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ITGA11 (integrin, alpha 11)

Written2008-04Svetlana N Popova, Donald Gullberg
Department of Biomedicine, University of Bergen, Jonas Lies vei 91, NO-5009 Bergen, Norway

(Note : for Links provided by Atlas : click)

Identity

Other aliasHsT18964
LocusID (NCBI) 22801
Atlas_Id 41001
Location 15q23  [Link to chromosome band 15q23]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CARD11 (7p22.2) / ITGA11 (15q23)ITGA11 (15q23) / ITGA11 (15q23)

DNA/RNA

Description The gene contains 30 exons and 29 introns; it is composed of a 30 nt long 5' untranslated region, a 3564-nucleotide open reading frame, a 329-nucleotide 3' noncoding sequence and a polyA tail.
Transcription Gene analysis in silico reveals several potential splice variants, which still remain to be validated at the RNA level. The basal promoter is regulated by Sp1/ Sp3/ Ets-1 binding sites. How occupation of these cis-binding sites in the promoter results in a fibroblast-specific α11 expression pattern remains to be shown. One working hypothesis is that the combined binding of Sp1 with a specific member of the Ets family of transcription factors contributes to the tissue-specific expression pattern.

Protein

 
  Scematic structure of the I-domain containing α11 integrin.
A. The integrin's α subunit primary structure, including predicted divalent cation-binding sites (Mg2 as red star, and Ca2 as gray stars) is shown. The position of the inserted sequence of 22 amino acids in the Calf-1 domain is marked.
B. Schematic representations of straightened (active) conformations of the integrin. The arrangement of domains is based on the 3-dimensional crystal structure of the αvβ3-integrin, with an I domain added between the second and third β-propeller repeats.
I-d indicates I domain; PSI, plexin/semaphorin/integrin; and TM, -tail domain of integrin β subunit.
Description The mature α11 peptide is 1166-amino acid-long (M.W. 145 kDa in SDS-PAGE under non-reducing conditions), which is longer than any other currently identified integrin α-chain (with the closest being αE, which is composed of 1160 amino acids). The extracellular domain contains seven FG-GAP repeats in the amino-terminal end with an inserted I domain between repeats 2 and 3. The I domain consists of 195 amino acids and includes a conserved metal ion-dependent adhesion site motif. In addition to the metal chelating site in the I domain, three potential divalent cation binding motifs with the consensus sequence DXD/NXDXXXD are present in repeats 5-7. A total of 20 cysteines are located in the extracellular domain. Of these, 16 are conserved in the most closely related integrin α10- and α1-chains, and they may contribute to intramolecular disulfide bonds. There is an inserted 22 amino acid sequence in the calf-1 domain in the stalk region at amino acids 804-826, distinguishing α11 from other integrin α-chains. The transmembrane region (amino acids 1142-1164) is 23 amino acids long and is followed by a cytoplasmic tail of 24 amino acids. The cytoplasmic tail contains the sequence GFFRS instead of the conserved GFFKR sequence found in all other alpha-chains except ITGA8 - alpha 10.
Expression Analysis of α11 protein and mRNA expression and distribution in human and mouse embryos revealed a restricted expression on mesenchymal non-muscle cells in areas of highly organized interstitial collagen networks.
Localisation Membrane-bound
Function Integrin α11 subunit binds integrin beta 1 subunit to form a heterodimer and function as a receptor for interstitial collagens (with highest affinity for collagen type I). It is involved in cell attachment, cell migration and collagen reorganization on mesenchymal non-muscle cells.
Homology When compared with other I domain-containing collagen-binding integrin subunits, α11 amino acid sequence shows the highest overall identity with integrin alpha 10 (42% identity) followed by integrin alpha 1 (37% identity), and integrin alpha 2 (35% identity). Of the non-I domain-containing integrins, integrin alpha 4 and integrin alpha 9 show the highest sequence similarity to α11. ITGA11 shows 86% identity with mouse integrin α11 at the nucleotide level, translating to 89% identity at the amino-acid level.

Implicated in

Note
  
Entity Lung cancer
Disease Lung cancer, the most common cause of cancer-related death in men and the second most common in women, is responsible for 1.3 million deaths worldwide annually. For treatment purposes, lung cancer is grouped into 2 major types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). The latter group is a heterogeneous disease which can be classified histologically into many types, with the 4 major ones being adenocarcinomas, squamous cell carcinoma, large cell carcinoma and adenosquamous carcinoma. Adenocarcinoma accounts for about one third of lung cancers, with a majority arising in the peripheral lung tissue. In the Western world, most cases of adenocarcinoma are associated with smoking. However, among people who have never smoked, adenocarcinoma is the most common form of lung cancer. Elevated expression of ITGA11 was reported in non-small cells carcinomas and associated with stromal fibroblasts. The possible involvement of integrin α11 in other types of tumor-stroma interactions remains to be defined.
Prognosis The overall 5-year survival rate of lung cancer is 15%. In NSCLC, survival rate is primarily determined by the tumor stage, i.e. the extend of spread of tumor cells at the time of diagnosis.
Oncogenesis Interactions of tumor cells with the stroma play a critical role in tumor growth, invasion, metastases, angiogenesis, and chemoresistance. Factors derived from the carcinoma-associated fibroblast (CAF) or activated fibroblast can contribute to the transformation of epithelial cells and enhance the tumorigenicity of cancer cells possibly through paracrine secretion of growth factors. It was recently shown that CAFs in NSCLC express higher levels of integrin α11. One of the factors which is affected by higher levels of ITGA11 during tumor growth is IGF2. Higher levels of IGF2 in turn can stimulate growth of the tumor epithelial cells leading to tumor progression and metastasis.
  

Bibliography

Great potential of a panel of multiple hMTH1, SPD, ITGA11 and COL11A1 markers for diagnosis of patients with non-small cell lung cancer.
Chong IW, Chang MY, Chang HC, Yu YP, Sheu CC, Tsai JR, Hung JY, Chou SH, Tsai MS, Hwang JJ, Lin SR.
Oncol Rep. 2006 Nov;16(5):981-8.
PMID 17016581
 
Second-line treatment for advanced-stage non-small-cell lung cancer: current and future options.
Ho C, Davies AM, Lara PN Jr, Gandara DR.
Clin Lung Cancer. 2006 May;7 Suppl 4:S118-25. (review)
PMID 16764752
 
Tandem Sp1/Sp3 sites together with an Ets-1 site cooperate to mediate alpha11 integrin chain expression in mesenchymal cells.
Lu N, Heuchel R, Barczyk M, Zhang WM, Gullberg D.
Matrix Biol. 2006 Mar;25(2):118-29.
PMID 16300938
 
Cytogenetic and molecular aspects of lung cancer.
Panani AD, Roussos C.
Cancer Lett. 2006 Jul 28;239(1):1-9. (review)
PMID 16112428
 
Physiology and pathology of collagen receptors.
Popova SN, Lundgren-Akerlund E, Wiig H, Gullberg D.
Acta Physiol (Oxf). 2007 Jul;190(3):179-87. (review)
PMID 17581134
 
The mesenchymal alpha11beta1 integrin attenuates PDGF-BB-stimulated chemotaxis of embryonic fibroblasts on collagens.
Popova SN, Rodriguez-Sanchez B, Liden A, Betsholtz C, Van Den Bos T, Gullberg D.
Dev Biol. 2004 Jun 15;270(2):427-42.
PMID 15183724
 
Cell-surface association between matrix metalloproteinases and integrins: role of the complexes in leukocyte migration and cancer progression.
Stefanidakis M, Koivunen E.
Blood. 2006 Sep 1;108(5):1441-50. (review)
PMID 16609063
 
Lung cancer in never smokers: a review.
Subramanian J, Govindan R.
J Clin Oncol. 2007 Feb 10;25(5):561-70. (review)
PMID 17290066
 
alpha11beta1 integrin is a receptor for interstitial collagens involved in cell migration and collagen reorganization on mesenchymal nonmuscle cells.
Tiger CF, Fougerousse F, Grundstrom G, Velling T, Gullberg D.
Dev Biol. 2001 Sep 1;237(1):116-29.
PMID 11518510
 
cDNA cloning and chromosomal localization of human alpha(11) integrin. A collagen-binding, I domain-containing, beta(1)-associated integrin alpha-chain present in muscle tissues.
Velling T, Kusche-Gullberg M, Sejersen T, Gullberg D.
J Biol Chem. 1999 Sep 3;274(36):25735-42.
PMID 10464311
 
Novel candidate tumor marker genes for lung adenocarcinoma.
Wang KK, Liu N, Radulovich N, Wigle DA, Johnston MR, Shepherd FA, Minden MD, Tsao MS.
Oncogene. 2002 Oct 24;21(49):7598-604.
PMID 12386823
 
Analysis of the human integrin alpha11 gene (ITGA11) and its promoter.
Zhang WM, Popova SN, Bergman C, Velling T, Gullberg MK, Gullberg D.
Matrix Biol. 2002 Oct;21(6):513-23.
PMID 12392762
 
Integrin alpha 11 regulates IGF2 expression in fibroblasts to enhance tumorigenicity of human non-small-cell lung cancer cells.
Zhu CQ, Popova SN, Brown ER, Barsyte-Lovejoy D, Navab R, Shih W, Li M, Lu M, Jurisica I, Penn LZ, Gullberg D, Tsao MS.
Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11754-9.
PMID 17600088
 

Citation

This paper should be referenced as such :
Popova, SN ; Gullberg, D
ITGA11 (integrin, alpha 11)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(3):210-212.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/ITGA11ID41001ch15q23.html


External links

Nomenclature
Cards
AtlasITGA11ID41001ch15q23.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)22801
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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