CD11a

Integrin, alpha L (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide)

PDB rendering based on 1cqp.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1CQP, 1DGQ, 1IJ4, 1LFA, 1MJN, 1MQ8, 1MQ9, 1MQA, 1RD4, 1T0P, 1XDD, 1XDG, 1XUO, 1ZON, 1ZOO, 1ZOP, 2ICA, 2K8O, 2M3E, 2O7N, 3BN3, 3BQM, 3BQN, 3E2M, 3EOA, 3EOB, 3F74, 3F78, 3HI6, 3M6F, 3TCX, 4IXD

Identifiers

Symbols

ITGAL ; CD11A; LFA-1; LFA1A

External IDs

OMIM: 153370 MGI: 96606 HomoloGene: 1666 ChEMBL: 1803 GeneCards: ITGAL Gene

Gene ontology
Molecular function	• protein binding • ICAM-3 receptor activity • metal ion binding • cell adhesion molecule binding
Cellular component	• immunological synapse • plasma membrane • cell-cell junction • integrin complex • external side of plasma membrane • cell surface • membrane • integrin alphaL-beta2 complex • extracellular exosome
Biological process	• T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell • movement of cell or subcellular component • inflammatory response • cell adhesion • heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules • leukocyte cell-cell adhesion • cell-matrix adhesion • signal transduction • integrin-mediated signaling pathway • blood coagulation • extracellular matrix organization • positive regulation of T cell proliferation • receptor clustering • regulation of immune response • activated T cell proliferation • positive regulation of calcium-mediated signaling • leukocyte migration
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 16:
30.47 – 30.52 Mb

Chr 7:
127.3 – 127.34 Mb

PubMed search

Integrin, alpha L (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide), also known as ITGAL, is a human gene which functions in the immune system. It is involved in cellular adhesion and costimulatory signaling. It is the target of the drug efalizumab.

Function

ITGAL encodes the integrin alpha L chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form the integrin lymphocyte function-associated antigen-1 (LFA-1), which is expressed on all leukocytes. LFA-1 plays a central role in leukocyte intercellular adhesion through interactions with its ligands, ICAMs 1-3 (intercellular adhesion molecules 1 through 3), and also functions in lymphocyte costimulatory signaling.^[1]

CD11a is one of the two components, along with CD18, which form lymphocyte function-associated antigen-1.

Efalizumab acted as an immunosuppressant by binding to CD11a, but was withdrawn in 2009 due to severe side effects being associated with the drug.

Interactions

CD11a has been shown to interact with ICAM-1.^[2]^[3]^[4]

References

↑ "Entrez Gene: ITGAL integrin, alpha L (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide)".
↑ 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". J. Biol. Chem. 276 (18): 14642–8. doi:10.1074/jbc.M100600200. PMID 11279101.
↑ Shimaoka M, Xiao T, Liu JH, Yang Y, Dong Y, Jun CD, McCormack A, Zhang R, Joachimiak A, Takagi J, Wang JH, Springer TA (Jan 2003). "Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation". Cell 112 (1): 99–111. doi:10.1016/S0092-8674(02)01257-6. PMID 12526797.
↑ Yusuf-Makagiansar H, Makagiansar IT, Hu Y, Siahaan TJ (Dec 2001). "Synergistic inhibitory activity of alpha- and beta-LFA-1 peptides on LFA-1/ICAM-1 interaction". Peptides 22 (12): 1955–62. doi:10.1016/S0196-9781(01)00546-0. PMID 11786177.

Lub M, van Kooyk Y, Figdor CG (1995). "Ins and outs of LFA-1.". Immunol. Today 16 (10): 479–83. doi:10.1016/0167-5699(95)80031-X. PMID 7576051.
Dickeson SK, Santoro SA (1998). "Ligand recognition by the I domain-containing integrins.". Cell. Mol. Life Sci. 54 (6): 556–66. doi:10.1007/s000180050184. PMID 9676575.
Porter JC, Hogg N (1999). "Integrins take partners: cross-talk between integrins and other membrane receptors.". Trends Cell Biol. 8 (10): 390–6. doi:10.1016/S0962-8924(98)01344-0. PMID 9789327.
Giblin PA, Lemieux RM (2006). "LFA-1 as a key regulator of immune function: approaches toward the development of LFA-1-based therapeutics.". Curr. Pharm. Des. 12 (22): 2771–95. doi:10.2174/138161206777947731. PMID 16918410.
Maurer D, Holter W, Majdic O, Fischer GF, Knapp W (1991). "CD27 expression by a distinct subpopulation of human B lymphocytes.". Eur. J. Immunol. 20 (12): 2679–84. doi:10.1002/eji.1830201223. PMID 1702722.
Kalter DC, Gendelman HE, Meltzer MS (1992). "Inhibition of human immunodeficiency virus infection in monocytes by monoclonal antibodies against leukocyte adhesion molecules.". Immunol. Lett. 30 (2): 219–27. doi:10.1016/0165-2478(91)90029-A. PMID 1757107.
Alvarez V, Pulido R, Campanero MR, Paraiso V, de Landázuri MO, Sánchez-Madrid F (1992). "Differentially regulated cell surface expression of leukocyte adhesion receptors on neutrophils.". Kidney Int. 40 (5): 899–905. doi:10.1038/ki.1991.291. PMID 1762294.
Valentin A, Lundin K, Patarroyo M, Asjö B (1990). "The leukocyte adhesion glycoprotein CD18 participates in HIV-1-induced syncytia formation in monocytoid and T cells.". J. Immunol. 144 (3): 934–7. PMID 1967280.
Larson RS, Corbi AL, Berman L, Springer T (1989). "Primary structure of the leukocyte function-associated molecule-1 alpha subunit: an integrin with an embedded domain defining a protein superfamily". J. Cell Biol. 108 (2): 703–12. doi:10.1083/jcb.108.2.703. PMC 2115430. PMID 2537322.
Hildreth JE, Orentas RJ (1989). "Involvement of a leukocyte adhesion receptor (LFA-1) in HIV-induced syncytium formation". Science 244 (4908): 1075–8. doi:10.1126/science.2543075. PMID 2543075.
Sanders ME, Makgoba MW, Sharrow SO, Stephany D, Springer TA, Young HA, Shaw S (1988). "Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production". J. Immunol. 140 (5): 1401–7. PMID 2894392.
Corbi AL, Larson RS, Kishimoto TK, Springer TA, Morton CC (1988). "Chromosomal location of the genes encoding the leukocyte adhesion receptors LFA-1, Mac-1 and p150,95. Identification of a gene cluster involved in cell adhesion". J. Exp. Med. 167 (5): 1597–607. doi:10.1084/jem.167.5.1597. PMC 2188934. PMID 3284962.
te Velde AA, Keizer GD, Figdor CG (1987). "Differential function of LFA-1 family molecules (CD11 and CD18) in adhesion of human monocytes to melanoma and endothelial cells". Immunology 61 (3): 261–7. PMC 1453405. PMID 3301632.
Qu A, Leahy DJ (1995). "Crystal structure of the I-domain from the CD11a/CD18 (LFA-1, alpha L beta 2) integrin". Proc. Natl. Acad. Sci. U.S.A. 92 (22): 10277–81. doi:10.1073/pnas.92.22.10277. PMC 40779. PMID 7479767.
Turner ML, McIlwaine K, Anthony RS, Parker AC (1995). "Differential expression of cell adhesion molecules by human hematopoietic progenitor cells from bone marrow and mobilized adult peripheral blood". Stem Cells 13 (3): 311–6. doi:10.1002/stem.5530130312. PMID 7542116.
Marzusch K, Ruck P, Geiselhart A, Handgretinger R, Dietl JA, Kaiserling E, Horny HP, Vince G, Redman CW (1993). "Distribution of cell adhesion molecules on CD56++, CD3-, CD16- large granular lymphocytes and endothelial cells in first-trimester human decidua". Hum. Reprod. 8 (8): 1203–8. PMID 7691868.
Capobianchi MR, Ameglio F, Cordiali Fei P, Castilletti C, Mercuri F, Fais S, Dianzani F (1994). "Coordinate induction of interferon alpha and gamma by recombinant HIV-1 glycoprotein 120". AIDS Res. Hum. Retroviruses 9 (10): 957–62. doi:10.1089/aid.1993.9.957. PMID 7904170.
Berman PW, Nakamura GR (1994). "Adhesion mediated by intercellular adhesion molecule 1 attenuates the potency of antibodies that block HIV-1 gp160-dependent syncytium formation". AIDS Res. Hum. Retroviruses 10 (5): 585–93. doi:10.1089/aid.1994.10.585. PMID 7917519.
Chirmule N, Oyaizu N, Saxinger C, Pahwa S (1994). "Nef protein of HIV-1 has B-cell stimulatory activity". AIDS 8 (6): 733–4. doi:10.1097/00002030-199406000-00002. PMID 8086129.

PDB gallery

1cqp: CRYSTAL STRUCTURE ANALYSIS OF THE COMPLEX LFA-1 (CD11A) I-DOMAIN / LOVASTATIN AT 2.6 A RESOLUTION

1dgq: NMR SOLUTION STRUCTURE OF THE INSERTED DOMAIN OF HUMAN LEUKOCYTE FUNCTION ASSOCIATED ANTIGEN-1

1lfa: CD11A I-DOMAIN WITH BOUND MN++

1mjn: Crystal Structure of the intermediate affinity aL I domain mutant

1mq8: Crystal structure of alphaL I domain in complex with ICAM-1

1mq9: Crystal structure of high affinity alphaL I domain with ligand mimetic crystal contact

1mqa: Crystal structure of high affinity alphaL I domain in the absence of ligand or metal

1rd4: An allosteric inhibitor of LFA-1 bound to its I-domain

1t0p: Structural Basis of ICAM recognition by integrin alpahLbeta2 revealed in the complex structure of binding domains of ICAM-3 and alphaLbeta2 at 1.65 A

1xdd: X-ray structure of LFA-1 I-domain in complex with LFA703 at 2.2A resolution

1xdg: X-ray structure of LFA-1 I-domain in complex with LFA878 at 2.1A resolution

1xuo: X-ray structure of LFA-1 I-domain bound to a 1,4-diazepane-2,5-dione inhibitor at 1.8A resolution

1zon: CD11A I-DOMAIN WITHOUT BOUND CATION

1zoo: CD11A I-DOMAIN WITH BOUND MAGNESIUM ION

1zop: CD11A I-DOMAIN WITH BOUND MAGNESIUM ION

2ica: CD11a (LFA1) I-domain complexed with BMS-587101 aka 5-[(5S, 9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro [4.4]non-7-yl]methyl]-3-thiophenecarboxylicacid

2o7n: CD11A (LFA1) I-domain complexed with 7A-[(4-cyanophenyl)methyl]-6-(3,5-dichlorophenyl)-5-oxo-2,3,5,7A-tetrahydro-1H-pyrrolo[1,2-A]pyrrole-7-carbonitrile

External links

CD11a Antigen at the US National Library of Medicine Medical Subject Headings (MeSH)
ITGAL Info with links in the Cell Migration Gateway

Proteins: clusters of differentiation (see also list of human clusters of differentiation)

1-50	CD1 a-c 1A 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

Integrins

Alpha

Beta

Dimers

Cytoadhesin receptor:	Integrin alpha6beta4 Glycoprotein IIb/IIIa ITGA2B+ITGB3

Fibrinogen receptor:	Macrophage-1 antigen CD11b+CD18

Fibronectin receptor:	Integrin alpha2beta1 Integrin alpha4beta1 Integrin alpha5beta1

Leukocyte-adhesion receptor:	LFA-1 CD11a+CD18 Macrophage-1 antigen CD11b+CD18 Integrin alphaXbeta2 CD11c+CD18

Very late antigen receptor:	Integrin alpha1beta1 Integrin alpha2beta1 Integrin alpha3beta1 VLA-4 CD49d+CD29 Alpha-5 beta-1 Integrin alpha6beta1

Vitronectin receptor:	Alpha-v beta-3 Alpha-v beta-5

see also cell surface receptor deficiencies

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CD11a

Function

Interactions

See also

References

Further reading

External links