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ITGAL integrin subunit alpha L [ Homo sapiens (human) ]

Gene ID: 3683, updated on 1-Jun-2020

Summary

Official Symbol
ITGALprovided by HGNC
Official Full Name
integrin subunit alpha Lprovided by HGNC
Primary source
HGNC:HGNC:6148
See related
Ensembl:ENSG00000005844 MIM:153370
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CD11A; LFA-1; LFA1A
Summary
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]
Expression
Biased expression in lymph node (RPKM 36.8), spleen (RPKM 35.7) and 11 other tissues See more
Orthologs

Genomic context

See ITGAL in Genome Data Viewer
Location:
16p11.2
Exon count:
31
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 16 NC_000016.10 (30472683..30523185)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (30483983..30534506)

Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene dCTP pyrophosphatase 1 Neighboring gene selenophosphate synthetase 2 Neighboring gene RNA, U7 small nuclear 61 pseudogene Neighboring gene microRNA 4518 Neighboring gene zinc finger protein 768 Neighboring gene Sharpr-MPRA regulatory region 7881 Neighboring gene uncharacterized LOC107984875 Neighboring gene zinc finger protein 747

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Genome-wide association study of primary dentition pit-and-fissure and smooth surface caries.
NHGRI GWA Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 replication is delayed in LFA-1 negative T cells after Dendritic cell (DC)-mediated transmission; activation of LFA-1 is crucial for efficient DC-mediated HIV-1 transmission, suggesting an interaction between LFA-1 and HIV-1 gp120 PubMed
env Anti-CD18 monoclonal antibodies completely block cell fusion between HIV-1 infected U-937 cells and MT-4 T cells, indicating participation of CD18, or of the protein complex CD11a-c/CD18, in addition to CD4, in the infection and cytopathic effect of HIV-1 PubMed
env HIV-1 gp120 induces CD4 association with lymphocyte surface molecules CD3, CD11a, CD27, CD45RA, CD45RB, CD45RO, CD49d, CD38, CD26, CD59, CD95 and class I MHC molecules PubMed
env The interaction of CD4+ T cells with HIV-1 gp120 on bilayers triggers LFA-1 activation and the LFA-1-ICAM-1 interaction rearrangement PubMed
env Infectivity of an HIV-1 Matrix mutant that carries a suboptimal amount of HIV-1 gp120/41 is restored to a certain degree by the presence of ICAM-1 when infection is performed in cells expressing an activated form of its natural counter-ligand, LFA-1 PubMed
env The gp120-integrin alpha4beta7 complex mediates LFA-1 activation on T cells and increases the efficiency of infection by promoting synapse formation PubMed
env Cells treated with monoclonal antibodies to ICAM-1 and LFA-1 adhesion molecules show an impaired release of IFN after HIV-1 gp120 stimulation, suggesting a crucial role of cell-to-cell interactions in the process leading to IFN production PubMed
Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 is identified to have a physical interaction with integrin, alpha L (ITGAL) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
env HIV-1 gp160 downregulates lymphocyte function-associated antigen-1 (LFA-1)-dependent adhesion between CD4+ T cells and B cells; this downregulation is shown to be p56lck-dependent PubMed
env Antibodies against cell surface molecules LFA-1, ICAM-1, HLA-DR, and CD28 inhibit the HIV-1 gp160-induced B cell differentiation response; gp160 also induces IL-6R and CD23 molecule expression on B cells PubMed
env ICAM-1 promotes HIV-1 gp160-mediated syncytium formation, and the ICAM-1 contrareceptor LFA-1 attenuates the syncytium-inhibiting activity of virus-neutralizing monoclonal antibodies and soluble CD4 PubMed
env PI3-kinase activation induced by HIV-1 gp160 leads to downregulation of LFA-1-mediated T cell adhesion to B cells PubMed
Nef nef HIV-1 Nef-mediated downregulation of LFA1 requires the myristoylation site, the basic region , or the SH3 domain of Nef PubMed
nef Monoclonal antibodies to the cell surface molecule leukocyte function-associated molecule (LFA)-1 alpha inhibit the Nef-induced B-cell differentiation response, suggesting an interaction between Nef and LFA-1alpha PubMed
Tat tat HIV-1 Tat inhibits the rise in intracellular free calcium concentration in Natural Killer (NK) cells upon cross-linking of the adhesion molecule CD11a and the activation molecule CD16, indicating Tat is involved in the impairment of NK cell function PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ICAM-3 receptor activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
cell adhesion molecule binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
cell adhesion molecule binding IPI
Inferred from Physical Interaction
more info
PubMed 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein-containing complex binding IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell IMP
Inferred from Mutant Phenotype
more info
PubMed 
cell adhesion NAS
Non-traceable Author Statement
more info
PubMed 
cell-cell adhesion ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
cell-matrix adhesion IMP
Inferred from Mutant Phenotype
more info
PubMed 
extracellular matrix organization TAS
Traceable Author Statement
more info
 
heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules IMP
Inferred from Mutant Phenotype
more info
PubMed 
inflammatory response NAS
Non-traceable Author Statement
more info
PubMed 
integrin-mediated signaling pathway IEA
Inferred from Electronic Annotation
more info
 
leukocyte cell-cell adhesion IMP
Inferred from Mutant Phenotype
more info
PubMed 
leukocyte migration TAS
Traceable Author Statement
more info
 
memory T cell extravasation IDA
Inferred from Direct Assay
more info
PubMed 
neutrophil degranulation TAS
Traceable Author Statement
more info
 
phagocytosis IEA
Inferred from Electronic Annotation
more info
 
receptor clustering IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of immune response TAS
Traceable Author Statement
more info
 
signal transduction NAS
Non-traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
cell surface HDA PubMed 
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
extracellular exosome HDA PubMed 
integrin alphaL-beta2 complex IDA
Inferred from Direct Assay
more info
PubMed 
integrin complex NAS
Non-traceable Author Statement
more info
PubMed 
membrane HDA PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
specific granule membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
integrin alpha-L
Names
CD11 antigen-like family member A
LFA-1 alpha
LFA-1A
antigen CD11A (p180), lymphocyte function-associated antigen 1, alpha polypeptide
integrin gene promoter
integrin, alpha L (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide)
leukocyte adhesion glycoprotein LFA-1 alpha chain
leukocyte function-associated molecule 1 alpha chain
lymphocyte function-associated antigen 1, alpha polypeptide

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001114380.2NP_001107852.1  integrin alpha-L isoform b precursor

    See identical proteins and their annotated locations for NP_001107852.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame segment and uses an alternate in-frame splice junction compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.
    Source sequence(s)
    BC008777, CA430398
    Consensus CDS
    CCDS45461.1
    UniProtKB/Swiss-Prot
    P20701
    Related
    ENSP00000350886.5, ENST00000358164.9
    Conserved Domains (4) summary
    smart00191
    Location:434486
    Int_alpha; Integrin alpha (beta-propellor repeats)
    pfam00357
    Location:10291043
    Integrin_alpha; Integrin alpha cytoplasmic region
    pfam08441
    Location:529899
    Integrin_alpha2; Integrin alpha
    cl00057
    Location:106240
    vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...
  2. NM_002209.3NP_002200.2  integrin alpha-L isoform a precursor

    See identical proteins and their annotated locations for NP_002200.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).
    Source sequence(s)
    AK314246, BC008777, CA430398
    Consensus CDS
    CCDS32433.1
    UniProtKB/Swiss-Prot
    P20701
    UniProtKB/TrEMBL
    B2RAL6
    Related
    ENSP00000349252.5, ENST00000356798.11
    Conserved Domains (3) summary
    smart00191
    Location:517569
    Int_alpha; Integrin alpha (beta-propellor repeats)
    cd01469
    Location:155323
    vWA_integrins_alpha_subunit; Integrins are a class of adhesion receptors that link the extracellular matrix to the cytoskeleton and cooperate with growth factor receptors to promote celll survival, cell cycle progression and cell migration. Integrins consist of an alpha and a beta ...
    pfam08441
    Location:612983
    Integrin_alpha2; Integrin alpha

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000016.10 Reference GRCh38.p13 Primary Assembly

    Range
    30472683..30523185
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024450262.1XP_024306030.1  integrin alpha-L isoform X3

    Conserved Domains (3) summary
    smart00191
    Location:421473
    Int_alpha; Integrin alpha (beta-propellor repeats)
    cd01469
    Location:59227
    vWA_integrins_alpha_subunit; Integrins are a class of adhesion receptors that link the extracellular matrix to the cytoskeleton and cooperate with growth factor receptors to promote celll survival, cell cycle progression and cell migration. Integrins consist of an alpha and a beta ...
    pfam08441
    Location:516903
    Integrin_alpha2; Integrin alpha
  2. XM_006721044.1XP_006721107.1  integrin alpha-L isoform X2

    Conserved Domains (4) summary
    smart00191
    Location:434486
    Int_alpha; Integrin alpha (beta-propellor repeats)
    pfam00357
    Location:10301044
    Integrin_alpha; Integrin alpha cytoplasmic region
    pfam08441
    Location:529900
    Integrin_alpha2; Integrin alpha
    cl00057
    Location:106240
    vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...
  3. XM_005255313.1XP_005255370.1  integrin alpha-L isoform X1

    Conserved Domains (3) summary
    smart00191
    Location:517569
    Int_alpha; Integrin alpha (beta-propellor repeats)
    cd01469
    Location:155323
    vWA_integrins_alpha_subunit; Integrins are a class of adhesion receptors that link the extracellular matrix to the cytoskeleton and cooperate with growth factor receptors to promote celll survival, cell cycle progression and cell migration. Integrins consist of an alpha and a beta ...
    pfam08441
    Location:612982
    Integrin_alpha2; Integrin alpha
  4. XM_011545849.1XP_011544151.1  integrin alpha-L isoform X3

    Conserved Domains (3) summary
    smart00191
    Location:421473
    Int_alpha; Integrin alpha (beta-propellor repeats)
    cd01469
    Location:59227
    vWA_integrins_alpha_subunit; Integrins are a class of adhesion receptors that link the extracellular matrix to the cytoskeleton and cooperate with growth factor receptors to promote celll survival, cell cycle progression and cell migration. Integrins consist of an alpha and a beta ...
    pfam08441
    Location:516903
    Integrin_alpha2; Integrin alpha

RNA

  1. XR_950794.1 RNA Sequence

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