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P23469 (PTPRE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Receptor-type tyrosine-protein phosphatase epsilon

Short name=Protein-tyrosine phosphatase epsilon
Short name=R-PTP-epsilon
EC=3.1.3.48
Gene names
Name:PTPRE
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length700 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

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.

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 activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Subunit structure

Monomer. Isoform 2:Homodimer. Can form oligomers. Dimerization is increased by oxidative stress and decreased by EGFR. Isoform 2 interacts with GRB2 By similarity. Ref.10 Ref.12

Subcellular location

Isoform 1: Cell membrane; Single-pass type I membrane protein Ref.7 Ref.10.

Isoform 2: Cytoplasm Ref.7 Ref.10. Note: Predominantly cytoplasmic. A small fraction is also associated with nucleus and membrane. Insulin induces translocation to the membrane By similarity. Ref.7 Ref.10

Isoform 3: Cytoplasm Ref.7 Ref.10.

Tissue specificity

Expressed in giant cell tumor (osteoclastoma rich in multinucleated osteoclastic cells). Ref.8

Induction

Up-regulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) in HL-60 cells. Ref.7

Domain

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.

Post-translational modification

A catalytically active cytoplasmic form (p65) is produced by proteolytic cleavage of either isoform 1, isoform 2 or isoform 3.

Isoform 1 and isoform 2 are phosphorylated on tyrosine residues by tyrosine kinase Neu. Ref.10

Isoform 1 is glycosylated. Ref.10

Sequence similarities

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

Contains 2 tyrosine-protein phosphatase domains.

Sequence caution

The sequence AAC50324.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the C-terminal part.

Alternative products

This entry describes 3 isoforms produced by alternative promoter usage and alternative initiation. [Align] [Select]
Isoform 1 (identifier: P23469-1)

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.
Note: Produced by alternative promoter usage.
Isoform 2 (identifier: P23469-2)

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.
Isoform 3 (identifier: P23469-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Chain20 – 700681Receptor-type tyrosine-protein phosphatase epsilon
PRO_0000025439

Regions

Topological domain20 – 4627Extracellular Potential
Transmembrane47 – 6923Helical; Potential
Topological domain70 – 700631Cytoplasmic Potential
Domain135 – 394260Tyrosine-protein phosphatase 1
Domain426 – 689264Tyrosine-protein phosphatase 2
Region335 – 3417Substrate binding By similarity

Sites

Active site3351Phosphocysteine intermediate By similarity
Active site6301Phosphocysteine intermediate By similarity
Binding site3031Substrate By similarity
Binding site3791Substrate By similarity

Amino acid modifications

Modified residue6961Phosphotyrosine Ref.11
Glycosylation231N-linked (GlcNAc...) Potential
Glycosylation301N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 8585Missing in isoform 3.
VSP_038490
Alternative sequence1 – 7070MEPLC…AYFFR → MSNRSSFSRLTW in isoform 2.
VSP_007778

Experimental info

Sequence conflict5161E → D in CAC86583. Ref.2

Secondary structure

......................................................................................... 700
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (PTPeM) (RPTPe) (tm-PTPe) [UniParc].

Last modified November 1, 1991. Version 1.
Checksum: D096BCADCEA65708

FASTA70080,642
        10         20         30         40         50         60 
MEPLCPLLLV GFSLPLARAL RGNETTADSN ETTTTSGPPD PGASQPLLAW LLLPLLLLLL 

        70         80         90        100        110        120 
VLLLAAYFFR FRKQRKAVVS TSDKKMPNGI LEEQEQQRVM LLSRSPSGPK KYFPIPVEHL 

       130        140        150        160        170        180 
EEEIRIRSAD DCKQFREEFN SLPSGHIQGT FELANKEENR EKNRYPNILP NDHSRVILSQ 

       190        200        210        220        230        240 
LDGIPCSDYI NASYIDGYKE KNKFIAAQGP KQETVNDFWR MVWEQKSATI VMLTNLKERK 

       250        260        270        280        290        300 
EEKCHQYWPD QGCWTYGNIR VCVEDCVVLV DYTIRKFCIQ PQLPDGCKAP RLVSQLHFTS 

       310        320        330        340        350        360 
WPDFGVPFTP IGMLKFLKKV KTLNPVHAGP IVVHCSAGVG RTGTFIVIDA MMAMMHAEQK 

       370        380        390        400        410        420 
VDVFEFVSRI RNQRPQMVQT DMQYTFIYQA LLEYYLYGDT ELDVSSLEKH LQTMHGTTTH 

       430        440        450        460        470        480 
FDKIGLEEEF RKLTNVRIMK ENMRTGNLPA NMKKARVIQI IPYDFNRVIL SMKRGQEYTD 

       490        500        510        520        530        540 
YINASFIDGY RQKDYFIATQ GPLAHTVEDF WRMIWEWKSH TIVMLTEVQE REQDKCYQYW 

       550        560        570        580        590        600 
PTEGSVTHGE ITIEIKNDTL SEAISIRDFL VTLNQPQARQ EEQVRVVRQF HFHGWPEIGI 

       610        620        630        640        650        660 
PAEGKGMIDL IAAVQKQQQQ TGNHPITVHC SAGAGRTGTF IALSNILERV KAEGLLDVFQ 

       670        680        690        700 
AVKSLRLQRP HMVQTLEQYE FCYKVVQDFI DIFSDYANFK 

« Hide

Isoform 2 (PTPeC) (cyt-PTPe) [UniParc].

Checksum: D39B2835A8D7D949
Show »

FASTA64274,595
Isoform 3 (p67) [UniParc].

Checksum: F4FD48DDAAA0B302
Show »

FASTA61571,382

References

« Hide 'large scale' references
[1]"Structural diversity and evolution of human receptor-like protein tyrosine phosphatases."
Krueger N.X., Streuli M., Saito H.
EMBO J. 9:3241-3252(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Placenta.
[2]"Expression of human protein tyrosine phosphatase epsilon in leucocytes: a potential ERK pathway-regulating phosphatase."
Wabakken T.K., Hauge H., Finne E.F., Wiedlocha A., Aasheim H.-C.
Scand. J. Immunol. 56:195-203(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[7]"Identification of a cytoplasmic, phorbol ester-inducible isoform of protein tyrosine phosphatase epsilon."
Elson A., Leder P.
Proc. Natl. Acad. Sci. U.S.A. 92:12235-12239(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-98 (ISOFORM 2), SUBCELLULAR LOCATION, INDUCTION.
[8]"Protein-tyrosine phosphatase activity regulates osteoclast formation and function: inhibition by alendronate."
Schmidt A., Rutledge S.J., Endo N., Opas E., Tanaka H., Wesolowski G., Leu C.T., Huang Z., Ramachandaran C., Rodan S.B., Rodan G.A.
Proc. Natl. Acad. Sci. U.S.A. 93:3068-3073(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[9]"Distinct promoters control transmembrane and cytosolic protein tyrosine phosphatase epsilon expression during macrophage differentiation."
Tanuma N., Nakamura K., Kikuchi K.
Eur. J. Biochem. 259:46-54(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE PROMOTER USAGE.
[10]"Generation of novel cytoplasmic forms of protein tyrosine phosphatase epsilon by proteolytic processing and translational control."
Gil-Henn H., Volohonsky G., Toledano-Katchalski H., Gandre S., Elson A.
Oncogene 19:4375-4384(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION (ISOFORM 3), ALTERNATIVE INITIATION, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, PHOSPHORYLATION, GLYCOSYLATION, INTERACTION WITH GRB2.
[11]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-696, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[12]"Large-scale structural analysis of the classical human protein tyrosine phosphatome."
Barr A.J., Ugochukwu E., Lee W.H., King O.N.F., Filippakopoulos P., Alfano I., Savitsky P., Burgess-Brown N.A., Mueller S., Knapp S.
Cell 136:352-363(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 107-697, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X54134 mRNA. Translation: CAA38069.1.
AJ315969 mRNA. Translation: CAC86583.1.
AK291828 mRNA. Translation: BAF84517.1.
AL390236 Genomic DNA. Translation: CAH73173.1.
AL390236 Genomic DNA. Translation: CAH73174.1.
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.
PIRS12053.
RefSeqNP_006495.1. NM_006504.4.
NP_569119.1. NM_130435.3.
XP_005252748.1. XM_005252691.1.
XP_005252749.1. XM_005252692.1.
XP_005252750.1. XM_005252693.1.
UniGeneHs.127022.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2JJDX-ray3.20A/B/C/D/E/F107-697[»]
ProteinModelPortalP23469.
SMRP23469. Positions 111-691.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111755. 5 interactions.
IntActP23469. 3 interactions.
MINTMINT-1349810.
STRING9606.ENSP00000254667.

Chemistry

BindingDBP23469.
ChEMBLCHEMBL4850.

PTM databases

PhosphoSiteP23469.

Polymorphism databases

DMDM126471.

Proteomic databases

PaxDbP23469.
PRIDEP23469.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000254667; ENSP00000254667; ENSG00000132334. [P23469-1]
ENST00000306042; ENSP00000303350; ENSG00000132334. [P23469-2]
ENST00000419012; ENSP00000402337; ENSG00000132334. [P23469-1]
GeneID5791.
KEGGhsa:5791.
UCSCuc001lkb.3. human. [P23469-1]
uc001lkd.3. human. [P23469-2]

Organism-specific databases

CTD5791.
GeneCardsGC10P129705.
HGNCHGNC:9669. PTPRE.
HPAHPA015870.
HPA021872.
MIM600926. gene.
neXtProtNX_P23469.
PharmGKBPA34014.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5599.
HOGENOMHOG000231465.
HOVERGENHBG053758.
InParanoidP23469.
KOK01104.
OMAPDGCKAP.
OrthoDBEOG7B31M8.
PhylomeDBP23469.
TreeFamTF351829.

Enzyme and pathway databases

SignaLinkP23469.

Gene expression databases

ArrayExpressP23469.
BgeeP23469.
CleanExHS_PTPRE.
GenevestigatorP23469.

Family and domain databases

InterProIPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
IPR000242. Tyr_Pase_rcpt/non-rcpt.
IPR016336. Tyr_Pase_rcpt_a/e-type.
[Graphical view]
PfamPF00102. Y_phosphatase. 2 hits.
[Graphical view]
PIRSFPIRSF002006. PTPR_alpha_epsilon. 1 hit.
PRINTSPR00700. PRTYPHPHTASE.
SMARTSM00194. PTPc. 2 hits.
[Graphical view]
PROSITEPS00383. TYR_PHOSPHATASE_1. 2 hits.
PS50056. TYR_PHOSPHATASE_2. 2 hits.
PS50055. TYR_PHOSPHATASE_PTP. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP23469.
GeneWikiPTPRE.
GenomeRNAi5791.
NextBio22544.
PROP23469.
SOURCESearch...

Entry information

Entry namePTPRE_HUMAN
AccessionPrimary (citable) accession number: P23469
Secondary accession number(s): Q13345 expand/collapse secondary AC list , Q5VWH3, Q5VWH4, Q96KQ6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: March 19, 2014
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM