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ITGA9 (integrin, alpha 9)

Written2013-10Carla Molist, Ana Almazán-Moga, Isaac Vidal, Aroa Soriano, Luz Jubierre, Miguel F Segura, Josep Sánchez de Toledo, Soledad Gallego, Josep Roma
Laboratory of Translational Research in Paediatric Cancer, Vall d'Hebron Research Institute, Barcelona, Spain (CM, AAM, IV, AS, LJ, MFS, JSdT, SG, JR); Paediatric Oncology, Haematology, Vall d'Hebron Hospital, Barcelona, Spain (JSdT, SG)

(Note : for Links provided by Atlas : click)

Identity

Alias_namesalpha 4-like
Alias_symbol (synonym)RLC
ITGA4L
ALPHA-RLC
HGNC (Hugo) ITGA9
LocusID (NCBI) 3680
Atlas_Id 41010
Location 3p22.2  [Link to chromosome band 3p22]
Location_base_pair Starts at 37493813 and ends at 37861281 bp from pter ( according to hg19-Feb_2009)  [Mapping ITGA9.png]
Fusion genes
(updated 2016)
ITGA9 (3p22.2) / CTDSPL (3p22.2)ITGA9 (3p22.2) / SEC13 (3p25.3)MLH1 (3p22.2) / ITGA9 (3p22.2)
NTPCR (1q42.2) / ITGA9 (3p22.2)PHLDB1 (11q23.3) / ITGA9 (3p22.2)SPG11 (15q21.1) / ITGA9 (3p22.2)
XYLB (3p22.2) / ITGA9 (3p22.2)

DNA/RNA

 
Description Chromosome 3: 37493606-37865005; forward strand. Segons omim: 3:37493812 - 37861280.
Transcription Exons: 28; Coding exons: 28; Transcript length: 7889 bps; Translation length: 1035 residues.
4 splice variants described (7889, 2282, 609 and 428bp), three of which with protein translation (1035, 632 and 609 aa).

Protein

Note Alpha9-Integrin.
 
Description Alpha-integrins, such as Alpha9-Integrin, are cell surface glycoproteins that contain a large N-terminal extracellular domain with 7 conserved repeats of putative metal-binding domains, a transmembrane segment, and a short C-terminal cytoplasmic tail. ITGA9, like ITGA4, lacks the domain I and the post-translational cleavage that usually occurs in the rest of alpha-integrins. Alpha9-Integrin forms a functional heterodimer with beta1-integrin.
Expression ITGA9 expression is widely distributed in normal human epithelia and muscle. For instance, it has been found in airway epithelium, basal layer of squamous epithelium, smooth muscle and skeletal muscle. Furthermore, its expression has been found in hepatocytes, breast tissue, neutrophils and polymorphonuclear leukocytes.
Localisation Cell membrane.
Function Adhesion with extracellular-matrix proteins, cell-cell interactions and signal transduction. ITGA9 has been shown to bind a plethora of ligands: tenascin, VCAM-1, osteopontin, uPAR, plasmin, angiostatin, several ADAMs (ADAM1, ADAM2, ADAM3, ADAM7, ADAM8, ADAM9, ADAM12, ADAM15, ADAM28 and ADAM33), EMILIN1, fibronectin, VEGF-A, VEGF-C and VEGF-D.
Alpha9 knockout mice died from respiratory failure before day 12 after birth and showed chylothorax, defective lymphatic and venous valve morphogenesis, impaired development of neutrophils, improper re-epithelialisation during cutaneous wound-healing, impaired bone resorption and abnormal osteoclasts.
In cancer, the heterodimer alpha9-beta1 has recently been shown to have an oncogenic role by inducing epithelial-mesenchymal transition and cell migration and metastatic ability in several cancers such as glioma, breast, colon and rhabdomyosarcoma. However, other authors have reported a tumour suppressor function for ITGA9 in a wide variety of tumours based on deletion or methylation states in varying percentages of patients. Furthermore, a very small percentage of patients (1%) with point mutations has also been reported.
Homology Alpha- and beta-integrins are completely distinct, with no detectable homology between them. Sequence identity among alpha-integrins is around 45%. All alpha-integrins are thought to have evolved from a common ancestor. Among all alpha-subunits, alpha-9 shows the greatest homology with alpha-4.

Mutations

 

Implicated in

Note
Entity Small cell lung cancer (SCLC)
Note Yamakawa et al. (1993) identified a region of homozygous deletions in chromosome 3p21.3 in lung cancer cell lines, where the ITGA9 gene is located. Furthermore, Hibi et al. (1994) reported an upregulation of the ITGA9 gene in SCLC cell lines and primary tumours, suggesting that an altered expression of the ITGA9 may contribute to the phenotype of this cancer.
An activation of ITGA9 expression has been shown in different human tumours and cancer cells, for example small cell lung cancer, medulloblastoma, astrocytoma and glioblastoma.
On the other hand, several genetic and epigenetic aberrations (deletions and methylations) of ITGA9 have been described in several types of cancer such as kidney, lung, breast, ovarian, cervical, prostate and colorectal.
  

Bibliography

Functional classification of ADAMs based on a conserved motif for binding to integrin alpha 9beta 1: implications for sperm-egg binding and other cell interactions.
Eto K, Huet C, Tarui T, Kupriyanov S, Liu HZ, Puzon-McLaughlin W, Zhang XP, Sheppard D, Engvall E, Takada Y.
J Biol Chem. 2002 May 17;277(20):17804-10. Epub 2002 Mar 6.
PMID 11882657
 
Integrin α9β1 promotes malignant tumor growth and metastasis by potentiating epithelial-mesenchymal transition.
Gupta SK, Oommen S, Aubry MC, Williams BP, Vlahakis NE.
Oncogene. 2013 Jan 10;32(2):141-50. doi: 10.1038/onc.2012.41. Epub 2012 Feb 27.
PMID 22370635
 
Aberrant upregulation of a novel integrin alpha subunit gene at 3p21.3 in small cell lung cancer.
Hibi K, Yamakawa K, Ueda R, Horio Y, Murata Y, Tamari M, Uchida K, Takahashi T, Nakamura Y, Takahashi T.
Oncogene. 1994 Feb;9(2):611-9.
PMID 8290272
 
The newcomer in the integrin family: integrin α9 in biology and cancer.
Hoye AM, Couchman JR, Wewer UM, Fukami K, Yoneda A.
Adv Biol Regul. 2012 May;52(2):326-39. doi: 10.1016/j.jbior.2012.03.004. Epub 2012 Mar 30. (REVIEW)
PMID 22781746
 
The EIIIA segment of fibronectin is a ligand for integrins alpha 9beta 1 and alpha 4beta 1 providing a novel mechanism for regulating cell adhesion by alternative splicing.
Liao YF, Gotwals PJ, Koteliansky VE, Sheppard D, Van De Water L.
J Biol Chem. 2002 Apr 26;277(17):14467-74. Epub 2002 Feb 11.
PMID 11839764
 
Co-expression of α9β1 integrin and VEGF-D confers lymphatic metastatic ability to a human breast cancer cell line MDA-MB-468LN.
Majumder M, Tutunea-Fatan E, Xin X, Rodriguez-Torres M, Torres-Garcia J, Wiebe R, Timoshenko AV, Bhattacharjee RN, Chambers AF, Lala PK.
PLoS One. 2012;7(4):e35094. doi: 10.1371/journal.pone.0035094. Epub 2012 Apr 24.
PMID 22545097
 
Human neutrophil integrin alpha9beta1: up-regulation by cell activation and synergy with beta2 integrins during adhesion to endothelium under flow.
Mambole A, Bigot S, Baruch D, Lesavre P, Halbwachs-Mecarelli L.
J Leukoc Biol. 2010 Aug;88(2):321-7. doi: 10.1189/jlb.1009704. Epub 2010 Apr 30.
PMID 20435742
 
Notch-mediated induction of N-cadherin and α9-integrin confers higher invasive phenotype on rhabdomyosarcoma cells.
Masia A, Almazan-Moga A, Velasco P, Reventos J, Toran N, Sanchez de Toledo J, Roma J, Gallego S.
Br J Cancer. 2012 Oct 9;107(8):1374-83. doi: 10.1038/bjc.2012.411. Epub 2012 Sep 13.
PMID 22976797
 
Integrin alpha9 (ITGA9) expression and epigenetic silencing in human breast tumors.
Mostovich LA, Prudnikova TY, Kondratov AG, Loginova D, Vavilov PV, Rykova VI, Sidorov SV, Pavlova TV, Kashuba VI, Zabarovsky ER, Grigorieva EV.
Cell Adh Migr. 2011 Sep-Oct;5(5):395-401. doi: 10.4161/cam.5.5.17949.
PMID 21975548
 
Sequence and tissue distribution of the integrin alpha 9 subunit, a novel partner of beta 1 that is widely distributed in epithelia and muscle.
Palmer EL, Ruegg C, Ferrando R, Pytela R, Sheppard D.
J Cell Biol. 1993 Dec;123(5):1289-97.
PMID 8245132
 
alpha9beta1 integrin is expressed on human neutrophils and contributes to neutrophil migration through human lung and synovial fibroblast barriers.
Shang T, Yednock T, Issekutz AC.
J Leukoc Biol. 1999 Nov;66(5):809-16.
PMID 10577513
 
The integrins.
Takada Y, Ye X, Simon S.
Genome Biol. 2007;8(5):215. (REVIEW)
PMID 17543136
 
The integrin alpha9beta1 mediates adhesion to activated endothelial cells and transendothelial neutrophil migration through interaction with vascular cell adhesion molecule-1.
Taooka Y, Chen J, Yednock T, Sheppard D.
J Cell Biol. 1999 Apr 19;145(2):413-20.
PMID 10209034
 
Integrin α9β1-mediated cell migration in glioblastoma via SSAT and Kir4.2 potassium channel pathway.
Veeravalli KK, Ponnala S, Chetty C, Tsung AJ, Gujrati M, Rao JS.
Cell Signal. 2012 Jan;24(1):272-81. doi: 10.1016/j.cellsig.2011.09.011. Epub 2011 Sep 17.
PMID 21946432
 
Frequent homozygous deletions in lung cancer cell lines detected by a DNA marker located at 3p21.3-p22.
Yamakawa K, Takahashi T, Horio Y, Murata Y, Takahashi E, Hibi K, Yokoyama S, Ueda R, Takahashi T, Nakamura Y.
Oncogene. 1993 Feb;8(2):327-30.
PMID 8381220
 

Citation

This paper should be referenced as such :
Molist, C ; Almazn, A ; Vidal, I ; Soriano, A ; Jubierre, L ; Segura, MF ; Snchez, de Toledo J ; Gallego, S ; Roma, J
ITGA9 (integrin, alpha 9)
Atlas Genet Cytogenet Oncol Haematol. 2014;18(5):321-323.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/ITGA9ID41010ch3p22.html


External links

Nomenclature
HGNC (Hugo)ITGA9   6145
Cards
AtlasITGA9ID41010ch3p22
Entrez_Gene (NCBI)ITGA9  3680  integrin subunit alpha 9
AliasesALPHA-RLC; ITGA4L; RLC
GeneCards (Weizmann)ITGA9
Ensembl hg19 (Hinxton)ENSG00000144668 [Gene_View]  chr3:37493813-37861281 [Contig_View]  ITGA9 [Vega]
Ensembl hg38 (Hinxton)ENSG00000144668 [Gene_View]  chr3:37493813-37861281 [Contig_View]  ITGA9 [Vega]
ICGC DataPortalENSG00000144668
TCGA cBioPortalITGA9
AceView (NCBI)ITGA9
Genatlas (Paris)ITGA9
WikiGenes3680
SOURCE (Princeton)ITGA9
Genetics Home Reference (NIH)ITGA9
Genomic and cartography
GoldenPath hg19 (UCSC)ITGA9  -     chr3:37493813-37861281 +  3p21.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)ITGA9  -     3p21.3   [Description]    (hg38-Dec_2013)
EnsemblITGA9 - 3p21.3 [CytoView hg19]  ITGA9 - 3p21.3 [CytoView hg38]
Mapping of homologs : NCBIITGA9 [Mapview hg19]  ITGA9 [Mapview hg38]
OMIM603963   
Gene and transcription
Genbank (Entrez)AK026826 AK123884 BC030198 BX647350 D25303
RefSeq transcript (Entrez)NM_002207
RefSeq genomic (Entrez)NC_000003 NC_018914 NG_016166 NT_022517 NW_004929309
Consensus coding sequences : CCDS (NCBI)ITGA9
Cluster EST : UnigeneHs.113157 [ NCBI ]
CGAP (NCI)Hs.113157
Alternative Splicing GalleryENSG00000144668
Gene ExpressionITGA9 [ NCBI-GEO ]   ITGA9 [ EBI - ARRAY_EXPRESS ]   ITGA9 [ SEEK ]   ITGA9 [ MEM ]
Gene Expression Viewer (FireBrowse)ITGA9 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3680
GTEX Portal (Tissue expression)ITGA9
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13797   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ13797  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ13797
Splice isoforms : SwissVarQ13797
PhosPhoSitePlusQ13797
Domaine pattern : Prosite (Expaxy)FG_GAP (PS51470)    INTEGRIN_ALPHA (PS00242)   
Domains : Interpro (EBI)FG-GAP    Int_alpha_beta-p    Integrin_alpha    Integrin_alpha-2    Integrin_alpha_C_CS    Integrin_dom   
Domain families : Pfam (Sanger)FG-GAP (PF01839)    Integrin_alpha2 (PF08441)   
Domain families : Pfam (NCBI)pfam01839    pfam08441   
Domain families : Smart (EMBL)Int_alpha (SM00191)  
Conserved Domain (NCBI)ITGA9
DMDM Disease mutations3680
Blocks (Seattle)ITGA9
SuperfamilyQ13797
Human Protein AtlasENSG00000144668
Peptide AtlasQ13797
HPRD04910
IPIIPI00015181   IPI00927444   IPI00927265   
Protein Interaction databases
DIP (DOE-UCLA)Q13797
IntAct (EBI)Q13797
FunCoupENSG00000144668
BioGRIDITGA9
STRING (EMBL)ITGA9
ZODIACITGA9
Ontologies - Pathways
QuickGOQ13797
Ontology : AmiGOcollagen binding  plasma membrane  cell adhesion  integrin-mediated signaling pathway  integrin complex  basal plasma membrane  extracellular matrix organization  neutrophil chemotaxis  integrin alpha9-beta1 complex  wound healing  laminin binding  metal ion binding  
Ontology : EGO-EBIcollagen binding  plasma membrane  cell adhesion  integrin-mediated signaling pathway  integrin complex  basal plasma membrane  extracellular matrix organization  neutrophil chemotaxis  integrin alpha9-beta1 complex  wound healing  laminin binding  metal ion binding  
Pathways : KEGGPI3K-Akt signaling pathway    Focal adhesion    ECM-receptor interaction    Cell adhesion molecules (CAMs)    Regulation of actin cytoskeleton    Hypertrophic cardiomyopathy (HCM)    Arrhythmogenic right ventricular cardiomyopathy (ARVC)    Dilated cardiomyopathy   
REACTOMEQ13797 [protein]
REACTOME PathwaysR-HSA-445144 Signal transduction by L1 [pathway]
REACTOME PathwaysR-HSA-3000178 ECM proteoglycans [pathway]
REACTOME PathwaysR-HSA-216083 Integrin cell surface interactions [pathway]
NDEx NetworkITGA9
Atlas of Cancer Signalling NetworkITGA9
Wikipedia pathwaysITGA9
Orthology - Evolution
OrthoDB3680
GeneTree (enSembl)ENSG00000144668
Phylogenetic Trees/Animal Genes : TreeFamITGA9
HOVERGENQ13797
HOGENOMQ13797
Homologs : HomoloGeneITGA9
Homology/Alignments : Family Browser (UCSC)ITGA9
Gene fusions - Rearrangements
Fusion : MitelmanITGA9/SEC13 [3p22.2/3p25.3]  
Fusion : MitelmanXYLB/ITGA9 [3p22.2/3p22.2]  [t(3;3)(p22;p22)]  
Fusion: TCGAITGA9 3p22.2 SEC13 3p25.3 LUAD
Fusion: TCGAXYLB 3p22.2 ITGA9 3p22.2 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerITGA9 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ITGA9
dbVarITGA9
ClinVarITGA9
1000_GenomesITGA9 
Exome Variant ServerITGA9
ExAC (Exome Aggregation Consortium)ITGA9 (select the gene name)
Genetic variants : HAPMAP3680
Genomic Variants (DGV)ITGA9 [DGVbeta]
DECIPHER (Syndromes)3:37493813-37861281  ENSG00000144668
CONAN: Copy Number AnalysisITGA9 
Mutations
ICGC Data PortalITGA9 
TCGA Data PortalITGA9 
Broad Tumor PortalITGA9
OASIS PortalITGA9 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICITGA9  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDITGA9
intOGen PortalITGA9
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch ITGA9
DgiDB (Drug Gene Interaction Database)ITGA9
DoCM (Curated mutations)ITGA9 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ITGA9 (select a term)
intoGenITGA9
NCG5 (London)ITGA9
Cancer3DITGA9(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM603963   
Orphanet
MedgenITGA9
Genetic Testing Registry ITGA9
NextProtQ13797 [Medical]
TSGene3680
GENETestsITGA9
Huge Navigator ITGA9 [HugePedia]
snp3D : Map Gene to Disease3680
BioCentury BCIQITGA9
ClinGenITGA9
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD3680
Chemical/Pharm GKB GenePA29945
Clinical trialITGA9
Miscellaneous
canSAR (ICR)ITGA9 (select the gene name)
Probes
Litterature
PubMed50 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineITGA9
EVEXITGA9
GoPubMedITGA9
iHOPITGA9
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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