ITGAL
Integrin alpha-L
Also known as: CD11A, ITAL_HUMAN, LFA-1, LFA1A
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P20701
- Gene
- ITGAL
- Ensembl
- ENSG00000005844
- Chromosome
- 16
- Canonical length
- 1170 aa
- Protein class
- CD markers, FDA approved drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters
OverviewNCBI Gene
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. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
1170 residues, UniProt reviewed canonical sequence.
>P20701|ITGAL
1 MKDSCITVMA MALLSGFFFF APASSYNLDV RGARSFSPPR AGRHFGYRVL QVGNGVIVGA
61 PGEGNSTGSL YQCQSGTGHC LPVTLRGSNY TSKYLGMTLA TDPTDGSILA CDPGLSRTCD
121 QNTYLSGLCY LFRQNLQGPM LQGRPGFQEC IKGNVDLVFL FDGSMSLQPD EFQKILDFMK
181 DVMKKLSNTS YQFAAVQFST SYKTEFDFSD YVKRKDPDAL LKHVKHMLLL TNTFGAINYV
241 ATEVFREELG ARPDATKVLI IITDGEATDS GNIDAAKDII RYIIGIGKHF QTKESQETLH
301 KFASKPASEF VKILDTFEKL KDLFTELQKK IYVIEGTSKQ DLTSFNMELS SSGISADLSR
361 GHAVVGAVGA KDWAGGFLDL KADLQDDTFI GNEPLTPEVR AGYLGYTVTW LPSRQKTSLL
421 ASGAPRYQHM GRVLLFQEPQ GGGHWSQVQT IHGTQIGSYF GGELCGVDVD QDGETELLLI
481 GAPLFYGEQR GGRVFIYQRR QLGFEEVSEL QGDPGYPLGR FGEAITALTD INGDGLVDVA
541 VGAPLEEQGA VYIFNGRHGG LSPQPSQRIE GTQVLSGIQW FGRSIHGVKD LEGDGLADVA
601 VGAESQMIVL SSRPVVDMVT LMSFSPAEIP VHEVECSYST SNKMKEGVNI TICFQIKSLI
661 PQFQGRLVAN LTYTLQLDGH RTRRRGLFPG GRHELRRNIA VTTSMSCTDF SFHFPVCVQD
721 LISPINVSLN FSLWEEEGTP RDQRAQGKDI PPILRPSLHS ETWEIPFEKN CGEDKKCEAN
781 LRVSFSPARS RALRLTAFAS LSVELSLSNL EEDAYWVQLD LHFPPGLSFR KVEMLKPHSQ
841 IPVSCEELPE ESRLLSRALS CNVSSPIFKA GHSVALQMMF NTLVNSSWGD SVELHANVTC
901 NNEDSDLLED NSATTIIPIL YPINILIQDQ EDSTLYVSFT PKGPKIHQVK HMYQVRIQPS
961 IHDHNIPTLE AVVGVPQPPS EGPITHQWSV QMEPPVPCHY EDLERLPDAA EPCLPGALFR
1021 CPVVFRQEIL VQVIGTLELV GEIEASSMFS LCSSLSISFN SSKHFHLYGS NASLAQVVMK
1081 VDVVYEKQML YLYVLSGIGG LLLLLLIFIV LYKVGFFKRN LKEKMEAGRG VPNGIPAEDS
1141 EQLASGQEAG DPGCLKPLHE KDSESGGGKDLocalizationUniProt · AlphaFold · HPA
Whether an antibody against ITGAL can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 1
- Mean surface accessibility (rSASA)
- 0.29
- Highest tissue expression
- 59 nTPM
Expression across tissuesHPA
Tissue
- lymph node: 59 nTPM
- spleen: 52 nTPM
- thymus: 52 nTPM
- tonsil: 44 nTPM
- appendix: 35 nTPM
- bone marrow: 35 nTPM
Single-cell type
- neutrophils: 311 nCPM
- nk-cells: 293 nCPM
- t-cells: 187 nCPM
- thymocytes: 100 nCPM
- monocytes: 98 nCPM
- neutrophil progenitors: 77 nCPM
Immune cell
- non-classical monocyte: 122 nTPM
- gdT-cell: 57 nTPM
- intermediate monocyte: 48 nTPM
- total PBMC: 44 nTPM
- memory CD8 T-cell: 43 nTPM
- naive CD8 T-cell: 30 nTPM
Brain region
- white matter: 4.4 nTPM
- medulla oblongata: 3.1 nTPM
- thalamus: 2.9 nTPM
- pons: 2.3 nTPM
- spinal cord: 1.2 nTPM
- midbrain: 0.9 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about ITGAL.
Disease | ImmuneIEDB
Conditions an epitope on ITGAL was assayed in.
- Lyme disease T cell
ReferencesPubMed · IEDB
Publications for ITGAL from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
6 publications
- Neutrophil antibody specificity in different types of childhood autoimmune neutropenia.
1999 · Blood · RCR 1.7 · 61 citations - Circulating leukocyte integrin expression in Wegener's granulomatosis.
1996 · J Am Soc Nephrol · RCR 1 · 38 citations - LFA-1 Controls Th1 and Th17 Motility Behavior in the Inflamed Central Nervous System.
2019 · Front Immunol · RCR 0.9 · 24 citations - Differential roles for beta2 integrins in experimental autoimmune bullous pemphigoid.
2006 · Blood · RCR 0.7 · 32 citations - Adhesion molecule monoclonal antibodies inhibit experimental autoimmune thyroiditis.
1993 · Immunology · RCR 0.5 · 21 citations
Show 1 more
- Anti-LFA-1 (CD11a) monoclonal antibody interferes with neonatal induction of tolerance to alloantigens.
1994 · Eur J Immunol · RCR 0.1 · 4 citations
Reference: T cellIEDB
3 publications
- Molecular mimicry in Lyme arthritis demonstrated at the single cell level: LFA-1 alpha L is a partial agonist for outer surface protein A-reactive T cells.
2001 · J Immunol · RCR 1.7 · 70 citations - Human T lymphocyte response to Borrelia burgdorferi infection: no correlation between human leukocyte function antigen type 1 peptide response and clinical status.
2003 · J Infect Dis · RCR 0.8 · 29 citations - IFNgamma production in peripheral blood of early Lyme disease patients to hLFAalphaL (aa326-345).
2002 · BMC Musculoskelet Disord · RCR 0 · 2 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.41
- gnomAD pLI
- 0
- gnomAD missense Z
- 2.18
- DepMap mean gene effect
- 0
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cell adhesion
- cell-cell adhesion
- cell-matrix adhesion
- heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
- inflammatory response
- integrin-mediated signaling pathway
- leukocyte cell-cell adhesion
- memory T cell extravasation
- phagocytosis
- receptor clustering
- signal transduction
- T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell
Molecular functions
- cell adhesion molecule binding
- ICAM-3 receptor activity
- metal ion binding
- protein-containing complex binding
- signaling receptor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Integrin alpha chain
- von Willebrand factor, type A
- FG-GAP repeat
- Integrin alpha beta-propellor
- Integrin alpha, first immunoglubulin-like domain
- Integrin alpha chain, C-terminal cytoplasmic region, conserved site
- Integrin alpha, N-terminal
- Integrin domain superfamily
- von Willebrand factor A-like domain superfamily
- Integrin alpha, second immunoglobulin-like domain
- von Willebrand factor type A domain
- Integrin alpha cytoplasmic region
- FG-GAP repeat
- Integrin alpha Ig-like domain 1
- Integrin alpha Ig-like domain 2
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of ITGAL in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads ITGAL as an antibody target. Whether an autoantibody or antibody against ITGAL could matter depends on whether native ITGAL is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
ITGAL is annotated at the cell surface, where native ITGAL is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label ITGAL as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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