CD18

S Wikipedije, slobodne enciklopedije
ITGB2
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1L3Y, 1YUK, 2JF1, 2P26, 2P28, 3K6S, 3K71, 3K72, 2V7D, 4NEH, 4NEN, 5E6X, 5E6V, 5E6S, 5E6R, 5E6W, 5ES4, 5E6U

Identifikatori
AliasiITGB2
Vanjski ID-jeviOMIM: 600065 MGI: 96611 HomoloGene: 20092 GeneCards: ITGB2
Lokacija gena (čovjek)
Hromosom 21 (čovjek)
Hrom.Hromosom 21 (čovjek)[1]
Hromosom 21 (čovjek)
Genomska lokacija za ITGB2
Genomska lokacija za ITGB2
Bend21q22.3Početak44,885,953 bp[1]
Kraj44,931,989 bp[1]
Lokacija gena (miš)
Hromosom 10 (miš)
Hrom.Hromosom 10 (miš)[2]
Hromosom 10 (miš)
Genomska lokacija za ITGB2
Genomska lokacija za ITGB2
Bend10 C1|10 39.72 cMPočetak77,366,086 bp[2]
Kraj77,401,542 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija GO:0032403 protein-containing complex binding
metal ion binding
GO:0001948, GO:0016582 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 activity
Ćelijska komponenta integral component of membrane
extracellular vesicle
integrin alphaL-beta2 complex
membrana
Ćelijska membrana
receptor complex
cell surface
integrin complex
Egzosom
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
Lipidni splav
cytoplasmic region
GO:0009327 protein-containing complex
Biološki proces leukocyte 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
GO:0010260 Starenje
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
Ćelijska adhezija
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
GO:0097285 Apoptoza
Fagocitoza
neutrophil degranulation
microglial cell activation
receptor-mediated endocytosis
phagocytosis, engulfment
Ćelijska migracija
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 cell
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_000211
NM_001127491
NM_001303238

NM_008404

RefSeq (bjelančevina)

NP_000202
NP_001120963
NP_001290167

NP_032430

Lokacija (UCSC)Chr 21: 44.89 – 44.93 MbChr 10: 77.37 – 77.4 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Integrinski beta lanac-2 (CD18 ) jest protein integrinskog koji je kod ljudi kodiran genom ITGB2 sa hromosoma 21.[5] Nakon vezivanja sa jednim od brojnih alfa lanaca, CD18 je sposoban da formira više heterodimera, koji imaju značajnu ulogu u ćelijskoj adheziji i signalizaciji ćelijske površine, kao i važnu ulogu u imunskim odgovorima.[5][6] CD18 takođe postoji u rastvorljivim oblicima koji se vezuju za ligand. Nedostaci u ekspresiji CD18 mogu dovesti do poremećaja adhezije u cirkulirajućim bijelim krvnim zrncima kod ljudi, smanjujući sposobnost imunskog sistema da se bori protiv stranih antigena.

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 769 aminokiselina, a molekulska težina 84.782 Da.[5]

1020304050
MLGLRPPLLALVGLLSLGCVLSQECTKFKVSSCRECIESGPGCTWCQKLN
FTGPGDPDSIRCDTRPQLLMRGCAADDIMDPTSLAETQEDHNGGQKQLSP
QKVTLYLRPGQAAAFNVTFRRAKGYPIDLYYLMDLSYSMLDDLRNVKKLG
GDLLRALNEITESGRIGFGSFVDKTVLPFVNTHPDKLRNPCPNKEKECQP
PFAFRHVLKLTNNSNQFQTEVGKQLISGNLDAPEGGLDAMMQVAACPEEI
GWRNVTRLLVFATDDGFHFAGDGKLGAILTPNDGRCHLEDNLYKRSNEFD
YPSVGQLAHKLAENNIQPIFAVTSRMVKTYEKLTEIIPKSAVGELSEDSS
NVVQLIKNAYNKLSSRVFLDHNALPDTLKVTYDSFCSNGVTHRNQPRGDC
DGVQINVPITFQVKVTATECIQEQSFVIRALGFTDIVTVQVLPQCECRCR
DQSRDRSLCHGKGFLECGICRCDTGYIGKNCECQTQGRSSQELEGSCRKD
NNSIICSGLGDCVCGQCLCHTSDVPGKLIYGQYCECDTINCERYNGQVCG
GPGRGLCFCGKCRCHPGFEGSACQCERTTEGCLNPRRVECSGRGRCRCNV
CECHSGYQLPLCQECPGCPSPCGKYISCAECLKFEKGPFGKNCSAACPGL
QLSNNPVKGRTCKERDSEGCWVAYTLEQQDGMDRYLIYVDESRECVAGPN
IAAIVGGTVAGIVLIGILLLVIWKALIHLSDLREYRRFEKEKLKSQWNND
NPLFKSATTTVMNPKFAES

Struktura i funkcija[uredi | uredi izvor]

ITGB2 proteinski proizvod je CD18. Integrini su integralni proteini na površini ćelije koji se sastoje od alfa-lanca i beta-lanca, a ključni su za ćelije da se efikasno vežu za vanćelijski matriks.[5] Ovo je posebno važno za neutrofile , jer ćelijska adhezija ima veliku ulogu u ekstravazaciji iz krvnih sudova. Dati lanac može se kombinovati sa više partnera, što rezultira različitim integrinima.

Poznati vezujući partneri CD18 su CD11a,[7] CD11b,[8] CD11c i CD11d.[5] Vezivanje CD18 i CD11 rezultira formiranjem antigena 1 povezanog sa funkcijama limfocita (LFA-1),[7] proteina koji se nalazi na B-ćelijama, svim T-ćelijama, makrofagima, neutrofili mai NK-ćelijama. LFA-1 je uključen u adheziju i vezivanje za ćelije koje prezrntiraju antigen, interakcijom sa površinskim proteinom ICAM-1

Vezivanje CD18 i CD11b-d dovodi do formiranja komplementnog receptora (npr. receptora antigena makrofaga 1, Mac-1, kada je vezan za CD11b),[8] koji su proteini na neutrofilima, makrofagima i NK-ćelijama. Ovi receptori komplementa učestvuju u urođenom imunskom odgovoru, tako što prepoznaju strane peptide i fagocitiraju ih, uništavajući tako antigene.

Klinički značaj[uredi | uredi izvor]

Kod ljudi, nedostatak funkcionalnog CD18 uzrokuje nedostatak leukocitne adhezije, bolest definiranu nedostatkom leukocitnih ekstravazacija iz krvi u tkiva, zbog nesposobnosti cirkulirajućih leukocita da odgovore na strana tijela prisutna u tkivu..[9] Ovo naknadno smanjuje sposobnost imunskog sistema osobe da se bori protiv infekcije, što ga čini podložnijim stranim infekcijama od onih sa funkcionalnim CD18 proteinima. Beta 2 integrin]i također su pronađeni u rastvorljivom obliku, što znači da nisu usidreni u ćeliskim plazmamembranama, već postoje izvan ćelije u plazmi i sposobni su da se vežu za ligand.[10] Rastvorljivi ntegrini beta 2 vezuju se za ligand i nivoi u plazmi su obrnuto povezani sa aktivnošću bolesti kod autoimunske bolesti spondiloartritis.[11]

Interakcije[uredi | uredi izvor]

Pokazalo se da CD18 ima interakcije sa:

Također pogledajte[uredi | uredi izvor]

Reference[uredi | uredi izvor]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000160255 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000290 - Ensembl, maj 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 e Amin Aanout, M. (March 1, 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 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. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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. PMID 10352278.
  15. ^ 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.
  16. ^ 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.
  17. ^ 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.
  18. ^ 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.

Dopunska literatura[uredi | uredi izvor]

  • 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.

Vanjski linkovi[uredi | uredi izvor]