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

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; AllianceGenome:HGNC:6148
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: mouse all
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Genomic context

Location:: 16p11.2

Exon count:: 32

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (30472742..30523185)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (30859706..30910154)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (30484063..30534506)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

LFA-1 nanoclusters integrate TCR stimulation strength to tune T-cell cytotoxic activity.
Title: LFA-1 nanoclusters integrate TCR stimulation strength to tune T-cell cytotoxic activity.
lncRNA PCBP1-AS1 mediated downregulation of ITGAL as a prognostic biomarker in lung adenocarcinoma.
Title: lncRNA PCBP1-AS1 mediated downregulation of ITGAL as a prognostic biomarker in lung adenocarcinoma.
LFA-1 activation enriches tumor-specific T cells in a cold tumor model and synergizes with CTLA-4 blockade.
Title: LFA-1 activation enriches tumor-specific T cells in a cold tumor model and synergizes with CTLA-4 blockade.
CD64, CD11a and CD18 leukocytes expression in children with SARS-CoV-2 multisystem inflammatory syndrome versus children with Kawasaki disease: Similar but not the same.
Title: CD64, CD11a and CD18 leukocytes expression in children with SARS-CoV-2 multisystem inflammatory syndrome versus children with Kawasaki disease: Similar but not the same.
Aggregatibacter actinomycetemcomitans LtxA has a strong affinity for the cytosolic domains of both the alphaL and beta2 subunits (Kd = 15 and 4.2 nM, respectively) of human LFA-1 and a significantly lower affinity for the cytoplasmic domains of other integrin alphaM , alphaX , and beta3 subunits (Kd = 400, 180, and 230 nM, respectively), used as controls.
Title: Aggregatibacter actinomycetemcomitans leukotoxin causes activation of lymphocyte function-associated antigen 1.
The down-regulation of hsa_circ_0012919, the sponge for miR-125a-3p, contributes to DNA methylation of CD11a and CD70 in CD4(+) T cells of systemic lupus erythematous
Title: The down-regulation of hsa_circ_0012919, the sponge for miR-125a-3p, contributes to DNA methylation of CD11a and CD70 in CD4(+) T cells of systemic lupus erythematous.
LFA-1 cross-linking recruits and activates FAK1 and PYK2 to phosphorylate LAT selectively on a single Y-171 site that binds to the GRB2-SKAP1 complex and limits dwell times of T-cells with dendritic cells
Title: LFA-1 activates focal adhesion kinases FAK1/PYK2 to generate LAT-GRB2-SKAP1 complexes that terminate T-cell conjugate formation.
Data show that integrin alphaLbeta2 (LFA-1) is oriented relative to actin retrograde flow.
Title: Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration.
These results demonstrated that histone demethylase JMJD3 regulates CD11a expression in lupus T cells by affecting the H3K27me3 levels in the ITGAL (CD11a) promoter region, and JMJD3 might thereby serve as a potential therapeutic target for SLE.
Title: Histone demethylase JMJD3 regulates CD11a expression through changes in histone H3K27 tri-methylation levels in CD4+ T cells of patients with systemic lupus erythematosus.
Data show a nadir of CD11a expression at 2 years of natalizumab treatment in multiple sclerosis, at the peak of incidence of progressive multifocal leukoencephalopathy, indirectly suggesting that a lack of these molecules may play a role in the onset of PML in NTZ-treated patients.
Title: Natalizumab treatment alters the expression of T-cell trafficking marker LFA-1 α-chain (CD11a) in MS patients.

Submit: New GeneRIF Correction See all GeneRIFs (128)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH80563 (e-PCR)
- UniSTS:83990

Myln (e-PCR), detects polymorphism
- UniSTS:143966

RH48619 (e-PCR)
- UniSTS:87921

D16S1292 (e-PCR)
- UniSTS:154497

D5S1597E (e-PCR)
- UniSTS:151019

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ICAM-3 receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables cell adhesion molecule binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables cell adhesion molecule binding	IPI Inferred from Physical Interaction more info	PubMed
enables integrin binding	IBA Inferred from Biological aspect of Ancestor more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in 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
involved_in cell adhesion	NAS Non-traceable Author Statement more info	PubMed
involved_in cell adhesion mediated by integrin	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell-cell adhesion	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell-cell adhesion	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in cell-matrix adhesion	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell-matrix adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in inflammatory response	NAS Non-traceable Author Statement more info	PubMed
involved_in integrin-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in leukocyte cell-cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in memory T cell extravasation	IDA Inferred from Direct Assay more info	PubMed
involved_in phagocytosis	IEA Inferred from Electronic Annotation more info
involved_in receptor clustering	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in signal transduction	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in cell surface	HDA more info	PubMed
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular exosome	HDA more info	PubMed
part_of integrin alphaL-beta2 complex	IDA Inferred from Direct Assay more info	PubMed
part_of integrin complex	IBA Inferred from Biological aspect of Ancestor more info
part_of integrin complex	NAS Non-traceable Author Statement more info	PubMed
located_in membrane	HDA more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in specific granule membrane	TAS Traceable Author Statement more info

General protein information

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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)

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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)

NM_001114380.2 → NP_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/TrEMBL

B2RAL6

Related

ENSP00000350886.5, ENST00000358164.9

Conserved Domains (4) summary

smart00191
Location:434 → 486

Int_alpha; Integrin alpha (beta-propellor repeats)

pfam00357
Location:1029 → 1043

Integrin_alpha; Integrin alpha cytoplasmic region

pfam08441
Location:529 → 899

Integrin_alpha2; Integrin alpha

cl00057
Location:106 → 240

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 ...
NM_002209.3 → NP_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

O43746, P20701, Q45H73, Q96HB1, Q9UBC8

UniProtKB/TrEMBL

B2RAL6

Related

ENSP00000349252.5, ENST00000356798.11

Conserved Domains (3) summary

smart00191
Location:517 → 569

Int_alpha; Integrin alpha (beta-propellor repeats)

cd01469
Location:155 → 323

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:612 → 983

Integrin_alpha2; Integrin alpha

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000016.10 Reference GRCh38.p14 Primary Assembly

Range

30472742..30523185

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005255313.1 → XP_005255370.1 integrin alpha-L isoform X1

UniProtKB/TrEMBL

B2RAL6

Conserved Domains (3) summary

smart00191
Location:517 → 569

Int_alpha; Integrin alpha (beta-propellor repeats)

cd01469
Location:155 → 323

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:612 → 982

Integrin_alpha2; Integrin alpha
XM_006721044.2 → XP_006721107.1 integrin alpha-L isoform X2

UniProtKB/TrEMBL

B2RAL6

Conserved Domains (4) summary

smart00191
Location:434 → 486

Int_alpha; Integrin alpha (beta-propellor repeats)

pfam00357
Location:1030 → 1044

Integrin_alpha; Integrin alpha cytoplasmic region

pfam08441
Location:529 → 900

Integrin_alpha2; Integrin alpha

cl00057
Location:106 → 240

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 ...
XM_047434073.1 → XP_047290029.1 integrin alpha-L isoform X4
XM_047434072.1 → XP_047290028.1 integrin alpha-L isoform X3