CD18

ITGB2
Dostupne strukture
PDB	Pretraga 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
Aliasi	ITGB2
Vanjski ID-jevi	OMIM: 600065 MGI: 96611 HomoloGene: 20092 GeneCards: ITGB2
Lokacija gena (čovjek)
Hrom.	Hromosom 21 (čovjek)
Kraj	44,931,989 bp
Lokacija gena (miš)
Hrom.	Hromosom 10 (miš)
Kraj	77,401,542 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• GO:0032403 protein-containing complex binding; • vezivanje iona metala; • GO:0001948, GO:0016582 vezivanje za proteine; • 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 makromolekulani kompleks;
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
	3689
	16414
	ENSG00000160255
	ENSMUSG00000000290
	P05107
	P11835
	NM_000211; NM_001127491; NM_001303238
	NM_008404
	NP_000202; NP_001120963; NP_001290167
	NP_032430
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/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]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MLGLRPPLLA	LVGLLSLGCV	LSQECTKFKV	SSCRECIESG	PGCTWCQKLN
FTGPGDPDSI	RCDTRPQLLM	RGCAADDIMD	PTSLAETQED	HNGGQKQLSP
QKVTLYLRPG	QAAAFNVTFR	RAKGYPIDLY	YLMDLSYSML	DDLRNVKKLG
GDLLRALNEI	TESGRIGFGS	FVDKTVLPFV	NTHPDKLRNP	CPNKEKECQP
PFAFRHVLKL	TNNSNQFQTE	VGKQLISGNL	DAPEGGLDAM	MQVAACPEEI
GWRNVTRLLV	FATDDGFHFA	GDGKLGAILT	PNDGRCHLED	NLYKRSNEFD
YPSVGQLAHK	LAENNIQPIF	AVTSRMVKTY	EKLTEIIPKS	AVGELSEDSS
NVVQLIKNAY	NKLSSRVFLD	HNALPDTLKV	TYDSFCSNGV	THRNQPRGDC
DGVQINVPIT	FQVKVTATEC	IQEQSFVIRA	LGFTDIVTVQ	VLPQCECRCR
DQSRDRSLCH	GKGFLECGIC	RCDTGYIGKN	CECQTQGRSS	QELEGSCRKD
NNSIICSGLG	DCVCGQCLCH	TSDVPGKLIY	GQYCECDTIN	CERYNGQVCG
GPGRGLCFCG	KCRCHPGFEG	SACQCERTTE	GCLNPRRVEC	SGRGRCRCNV
CECHSGYQLP	LCQECPGCPS	PCGKYISCAE	CLKFEKGPFG	KNCSAACPGL
QLSNNPVKGR	TCKERDSEGC	WVAYTLEQQD	GMDRYLIYVD	ESRECVAGPN
IAAIVGGTVA	GIVLIGILLL	VIWKALIHLS	DLREYRRFEK	EKLKSQWNND
NPLFKSATTT	VMNPKFAES

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]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000160255 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000000290 - Ensembl, maj 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 ^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.
^ "ITGB2 integrin subunit beta 2 [ Homo sapiens (human) ]".
^ ^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.
^ ^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.
^ 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, 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.
^ 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.
^ 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. PMID 10352278.
^ 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.

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]

CD18 antigen na US National Library of Medicine Medical Subject Headings (MeSH)
ITGB2 Info with links in the Cell Migration Gateway Arhivirano 11. 12. 2014. na Wayback Machine
Lokacija ljudskog genoma ITGB2 i stranica sa detaljima o genu ITGB2 u UCSC Genome Browseru.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000160255 - Ensembl, maj 2017

[refGRCm38Ensembl-2] 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.

[AAM1990-5] 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) ]".

[LFA-1-7] 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.

[Mac-1-8] 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.

[pmid10906324-12] 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.

[pmid9442085-13] 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.

[pmid10352278-14] 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.

[pmid11279101-15] 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.

[pmid7642561-16] 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.

[pmid9765275-17] 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.

[pmid10835351-18] 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.

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p r u Proteini: Klasteri diferencijacije (također pogledati Lista ljudskih klastera diferencijacije)
1–50	CD1 a-c 1A 1B 1D 1E CD2 CD3 γ δ ε CD4 CD5 CD6 CD7 CD8 a CD9 CD10 CD11 a b c d CD13 CD14 CD15 CD16 A B CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 A B CD33 CD34 CD35 CD36 CD37 CD38 CD39 CD40 CD41 CD42 a b c d CD43 CD44 CD45 CD46 CD47 CD48 CD49 a b c d e f CD50
51–100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 E L P CD63 CD64 A B C CD66 a b c d e f CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD78 CD79 a b CD80 CD81 CD82 CD83 CD84 CD85 a d e h j k CD86 CD87 CD88 CD89 CD90 CD91 - CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100
101–150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 a b CD108 CD109 CD110 CD111 CD112 CD113 CD114 CD115 CD116 CD117 CD118 CD119 CD120 a b CD121 a b CD122 CD123 CD124 CD125 CD126 CD127 CD129 CD130 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150
151–200	CD151 CD152 CD153 CD154 CD155 CD156 a b c CD157 CD158 (a d e i k) CD159 a c CD160 CD161 CD162 CD163 CD164 CD166 CD167 a b CD168 CD169 CD170 CD171 CD172 a b g CD174 CD177 CD178 CD179 a b CD180 CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200
201–250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 a b CD212 CD213a 1 2 CD217 CD218 (a b) CD220 CD221 CD222 CD223 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD233 CD234 CD235 a b CD236 CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 - CD248 CD249
251–300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299
301–350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD320 CD321 CD322 CD324 CD325 CD326 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350