Integrin beta 1

ITGB1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4WK4, 3G9W, 3T9K, 3VI3, 3VI4, 4DX9, 4WJK, 4WK0, 4WK2
Identifiers
Aliases	ITGB1, CD29, FNRB, GPIIA, MDF2, MSK12, VLA-BETA, VLAB, integrin subunit beta 1
External IDs	OMIM: 135630; MGI: 96610; HomoloGene: 22999; GeneCards: ITGB1; OMA:ITGB1 - orthologs
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10p11.22 Start 32,900,319 bp[1] End 33,005,792 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 E2 Start 129,412,135 bp[2] End 129,459,681 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in visceral pleura seminal vesicula tail of epididymis parietal pleura stromal cell of endometrium tibia smooth muscle tissue superficial temporal artery Descending thoracic aorta palpebral conjunctiva Top expressed in Ileal epithelium stroma of bone marrow lactiferous gland left lung lobe cardiac muscle tissue of left ventricle belly cord atrium uterus calvaria extraocular muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function virus receptor activity metal ion binding integrin binding protein binding laminin binding cell adhesion molecule binding collagen binding involved in cell-matrix adhesion coreceptor activity protease binding fibronectin binding actin binding C-X3-C chemokine binding protein heterodimerization activity protein-containing complex binding cadherin binding signaling receptor activity Cellular component cytoplasm endosome membrane melanosome ruffle integrin alpha8-beta1 complex synapse ruffle membrane integrin complex perinuclear region of cytoplasm cell projection dendritic spine cell surface cleavage furrow integrin alpha7-beta1 complex extracellular exosome lamellipodium integral component of membrane recycling endosome integrin alpha1-beta1 complex intercalated disc filopodium neuromuscular junction receptor complex plasma membrane integrin alpha11-beta1 complex myelin sheath abaxonal region synaptic membrane integrin alpha10-beta1 complex cell junction integrin alpha2-beta1 complex sarcolemma external side of plasma membrane cytoplasmic vesicle integrin alpha3-beta1 complex membrane raft focal adhesion glial cell projection Schaffer collateral - CA1 synapse glutamatergic synapse integral component of synaptic membrane protein-containing complex Biological process leukocyte cell-cell adhesion cell migration involved in sprouting angiogenesis stress fiber assembly viral entry into host cell B cell differentiation neuron projection development transforming growth factor beta receptor signaling pathway regulation of collagen catabolic process negative regulation of cell differentiation cardiac muscle cell differentiation cellular response to low-density lipoprotein particle stimulus in utero embryonic development cell-substrate adhesion positive regulation of GTPase activity regulation of immune response viral process dendrite morphogenesis cell fate specification G1 phase heterotypic cell-cell adhesion extracellular matrix organization cell-cell adhesion mediated by integrin cellular defense response cell adhesion formation of radial glial scaffolds axon extension leukocyte tethering or rolling integrin-mediated signaling pathway cell-matrix adhesion sarcomere organization negative regulation of anoikis leukocyte migration homophilic cell adhesion via plasma membrane adhesion molecules visual learning calcium-independent cell-matrix adhesion cardiac muscle tissue development negative regulation of Rho protein signal transduction receptor internalization regulation of cell cycle positive regulation of cell population proliferation positive regulation of apoptotic process mesodermal cell differentiation cell migration germ cell migration cell adhesion mediated by integrin basement membrane organization positive regulation of protein localization to plasma membrane G1/S transition of mitotic cell cycle phagocytosis cytokine-mediated signaling pathway cell projection organization lamellipodium assembly positive regulation of angiogenesis modulation of chemical synaptic transmission positive regulation of protein kinase B signaling positive regulation of signaling receptor activity positive regulation of cell migration Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3688 16412 Ensembl ENSG00000150093 ENSMUSG00000025809 UniProt P05556 P09055 RefSeq (mRNA) NM_002211 NM_033666 NM_033667 NM_033668 NM_033669 NM_133376 NM_010578 RefSeq (protein) NP_002202 NP_391988 NP_596867 NP_034708 Location (UCSC) Chr 10: 32.9 – 33.01 Mb Chr 8: 129.41 – 129.46 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Integrin beta-1 (ITGB1), also known as CD29, is a cell surface receptor that in humans is encoded by the ITGB1 gene.^[5] This integrin associates with integrin alpha 1 and integrin alpha 2 to form integrin complexes which function as collagen receptors. It also forms dimers with integrin alpha 3 to form integrin receptors for netrin 1 and reelin. These and other integrin beta 1 complexes have been historically known as very late activation (VLA) antigens.

Integrin beta 1 is expressed as at least four different isoforms. In cardiac muscle and skeletal muscle, the integrin beta-1D isoform is specifically expressed, and localizes to costameres, where it aids in the lateral force transmission from the Z-discs to the extracellular matrix. Abnormal levels of integrin beta-1D have been found in limb girdle muscular dystrophy and polyneuropathy.

Structure

Integrin beta-1 can exist as different isoforms via alternative splicing. Six alternatively spliced variants have been found for this gene which encode five proteins with alternate C-termini.^[6] Integrin receptors exist as heterodimers, and greater than 20 different integrin heterodimeric receptors have been described. All integrins, alpha and beta forms, have large extracellular and short intracellular domains.^[7] The cytoplasmic domain of integrin beta-1 binds to the actin cytoskeleton.^[8] Integrin beta-1 is the most abundant beta-integrin expressed and associates with at least 10 different integrin-alpha subunits.^[7]

Function

Integrin family members are membrane receptors involved in cell adhesion and recognition in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic diffusion of tumor cells.^[7] Integrins link the actin cytoskeleton with the extracellular matrix and they transmit signals bidirectionally between the extracellular matrix and cytoplasmic domains.^[9][10] Beta-integrins are primarily responsible for targeting integrin dimers to the appropriate subcellular locations, which in adhesive cells is mainly focal adhesions.^[8][11] Integrin beta-1 mutants lose the ability to target to sites of focal adhesions.^[12][13]

Three novel isoforms of integrin beta-1 have been identified, termed beta-1B, beta-1C and beta-1D. Integrin beta-1B is transcribed when the proximal 26 amino acids of the cytoplasmic domain in exon 6 are retained and then succeeded by a 12 amino acid stretch from an adjacent intronic region.^[14] The integrin beta-1B isoform appears to act as a dominant negative in that it inhibits cell adhesion.^[15] A second integrin beta-1 isoform, termed beta-1C, was described to have an additional 48 amino acids appended to the 26 amino acids in the cytoplasmic domain;^[16] the function of this isoform was an inhibitory one on DNA synthesis in the G1 phase of the cell cycle.^[17] The third isoform, termed beta-1D, is a striated muscle-specific isoform, which replaces the canonical beta-1A isoform in cardiac and skeletal muscle cells. This isoform is produced from splicing into a novel additional exon between exons 6 and 7. The cytoplasmic domain of integrin beta-1D replaces the distal 21 amino acids (present in integrin beta-1A) with an alternative stretch of 24 amino acids (13 unique).^[18][19]

Integrin beta-1D appears to be developmentally regulated during myofibrilogenesis,^[19] appearing immediately following the fusion of myoblasts in C2C12 cell with rising levels throughout myofibrillar differentiation.^[20] Integrin beta-1D is specifically localized to costameres and intercalated discs of cardiac muscle and costameres, myotendinous junctions and neuromuscular junctions of skeletal muscle, and it appears to function in general like other integrins, as the clustering of beta-1D integrins on the surface of CHO cells resulted in tyrosine phosphorylation of pp125FAK and induced mitogen-activated protein kinase activation.^[20]

Clinical significance

In patients with limb girdle muscular dystrophy, type 2C, beta-1D integrin has been shown to be severely reduced in skeletal muscle biopsies, coordinate with a reduction in alpha 7B-integrin and filamin 2.^[21]

In patients with sensitive-motor polyneuropathy, levels of integrin alpha-7B, integrin beta-1D and agrin were significantly reduced nearly to undetectable levels; and this corresponded with lower mRNA levels.^[22]

Interactions

CD29 has been shown to interact with

• ACTN1;^[23][24]
• CD46,^[25]
• CD9,^[26][27]
• FHL2,^[28]
• Filamin,^[29][30]
• FLNB,^[29]
• CD81,^[27][31]
• GNB2L1,^[32][33]
• ITGB1BP1,^[34][35]
• LGALS8,^[36]
• MAP4K4,^[37]
• NME1,^[38]
• PKC alpha,^[32][39]
• TLN1,^[40][41]
• TSPAN4,^[42] and
• YWHAB.^[43]

References

1. GRCh38: Ensembl release 89: ENSG00000150093 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000025809 – 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. Goodfellow PJ, Nevanlinna HA, Gorman P, Sheer D, Lam G, Goodfellow PN (Jan 1989). "Assignment of the gene encoding the beta-subunit of the human fibronectin receptor (beta-FNR) to chromosome 10p11.2". Annals of Human Genetics. 53 (Pt 1): 15–22. doi:10.1111/j.1469-1809.1989.tb01118.x. PMID 2524991. S2CID 36485270.
6. "Entrez Gene: ITGB1 integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12)".
7. Hynes RO (Apr 1992). "Integrins: versatility, modulation, and signaling in cell adhesion". Cell. 69 (1): 11–25. doi:10.1016/0092-8674(92)90115-s. PMID 1555235. S2CID 32774108.
8. Sastry SK, Horwitz AF (Oct 1993). "Integrin cytoplasmic domains: mediators of cytoskeletal linkages and extra- and intracellular initiated transmembrane signaling". Current Opinion in Cell Biology. 5 (5): 819–31. doi:10.1016/0955-0674(93)90031-k. PMID 8240826.
9. Burridge K, Chrzanowska-Wodnicka M (1996). "Focal adhesions, contractility, and signaling". Annual Review of Cell and Developmental Biology. 12: 463–518. doi:10.1146/annurev.cellbio.12.1.463. PMID 8970735. S2CID 28558568.
10. Schwartz MA, Schaller MD, Ginsberg MH (1995). "Integrins: emerging paradigms of signal transduction". Annual Review of Cell and Developmental Biology. 11: 549–99. doi:10.1146/annurev.cb.11.110195.003001. PMID 8689569.
11. LaFlamme SE, Akiyama SK, Yamada KM (Apr 1992). "Regulation of fibronectin receptor distribution". The Journal of Cell Biology. 117 (2): 437–47. doi:10.1083/jcb.117.2.437. PMC 2289425. PMID 1373145.
12. Akiyama SK, Yamada SS, Yamada KM, LaFlamme SE (Jun 1994). "Transmembrane signal transduction by integrin cytoplasmic domains expressed in single-subunit chimeras". The Journal of Biological Chemistry. 269 (23): 15961–4. doi:10.1016/S0021-9258(17)33955-8. PMID 7515874.
13. Reszka AA, Hayashi Y, Horwitz AF (Jun 1992). "Identification of amino acid sequences in the integrin beta 1 cytoplasmic domain implicated in cytoskeletal association". The Journal of Cell Biology. 117 (6): 1321–30. doi:10.1083/jcb.117.6.1321. PMC 2289496. PMID 1376731.
14. Altruda F, Cervella P, Tarone G, Botta C, Balzac F, Stefanuto G, Silengo L (Nov 1990). "A human integrin beta 1 subunit with a unique cytoplasmic domain generated by alternative mRNA processing". Gene. 95 (2): 261–6. doi:10.1016/0378-1119(90)90369-3. PMID 2249781.
15. Balzac F, Retta SF, Albini A, Melchiorri A, Koteliansky VE, Geuna M, Silengo L, Tarone G (Oct 1994). "Expression of beta 1B integrin isoform in CHO cells results in a dominant negative effect on cell adhesion and motility". The Journal of Cell Biology. 127 (2): 557–65. doi:10.1083/jcb.127.2.557. hdl:2318/39410. PMC 2120206. PMID 7523423.
16. Languino LR, Ruoslahti E (Apr 1992). "An alternative form of the integrin beta 1 subunit with a variant cytoplasmic domain". The Journal of Biological Chemistry. 267 (10): 7116–20. doi:10.1016/S0021-9258(19)50545-2. PMID 1551917.
17. Meredith J, Takada Y, Fornaro M, Languino LR, Schwartz MA (Sep 1995). "Inhibition of cell cycle progression by the alternatively spliced integrin beta 1C". Science. 269 (5230): 1570–2. Bibcode:1995Sci...269.1570M. doi:10.1126/science.7545312. PMID 7545312.
18. Zhidkova NI, Belkin AM, Mayne R (Sep 1995). "Novel isoform of beta 1 integrin expressed in skeletal and cardiac muscle". Biochemical and Biophysical Research Communications. 214 (1): 279–85. doi:10.1006/bbrc.1995.2285. PMID 7545396.
19. van der Flier A, Kuikman I, Baudoin C, van der Neut R, Sonnenberg A (Aug 1995). "A novel beta 1 integrin isoform produced by alternative splicing: unique expression in cardiac and skeletal muscle". FEBS Letters. 369 (2–3): 340–4. doi:10.1016/0014-5793(95)00814-p. PMID 7544298. S2CID 86638879.
20. Belkin AM, Zhidkova NI, Balzac F, Altruda F, Tomatis D, Maier A, Tarone G, Koteliansky VE, Burridge K (Jan 1996). "Beta 1D integrin displaces the beta 1A isoform in striated muscles: localization at junctional structures and signaling potential in nonmuscle cells". The Journal of Cell Biology. 132 (1–2): 211–26. doi:10.1083/jcb.132.1.211. PMC 2120711. PMID 8567725.
21. Anastasi G, Cutroneo G, Trimarchi F, Santoro G, Bruschetta D, Bramanti P, Pisani A, Favaloro A (Dec 2004). "Evaluation of sarcoglycans, vinculin-talin-integrin system and filamin2 in alpha- and gamma-sarcoglycanopathy: an immunohistochemical study". International Journal of Molecular Medicine. 14 (6): 989–99. doi:10.3892/ijmm.14.6.989. PMID 15547664.
22. Anastasi G, Cutroneo G, Santoro G, Arco A, Rizzo G, Bramanti P, Rinaldi C, Sidoti A, Amato A, Favaloro A (Sep 2008). "Costameric proteins in human skeletal muscle during muscular inactivity". Journal of Anatomy. 213 (3): 284–95. doi:10.1111/j.1469-7580.2008.00921.x. PMC 2732038. PMID 18537849.
23. Otey CA, Pavalko FM, Burridge K (Aug 1990). "An interaction between alpha-actinin and the beta 1 integrin subunit in vitro". The Journal of Cell Biology. 111 (2): 721–9. doi:10.1083/jcb.111.2.721. PMC 2116186. PMID 2116421.
24. Otey CA, Vasquez GB, Burridge K, Erickson BW (Oct 1993). "Mapping of the alpha-actinin binding site within the beta 1 integrin cytoplasmic domain". The Journal of Biological Chemistry. 268 (28): 21193–7. doi:10.1016/S0021-9258(19)36909-1. PMID 7691808.
25. Lozahic S, Christiansen D, Manié S, Gerlier D, Billard M, Boucheix C, Rubinstein E (Mar 2000). "CD46 (membrane cofactor protein) associates with multiple beta1 integrins and tetraspans". European Journal of Immunology. 30 (3): 900–7. doi:10.1002/1521-4141(200003)30:3<900::AID-IMMU900>3.0.CO;2-X. PMID 10741407.
26. Radford KJ, Thorne RF, Hersey P (May 1996). "CD63 associates with transmembrane 4 superfamily members, CD9 and CD81, and with beta 1 integrins in human melanoma". Biochemical and Biophysical Research Communications. 222 (1): 13–8. doi:10.1006/bbrc.1996.0690. PMID 8630057.
27. Mazzocca A, Carloni V, Sciammetta S, Cordella C, Pantaleo P, Caldini A, Gentilini P, Pinzani M (Sep 2002). "Expression of transmembrane 4 superfamily (TM4SF) proteins and their role in hepatic stellate cell motility and wound healing migration". Journal of Hepatology. 37 (3): 322–30. doi:10.1016/S0168-8278(02)00175-7. PMID 12175627.
28. Wixler V, Geerts D, Laplantine E, Westhoff D, Smyth N, Aumailley M, Sonnenberg A, Paulsson M (Oct 2000). "The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes". The Journal of Biological Chemistry. 275 (43): 33669–78. doi:10.1074/jbc.M002519200. PMID 10906324.
29. van der Flier A, Kuikman I, Kramer D, Geerts D, Kreft M, Takafuta T, Shapiro SS, Sonnenberg A (Jan 2002). "Different splice variants of filamin-B affect myogenesis, subcellular distribution, and determine binding to integrin [beta] subunits". The Journal of Cell Biology. 156 (2): 361–76. doi:10.1083/jcb.200103037. PMC 2199218. PMID 11807098.
30. Loo DT, Kanner SB, Aruffo A (Sep 1998). "Filamin binds to the cytoplasmic domain of the beta1-integrin. Identification of amino acids responsible for this interaction". The Journal of Biological Chemistry. 273 (36): 23304–12. doi:10.1074/jbc.273.36.23304. PMID 9722563.
31. Serru V, Le Naour F, Billard M, Azorsa DO, Lanza F, Boucheix C, Rubinstein E (May 1999). "Selective tetraspan-integrin complexes (CD81/alpha4beta1, CD151/alpha3beta1, CD151/alpha6beta1) under conditions disrupting tetraspan interactions". The Biochemical Journal. 340 (Pt 1): 103–11. doi:10.1042/0264-6021:3400103. PMC 1220227. PMID 10229664.
32. Lee HS, Millward-Sadler SJ, Wright MO, Nuki G, Al-Jamal R, Salter DM (Nov 2002). "Activation of Integrin-RACK1/PKCalpha signalling in human articular chondrocyte mechanotransduction". Osteoarthritis and Cartilage. 10 (11): 890–7. doi:10.1053/joca.2002.0842. PMID 12435334.
33. Liliental J, Chang DD (Jan 1998). "Rack1, a receptor for activated protein kinase C, interacts with integrin beta subunit". The Journal of Biological Chemistry. 273 (4): 2379–83. doi:10.1074/jbc.273.4.2379. PMID 9442085.
34. Chang DD, Wong C, Smith H, Liu J (Sep 1997). "ICAP-1, a novel beta1 integrin cytoplasmic domain-associated protein, binds to a conserved and functionally important NPXY sequence motif of beta1 integrin". The Journal of Cell Biology. 138 (5): 1149–57. doi:10.1083/jcb.138.5.1149. PMC 2136751. PMID 9281591.
35. Chang DD, Hoang BQ, Liu J, Springer TA (Mar 2002). "Molecular basis for interaction between Icap1 alpha PTB domain and beta 1 integrin". The Journal of Biological Chemistry. 277 (10): 8140–5. doi:10.1074/jbc.M109031200. PMID 11741908.
36. Hadari YR, Arbel-Goren R, Levy Y, Amsterdam A, Alon R, Zakut R, Zick Y (Jul 2000). "Galectin-8 binding to integrins inhibits cell adhesion and induces apoptosis". Journal of Cell Science. 113 (13): 2385–97. doi:10.1242/jcs.113.13.2385. PMID 10852818.
37. Poinat P, De Arcangelis A, Sookhareea S, Zhu X, Hedgecock EM, Labouesse M, Georges-Labouesse E (Apr 2002). "A conserved interaction between beta1 integrin/PAT-3 and Nck-interacting kinase/MIG-15 that mediates commissural axon navigation in C. elegans". Current Biology. 12 (8): 622–31. Bibcode:2002CBio...12..622P. doi:10.1016/S0960-9822(02)00764-9. PMID 11967148. S2CID 9977605.
38. Fournier HN, Dupé-Manet S, Bouvard D, Lacombe ML, Marie C, Block MR, Albiges-Rizo C (Jun 2002). "Integrin cytoplasmic domain-associated protein 1alpha (ICAP-1alpha ) interacts directly with the metastasis suppressor nm23-H2, and both proteins are targeted to newly formed cell adhesion sites upon integrin engagement". The Journal of Biological Chemistry. 277 (23): 20895–902. doi:10.1074/jbc.M200200200. PMID 11919189.
39. Parsons M, Keppler MD, Kline A, Messent A, Humphries MJ, Gilchrist R, Hart IR, Quittau-Prevostel C, Hughes WE, Parker PJ, Ng T (Aug 2002). "Site-directed perturbation of protein kinase C- integrin interaction blocks carcinoma cell chemotaxis". Molecular and Cellular Biology. 22 (16): 5897–911. doi:10.1128/MCB.22.16.5897-5911.2002. PMC 133968. PMID 12138200.
40. Tapley P, Horwitz A, Buck C, Duggan K, Rohrschneider L (Mar 1989). "Integrins isolated from Rous sarcoma virus-transformed chicken embryo fibroblasts". Oncogene. 4 (3): 325–33. PMID 2468126.
41. Horwitz A, Duggan K, Buck C, Beckerle MC, Burridge K (1986). "Interaction of plasma membrane fibronectin receptor with talin--a transmembrane linkage". Nature. 320 (6062): 531–3. Bibcode:1986Natur.320..531H. doi:10.1038/320531a0. PMID 2938015. S2CID 4356748.
42. Tachibana I, Bodorova J, Berditchevski F, Zutter MM, Hemler ME (Nov 1997). "NAG-2, a novel transmembrane-4 superfamily (TM4SF) protein that complexes with integrins and other TM4SF proteins". The Journal of Biological Chemistry. 272 (46): 29181–9. doi:10.1074/jbc.272.46.29181. PMID 9360996.
43. Han DC, Rodriguez LG, Guan JL (Jan 2001). "Identification of a novel interaction between integrin beta1 and 14-3-3beta". Oncogene. 20 (3): 346–57. doi:10.1038/sj.onc.1204068. PMID 11313964. S2CID 7405925.

Further reading

• Evans JP (Jul 2001). "Fertilin beta and other ADAMs as integrin ligands: insights into cell adhesion and fertilization". BioEssays. 23 (7): 628–39. doi:10.1002/bies.1088. PMID 11462216. S2CID 23712246.
• Armulik A (Jan 2002). "Splice variants of human beta 1 integrins: origin, biosynthesis and functions". Frontiers in Bioscience. 7 (1–3): d219-27. doi:10.2741/armulik. PMID 11779688.
• Brakebusch C, Fässler R (Sep 2005). "beta 1 integrin function in vivo: adhesion, migration and more". Cancer and Metastasis Reviews. 24 (3): 403–11. doi:10.1007/s10555-005-5132-5. PMID 16258728. S2CID 24210890.

External links

• CD29+Antigen at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Human ITGB1 genome location and ITGB1 gene details page in the UCSC Genome Browser.