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Integrin beta 2

December 03, 2023

In molecular biology, CD18 (Integrin beta chain-2) is an integrin beta chain protein that is encoded by the ITGB2 gene in humans.[5] Upon binding with one of a number of alpha chains, CD18 is capable of forming multiple heterodimers, which play significant roles in cellular adhesion and cell surface signaling, as well as important roles in immune responses.[5][6] CD18 also exists in soluble, ligand binding forms. Deficiencies in CD18 expression can lead to adhesion defects in circulating white blood cells in humans, reducing the immune system's ability to fight off foreign invaders.

ITGB2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesITGB2, CD18, LAD, LCAMB, LFA-1, MAC-1, MF17, MFI7, integrin subunit beta 2
External IDsOMIM: 600065 MGI: 96611 HomoloGene: 20092 GeneCards: ITGB2
Orthologs
SpeciesHumanMouse
Entrez

3689

16414

Ensembl

ENSG00000160255

ENSMUSG00000000290

UniProt

P05107

P11835

RefSeq (mRNA)

NM_000211
NM_001127491
NM_001303238

NM_008404

RefSeq (protein)

NP_000202
NP_001120963
NP_001290167

NP_032430

Location (UCSC)Chr 21: 44.89 – 44.93 MbChr 10: 77.37 – 77.4 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure and function edit

The ITGB2 protein product is CD18. Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain, and are crucial for cells to be able to efficiently bind to the extracellular matrix.[5] This is especially important for neutrophils, as cellular adhesion plays a large role in extravasation from the blood vessels. A given chain may combine with multiple partners resulting in different integrins.

The known binding partners of CD18 are CD11a,[7] CD11b,[8] CD11c and CD11d.[5] Binding of CD18 and CD11a results in the formation of lymphocyte function-associated antigen-1 (LFA-1),[7] a protein found on B cells, all T cells, monocytes, neutrophils and NK cells.[9] LFA-1 is involved in adhesion and binding to antigen presenting cells through interactions with the surface protein ICAM-1.[7]

Binding of CD18 and CD11b-d results in the formation of complement receptors (e.g. Macrophage-1 antigen receptor, Mac-1, when bound to CD11b),[8] which are proteins found largely on neutrophils, macrophages and NK cells. These complement receptors participate in the innate immune response by recognizing foreign antigen peptides and phagocytizing them, thus destroying the antigen.

Clinical significance edit

In humans, lack of functional CD18 causes leukocyte adhesion deficiency, a disease defined by a lack of leukocyte extravasation from blood into tissues, which is the inability of circulating leukocytes to respond to foreign bodies present in the tissue.[10] This subsequently reduces the ability of the individual's immune system to fight off infection, making them more susceptible to foreign infection than those with functional CD18 proteins. The beta 2 integrins have also been found in a soluble form, meaning they are not anchored into the plasma membrane of the cell, but rather exist outside of the cell in the plasma, and are capable of ligand binding.[11] The soluble beta 2 integrins are ligand binding and plasma levels are inversely associated with disease activity in the autoimmune disease spondyloarthritis.[12]

Interactions edit

CD18 has been shown to interact with:

See also edit

References edit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000160255 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000290 - 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. ^ a b c d Amin Aanout, M. (1 March 1990). "Structure and Function of the Leukocyte Adhesion Molecules CD11/CD18". Blood. 75 (5): 1037–1050. doi:10.1182/blood.V75.5.1037.1037. PMID 1968349.
  6. ^ "ITGB2 integrin subunit beta 2 [ Homo sapiens (human) ]".
  7. ^ a b c Verma NK, Kelleher D (August 2017). "Not Just an Adhesion Molecule: LFA-1 Contact Tunes the T Lymphocyte Program". Journal of Immunology. 199 (4): 1213–1221. doi:10.4049/jimmunol.1700495. PMID 28784685.
  8. ^ a b Todd, R (1996). "The continuing saga of complement receptor type 3 (CR3)". Journal of Clinical Investigation. 98 (1): 1–2. doi:10.1172/jci118752. PMC 507390. PMID 8690779.
  9. ^ Fekadu J, Modlich U, Bader P, Bakhtiar S (2022). "Understanding the Role of LFA-1 in Leukocyte Adhesion Deficiency Type I (LAD I): Moving towards Inflammation?". International Journal of Molecular Sciences. 23 (7): 3578. doi:10.3390/ijms23073578. PMC 8998723. PMID 35408940. 3578.
  10. ^ Kishimoto TK, Hollander N, Roberts TM, Anderson DC, Springer TA (July 1987). "Heterogeneous mutations in the beta subunit common to the LFA-1, Mac-1, and p150,95 glycoproteins cause leukocyte adhesion deficiency". Cell. 50 (2): 193–202. doi:10.1016/0092-8674(87)90215-7. PMID 3594570. S2CID 40388710.
  11. ^ Gjelstrup LC, Boesen T, Kragstrup TW, Jørgensen A, Klein NJ, Thiel S, Deleuran BW, Vorup-Jensen T (October 2010). "Shedding of large functionally active CD11/CD18 Integrin complexes from leukocyte membranes during synovial inflammation distinguishes three types of arthritis through differential epitope exposure". Journal of Immunology. 185 (7): 4154–68. doi:10.4049/jimmunol.1000952. PMID 20826754.
  12. ^ Kragstrup TW, Jalilian B, Hvid M, Kjærgaard A, Østgård R, Schiøttz-Christensen B, Jurik AG, Robinson WH, Vorup-Jensen T, Deleuran B (February 2014). "Decreased plasma levels of soluble CD18 link leukocyte infiltration with disease activity in spondyloarthritis". Arthritis Research & Therapy. 16 (1): R42. doi:10.1186/ar4471. PMC 3978678. PMID 24490631.
  13. ^ Wixler V, Geerts D, Laplantine E, Westhoff D, Smyth N, Aumailley M, Sonnenberg A, Paulsson M (October 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.
  14. ^ Liliental J, Chang DD (January 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.
  15. ^ Kotovuori A, Pessa-Morikawa T, Kotovuori P, Nortamo P, Gahmberg CG (June 1999). "ICAM-2 and a peptide from its binding domain are efficient activators of leukocyte adhesion and integrin affinity". Journal of Immunology. 162 (11): 6613–20. doi:10.4049/jimmunol.162.11.6613. PMID 10352278. S2CID 40796900.
  16. ^ Lu C, Takagi J, Springer TA (May 2001). "Association of the membrane proximal regions of the alpha and beta subunit cytoplasmic domains constrains an integrin in the inactive state". The Journal of Biological Chemistry. 276 (18): 14642–8. doi:10.1074/jbc.M100600200. PMID 11279101.
  17. ^ Huang C, Springer TA (August 1995). "A binding interface on the I domain of lymphocyte function-associated antigen-1 (LFA-1) required for specific interaction with intercellular adhesion molecule 1 (ICAM-1)". The Journal of Biological Chemistry. 270 (32): 19008–16. doi:10.1074/jbc.270.32.19008. PMID 7642561.
  18. ^ Rietzler M, Bittner M, Kolanus W, Schuster A, Holzmann B (October 1998). "The human WD repeat protein WAIT-1 specifically interacts with the cytoplasmic tails of beta7-integrins". The Journal of Biological Chemistry. 273 (42): 27459–66. doi:10.1074/jbc.273.42.27459. PMID 9765275.
  19. ^ Geiger C, Nagel W, Boehm T, van Kooyk Y, Figdor CG, Kremmer E, Hogg N, Zeitlmann L, Dierks H, Weber KS, Kolanus W (June 2000). "Cytohesin-1 regulates beta-2 integrin-mediated adhesion through both ARF-GEF function and interaction with LFA-1". The EMBO Journal. 19 (11): 2525–36. doi:10.1093/emboj/19.11.2525. PMC 212768. PMID 10835351.

Further reading edit

  • Bunting M, Harris ES, McIntyre TM, Prescott SM, Zimmerman GA (January 2002). "Leukocyte adhesion deficiency syndromes: adhesion and tethering defects involving beta 2 integrins and selectin ligands". Current Opinion in Hematology. 9 (1): 30–5. doi:10.1097/00062752-200201000-00006. PMID 11753075.
  • Roos D, Law SK (2003). "Hematologically important mutations: leukocyte adhesion deficiency". Blood Cells, Molecules & Diseases. 27 (6): 1000–4. doi:10.1006/bcmd.2001.0473. PMID 11831866.
  • Gahmberg CG, Fagerholm S (August 2002). "Activation of leukocyte beta2-integrins". Vox Sanguinis. 83 (Suppl 1): 355–8. doi:10.1111/j.1423-0410.2002.tb05333.x. PMID 12617168. S2CID 84695792.
  • Schymeinsky J, Mócsai A, Walzog B (August 2007). "Neutrophil activation via beta2 integrins (CD11/CD18): molecular mechanisms and clinical implications". Thrombosis and Haemostasis. 98 (2): 262–73. doi:10.1160/th07-02-0156. PMID 17721605. S2CID 41094726.

External links edit

December 03, 2023
integrin, beta, molecular, biology, cd18, integrin, beta, chain, integrin, beta, chain, protein, that, encoded, itgb2, gene, humans, upon, binding, with, number, alpha, chains, cd18, capable, forming, multiple, heterodimers, which, play, significant, roles, ce. In molecular biology CD18 Integrin beta chain 2 is an integrin beta chain protein that is encoded by the ITGB2 gene in humans 5 Upon binding with one of a number of alpha chains CD18 is capable of forming multiple heterodimers which play significant roles in cellular adhesion and cell surface signaling as well as important roles in immune responses 5 6 CD18 also exists in soluble ligand binding forms Deficiencies in CD18 expression can lead to adhesion defects in circulating white blood cells in humans reducing the immune system s ability to fight off foreign invaders ITGB2Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes1L3Y 1YUK 2JF1 2P26 2P28 3K6S 3K71 3K72 2V7D 4NEH 4NEN 5E6X 5E6V 5E6S 5E6R 5E6W 5ES4 5E6UIdentifiersAliasesITGB2 CD18 LAD LCAMB LFA 1 MAC 1 MF17 MFI7 integrin subunit beta 2External IDsOMIM 600065 MGI 96611 HomoloGene 20092 GeneCards ITGB2Gene location Human Chr Chromosome 21 human 1 Band21q22 3Start44 885 953 bp 1 End44 931 989 bp 1 Gene location Mouse Chr Chromosome 10 mouse 2 Band10 C1 10 39 72 cMStart77 366 086 bp 2 End77 401 542 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inmonocytebloodspleenbone marrow cellsappendixspongy bonelymph noderight lungupper lobe of left lungthymusTop expressed inspleenthymusbloodright lung lobeankle jointsubcutaneous adipose tissuesubmandibular glandcalvariabody of femurwhite adipose tissueMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionprotein containing complex binding metal ion binding protein binding protein heterodimerization activity ICAM 3 receptor activity protein kinase binding cell adhesion molecule binding heat shock protein binding amyloid beta binding complement component C3b binding integrin binding signaling receptor activity cargo receptor activityCellular componentintegral component of membrane extracellular vesicle integrin alphaL beta2 complex membrane plasma membrane receptor complex cell surface integrin complex extracellular exosome specific granule membrane tertiary granule membrane ficolin 1 rich granule membrane focal adhesion external side of plasma membrane integrin alphaM beta2 complex plasma membrane raft membrane raft cytoplasmic region protein containing complexBiological processleukocyte cell cell adhesion endodermal cell differentiation toll like receptor 4 signaling pathway positive regulation of nitric oxide biosynthetic process heterotypic cell cell adhesion cell cell signaling human ageing receptor internalization leukocyte migration involved in inflammatory response natural killer cell activation cellular response to low density lipoprotein particle stimulus extracellular matrix organization receptor clustering positive regulation of angiogenesis neutrophil chemotaxis cell adhesion positive regulation of NF kappaB transcription factor activity regulation of cell shape regulation of immune response cellular extravasation integrin mediated signaling pathway cell matrix adhesion inflammatory response endothelial cell migration leukocyte migration regulation of peptidyl tyrosine phosphorylation apoptotic process phagocytosis neutrophil degranulation microglial cell activation receptor mediated endocytosis phagocytosis engulfment cell migration cytokine mediated signaling pathway positive regulation of superoxide anion generation cell adhesion mediated by integrin positive regulation of neutrophil degranulation negative regulation of dopamine metabolic process positive regulation of protein targeting to membrane amyloid beta clearance cell cell adhesion cell cell adhesion via plasma membrane adhesion molecules positive regulation of neuron death positive regulation of microglial cell activation neutrophil migration positive regulation of prostaglandin E synthase activity positive regulation of leukocyte adhesion to vascular endothelial cellSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez368916414EnsemblENSG00000160255ENSMUSG00000000290UniProtP05107P11835RefSeq mRNA NM 000211NM 001127491NM 001303238NM 008404RefSeq protein NP 000202NP 001120963NP 001290167NP 032430Location UCSC Chr 21 44 89 44 93 MbChr 10 77 37 77 4 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Structure and function 2 Clinical significance 3 Interactions 4 See also 5 References 6 Further reading 7 External linksStructure and function editThe ITGB2 protein product is CD18 Integrins are integral cell surface proteins composed of an alpha chain and a beta chain and are crucial for cells to be able to efficiently bind to the extracellular matrix 5 This is especially important for neutrophils as cellular adhesion plays a large role in extravasation from the blood vessels A given chain may combine with multiple partners resulting in different integrins The known binding partners of CD18 are CD11a 7 CD11b 8 CD11c and CD11d 5 Binding of CD18 and CD11a results in the formation of lymphocyte function associated antigen 1 LFA 1 7 a protein found on B cells all T cells monocytes neutrophils and NK cells 9 LFA 1 is involved in adhesion and binding to antigen presenting cells through interactions with the surface protein ICAM 1 7 Binding of CD18 and CD11b d results in the formation of complement receptors e g Macrophage 1 antigen receptor Mac 1 when bound to CD11b 8 which are proteins found largely on neutrophils macrophages and NK cells These complement receptors participate in the innate immune response by recognizing foreign antigen peptides and phagocytizing them thus destroying the antigen Clinical significance editIn humans lack of functional CD18 causes leukocyte adhesion deficiency a disease defined by a lack of leukocyte extravasation from blood into tissues which is the inability of circulating leukocytes to respond to foreign bodies present in the tissue 10 This subsequently reduces the ability of the individual s immune system to fight off infection making them more susceptible to foreign infection than those with functional CD18 proteins The beta 2 integrins have also been found in a soluble form meaning they are not anchored into the plasma membrane of the cell but rather exist outside of the cell in the plasma and are capable of ligand binding 11 The soluble beta 2 integrins are ligand binding and plasma levels are inversely associated with disease activity in the autoimmune disease spondyloarthritis 12 Interactions editCD18 has been shown to interact with FHL2 13 GNB2L1 14 ICAM 1 15 16 17 and PSCD1 18 19 See also editleukocyte adhesion deficiency integrinReferences edit a b c GRCh38 Ensembl release 89 ENSG00000160255 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000000290 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b c d Amin Aanout M 1 March 1990 Structure and Function of the Leukocyte Adhesion Molecules CD11 CD18 Blood 75 5 1037 1050 doi 10 1182 blood V75 5 1037 1037 PMID 1968349 ITGB2 integrin subunit beta 2 Homo sapiens human a b c Verma NK Kelleher D August 2017 Not Just an Adhesion Molecule LFA 1 Contact Tunes the T Lymphocyte Program Journal of Immunology 199 4 1213 1221 doi 10 4049 jimmunol 1700495 PMID 28784685 a b Todd R 1996 The continuing saga of complement receptor type 3 CR3 Journal of Clinical Investigation 98 1 1 2 doi 10 1172 jci118752 PMC 507390 PMID 8690779 Fekadu J Modlich U Bader P Bakhtiar S 2022 Understanding the Role of LFA 1 in Leukocyte Adhesion Deficiency Type I LAD I Moving towards Inflammation International Journal of Molecular Sciences 23 7 3578 doi 10 3390 ijms23073578 PMC 8998723 PMID 35408940 3578 Kishimoto TK Hollander N Roberts TM Anderson DC Springer TA July 1987 Heterogeneous mutations in the beta subunit common to the LFA 1 Mac 1 and p150 95 glycoproteins cause leukocyte adhesion deficiency Cell 50 2 193 202 doi 10 1016 0092 8674 87 90215 7 PMID 3594570 S2CID 40388710 Gjelstrup LC Boesen T Kragstrup TW Jorgensen A Klein NJ Thiel S Deleuran BW Vorup Jensen T October 2010 Shedding of large functionally active CD11 CD18 Integrin complexes from leukocyte membranes during synovial inflammation distinguishes three types of arthritis through differential epitope exposure Journal of Immunology 185 7 4154 68 doi 10 4049 jimmunol 1000952 PMID 20826754 Kragstrup TW Jalilian B Hvid M Kjaergaard A Ostgard R Schiottz Christensen B Jurik AG Robinson WH Vorup Jensen T Deleuran B February 2014 Decreased plasma levels of soluble CD18 link leukocyte infiltration with disease activity in spondyloarthritis Arthritis Research amp Therapy 16 1 R42 doi 10 1186 ar4471 PMC 3978678 PMID 24490631 Wixler V Geerts D Laplantine E Westhoff D Smyth N Aumailley M Sonnenberg A Paulsson M October 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 Liliental J Chang DD January 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 Kotovuori A Pessa Morikawa T Kotovuori P Nortamo P Gahmberg CG June 1999 ICAM 2 and a peptide from its binding domain are efficient activators of leukocyte adhesion and integrin affinity Journal of Immunology 162 11 6613 20 doi 10 4049 jimmunol 162 11 6613 PMID 10352278 S2CID 40796900 Lu C Takagi J Springer TA May 2001 Association of the membrane proximal regions of the alpha and beta subunit cytoplasmic domains constrains an integrin in the inactive state The Journal of Biological Chemistry 276 18 14642 8 doi 10 1074 jbc M100600200 PMID 11279101 Huang C Springer TA August 1995 A binding interface on the I domain of lymphocyte function associated antigen 1 LFA 1 required for specific interaction with intercellular adhesion molecule 1 ICAM 1 The Journal of Biological Chemistry 270 32 19008 16 doi 10 1074 jbc 270 32 19008 PMID 7642561 Rietzler M Bittner M Kolanus W Schuster A Holzmann B October 1998 The human WD repeat protein WAIT 1 specifically interacts with the cytoplasmic tails of beta7 integrins The Journal of Biological Chemistry 273 42 27459 66 doi 10 1074 jbc 273 42 27459 PMID 9765275 Geiger C Nagel W Boehm T van Kooyk Y Figdor CG Kremmer E Hogg N Zeitlmann L Dierks H Weber KS Kolanus W June 2000 Cytohesin 1 regulates beta 2 integrin mediated adhesion through both ARF GEF function and interaction with LFA 1 The EMBO Journal 19 11 2525 36 doi 10 1093 emboj 19 11 2525 PMC 212768 PMID 10835351 Further reading editBunting M Harris ES McIntyre TM Prescott SM Zimmerman GA January 2002 Leukocyte adhesion deficiency syndromes adhesion and tethering defects involving beta 2 integrins and selectin ligands Current Opinion in Hematology 9 1 30 5 doi 10 1097 00062752 200201000 00006 PMID 11753075 Roos D Law SK 2003 Hematologically important mutations leukocyte adhesion deficiency Blood Cells Molecules amp Diseases 27 6 1000 4 doi 10 1006 bcmd 2001 0473 PMID 11831866 Gahmberg CG Fagerholm S August 2002 Activation of leukocyte beta2 integrins Vox Sanguinis 83 Suppl 1 355 8 doi 10 1111 j 1423 0410 2002 tb05333 x PMID 12617168 S2CID 84695792 Schymeinsky J Mocsai A Walzog B August 2007 Neutrophil activation via beta2 integrins CD11 CD18 molecular mechanisms and clinical implications Thrombosis and Haemostasis 98 2 262 73 doi 10 1160 th07 02 0156 PMID 17721605 S2CID 41094726 External links editCD18 antigen at the U S National Library of Medicine Medical Subject Headings MeSH ITGB2 Info with links in the Cell Migration Gateway Archived 11 December 2014 at the Wayback Machine Human ITGB2 genome location and ITGB2 gene details page in the UCSC Genome Browser Retrieved from https en wikipedia org w index php title Integrin beta 2 amp oldid 1188033123, wikipedia, wiki, book, books, library,

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