Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

ITGA9 (integrin, alpha 9)

Identity

Other namesALPHA-RLC
ITGA4L
RLC
HGNC (Hugo) ITGA9
LocusID (NCBI) 3680
Location 3p22.2
Location_base_pair Starts at 37493813 and ends at 37861281 bp from pter ( according to hg19-Feb_2009)  [Mapping]

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

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.
  

External links

Nomenclature
HGNC (Hugo)ITGA9   6145
Cards
AtlasITGA9ID41010ch3p22
Entrez_Gene (NCBI)ITGA9  3680  integrin, alpha 9
GeneCards (Weizmann)ITGA9
Ensembl (Hinxton) [Gene_View]  chr3:37493813-37861281 [Contig_View]  ITGA9 [Vega]
AceView (NCBI)ITGA9
Genatlas (Paris)ITGA9
WikiGenes3680
SOURCE (Princeton)NM_002207
Genomic and cartography
GoldenPath (UCSC)ITGA9  -  3p22.2   chr3:37493813-37861281 +  3p21.3   [Description]    (hg19-Feb_2009)
EnsemblITGA9 - 3p21.3 [CytoView]
Mapping of homologs : NCBIITGA9 [Mapview]
OMIM603963   
Gene and transcription
Genbank (Entrez)AK026826 AK123884 BC030198 BX647350 D25303
RefSeq transcript (Entrez)NM_002207
RefSeq genomic (Entrez)AC_000135 NC_000003 NC_018914 NG_016166 NT_022517 NW_001838877 NW_004929309
Consensus coding sequences : CCDS (NCBI)ITGA9
Cluster EST : UnigeneHs.113157 [ NCBI ]
CGAP (NCI)Hs.113157
Alternative Splicing : Fast-db (Paris)GSHG0020697
Gene ExpressionITGA9 [ NCBI-GEO ]     ITGA9 [ SEEK ]   ITGA9 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13797 (Uniprot)
NextProtQ13797  [Medical]
With graphics : InterProQ13797
Splice isoforms : SwissVarQ13797 (Swissvar)
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   
Related proteins : CluSTrQ13797
Domain families : Pfam (Sanger)FG-GAP (PF01839)    Integrin_alpha2 (PF08441)   
Domain families : Pfam (NCBI)pfam01839    pfam08441   
Domain families : Smart (EMBL)Int_alpha (SM00191)  
DMDM Disease mutations3680
Blocks (Seattle)Q13797
Peptide AtlasQ13797
HPRD04910
IPIIPI00015181   IPI00927444   IPI00927265   
Protein Interaction databases
DIP (DOE-UCLA)Q13797
IntAct (EBI)Q13797
BioGRIDITGA9
IntegromeDBITGA9
STRING (EMBL)ITGA9
Ontologies - Pathways
QuickGOQ13797
Ontology : AmiGOcollagen binding  plasma membrane  cell adhesion  integrin-mediated signaling pathway  axon guidance  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  axon guidance  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 PathwaysREACT_111045 Developmental Biology [pathway]
REACTOME PathwaysREACT_118779 Extracellular matrix organization [pathway]
Protein Interaction DatabaseITGA9
Wikipedia pathwaysITGA9
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)ITGA9
SNP (GeneSNP Utah)ITGA9
SNP : HGBaseITGA9
Genetic variants : HAPMAPITGA9
1000_GenomesITGA9 
CONAN: Copy Number AnalysisITGA9 
Somatic Mutations in Cancer : COSMICITGA9 
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
DECIPHER (Syndromes)3:37493813-37861281
Mutations and Diseases : HGMDITGA9
OMIM603963   
MedgenITGA9
GENETestsITGA9
Disease Genetic AssociationITGA9
Huge Navigator ITGA9 [HugePedia]  ITGA9 [HugeCancerGEM]
Genomic VariantsITGA9  ITGA9 [DGVbeta]
Exome VariantITGA9
dbVarITGA9
ClinVarITGA9
snp3D : Map Gene to Disease3680
General knowledge
Homologs : HomoloGeneITGA9
Homology/Alignments : Family Browser (UCSC)ITGA9
Phylogenetic Trees/Animal Genes : TreeFamITGA9
Chemical/Protein Interactions : CTD3680
Chemical/Pharm GKB GenePA29945
Clinical trialITGA9
Other databases
Probes
Litterature
PubMed47 Pubmed reference(s) in Entrez
CoreMineITGA9
GoPubMedITGA9
iHOPITGA9

Bibliography

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
 
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
 
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
 
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 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
 
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
 
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
 
The integrins.
Takada Y, Ye X, Simon S.
Genome Biol. 2007;8(5):215. (REVIEW)
PMID 17543136
 
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
 
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
 
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
 
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
 
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 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
 
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
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written10-2013Carla 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 and Haematology, Vall d'Hebron Hospital, Barcelona, Spain (JSdT, SG)

Citation

This paper should be referenced as such :
Molist C, Almazán-Moga A, Vidal I, Soriano A, Jubierre L, Segura MF, Sánchez de Toledo J, Gallego S, Roma J
ITGA9 (integrin, alpha 9);
Atlas Genet Cytogenet Oncol Haematol. October 2013
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/ITGA9ID41010ch3p22.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Nov 8 16:46:43 CET 2014

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.