PTPRB

Protein-coding gene in the species Homo sapiens
PTPRB
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

2AHS, 2H02, 2H03, 2H04, 2HC1, 2HC2, 2I3R, 2I3U, 2I4E, 2I4G, 2I4H, 2I5X

Identifiers
AliasesPTPRB, HPTP-BETA, HPTPB, PTPB, R-PTP-BETA, VEPTP, protein tyrosine phosphatase, receptor type B, protein tyrosine phosphatase receptor type B
External IDsOMIM: 176882; MGI: 97809; HomoloGene: 2125; GeneCards: PTPRB; OMA:PTPRB - orthologs
Gene location (Human)
Chromosome 12 (human)
Chr.Chromosome 12 (human)[1]
Chromosome 12 (human)
Genomic location for PTPRB
Genomic location for PTPRB
Band12q15Start70,515,870 bp[1]
End70,637,440 bp[1]
Gene location (Mouse)
Chromosome 10 (mouse)
Chr.Chromosome 10 (mouse)[2]
Chromosome 10 (mouse)
Genomic location for PTPRB
Genomic location for PTPRB
Band10|10 D2Start116,275,523 bp[2]
End116,389,535 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • endothelial cell

  • lower lobe of lung

  • visceral pleura

  • right lung

  • right ventricle

  • parietal pleura

  • upper lobe of lung

  • upper lobe of left lung

  • epithelium of colon

  • Skeletal muscle tissue of biceps brachii
Top expressed in
  • right lung

  • right lung lobe

  • left lung

  • external carotid artery

  • internal carotid artery

  • carotid body

  • left lung lobe

  • digastric muscle

  • lumbar subsegment of spinal cord

  • triceps brachii muscle
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
  • protein tyrosine phosphatase activity
  • phosphatase activity
  • transmembrane receptor protein tyrosine phosphatase activity
  • protein binding
  • phosphoprotein phosphatase activity
  • hydrolase activity
Cellular component
  • integral component of membrane
  • receptor complex
  • integral component of plasma membrane
  • membrane
  • plasma membrane
  • specific granule membrane
  • tertiary granule membrane
Biological process
  • phosphate-containing compound metabolic process
  • protein dephosphorylation
  • angiogenesis
  • dephosphorylation
  • peptidyl-tyrosine dephosphorylation
  • neutrophil degranulation
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

5787

19263

Ensembl

ENSG00000127329

ENSMUSG00000020154

UniProt

P23467

B2RU80

RefSeq (mRNA)

NM_001109754
NM_001206971
NM_001206972
NM_002837
NM_001330204

NM_029928

RefSeq (protein)

NP_001103224
NP_001193900
NP_001193901
NP_001317133
NP_002828

NP_084204

Location (UCSC)Chr 12: 70.52 – 70.64 MbChr 10: 116.28 – 116.39 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Receptor-type tyrosine-protein phosphatase beta or VE-PTP is an enzyme specifically expressed in endothelial cells that in humans is encoded by the PTPRB gene.[5][6]

Function

VE-PTP is a member of the classical protein tyrosine phosphatase (PTP) family. The deletion of the gene in mouse models was shown to be embryonically lethal,[7] thus indicating that it is important for vasculogenesis and blood vessel development. In addition, it was shown to participate in adherens junctions complex and regulate vascular permeability.[8][9] Recently, Soni et al. have shown that tyrosine phosphorylation of VE-PTP via Pyk2 kinase downstream of STIM1-induced calcium entry mediates disassembly of the endothelial adherens junctions.[9]

Interactions

VE-PTP contains an extracellular domain composed of multiple fibronectin type_III repeats, a single transmembrane segment and one intracytoplasmic catalytic domain, thus belongs to R3 receptor subtype PTPs. The extracellular region was shown to interact with the angiopoietin receptor Tie-2[6] and with the adhesion protein VE-cadherin.[9][10]

VE-PTP was also found to interact with Grb2 and plakoglobin through its cytoplasmatic domain.

Role in disease

Dysregulation of PTPRB correlates with the development of a variety of tumors. PTPRB promotes metastasis of colorectal cancer cells via inducing epithelial-mesenchymal transition (EMT).[11]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000127329 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020154 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: PTPRB protein tyrosine phosphatase, receptor type, B".
  6. ^ a b Fachinger G, Deutsch U, Risau W (October 1999). "Functional interaction of vascular endothelial-protein-tyrosine phosphatase with the angiopoietin receptor Tie-2". Oncogene. 18 (43): 5948–5953. doi:10.1038/sj.onc.1202992. PMID 10557082.
  7. ^ Bäumer S, Keller L, Holtmann A, Funke R, August B, Gamp A, et al. (June 2006). "Vascular endothelial cell-specific phosphotyrosine phosphatase (VE-PTP) activity is required for blood vessel development". Blood. 107 (12): 4754–4762. doi:10.1182/blood-2006-01-0141. PMID 16514057.
  8. ^ Broermann A, Winderlich M, Block H, Frye M, Rossaint J, Zarbock A, et al. (November 2011). "Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo". The Journal of Experimental Medicine. 208 (12): 2393–2401. doi:10.1084/jem.20110525. PMC 3256962. PMID 22025303.
  9. ^ a b c Soni D, Regmi SC, Wang DM, DebRoy A, Zhao YY, Vogel SM, et al. (June 2017). "Pyk2 phosphorylation of VE-PTP downstream of STIM1-induced Ca2+ entry regulates disassembly of adherens junctions". American Journal of Physiology. Lung Cellular and Molecular Physiology. 312 (6): L1003–L1017. doi:10.1152/ajplung.00008.2017. PMC 5495943. PMID 28385807.
  10. ^ Nawroth R, Poell G, Ranft A, Kloep S, Samulowitz U, Fachinger G, et al. (September 2002). "VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts". The EMBO Journal. 21 (18): 4885–4895. doi:10.1093/emboj/cdf497. PMC 126293. PMID 12234928.
  11. ^ Weng X, Chen W, Hu W, Xu K, Qi L, Chen J, et al. (April 2019). "PTPRB promotes metastasis of colorectal carcinoma via inducing epithelial-mesenchymal transition". Cell Death & Disease. 10 (5): 352. doi:10.1038/s41419-019-1554-9. PMC 6491493. PMID 31040266.

Further reading

  • Ramachandran C, Aebersold R, Tonks NK, Pot DA (May 1992). "Sequential dephosphorylation of a multiply phosphorylated insulin receptor peptide by protein tyrosine phosphatases". Biochemistry. 31 (17): 4232–4238. doi:10.1021/bi00132a012. PMID 1373652.
  • Harder KW, Anderson LL, Duncan AM, Jirik FR (1993). "The gene for receptor-like protein tyrosine phosphatase (PTPRB) is assigned to chromosome 12q15-->q21". Cytogenetics and Cell Genetics. 61 (4): 269–270. doi:10.1159/000133419. PMID 1486802.
  • Krueger NX, Streuli M, Saito H (October 1990). "Structural diversity and evolution of human receptor-like protein tyrosine phosphatases". The EMBO Journal. 9 (10): 3241–3252. doi:10.1002/j.1460-2075.1990.tb07523.x. PMC 552056. PMID 2170109.
  • Gaits F, Li RY, Ragab A, Ragab-Thomas JM, Chap H (October 1995). "Increase in receptor-like protein tyrosine phosphatase activity and expression level on density-dependent growth arrest of endothelial cells". The Biochemical Journal. 311 ( Pt 1) (Pt 1): 97–103. doi:10.1042/bj3110097. PMC 1136124. PMID 7575486.
  • Feito MJ, Bragardo M, Buonfiglio D, Bonissoni S, Bottarel F, Malavasi F, Dianzani U (August 1997). "gp 120s derived from four syncytium-inducing HIV-1 strains induce different patterns of CD4 association with lymphocyte surface molecules". International Immunology. 9 (8): 1141–1147. doi:10.1093/intimm/9.8.1141. PMID 9263011.
  • Nawroth R, Poell G, Ranft A, Kloep S, Samulowitz U, Fachinger G, et al. (September 2002). "VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts". The EMBO Journal. 21 (18): 4885–4895. doi:10.1093/emboj/cdf497. PMC 126293. PMID 12234928.
  • v
  • t
  • e
  • 2ahs: Crystal Structure of the Catalytic Domain of Human Tyrosine Receptor Phosphatase Beta
    2ahs: Crystal Structure of the Catalytic Domain of Human Tyrosine Receptor Phosphatase Beta
  • 2h02: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors
    2h02: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors
  • 2h03: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors
    2h03: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors
  • 2h04: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors
    2h04: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors
  • 2hc1: Engineered catalytic domain of protein tyrosine phosphatase HPTPbeta.
    2hc1: Engineered catalytic domain of protein tyrosine phosphatase HPTPbeta.
  • 2hc2: Engineered protein tyrosine phosphatase beta catalytic domain
    2hc2: Engineered protein tyrosine phosphatase beta catalytic domain
  • 2i3r: Engineered catalytic domain of protein tyrosine phosphatase HPTPbeta
    2i3r: Engineered catalytic domain of protein tyrosine phosphatase HPTPbeta
  • 2i3u: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors
    2i3u: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors
  • 2i4e: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors
    2i4e: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors
  • 2i4g: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with a sulfamic acid (soaking experiment)
    2i4g: Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with a sulfamic acid (soaking experiment)
  • 2i4h: Structural studies of protein tyrosine phosphatase beta catalytic domain co-crystallized with a sulfamic acid inhibitor
    2i4h: Structural studies of protein tyrosine phosphatase beta catalytic domain co-crystallized with a sulfamic acid inhibitor
  • 2i5x: Engineering the PTPbeta catalytic domain with improved crystallization properties
    2i5x: Engineering the PTPbeta catalytic domain with improved crystallization properties
  • v
  • t
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Class I
Classical PTPs
Receptor type PTPs
Non receptor type PTPs
VH1-like or
dual specific
phosphatases
(DSPs)
MAPK phosphatases (MKPs)
Slingshots
PRLs
CDC14s
Atypical DSPs
Phosphatase and tensin
homologs (PTENs)
Myotubularins
Class II
Class III
Class IV
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