World Library  
Flag as Inappropriate
Email this Article

Cd63

Article Id: WHEBN0012303543
Reproduction Date:

Title: Cd63  
Author: World Heritage Encyclopedia
Language: English
Subject: CD82 (gene), CD81, CD117, CD37, CD53
Collection: Clusters of Differentiation
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Cd63

CD63 molecule
Identifiers
Symbols  ; LAMP-3; ME491; MLA1; OMA81H; TSPAN30
External IDs GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

CD63 antigen is a protein that in humans is encoded by the CD63 gene.[1] CD63 is mainly associated with membranes of intracellular vesicles, although cell surface expression may be induced.

Contents

  • Function 1
  • Allergy Diagnosis 2
  • Research 3
  • Interactions 4
  • See also 5
  • References 6
  • Further reading 7
  • External links 8

Function

The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility.

This encoded protein is a cell surface glycoprotein that is known to complex with integrins. It may function as a blood platelet activation marker. Deficiency of this protein is associated with Hermansky-Pudlak syndrome. Also this gene has been associated with tumor progression. The use of alternate polyadenylation sites has been found for this gene. Alternative splicing results in multiple transcript variants encoding different proteins.[1]

Allergy Diagnosis

CD63 is a good marker for flow cytometric quantification of in vitro activated basophils for diagnosis of IgE-mediated allergy. The test is commonly designated as basophil activation test (BAT).

Research

Initially, deletion and point mutants were used to investigate the role of the C-terminus, which contains a putative lysosomal-targeting/internalisation motif (GYEVM). C-terminal mutants showed increased surface expression and decreased intracellular localisation relative to CD63Wt. Antibody induced internalisation was reduced in C-terminal deletion mutants and abolished in G→A and Y→A mutants, showing the crucial role of these residues in internalisation.

CD63 is extensively and variably glycosylated and the EC2 region contain three potential N-linked glycosylation sites (N130, N150 and N172). Mutants N130A and N150A were similar to hCD63Wt with respect to intracellular localisation and internalisation. However, the hCD63N172A mutant showed a mainly cell surface localisation and low internalisation. Expression of a mutant lacking all three glycosylation sites was very unstable. It was speculated that the reduced internalisation of CD63N172A might be due to changes in its interaction with cell surface molecules. Immunoprecipitation experiments showed some evidence of a protein (100kDa) associating with CD63N172A, but this was not consistent. However, an association between CD63Wt and β2 integrin (CD18) was shown by co-internalisation of these proteins. Interactions with CD63 may therefore affect the trafficking and function of β2 integrins. Recent work by other groups suggests that CD63 functions as an “adaptor”, controlling the functions of interacting proteins such as integrins, by inducing their internalisation. Our findings indicate that CD63 glycosylation status can affect this role (2).

A recent investigation showed that expression of CD63 positively correlates with the invasiveness of ovarian cancer. [2]

Interactions

CD63 has been shown to interact with CD117[3] and CD82.[4]

See also

References

  1. ^ a b "Entrez Gene: CD63 CD63 molecule". 
  2. ^ Kobayashi M (Jan 2014). "Ovarian cancer cell invasiveness is associated with discordant exosomal sequestration of Let-7 miRNA and miR-200". J Transl Med. 12.  
  3. ^ Anzai, Naoyuki; Lee Younghee; Youn Byung-S; Fukuda Seiji; Kim Young-June; Mantel Charlie; Akashi Makoto; Broxmeyer Hal E (Jun 2002). "C-kit associated with the transmembrane 4 superfamily proteins constitutes a functionally distinct subunit in human hematopoietic progenitors". Blood (United States) 99 (12): 4413–4421.  
  4. ^ Hammond, C; Denzin L K; Pan M; Griffith J M; Geuze H J; Cresswell P (Oct 1998). "The tetraspan protein CD82 is a resident of MHC class II compartments where it associates with HLA-DR, -DM, and -DO molecules". J. Immunol. (UNITED STATES) 161 (7): 3282–91.  

Gorakh Mal (2012). Investigation of cellular functions of tetraspanin CD63. ISBN 978-3-659-18758-2; Publishers: LAP LAMBERT Academic Publishing (LAP), GmbH & Co., Germany.

Further reading

  • Horejsí V, Vlcek C (1991). "Novel structurally distinct family of leucocyte surface glycoproteins including CD9, CD37, CD53 and CD63". FEBS Lett. 288 (1–2): 1–4.  
  • Berditchevski F (2002). "Complexes of tetraspanins with integrins: more than meets the eye". J. Cell. Sci. 114 (Pt 23): 4143–51.  
  • Wang MX, Earley JJ, Shields JA, Donoso LA (1992). "An ocular melanoma-associated antigen. Molecular characterization". Arch. Ophthalmol. 110 (3): 399–404.  
  • Hotta H, Miyamoto H, Hara I et al. (1992). "Genomic structure of the ME491/CD63 antigen gene and functional analysis of the 5'-flanking regulatory sequences". Biochem. Biophys. Res. Commun. 185 (1): 436–442.  
  • Metzelaar MJ, Wijngaard PL, Peters PJ et al. (1991). "CD63 antigen. A novel lysosomal membrane glycoprotein, cloned by a screening procedure for intracellular antigens in eukaryotic cells". J. Biol. Chem. 266 (5): 3239–45.  
  • Rapp G, Freudenstein J, Klaudiny J et al. (1990). "Characterization of three abundant mRNAs from human ovarian granulosa cells". DNA Cell Biol. 9 (7): 479–485.  
  • Hotta H, Takahashi N, Homma M (1990). "Transcriptional enhancement of the human gene encoding for a melanoma-associated antigen (ME491) in association with malignant transformation". Jpn. J. Cancer Res. 80 (12): 1186–91.  
  • Hotta H, Ross AH, Huebner K et al. (1988). "Molecular cloning and characterization of an antigen associated with early stages of melanoma tumor progression". Cancer Res. 48 (11): 2955–62.  
  • Ross AH, Dietzschold B, Jackson DM et al. (1985). "Isolation and amino terminal sequencing of a novel melanoma-associated antigen". Arch. Biochem. Biophys. 242 (2): 540–548.  
  • Berditchevski F, Bazzoni G, Hemler ME (1995). "Specific association of CD63 with the VLA-3 and VLA-6 integrins". J. Biol. Chem. 270 (30): 17784–17790.  
  • Nishibori M, Cham B, McNicol A et al. (1993). "The protein CD63 is in platelet dense granules, is deficient in a patient with Hermansky-Pudlak syndrome, and appears identical to granulophysin". J. Clin. Invest. 91 (4): 1775–1782.  
  • Radford KJ, Thorne RF, Hersey P (1996). "CD63 associates with transmembrane 4 superfamily members, CD9 and CD81, and with beta 1 integrins in human melanoma". Biochem. Biophys. Res. Commun. 222 (1): 13–18.  
  • Gwynn B, Eicher EM, Peters LL (1996). "Genetic localization of Cd63, a member of the transmembrane 4 superfamily, reveals two distinct loci in the mouse genome". Genomics 35 (2): 389–391.  
  • Mannion BA, Berditchevski F, Kraeft SK et al. (1996). "Transmembrane-4 superfamily proteins CD81 (TAPA-1), CD82, CD63, and CD53 specifically associated with integrin alpha 4 beta 1 (CD49d/CD29)". J. Immunol. 157 (5): 2039–47.  
  • Skubitz KM, Campbell KD, Iida J, Skubitz AP (1996). "CD63 associates with tyrosine kinase activity and CD11/CD18, and transmits an activation signal in neutrophils". J. Immunol. 157 (8): 3617–26.  
  • Berditchevski F, Tolias KF, Wong K et al. (1997). "A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase". J. Biol. Chem. 272 (5): 2595–2598.  
  • Sincock PM, Mayrhofer G, Ashman LK (1997). "Localization of the transmembrane 4 superfamily (TM4SF) member PETA-3 (CD151) in normal human tissues: comparison with CD9, CD63, and alpha5beta1 integrin". J. Histochem. Cytochem. 45 (4): 515–25.  
  • Berditchevski F, Chang S, Bodorova J, Hemler ME (1997). "Generation of monoclonal antibodies to integrin-associated proteins. Evidence that alpha3beta1 complexes with EMMPRIN/basigin/OX47/M6". J. Biol. Chem. 272 (46): 29174–29180.  
  • Tachibana I, Bodorova J, Berditchevski F et al. (1997). "NAG-2, a novel transmembrane-4 superfamily (TM4SF) protein that complexes with integrins and other TM4SF proteins". J. Biol. Chem. 272 (46): 29181–29189.  

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 


Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.