1 is expressed in osteoclasts and not in osteoblasts and its expression is related to osteoclast differentiation. It is also expressed in the erythrocytes. Isoform 2 is strongly expressed in skeletal muscle and L6 skeletal muscle cell line.5 Publications

Inductioni

Isoform 2 is induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) and its induction is dependent upon PKC activity.1 Publication

Gene expression databases

BgeeiENSMUSG00000041836.
CleanExiMM_PTPRE.
GenevisibleiP49446. MM.

Interactioni

Subunit structurei

Monomer (By similarity). 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

GO - Molecular functioni

  • protein homodimerization activity Source: MGI

Protein-protein interaction databases

BioGridi202496. 1 interactor.
IntActiP49446. 6 interactors.
STRINGi10090.ENSMUSP00000073616.

Structurei

3D structure databases

ProteinModelPortaliP49446.
SMRiP49446.
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

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.1 Publication

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.
HOVERGENiHBG053758.
InParanoidiP49446.
KOiK18033.
OMAiANDKKMP.
OrthoDBiEOG091G02ID.
PhylomeDBiP49446.
TreeFamiTF351829.

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: P49446-1) [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 SFSLSLARAG QGNDTTPTES NWTSTTAGPP DPGASQPLLT
60 70 80 90 100
WLLLPLLLLL FLLAAYFFRF RKQRKAVVSS NDKKMPNGIL EEQEQQRVML
110 120 130 140 150
LSRSPSGPKK FFPIPVEHLE EEIRVRSADD CKRFREEFNS LPSGHIQGTF
160 170 180 190 200
ELANKEENRE KNRYPNILPN DHCRVILSQV 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 QTLHSTATHF 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 EAISVRDFLV TFKQPLARQE EQVRMVRQFH FHGWPEVGIP
610 620 630 640 650
AEGKGMIDLI AAVQKQQQQT GNHPITVHCS AGAGRTGTFI ALSNILERVK
660 670 680 690
AEGLLDVFQA VKSLRLQRPH MVQTLEQYEF CYKVVQDFID IFSDYANFK
Note: Produced by alternative promoter usage.
Length:699
Mass (Da):80,688
Last modified:December 15, 2009 - v3
Checksum:i581EF9CB881BC05B
GO
Isoform 2 (identifier: P49446-2) [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):74,735
Checksum:i92F99E9729D8F1F3
GO
Isoform 3 (identifier: P49446-3) [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):71,467
Checksum:i56E0BE70BB2BB59C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti137E → K in BAE32920 (PubMed:16141072).Curated1
Sequence conflicti500G → A in BAA11927 (Ref. 4) Curated1
Sequence conflicti506V → G in AAC52281 (PubMed:7592814).Curated1
Sequence conflicti506V → G in AAC52331 (PubMed:8618876).Curated1
Sequence conflicti506V → G in AAB04553 (Ref. 5) Curated1
Sequence conflicti521 – 522IV → ML in BAA11927 (Ref. 4) Curated2
Sequence conflicti606M → I in AAC52281 (PubMed:7592814).Curated1
Sequence conflicti606M → I in AAC52331 (PubMed:8618876).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0384911 – 84Missing in isoform 3. CuratedAdd BLAST84
Alternative sequenceiVSP_0384921 – 69MEPFC…AYFFR → MSSRKNFSRLTW in isoform 2. 2 PublicationsAdd BLAST69

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U35368 mRNA. Translation: AAC52281.1.
U36758 mRNA. Translation: AAC52331.1.
U40280 mRNA. Translation: AAB02190.1.
D83484 mRNA. Translation: BAA11927.1.
U62387 mRNA. Translation: AAB04553.1.
AK154910 mRNA. Translation: BAE32920.1.
CH466531 Genomic DNA. Translation: EDL17805.1.
CH466531 Genomic DNA. Translation: EDL17807.1.
Z23052 mRNA. Translation: CAA80587.1.
Z23053 mRNA. Translation: CAA80588.1.
CCDSiCCDS21944.1. [P49446-1]
PIRiB61180.
JC6132.
S40284.
RefSeqiNP_001303607.1. NM_001316678.1.
NP_001303608.1. NM_001316679.1. [P49446-1]
NP_001303609.1. NM_001316680.1.
NP_001303610.1. NM_001316681.1. [P49446-2]
NP_035342.3. NM_011212.3. [P49446-1]
UniGeneiMm.945.

Genome annotation databases

EnsembliENSMUST00000073961; ENSMUSP00000073616; ENSMUSG00000041836. [P49446-1]
ENSMUST00000209979; ENSMUSP00000147613; ENSMUSG00000041836. [P49446-2]
ENSMUST00000210833; ENSMUSP00000147313; ENSMUSG00000041836. [P49446-1]
ENSMUST00000211140; ENSMUSP00000147957; ENSMUSG00000041836. [P49446-1]
GeneIDi19267.
KEGGimmu:19267.
UCSCiuc009kee.1. mouse. [P49446-1]
uc009kek.1. mouse. [P49446-2]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative promoter usage

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U35368 mRNA. Translation: AAC52281.1.
U36758 mRNA. Translation: AAC52331.1.
U40280 mRNA. Translation: AAB02190.1.
D83484 mRNA. Translation: BAA11927.1.
U62387 mRNA. Translation: AAB04553.1.
AK154910 mRNA. Translation: BAE32920.1.
CH466531 Genomic DNA. Translation: EDL17805.1.
CH466531 Genomic DNA. Translation: EDL17807.1.
Z23052 mRNA. Translation: CAA80587.1.
Z23053 mRNA. Translation: CAA80588.1.
CCDSiCCDS21944.1. [P49446-1]
PIRiB61180.
JC6132.
S40284.
RefSeqiNP_001303607.1. NM_001316678.1.
NP_001303608.1. NM_001316679.1. [P49446-1]
NP_001303609.1. NM_001316680.1.
NP_001303610.1. NM_001316681.1. [P49446-2]
NP_035342.3. NM_011212.3. [P49446-1]
UniGeneiMm.945.

3D structure databases

ProteinModelPortaliP49446.
SMRiP49446.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202496. 1 interactor.
IntActiP49446. 6 interactors.
STRINGi10090.ENSMUSP00000073616.

PTM databases

iPTMnetiP49446.
PhosphoSitePlusiP49446.

Proteomic databases

MaxQBiP49446.
PaxDbiP49446.
PeptideAtlasiP49446.
PRIDEiP49446.

Protocols and materials databases

DNASUi19267.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000073961; ENSMUSP00000073616; ENSMUSG00000041836. [P49446-1]
ENSMUST00000209979; ENSMUSP00000147613; ENSMUSG00000041836. [P49446-2]
ENSMUST00000210833; ENSMUSP00000147313; ENSMUSG00000041836. [P49446-1]
ENSMUST00000211140; ENSMUSP00000147957; ENSMUSG00000041836. [P49446-1]
GeneIDi19267.
KEGGimmu:19267.
UCSCiuc009kee.1. mouse. [P49446-1]
uc009kek.1. mouse. [P49446-2]

Organism-specific databases

CTDi5791.
MGIiMGI:97813. Ptpre.

Phylogenomic databases

eggNOGiKOG4228. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00760000118900.
HOVERGENiHBG053758.
InParanoidiP49446.
KOiK18033.
OMAiANDKKMP.
OrthoDBiEOG091G02ID.
PhylomeDBiP49446.
TreeFamiTF351829.

Miscellaneous databases

ChiTaRSiPtpre. mouse.
PROiP49446.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000041836.
CleanExiMM_PTPRE.
GenevisibleiP49446. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: P49446
Secondary accession number(s): Q3U369
, Q60986, Q61042, Q62134, Q62444, Q64496
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: December 15, 2009
Last modified: November 2, 2016
This is version 146 of the entry and version 3 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.