Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   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

PARVB (parvin, beta)

Written2010-04Cameron N Johnstone
Cancer Metastasis Laboratory, Research Division, Peter MacCallum Cancer Centre, 2 St Andrew's Place, East Melbourne, 3002, Victoria, Australia

(Note : for Links provided by Atlas : click)


Alias (NCBI)CGI-56
HGNC Alias symbCGI-56
HGNC Alias nameaffixin
LocusID (NCBI) 29780
Atlas_Id 46486
Location 22q13.31  [Link to chromosome band 22q13]
Location_base_pair Starts at 44024277 and ends at 44169232 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping PARVB.png]
Local_order PARVB is located telomeric to the SAMM50 gene and centromeric to the PARVG gene at 22q13.31.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CHEK2 (22q12.1)::PARVB (22q13.31)PARVB (22q13.31)::SAMM50 (22q13.31)


Note Genethon marker D22S1171 is located at the 5' end of the gene (Mongroo et al., 2004). Genethon marker D22S1171 is located between exon 2 and exon 1A of the PARVB gene.
The gene is located at 11p15.3.
  Figure A. Generation of transcript diversity by alternative promoter usage. Horizontal lines above the gene structure indicate human genomic DNA BAC clones. The NCBI accession numbers of the clones, and clone names (in brackets) are shown. Figure adapted from Mongroo et al., 2004.
Figure B. Human polyA+ RNA Multiple Tissue Northern blot (Origene) probed with full-length PARVB1 cDNA probe radiolabeled to a specific activity of > 5 x 108 cpm / mg (Johnstone C.N., unpublished). The two PARVB mRNA transcripts are indicated. The higher M.W. band most likely corresponds to non-specific hybridization (n/s).
Description PARVB3/CLINT, which encodes the longer Parvin-beta protein isoform is transcribed from promoter 1 and contains two additional 5' exons (exons 1 and 2) not present in PARVB1, and comprises 14 exons in total. PARVB1 encodes the shorter Parvin-beta protein isoform, is transcribed from promoter 1A, and comprises 13 exons in total. Both promoters contain CpG islands that span the transcription start sites. PARVB3/CLINT contains 70 unique N-terminal amino acids not present in the short isoform. (See figure A).
Transcription As with PARVA, human PARVB mRNA expression is highest in heart, followed by skeletal muscle, where it localises to the sarcolemma (Yamaji et al., 2001; Matsuda et al., 2005). Both PARVB mRNA transcripts are essentially ubiquitously expressed (Korenbaum et al., 2001), but with lower expression in gastrointestinal tissues (stomach, small intestine, colon). (See figure B).


  Depiction of functional domains of Parvin-beta(long) and Parvin-beta(short). NLS, nuclear localization sequence; ABS, actin binding sequence; CH, calponin homology. Adapted from Sepulveda and Wu, 2006.
Description The major functional domains of Parvin-beta are two 'atypical' calponin homology (CH) domains, termed CH1 (106 amino acids) and CH2 (107 amino acids). Each CH domain contains two actin binding sequences (ABS), although Parvin-beta has not been shown to bind actin directly (Korenbaum et al., 2001; Sepulveda and Wu, 2006). Parvin-beta physically interacts with Dysferlin and ARHGEF6 (alpha-PIX) through the CH1 domain (Matsuda et al., 2005; Rosenberger et al., 2003) and with ILK and alpha-actinin through the CH2 domain (Yamaji et al., 2001; Yamaji et al., 2004). Parvin-beta was also recently reported to directly interact with AKT (Kimura et al., 2010).
Expression PARVB is essentially ubiquitously expressed.
Localisation Parvin-beta localises to focal adhesions but also to the nucleus, which is most likely due to NLS motifs in the N-terminal region (Mongroo et al., 2004; Johnstone et al., 2008). Parvin-beta is incorporated into focal adhesions as part of the heterotrimeric 'IPP complex'. The ternary complex contains 1 molecule of integrin linked kinase (ILK), 1 Parvin isoform, and 1 PINCH (LIMS) isoform, (Legate et al., 2006). Binding of Parvin-alpha and Parvin-beta to the kinase domain of ILK is mutually exclusive (Zhang et al., 2004). Formation of the IPP complex also dictates total protein levels of each component, as any excess ILK, Parvin, or PINCH not incorporated into IPP is degraded in a proteasome-dependent manner (Fukuda et al., 2003).
Function Parvin-beta participates in focal adhesion dynamics through involvement in the IPP complex. The high expression levels in cardiac and skeletal muscle suggest important function(s) in these organs. In skeletal muscle, it binds dysferlin at the sarcolemma and thus may be involved with membrane repair (Yamaji et al., 2001; Matsuda et al., 2005; Legate et al., 2006). Parvin-beta and Parvin-alpha appear to negatively regulate the expression of each other (Zhang et al., 2004; Johnstone et al., 2008). Parvin-beta may modulate signalling through ILK as overexpression of Parvin-beta reduced AKT (S473) and GSK3beta (S9) phosphorylation in response to EGF stimulation (Mongroo et al., 2004). Parvin-beta was recently reported to directly interact with AKT (Kimura et al., 2010), which may explain its effects on AKT phosphorylation. Parvin-beta interacts with ARHGEF6 (alpha-PIX), an exchange factor for RAC1, thus implicating Parvin-beta in regulation of RAC signalling downstream of integrin engagement (Rosenberger et al., 2003). Finally, Parvin-beta may affect metabolic pathways through promotion of CDK9-mediated phosphorylation and activation of PPARgamma transcriptional activity in the nucleus (Johnstone et al., 2008). Interestingly, Parvb knockout mice were recently generated. Whilst constitutive Parva null mice feature kidney and cardiovascular defects and die between E10.5 and E14.5 (Lange et al., 2009; Montanez et al., 2009), constitutive Parvb null mice are viable (Wickström et al., 2010), although a detailed phenotypic analysis has not yet been described.
Homology Human Parvin-beta is most closely related to Parvin-alpha [75% identity with Parvin-beta(short) and 67% identity with Parvin-beta(long)] and more distantly to Parvin-gamma [41% identity with both Parvin-beta(short) and Parvin-beta(long)].


Note No mutations reported to date.
Germinal Germline SNPs are identified in the PARVB gene by direct sequencing of PCR products amplified from cDNA prepared from 16 primary ductal adenocarcinomasand adjacent normal mammary gland from the same patient. Two non-synonymous SNPs were identified, W37R, and E175K (Johnstone et al., manuscript in preparation).
Base Position†
Amino Acid Position‡
Amino Acid change
No. of Alleles
Intron 1
Exon 2
Exon 5
Exon 6
Exon 7
Exon 12
Exon 13
† Relative to transcription start site
‡ Relative to translation start site
^ Occur as a haplotype
** Relative to splice site
Somatic No somatic mutations were found in an analysis of 16 breast adenocarcinomas as presented above (Johnstone et al., manuscript in preparation). According to the C.O.S.M.I.C. online database (Forbes et al., 2008), 171 unique cancer samples have been analysed for alterations in the PARVB gene, with no somatic changes found. A breakdown of the samples analysed is given below.
Cancer TypeNo. of SpecimensReference
Sjöblom et al., 2006
Parsons et al., 2008
Clear Cell Renal
Dalgliesh et al., 2010
Sjöblom et al., 2006
Lung (cell lines)
Pancreas (cell lines)
Mesothelioma (cell lines)
Melanoma (cell lines)
Urinary tract (cell lines)
HNSCC (cell lines)

Implicated in

Entity Breast cancer
Note Parvin-beta mRNA levels are reduced in primary human ductal adenocarcinoma compared with adjacent normal mammary gland. PARVB mRNA levels are also reduced in MDA-MB-231 and MDA-MB-453 cell lines. Post-transcriptional downregulation of protein expression may also occur in cancer cells such as MCF7 (Mongroo et al., 2004). Ectopic Parvin-beta expression in MDA-MB-231 metastatic breast cancer cells increased adhesion and reduced invasion. Ectopic expression also reduced tumorigenicity of the same cell line in nude mice in vivo. Parvin-beta expression did not affect proliferation of the cells in vitro, but reduced Ki-67 staining was observed in Parvin-beta transfectants in vivo (Johnstone et al., 2008). Parvin-beta overexpression was also reported to promote apoptosis in HeLa cervical cancer cells (Zhang et al., 2004).
Prognosis Association with prognosis has not been studied to date.


Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes.
Dalgliesh GL, Furge K, Greenman C, Chen L, Bignell G, Butler A, Davies H, Edkins S, Hardy C, Latimer C, Teague J, Andrews J, Barthorpe S, Beare D, Buck G, Campbell PJ, Forbes S, Jia M, Jones D, Knott H, Kok CY, Lau KW, Leroy C, Lin ML, McBride DJ, Maddison M, Maguire S, McLay K, Menzies A, Mironenko T, Mulderrig L, Mudie L, O'Meara S, Pleasance E, Rajasingham A, Shepherd R, Smith R, Stebbings L, Stephens P, Tang G, Tarpey PS, Turrell K, Dykema KJ, Khoo SK, Petillo D, Wondergem B, Anema J, Kahnoski RJ, Teh BT, Stratton MR, Futreal PA.
Nature. 2010 Jan 21;463(7279):360-3. Epub 2010 Jan 6.
PMID 20054297
The Catalogue of Somatic Mutations in Cancer (COSMIC).
Forbes SA, Bhamra G, Bamford S, Dawson E, Kok C, Clements J, Menzies A, Teague JW, Futreal PA, Stratton MR.
Curr Protoc Hum Genet. 2008 Apr;Chapter 10:Unit 10.11.
PMID 18428421
PINCH-1 is an obligate partner of integrin-linked kinase (ILK) functioning in cell shape modulation, motility, and survival.
Fukuda T, Chen K, Shi X, Wu C.
J Biol Chem. 2003 Dec 19;278(51):51324-33. Epub 2003 Oct 8.
PMID 14551191
Parvin-beta inhibits breast cancer tumorigenicity and promotes CDK9-mediated peroxisome proliferator-activated receptor gamma 1 phosphorylation.
Johnstone CN, Mongroo PS, Rich AS, Schupp M, Bowser MJ, Delemos AS, Tobias JW, Liu Y, Hannigan GE, Rustgi AK.
Mol Cell Biol. 2008 Jan;28(2):687-704. Epub 2007 Nov 12.
PMID 17998334
Functional molecular imaging of ILK-mediated Akt/PKB signaling cascades and the associated role of beta-parvin.
Kimura M, Murakami T, Kizaka-Kondoh S, Itoh M, Yamamoto K, Hojo Y, Takano M, Kario K, Shimada K, Kobayashi E.
J Cell Sci. 2010 Mar 1;123(Pt 5):747-55.
PMID 20164304
Genomic organization and expression profile of the parvin family of focal adhesion proteins in mice and humans.
Korenbaum E, Olski TM, Noegel AA.
Gene. 2001 Nov 14;279(1):69-79.
PMID 11722847
Integrin-linked kinase is an adaptor with essential functions during mouse development.
Lange A, Wickstrom SA, Jakobson M, Zent R, Sainio K, Fassler R.
Nature. 2009 Oct 15;461(7266):1002-6.
PMID 19829382
ILK, PINCH and parvin: the tIPP of integrin signalling.
Legate KR, Montanez E, Kudlacek O, Fassler R.
Nat Rev Mol Cell Biol. 2006 Jan;7(1):20-31. (REVIEW)
PMID 16493410
Dysferlin interacts with affixin (beta-parvin) at the sarcolemma.
Matsuda C, Kameyama K, Tagawa K, Ogawa M, Suzuki A, Yamaji S, Okamoto H, Nishino I, Hayashi YK.
J Neuropathol Exp Neurol. 2005 Apr;64(4):334-40.
PMID 15835269
Beta-parvin inhibits integrin-linked kinase signaling and is downregulated in breast cancer.
Mongroo PS, Johnstone CN, Naruszewicz I, Leung-Hagesteijn C, Sung RK, Carnio L, Rustgi AK, Hannigan GE.
Oncogene. 2004 Nov 25;23(55):8959-70.
PMID 15467740
Alpha-parvin controls vascular mural cell recruitment to vessel wall by regulating RhoA/ROCK signalling.
Montanez E, Wickstrom SA, Altstatter J, Chu H, Fassler R.
EMBO J. 2009 Oct 21;28(20):3132-44. Epub 2009 Oct 1.
PMID 19798050
An integrated genomic analysis of human glioblastoma multiforme.
Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW.
Science. 2008 Sep 26;321(5897):1807-12. Epub 2008 Sep 4.
PMID 18772396
Interaction of alphaPIX (ARHGEF6) with beta-parvin (PARVB) suggests an involvement of alphaPIX in integrin-mediated signaling.
Rosenberger G, Jantke I, Gal A, Kutsche K.
Hum Mol Genet. 2003 Jan 15;12(2):155-67.
PMID 12499396
The parvins.
Sepulveda JL, Wu C.
Cell Mol Life Sci. 2006 Jan;63(1):25-35. (REVIEW)
PMID 16314921
The consensus coding sequences of human breast and colorectal cancers.
Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE.
Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7.
PMID 16959974
The ILK/PINCH/parvin complex: the kinase is dead, long live the pseudokinase!
Wickstrom SA, Lange A, Montanez E, Fassler R.
EMBO J. 2010 Jan 20;29(2):281-91. Epub 2009 Dec 24. (REVIEW)
PMID 20033063
Affixin interacts with alpha-actinin and mediates integrin signaling for reorganization of F-actin induced by initial cell-substrate interaction.
Yamaji S, Suzuki A, Kanamori H, Mishima W, Yoshimi R, Takasaki H, Takabayashi M, Fujimaki K, Fujisawa S, Ohno S, Ishigatsubo Y.
J Cell Biol. 2004 May 24;165(4):539-51.
PMID 15159419
Distinct roles of two structurally closely related focal adhesion proteins, alpha-parvins and beta-parvins, in regulation of cell morphology and survival.
Zhang Y, Chen K, Tu Y, Wu C.
J Biol Chem. 2004 Oct 1;279(40):41695-705. Epub 2004 Jul 28.
PMID 15284246


This paper should be referenced as such :
Johnstone, CN
PARVB (parvin, beta)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(1):34-38.
Free journal version : [ pdf ]   [ DOI ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  del(13q) in chronic lymphocytic leukemia

External links

HGNC (Hugo)PARVB   14653
Entrez_Gene (NCBI)PARVB    parvin beta
GeneCards (Weizmann)PARVB
Ensembl hg19 (Hinxton)ENSG00000188677 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000188677 [Gene_View]  ENSG00000188677 [Sequence]  chr22:44024277-44169232 [Contig_View]  PARVB [Vega]
ICGC DataPortalENSG00000188677
Genatlas (Paris)PARVB
Genetics Home Reference (NIH)PARVB
Genomic and cartography
GoldenPath hg38 (UCSC)PARVB  -     chr22:44024277-44169232 +  22q13.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PARVB  -     22q13.31   [Description]    (hg19-Feb_2009)
GoldenPathPARVB - 22q13.31 [CytoView hg19]  PARVB - 22q13.31 [CytoView hg38]
Genome Data Viewer NCBIPARVB [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AB048276 AF151814 AF237769 AF303887 AK308443
RefSeq transcript (Entrez)NM_001003828 NM_001243385 NM_001243386 NM_013327
Consensus coding sequences : CCDS (NCBI)PARVB
Gene Expression Viewer (FireBrowse)PARVB [ Firebrowse - Broad ]
GenevisibleExpression of PARVB in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)29780
GTEX Portal (Tissue expression)PARVB
Human Protein AtlasENSG00000188677-PARVB [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)PARVB
Human Protein Atlas [tissue]ENSG00000188677-PARVB [tissue]
Protein Interaction databases
Ontologies - Pathways
PubMed57 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Oct 8 21:24:32 CEST 2021

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

For comments and suggestions or contributions, please contact us