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UniProtKB - P23469 (PTPRE_HUMAN)

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Protein

Receptor-type tyrosine-protein phosphatase epsilon

Gene

PTPRE

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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).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 sitei303SubstrateBy similarity1
Active sitei335Phosphocysteine intermediateBy similarity1
Binding sitei379SubstrateBy similarity1
Active sitei630Phosphocysteine intermediateBy similarity1

GO - Molecular functioni

  • transmembrane receptor protein tyrosine phosphatase activity Source: ProtInc
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • negative regulation of insulin receptor signaling pathway Source: UniProtKB
  • protein dephosphorylation Source: ProtInc
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionHydrolase, Protein phosphatase

Enzyme and pathway databases

BRENDAi3.1.3.48 2681
SignaLinkiP23469
SIGNORiP23469

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000132334.16
HGNCiHGNC:9669 PTPRE
MIMi600926 gene
neXtProtiNX_P23469

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 46ExtracellularSequence analysisAdd BLAST27
Transmembranei47 – 69HelicalSequence analysisAdd BLAST23
Topological domaini70 – 700CytoplasmicSequence analysisAdd BLAST631

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi5791
OpenTargetsiENSG00000132334
PharmGKBiPA34014

Chemistry databases

ChEMBLiCHEMBL4850
DrugBankiDB00630 Alendronic acid

Polymorphism and mutation databases

BioMutaiPTPRE
DMDMi126471

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000002543920 – 700Receptor-type tyrosine-protein phosphatase epsilonAdd BLAST681

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi23N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi30N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei696PhosphotyrosineCombined 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.1 Publication
Isoform 1 is glycosylated.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP23469
PaxDbiP23469
PeptideAtlasiP23469
PRIDEiP23469
ProteomicsDBi54107
54108 [P23469-2]
54109 [P23469-3]

PTM databases

DEPODiP23469
iPTMnetiP23469
PhosphoSitePlusiP23469

Expressioni

Tissue specificityi

Expressed in giant cell tumor (osteoclastoma rich in multinucleated osteoclastic cells).1 Publication

Inductioni

Up-regulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) in HL-60 cells.1 Publication

Gene expression databases

BgeeiENSG00000132334
CleanExiHS_PTPRE
ExpressionAtlasiP23469 baseline and differential
GenevisibleiP23469 HS

Organism-specific databases

HPAiHPA015870
HPA021872

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

BioGridi111755, 37 interactors
IntActiP23469, 10 interactors
MINTiP23469
STRINGi9606.ENSP00000254667

Chemistry databases

BindingDBiP23469

Structurei

Secondary structure

1700
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi117 – 119Combined sources3
Helixi120 – 126Combined sources7
Helixi139 – 141Combined sources3
Turni152 – 155Combined sources4
Helixi157 – 162Combined sources6
Beta strandi172 – 177Combined sources6
Turni185 – 188Combined sources4
Beta strandi189 – 197Combined sources9
Beta strandi200 – 207Combined sources8
Helixi212 – 214Combined sources3
Helixi215 – 224Combined sources10
Beta strandi229 – 232Combined sources4
Beta strandi236 – 238Combined sources3
Beta strandi250 – 256Combined sources7
Beta strandi259 – 268Combined sources10
Beta strandi270 – 280Combined sources11
Beta strandi291 – 298Combined sources8
Beta strandi303 – 305Combined sources3
Helixi311 – 323Combined sources13
Beta strandi331 – 334Combined sources4
Beta strandi336 – 340Combined sources5
Helixi341 – 358Combined sources18
Beta strandi359 – 361Combined sources3
Helixi363 – 371Combined sources9
Helixi381 – 396Combined sources16
Helixi426 – 434Combined sources9
Helixi444 – 447Combined sources4
Helixi449 – 452Combined sources4
Beta strandi464 – 469Combined sources6
Beta strandi481 – 487Combined sources7
Beta strandi490 – 492Combined sources3
Beta strandi496 – 499Combined sources4
Turni504 – 506Combined sources3
Helixi507 – 516Combined sources10
Beta strandi521 – 524Combined sources4
Beta strandi528 – 530Combined sources3
Beta strandi542 – 548Combined sources7
Beta strandi551 – 560Combined sources10
Beta strandi562 – 573Combined sources12
Beta strandi584 – 592Combined sources9
Beta strandi597 – 599Combined sources3
Helixi605 – 620Combined sources16
Beta strandi626 – 629Combined sources4
Beta strandi631 – 635Combined sources5
Helixi636 – 653Combined sources18
Beta strandi654 – 656Combined sources3
Helixi658 – 666Combined sources9
Helixi676 – 690Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JJDX-ray3.20A/B/C/D/E/F107-697[»]
ProteinModelPortaliP23469
SMRiP23469
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23469

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini135 – 394Tyrosine-protein phosphatase 1PROSITE-ProRule annotationAdd BLAST260
Domaini426 – 689Tyrosine-protein phosphatase 2PROSITE-ProRule annotationAdd BLAST264

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni335 – 341Substrate 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 (By similarity).By similarity

Sequence similaritiesi

Belongs to the protein-tyrosine phosphatase family. Receptor class 4 subfamily.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4228 Eukaryota
COG5599 LUCA
GeneTreeiENSGT00760000118900
HOGENOMiHOG000231465
HOVERGENiHBG053758
InParanoidiP23469
KOiK18033
OMAiWKSHTIV
OrthoDBiEOG091G02ID
PhylomeDBiP23469
TreeFamiTF351829

Family and domain databases

Gene3Di3.90.190.10, 2 hits
InterProiView protein in InterPro
IPR029021 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
PfamiView protein in Pfam
PF00102 Y_phosphatase, 2 hits
PIRSFiPIRSF002006 PTPR_alpha_epsilon, 1 hit
PRINTSiPR00700 PRTYPHPHTASE
SMARTiView protein in SMART
SM00194 PTPc, 2 hits
SM00404 PTPc_motif, 2 hits
SUPFAMiSSF52799 SSF52799, 2 hits
PROSITEiView protein in PROSITE
PS00383 TYR_PHOSPHATASE_1, 2 hits
PS50056 TYR_PHOSPHATASE_2, 2 hits
PS50055 TYR_PHOSPHATASE_PTP, 2 hits

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: P23469-1) [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
MEPLCPLLLV GFSLPLARAL RGNETTADSN ETTTTSGPPD PGASQPLLAW 
        60         70         80         90        100
LLLPLLLLLL VLLLAAYFFR FRKQRKAVVS TSDKKMPNGI LEEQEQQRVM 
       110        120        130        140        150
LLSRSPSGPK KYFPIPVEHL EEEIRIRSAD DCKQFREEFN SLPSGHIQGT 
       160        170        180        190        200
FELANKEENR EKNRYPNILP NDHSRVILSQ LDGIPCSDYI NASYIDGYKE 
       210        220        230        240        250
KNKFIAAQGP KQETVNDFWR MVWEQKSATI VMLTNLKERK EEKCHQYWPD 
       260        270        280        290        300
QGCWTYGNIR VCVEDCVVLV DYTIRKFCIQ PQLPDGCKAP RLVSQLHFTS 
       310        320        330        340        350
WPDFGVPFTP IGMLKFLKKV KTLNPVHAGP IVVHCSAGVG RTGTFIVIDA 
       360        370        380        390        400
MMAMMHAEQK VDVFEFVSRI RNQRPQMVQT DMQYTFIYQA LLEYYLYGDT 
       410        420        430        440        450
ELDVSSLEKH LQTMHGTTTH FDKIGLEEEF RKLTNVRIMK ENMRTGNLPA 
       460        470        480        490        500
NMKKARVIQI IPYDFNRVIL SMKRGQEYTD YINASFIDGY RQKDYFIATQ 
       510        520        530        540        550
GPLAHTVEDF WRMIWEWKSH TIVMLTEVQE REQDKCYQYW PTEGSVTHGE 
       560        570        580        590        600
ITIEIKNDTL SEAISIRDFL VTLNQPQARQ EEQVRVVRQF HFHGWPEIGI 
       610        620        630        640        650
PAEGKGMIDL IAAVQKQQQQ TGNHPITVHC SAGAGRTGTF IALSNILERV 
       660        670        680        690        700
KAEGLLDVFQ AVKSLRLQRP HMVQTLEQYE FCYKVVQDFI DIFSDYANFK
Note: Produced by alternative promoter usage.
Length:700
Mass (Da):80,642
Last modified:November 1, 1991 - v1
Checksum:iD096BCADCEA65708
GO
Isoform 2 (identifier: P23469-2) [UniParc]FASTAAdd to basket
Also known as: PTPeC, cyt-PTPe

The sequence of this isoform differs from the canonical sequence as follows:
     1-70: MEPLCPLLLV...VLLLAAYFFR → MSNRSSFSRLTW

Note: Produced by alternative promoter usage.
Show »
Length:642
Mass (Da):74,595
Checksum:iD39B2835A8D7D949
GO
Isoform 3 (identifier: P23469-3) [UniParc]FASTAAdd to basket
Also known as: p67

The sequence of this isoform differs from the canonical sequence as follows:
     1-85: Missing.

Note: Produced by alternative initiation at Met-86 of isoform 1.
Show »
Length:615
Mass (Da):71,382
Checksum:iF4FD48DDAAA0B302
GO

Sequence cautioni

The sequence AAC50324 differs from that shown. Contaminating sequence. Sequence of unknown origin in the C-terminal part.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti516E → D in CAC86583 (PubMed:12121439).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0384901 – 85Missing in isoform 3. CuratedAdd BLAST85
Alternative sequenceiVSP_0077781 – 70MEPLC…AYFFR → MSNRSSFSRLTW in isoform 2. 2 PublicationsAdd BLAST70

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54134 mRNA Translation: CAA38069.1
AJ315969 mRNA Translation: CAC86583.1
AK291828 mRNA Translation: BAF84517.1
AL390236 Genomic DNA No translation available.
CH471066 Genomic DNA Translation: EAW49180.1
CH471066 Genomic DNA Translation: EAW49181.1
CH471066 Genomic DNA Translation: EAW49182.1
CH471066 Genomic DNA Translation: EAW49184.1
BC050062 mRNA Translation: AAH50062.1
U36623 mRNA Translation: AAC50324.1 Sequence problems.
CCDSiCCDS7657.1 [P23469-1]
CCDS7658.1 [P23469-2]
PIRiS12053
RefSeqiNP_001303605.1, NM_001316676.1
NP_001303606.1, NM_001316677.1 [P23469-1]
NP_001310283.1, NM_001323354.1 [P23469-1]
NP_006495.1, NM_006504.5 [P23469-1]
NP_569119.1, NM_130435.4 [P23469-2]
XP_005252748.1, XM_005252691.2 [P23469-1]
XP_016871957.1, XM_017016468.1 [P23469-1]
UniGeneiHs.127022

Genome annotation databases

EnsembliENST00000254667; ENSP00000254667; ENSG00000132334 [P23469-1]
ENST00000306042; ENSP00000303350; ENSG00000132334 [P23469-2]
GeneIDi5791
KEGGihsa:5791
UCSCiuc001lkb.4 human [P23469-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative promoter usage

Similar proteinsi

Entry informationi

Entry nameiPTPRE_HUMAN
AccessioniPrimary (citable) accession number: P23469
Secondary accession number(s): Q13345
, Q5VWH3, Q5VWH4, Q96KQ6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: June 20, 2018
This is version 176 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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