Entry - *604160 - INTEGRIN, BETA-8; ITGB8 - OMIM - (OMIM.ORG)

 
 
* 604160

INTEGRIN, BETA-8; ITGB8


HGNC Approved Gene Symbol: ITGB8

Cytogenetic location: 7p21.1   Genomic coordinates (GRCh38) : 7:20,329,766-20,415,754 (from NCBI)


TEXT

▼ Cloning and Expression

The integrins are a class of cell surface glycoproteins that mediate cell-cell and cell-extracellular matrix interactions. Integrins are heterodimers composed of an alpha and a beta subunit bound noncovalently to each other. See 600536. Moyle et al. (1991) isolated rabbit and human cDNAs encoding a novel integrin beta subunit that they designated beta-8. The predicted 769-amino acid human protein is 90% identical to rabbit beta-8. Like other integrin beta subunits, beta-8 contains an N-terminal signal peptide, a large extracellular domain that includes 4 cysteine-rich repeats, a transmembrane domain, and a short C-terminal cytoplasmic domain. The authors stated that the observed molecular mass of approximately 95 kD for the beta-8 polypeptide is consistent with substantial glycosylation of the predicted 81-kD beta-8 gene product. Northern blot analysis revealed that human beta-8 is expressed as an approximately 8.5-kb mRNA in an osteosarcoma cell line. When expressed in mammalian cells, beta-8 associated with the alpha-V (193210) subunit to form a cell surface integrin complex. Nishimura et al. (1998) determined that the alpha-V/beta-8 heterodimer is present in mature synapses in mouse and rat brains, suggesting that it may play a role in synaptic function.


▼ Gene Function

Travis et al. (2007) showed that conditional loss of the TGF-beta (190180)-activating integrin alpha-V/beta-8 on leukocytes causes severe inflammatory bowel disease and age-related autoimmunity in mice. This autoimmune phenotype is largely due to lack of alpha-V/beta-8 on dendritic cells, as mice lacking alpha-V/beta-8 principally on dendritic cells develop identical immunologic abnormalities as mice lacking alpha-V/beta-8 on all leukocytes, whereas mice lacking alpha-V/beta-8 on T cells alone are phenotypically normal. Travis et al. (2007) further showed that dendritic cells lacking alpha-V/beta-8 failed to induce regulatory T cells in vitro, an effect that depends on TGF-beta activity. Furthermore, mice lacking alpha-V/beta-8 on dendritic cells had reduced proportions of regulatory T cells in colonic tissue. Travis et al. (2007) concluded that alpha-V/beta-8-mediated TGF-beta activation by dendritic cells is essential for preventing immune dysfunction that results in inflammatory bowel disease and autoimmunity, effects that are due, at least in part, to the ability of alpha-V/beta-8 on dendritic cells to induce and/or maintain tissue regulatory cells.


▼ REFERENCES

  1. Moyle, M., Napier, M. A., McLean, J. W. Cloning and expression of a divergent integrin subunit beta-8. J. Biol. Chem. 266: 19650-19658, 1991. [PubMed: 1918072, related citations]

  2. Nishimura, S. L., Boylen, K. P., Einheber, S., Milner, T. A., Ramos, D. M., Pytela, R. Synaptic and glial localization of the integrin alphavbeta8 in mouse and rat brain. Brain Res. 791: 271-282, 1998. [PubMed: 9593935, related citations] [Full Text]

  3. Travis, M. A., Reizis, B., Melton, A. C., Masteller, E., Tang, Q., Proctor, J. M., Wang, Y., Bernstein, X., Huang, X., Reichardt, L. F., Bluestone, J. A., Sheppard, D. Loss of integrin alpha-V/beta-8 on dendritic cells causes autoimmunity and colitis in mice. Nature 449: 361-365, 2007. [PubMed: 17694047, images, related citations] [Full Text]


Contributors:
Ada Hamosh - updated : 1/10/2008
Creation Date:
Rebekah S. Rasooly : 9/7/1999
Edit History:
alopez : 01/29/2008
terry : 1/10/2008
alopez : 9/7/1999

* 604160

INTEGRIN, BETA-8; ITGB8


HGNC Approved Gene Symbol: ITGB8

Cytogenetic location: 7p21.1   Genomic coordinates (GRCh38) : 7:20,329,766-20,415,754 (from NCBI)


TEXT

Cloning and Expression

The integrins are a class of cell surface glycoproteins that mediate cell-cell and cell-extracellular matrix interactions. Integrins are heterodimers composed of an alpha and a beta subunit bound noncovalently to each other. See 600536. Moyle et al. (1991) isolated rabbit and human cDNAs encoding a novel integrin beta subunit that they designated beta-8. The predicted 769-amino acid human protein is 90% identical to rabbit beta-8. Like other integrin beta subunits, beta-8 contains an N-terminal signal peptide, a large extracellular domain that includes 4 cysteine-rich repeats, a transmembrane domain, and a short C-terminal cytoplasmic domain. The authors stated that the observed molecular mass of approximately 95 kD for the beta-8 polypeptide is consistent with substantial glycosylation of the predicted 81-kD beta-8 gene product. Northern blot analysis revealed that human beta-8 is expressed as an approximately 8.5-kb mRNA in an osteosarcoma cell line. When expressed in mammalian cells, beta-8 associated with the alpha-V (193210) subunit to form a cell surface integrin complex. Nishimura et al. (1998) determined that the alpha-V/beta-8 heterodimer is present in mature synapses in mouse and rat brains, suggesting that it may play a role in synaptic function.


Gene Function

Travis et al. (2007) showed that conditional loss of the TGF-beta (190180)-activating integrin alpha-V/beta-8 on leukocytes causes severe inflammatory bowel disease and age-related autoimmunity in mice. This autoimmune phenotype is largely due to lack of alpha-V/beta-8 on dendritic cells, as mice lacking alpha-V/beta-8 principally on dendritic cells develop identical immunologic abnormalities as mice lacking alpha-V/beta-8 on all leukocytes, whereas mice lacking alpha-V/beta-8 on T cells alone are phenotypically normal. Travis et al. (2007) further showed that dendritic cells lacking alpha-V/beta-8 failed to induce regulatory T cells in vitro, an effect that depends on TGF-beta activity. Furthermore, mice lacking alpha-V/beta-8 on dendritic cells had reduced proportions of regulatory T cells in colonic tissue. Travis et al. (2007) concluded that alpha-V/beta-8-mediated TGF-beta activation by dendritic cells is essential for preventing immune dysfunction that results in inflammatory bowel disease and autoimmunity, effects that are due, at least in part, to the ability of alpha-V/beta-8 on dendritic cells to induce and/or maintain tissue regulatory cells.


REFERENCES

  1. Moyle, M., Napier, M. A., McLean, J. W. Cloning and expression of a divergent integrin subunit beta-8. J. Biol. Chem. 266: 19650-19658, 1991. [PubMed: 1918072]

  2. Nishimura, S. L., Boylen, K. P., Einheber, S., Milner, T. A., Ramos, D. M., Pytela, R. Synaptic and glial localization of the integrin alphavbeta8 in mouse and rat brain. Brain Res. 791: 271-282, 1998. [PubMed: 9593935] [Full Text: https://doi.org/10.1016/s0006-8993(98)00118-8]

  3. Travis, M. A., Reizis, B., Melton, A. C., Masteller, E., Tang, Q., Proctor, J. M., Wang, Y., Bernstein, X., Huang, X., Reichardt, L. F., Bluestone, J. A., Sheppard, D. Loss of integrin alpha-V/beta-8 on dendritic cells causes autoimmunity and colitis in mice. Nature 449: 361-365, 2007. [PubMed: 17694047] [Full Text: https://doi.org/10.1038/nature06110]


Contributors:
Ada Hamosh - updated : 1/10/2008

Creation Date:
Rebekah S. Rasooly : 9/7/1999

Edit History:
alopez : 01/29/2008
terry : 1/10/2008
alopez : 9/7/1999



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OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University.
Copyright® 1966-2025 Johns Hopkins University.

NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University.
Copyright® 1966-2025 Johns Hopkins University.
Printed: June 18, 2025