ITGA1 (integrin, alpha 1)

2014-10-01   Salah Boudjadi , Jean-François Beaulieu 

Laboratory of Intestinal Physiopathology, Department of Anatomy, Cell Biology, Faculty of Medicine, Health Sciences, Universite de Sherbrooke, 3001 12th Avenue N, Sherbrooke, QC J1H 5N4, Canada




The α1 integrin subunit (SU) belongs to a large family of α and β subunits that are noncovalently linked to constitute αβ transmembrane units. To date, 18 α and 8 β subunits are known to form 24 αβ units (Takada et al., 2007; Barczyk et al., 2010) which are involved in cell-cell and cell-matrix attachment and can drive inside-out and outside-in cell signaling (Shattil et al., 2010). Integrins are known to participate in different cell processes including cell shape, differentiation, migration, survival and proliferation (Giancotti, 1997; Vachon, 2011; Beauséjour et al., 2012). The α1 SU was discovered in 1986 as the Very Late Antigen 1 (VLA1) and is highly expressed in activated lymphocytes in the joints of patients with rheumatoid arthritis (Hemler et al., 1986). In fibroblasts, α1 is known to activate the RAS\/ERK proliferative pathway and has a pro-invasive function in certain cancers. In megakaryocyte differentiation α1 is silenced by DNA methylation but not histone modification (Cheli et al., 2007). Different transcription factors involved in cancer progression can bind to the ITGA1 promoter. Integrin α1 transcriptional regulation remains to be further defined.


Atlas Image
Figure 1. The human ITGA1 gene is located on chromosome 5 at locus q11.2 and contains 29 exons. Only exons 1 and 2 are presented in this diagram. The first intron of ITGA1, which is 69 kb, contains the two exons of the PELO gene. The proximal promoter sequence immediately preceeding the initiation transcription site (red line) includes a CpG island (underlined in orange) and is predicted to be methylated. This region contains possible regulatory elements for different transcription factors known to be involved in various cancers (see text below).


The ITGA1 gene is 165354 bp in length and contains 29 exons that encode a protein of 1179 aa.


Transcriptional regulation of the α1 integrin SU: transcriptional regulation of ITGA1 was first described in smooth muscle cells of the chicken in the proximal promoter of ITGA1 containing the CArG box for the serum response factor (SRF) (Obata et al., 1997). Cheli et al. also reported that ITGA1 expression is predominantly regulated by DNA methylation and not histone modification in human HEK293 cells (Cheli et al., 2007). The proximal promoter region of the ITGA1 gene contains CpG islands which are selectively and fully methylated during differentiation of mononuclear cells into the megakaryocyte lineage. This mechanism could be responsible for the silencing of ITGA1 expression in differentiated intestinal cells. Our in silico analysis of the proximal promoter of ITGA1 revealed the presence of a number of response elements for nuclear factors known to be implicated in cancer progression such as TCF/LEF and c-Myc (unpublished data). Further studies are needed to determine a functional relationship between these factors and ITGA1 expression.



Protein access number: P56199. NCBI reference sequence: NP_852478.1.
Atlas Image
Figure 2. αβ heterodimer domain composition. The two subunits have external domains, a transmembrane domain and a small cytoplasmic tail. α1 is the largest a subunit, but has the smallest cytoplasmic tail. It contains the I (inserted) domain implicated in collagen binding. α1 has no disulfide junctions (no cleavage under reduced conditions) and forms a heterodimer only with the β1 subunit. When inactive the integrin heterodimer is under a bent conformation. Once activated it becomes open and elongated which enhances ligand binding affinity (Arnaout et al., 2005; Shattil et al., 2010).


Expression and localisation: the α1 integrin SU (figure 2) is highly expressed in various areas of the stroma. As reported previously, α1 is present in fibroblasts, endothelial cells and smooth muscle cells (Gardner, 2014). In the gut, α1 is expressed in myofibroblast cells surrounding the crypts of the colon and small intestinal mucosa (Boudjadi et al., 2013). α1 is present in epithelial cells of the endometrium, kidney and intestine. In the latter, α1 is present only in proliferating crypt cells while its exclusive partner β1 is constitutively expressed in all intestinal cells (Beaulieu, 1992; Boudjadi et al., 2013). In these cells, α1 is observed in the basolateral portion of the cytoplasmic membrane (figure 3).
Atlas Image
Figure 3. Immunohistochemical images showing examples of α1 integrin subunit expression in the gut. (A) Resection margin and (B) corresponding matched colorectal adenocarcinoma specimens. α1 is predominantly expressed in the proliferative cells of the crypt (A; red arrows) at the basolateral domain of normal epithelial cells, and also in the endothelial cells (A; black arrow). In adenocarcinomas, α1 is highly expressed in tumour epithelial cells (B; red arrows) and reactive stromal cells (B; black arrows). Scale bars = 50 μm.


α1β1 is the main cell receptor for collagen IV and with a lower affinity for collagen I, whereas α2β1 has a higher affinity for collagen I (Barczyk et al., 2010). α1β1 recognizes the GEFOGER sequence within the tertiary structure of collagen IV. It is important for cell anchorage to the extracellular matrix and is implicated in focal adhesions and cell migration. The presence of α1β1 in proliferating cells is supported by the reported role for α1, via caveolin-1 and Shc, in the downstream activation of the Ras/MEK/ERK proliferative pathway (Giancotti, 2000). In endothelial cells, using a selective mutagenesis approach, specific amino acids in the α1 cytoplasmic tail are shown to drive various functions and pathways. While Lys1147 is important only for tubulogenesis, Pro1142 and Leu1145 are required for ERK activation and cell proliferation. Lys1146 is involved in cell adhesion, migration (activation of p38 MAPK) and tubulogenesis (activation of p38 MAPK and PI3K). Interestingly, substitution of the Lys1151 positively charged amino acid at the COOH-terminus of the α1 tail results in a complete loss of the above functions. This positively charged amino acid could be required for α1 orientation relative to the β1 tail, compromising binding to signal molecules (Abair et al., 2008).



No mutation known for human ITGA1 gene.

Implicated in

Entity name
Lung cancer
In mouse models, the α1β1 integrin mediates cell invasion through the regulation of stromelysin-1 expression (Lochter et al., 1999) and, together with the Kras oncogenic factor, potentiates tumour growth and cell motility (Macias-Perez et al., 2008).
Entity name
Colorectal cancer
Integrin α1β1 is up-regulated in 65% of colon adenocarcinomas compared to matched margins. Expression is found to be higher in epithelial cells and the surrounding reactive cells (Boudjadi et al., 2013). Also, α1β1 is present in the early stages of colorectal cancer which could constitute a useful early diagnostic marker.
Entity name
Hepatocellular carcinoma
In a fibrotic microenvironment similar to that of hepatocellular carcinoma, α1β1 has been reported to be able to enhance cell invasion through the fibrotic matrix (Yang et al., 2003).


Pubmed IDLast YearTitleAuthors
186479592008Functional analysis of the cytoplasmic domain of the integrin {alpha}1 subunit in endothelial cells.Abair TD et al
162125002005Integrin structure, allostery, and bidirectional signaling.Arnaout MA et al
196935432010Integrins.Barczyk M et al
15064251992Differential expression of the VLA family of integrins along the crypt-villus axis in the human small intestine.Beaulieu JF et al
224029812012Integrin/Fak/Src-mediated regulation of cell survival and anoikis in human intestinal epithelial crypt cells: selective engagement and roles of PI3-K isoform complexes.Beauséjour M et al
242523132013Integrin α1 subunit is up-regulated in colorectal cancer.Boudjadi S et al
176695162007Transcriptional and epigenetic regulation of the integrin collagen receptor locus ITGA1-PELO-ITGA2.Cheli Y et al
250231652014Integrin α1β1.Gardner H et al
106208162000Complexity and specificity of integrin signalling.Giancotti FG et al
30180431986Very late activation antigens on rheumatoid synovial fluid T lymphocytes. Association with stages of T cell activation.Hemler ME et al
99506761999alpha1 and alpha2 integrins mediate invasive activity of mouse mammary carcinoma cells through regulation of stromelysin-1 expression.Lochter A et al
186768352008Loss of integrin alpha1beta1 ameliorates Kras-induced lung cancer.Macias-Perez I et al
93342461997Smooth muscle cell phenotype-dependent transcriptional regulation of the alpha1 integrin gene.Obata H et al
203089862010The final steps of integrin activation: the end game.Shattil SJ et al
175431362007The integrins.Takada Y et al
217857232011Integrin signaling, cell survival, and anoikis: distinctions, differences, and differentiation.Vachon PH et al
146789902003Integrin alpha1beta1 and alpha2beta1 are the key regulators of hepatocarcinoma cell invasion across the fibrotic matrix microenvironment.Yang C et al

Other Information

Locus ID:

NCBI: 3672
MIM: 192968
HGNC: 6134
Ensembl: ENSG00000213949


dbSNP: 3672
ClinVar: 3672
TCGA: ENSG00000213949


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Focal adhesionKEGGko04510
ECM-receptor interactionKEGGko04512
Hematopoietic cell lineageKEGGko04640
Regulation of actin cytoskeletonKEGGko04810
Focal adhesionKEGGhsa04510
ECM-receptor interactionKEGGhsa04512
Hematopoietic cell lineageKEGGhsa04640
Regulation of actin cytoskeletonKEGGhsa04810
Hypertrophic cardiomyopathy (HCM)KEGGko05410
Hypertrophic cardiomyopathy (HCM)KEGGhsa05410
Arrhythmogenic right ventricular cardiomyopathy (ARVC)KEGGko05412
Arrhythmogenic right ventricular cardiomyopathy (ARVC)KEGGhsa05412
Dilated cardiomyopathyKEGGko05414
Dilated cardiomyopathyKEGGhsa05414
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
Platelet Adhesion to exposed collagenREACTOMER-HSA-75892
Muscle contractionREACTOMER-HSA-397014
Smooth Muscle ContractionREACTOMER-HSA-445355
Extracellular matrix organizationREACTOMER-HSA-1474244
Laminin interactionsREACTOMER-HSA-3000157
Integrin cell surface interactionsREACTOMER-HSA-216083
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
Semaphorin interactionsREACTOMER-HSA-373755
Other semaphorin interactionsREACTOMER-HSA-416700
L1CAM interactionsREACTOMER-HSA-373760
CHL1 interactionsREACTOMER-HSA-447041

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
151329902004VEGF-A promotes tissue repair-associated lymphatic vessel formation via VEGFR-2 and the alpha1beta1 and alpha2beta1 integrins.100
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
176034942007Alpha1beta1 integrin is crucial for accumulation of epidermal T cells and the development of psoriasis.78
256727542015Cutting edge: identification and characterization of human intrahepatic CD49a+ NK cells.71
197306832009The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors.59
154858562004Regulation of human beta-cell adhesion, motility, and insulin secretion by collagen IV and its receptor alpha1beta1.52
232849372012Discoidin domain receptors promote α1β1- and α2β1-integrin mediated cell adhesion to collagen by enhancing integrin activation.41
160434292005A novel binding site in collagen type III for integrins alpha1beta1 and alpha2beta1.39
229196612012An RGD helper sequence in CagL of Helicobacter pylori assists in interactions with integrins and injection of CagA.35
185870472008Integrins alpha1beta1 and alpha2beta1 are receptors for the rotavirus enterotoxin.34


Salah Boudjadi ; Jean-François Beaulieu

ITGA1 (integrin, alpha 1)

Atlas Genet Cytogenet Oncol Haematol. 2014-10-01

Online version: