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

ANKHD1 (ankyrin repeat and KH domain containing 1)

Written2015-03Joao Agostinho Machado-Neto, Fabiola Traina
Hematology and Hemotherapy Center-University of Campinas/Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas (JAMN, FT), Department of Internal Medicine, University of Sao Paulo at Ribeirao Preto Medical School, Ribeirao Preto (FT), Sao Paulo, Brazil. ftraina@fmrp.usp.br; fabiolatraina@gmail.com

Abstract ANKHD1 is differentially expressed in human cancers, and potentially regulates multiple cellular functions and participates as a scaffold for protein-protein interactions through its ankyrin-repeat domains. Recently, studies have indicated that ANKHD1 is involved in the regulation of important biological process that participate in the malignant phenotype, including cell cycle progression, proliferation, clonogenicity and migration. The present review on ANKHD1 contains data on DNA/RNA, protein encoded and where the gene is implicated.

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)MASK
FLJ20288
FLJ11979
FLJ10042
FLJ14127
KIAA1085
MASK1
HGNC (Hugo) ANKHD1
LocusID (NCBI) 54882
Atlas_Id 46476
Location 5q31.3  [Link to chromosome band 5q31]
Location_base_pair Starts at 139781399 and ends at 139852062 bp from pter ( according to hg19-Feb_2009)  [Mapping ANKHD1.png]
Fusion genes
(updated 2016)
ANKHD1 (5q31.3) / ANKHD1 (5q31.3)ANKHD1 (5q31.3) / CYSTM1 (5q31.3)ANKHD1 (5q31.3) / EIF4EBP3 (5q31.3)
ANKHD1 (5q31.3) / HMGXB4 (22q12.3)ANKHD1 (5q31.3) / PCDH1 (5q31.3)ANKHD1 (5q31.3) / TIAM2 (6q25.3)
CCDC80 (3q13.2) / ANKHD1 (5q31.3)ITGAV (2q32.1) / ANKHD1 (5q31.3)PCDHA11 (5q31.3) / ANKHD1 (5q31.3)
PIK3C2B (1q32.1) / ANKHD1 (5q31.3)SYT14 (1q32.2) / ANKHD1 (5q31.3)TMCC1 (3q22.1) / ANKHD1 (5q31.3)
VPS54 (2p14) / ANKHD1 (5q31.3)

DNA/RNA

Description The entire ANKHD1 gene is about 147 Kb (start: 139781399 and end: 139929163 bp; orientation: plus strand). The ANKHD1 gene encodes for 4 transcript variants. The transcript variant 1 (start: 139781399 and end: 139919441 bp; orientation: plus strand; 34 exons; mRNA: 8233 bp) is the longest transcript and encodes the isoform 1 (2542 aa protein). The transcript variant 2 (start: 139781399 and end: 139852062 bp; orientation: plus strand; 11 exons; mRNA: 2161 bp) uses an alternate in-frame splice site in the 5` coding region, lacks several exons, uses an alternate 3` terminal exon and encodes the isoform 2, which is shorter and presents a distinct C-terminus compared to isoform 1 (616 aa protein). Transcript variant 3 (start: 139781399 and end: 139852062 bp; orientation: plus strand; 11 exons; mRNA: 2194 bp) lacks several exons, uses an alternate 3` terminal exon and encodes the isoform 3 that also has a distinct C-terminus compared to isoform 1 (627 aa protein). Transcrit variant 4 (start: 139781399 and end: 139852062 bp; orientation: plus strand; 10 exons, mRNA: 2084 bp) also lacks several exons, uses an alternate 3` terminal exon, encodes the isoform 4 that has a distinct C-terminus compared to isoform 1 and is the shortest of all isoforms (581 aa protein). Additionally, ANKHD1-EIF4EBP3 is a readthrough transcript involving ANKHD1 and EIF4EBP3 genes, which encodes a protein that contains multiple ankyrin repeats, single KH-domain and a C-terminus with a portion from the EIF4EBP3 gene (start: 139781399 and end: 139929163 bp; orientation: plus strand; 36 exons, mRNA: 8349 bp; protein: 2617 aa). Data searched at GenBank NCBI (http://www.ncbi.nlm.nih.gov/genbank/) and UCSC Genome Browser (https://genome.ucsc.edu/).

Protein

 
Description The ANKHD1 protein has 4 isoforms. Isoforms 2, 3 and 4 are smaller and less characterized than isoform 1. Isoform 1 of ANKHD1 protein consists of 2542 amino acids with a molecular weight of 270 kDa, has 20 ankyrin repeats distributed in two blocks and a K homology (KH) domain in the C-terminal region. The schematic representation of ANKHD1 protein (isoform 1) is illustrated in Figure 1.
Expression Ubiquitous.
 
Localisation ANKHD1 is predominantly found in the cytoplasm (Figure 2).
 
Function The ANKHD1 protein contains 20 ankyrin repeats, which are highly conserved structures. The presence of ankyrin repeats domains suggests that this protein integrates multiple signaling pathways and participates as scaffold for protein-protein interactions (Jernigan and Bordenstein, 2015). A large part of the knowledge regarding the functions of ANKHD1 was obtained by experiments using its orthologous protein Mask (multiple ankyrin repeats single KH domain). In Drosophila, Mask acts in the signal transduction pathway mediated by Cws (Corkscrew; orthologous of SHP2) (Smith, et al., 2002), participates in the Hippo signaling pathway activation through its association with Yki (Yorkie, orthologous of YAP1) (Sidor, et al., 2013, Sansores-Garcia, et al., 2013) and potentially regulates Hop signaling pathway (Hopscotch, orthologous of JAK) (Muller, et al., 2005). In humans, ANKHD1 associates with SHP2, however the biologic consequence of this protein interaction remains indeterminate (Traina, et al., 2006). ANKHD1 and YAP1 interaction has also been confirmed in human cells (HEK293 and DU145 cells) and modulates the Hippo signaling pathway activation, proliferation and cell cycle progression (Sidor, et al., 2013, Sansores-Garcia, et al., 2013, Machado-Neto, et al., 2014). ANKHD1 interacts with SIVA and modulates the microtubule dynamics, cell proliferation and migration of human leukemia cells (Machado-Neto, et al., 2015). In addition, ANKHD1 modulates p21 (CDKN1A) expression and cell cycle progression in multiple myeloma cells (Dhyani, et al., 2015, Dhyani, et al., 2012). In NT2 cells, inhibition of the small isoform of ANKHD1 that lacks the KH domain (also designed as VBARP; isoform 3) triggered caspase-3/7 activation (Miles, et al., 2005), however no similar effect on apoptosis was observed in the other cell lines inhibited for all other ANKHD1 isoforms (Machado-Neto, et al., 2014, Machado-Neto, et al., 2015, Dhyani, et al., 2012). A potential model for ANKHD1 cellular functions and protein interactions is summarized in Figure 3.
 
Homology ANKHD1 shares high homology with ANKRD17 (ankyrin repeat domain 17), both orthologous proteins to Mask protein from Drosophila. ANKHD1 also shares high homology among different species (Table 1).

Mutations

Somatic Recurrent mutations in the ANKHD1 gene are rare, 180 substitution missense, 13 substitution nonsense, 58 substitution synonymous, 1 insertion frameshift and 1 deletion frameshift mutations are reported in COSMIC (Catalogue of somatic mutations in cancer; http://cancer.sanger.ac.uk/cancergenome/projects/cosmic).

Implicated in

Note
Entity Leukemia
Note ANKHD1 was reported as highly expressed in leukemia cell lines and in primary bone marrow samples from patients with acute myeloid leukemia and acute lymphoid leukemia (Traina, et al., 2006). Interestingly, ANKHD1 silencing reduced cell proliferation, clonogenicity, migration and tumorigenesis of leukemia cells (Machado-Neto, et al., 2015).
  
Entity Multiple myeloma
Disease Multiple myeloma cell lines and primary plasma cells from myeloma multiple patients presented a high expression of ANKHD1 (Dhyani, et al., 2012). In multiple myeloma cell lines, ANKHD1 inhibition resulted in a delay in cell cycle progression and lower cell proliferation, clonal growth, migration and tumor formation (Dhyani, et al., 2015, Dhyani, et al., 2012).
  
Entity Prostate cancer
Note High expression of ANKHD1 was observed in prostate cancer cell lines (Machado-Neto, et al., 2014). Using the siRNA approach, ANKHD1 silencing reduced proliferation, tumor formation, and cell cycle progression in prostate cancer cells (Machado-Neto, et al., 2014).
  
Entity Breast cancer
Prognosis In two independent cohorts of breast cancer patients, high expression of ANKHD1 was associated with worsened outcomes (Sansores-Garcia, et al., 2013).
  

To be noted

Although ANKHD1 presents high homology with ANKRD17 (both orthologous proteins of Mask), the Ankrd17 knockout mice presents embryonic lethality (Hou, et al., 2009), indicating that these proteins do not play redundant functions. Another interesting point is that, accordingly to current data, ANKHD1 participates in cell proliferation and cell cycle progression in different neoplastic cells; however the ANKHD1-interacting proteins appear to vary, depending on the cellular context.

Bibliography

ANKHD1 regulates cell cycle progression and proliferation in multiple myeloma cells
Dhyani A, Duarte AS, Machado-Neto JA, Favaro P, Ortega MM, Olalla Saad ST
FEBS Lett 2012 Dec 14;586(24):4311-8
PMID 23142581
 
ANKHD1 represses p21 (WAF1/CIP1) promoter and promotes multiple myeloma cell growth
Dhyani A, Machado-Neto JA, Favaro P, Saad ST
Eur J Cancer 2015 Jan;51(2):252-9
PMID 25483783
 
Ankrd17, an ubiquitously expressed ankyrin factor, is essential for the vascular integrity during embryogenesis
Hou SC, Chan LW, Chou YC, Su CY, Chen X, Shih YL, Tsai PC, Shen CK, Yan YT
FEBS Lett 2009 Sep 3;583(17):2765-71
PMID 19619540
 
Tandem-repeat protein domains across the tree of life
Jernigan KK, Bordenstein SR
PeerJ 2015 Jan 13;3:e732
PMID 25653910
 
Identification of JAK/STAT signalling components by genome-wide RNA interference
Müller P, Kuttenkeuler D, Gesellchen V, Zeidler MP, Boutros M
Nature 2005 Aug 11;436(7052):871-5
PMID 16094372
 
ANKHD1 silencing inhibits Stathmin 1 activity, cell proliferation and migration of leukemia cells
Machado-Neto JA, Lazarini M, Favaro P, de Melo Campos P, Scopim-Ribeiro R, Franchi GC Junior, Nowill AE, Lima PR, Costa FF, Benichou S, Olalla Saad ST, Traina F
Biochim Biophys Acta 2015 Mar;1853(3):583-593
PMID 25523139
 
Molecular and functional characterization of a novel splice variant of ANKHD1 that lacks the KH domain and its role in cell survival and apoptosis
Miles MC, Janket ML, Wheeler ED, Chattopadhyay A, Majumder B, Dericco J, Schafer EA, Ayyavoo V
FEBS J 2005 Aug;272(16):4091-102
PMID 16098192
 
Mask is required for the activity of the Hippo pathway effector Yki/YAP
Sansores-Garcia L, Atkins M, Moya IM, Shahmoradgoli M, Tao C, Mills GB, Halder G
Curr Biol 2013 Feb 4;23(3):229-35
PMID 23333314
 
Mask proteins are cofactors of Yorkie/YAP in the Hippo pathway
Sidor CM, Brain R, Thompson BJ
Curr Biol 2013 Feb 4;23(3):223-8
PMID 23333315
 
MASK, a large ankyrin repeat and KH domain-containing protein involved in Drosophila receptor tyrosine kinase signaling
Smith RK, Carroll PM, Allard JD, Simon MA
Development 2002 Jan;129(1):71-82
PMID 11782402
 
ANKHD1, ankyrin repeat and KH domain containing 1, is overexpressed in acute leukemias and is associated with SHP2 in K562 cells
Traina F, Favaro PM, Medina Sde S, Duarte Ada S, Winnischofer SM, Costa FF, Saad ST
Biochim Biophys Acta 2006 Sep;1762(9):828-34
PMID 16956752
 

Citation

This paper should be referenced as such :
Machado-Neto JA, Traina F
ANKHD1 (ankyrin repeat and KH domain containing 1);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/ANKHD1ID46476ch5q31.html


External links

Nomenclature
HGNC (Hugo)ANKHD1   24714
Cards
AtlasANKHD1ID46476ch5q31
Entrez_Gene (NCBI)ANKHD1  54882  ankyrin repeat and KH domain containing 1
AliasesMASK; MASK1; PP2500; VBARP
GeneCards (Weizmann)ANKHD1
Ensembl hg19 (Hinxton)ENSG00000131503 [Gene_View]  chr5:139781399-139852062 [Contig_View]  ANKHD1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000131503 [Gene_View]  chr5:139781399-139852062 [Contig_View]  ANKHD1 [Vega]
ICGC DataPortalENSG00000131503
TCGA cBioPortalANKHD1
AceView (NCBI)ANKHD1
Genatlas (Paris)ANKHD1
WikiGenes54882
SOURCE (Princeton)ANKHD1
Genetics Home Reference (NIH)ANKHD1
Genomic and cartography
GoldenPath hg19 (UCSC)ANKHD1  -     chr5:139781399-139852062 +  5q31.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)ANKHD1  -     5q31.3   [Description]    (hg38-Dec_2013)
EnsemblANKHD1 - 5q31.3 [CytoView hg19]  ANKHD1 - 5q31.3 [CytoView hg38]
Mapping of homologs : NCBIANKHD1 [Mapview hg19]  ANKHD1 [Mapview hg38]
OMIM610500   
Gene and transcription
Genbank (Entrez)AF217646 AF258557 AF521882 AI675547 AI870943
RefSeq transcript (Entrez)NM_001197030 NM_017747 NM_017978 NM_024668
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)ANKHD1
Cluster EST : UnigeneHs.594084 [ NCBI ]
CGAP (NCI)Hs.594084
Alternative Splicing GalleryENSG00000131503
Gene ExpressionANKHD1 [ NCBI-GEO ]   ANKHD1 [ EBI - ARRAY_EXPRESS ]   ANKHD1 [ SEEK ]   ANKHD1 [ MEM ]
Gene Expression Viewer (FireBrowse)ANKHD1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)54882
GTEX Portal (Tissue expression)ANKHD1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8IWZ3   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8IWZ3  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8IWZ3
Splice isoforms : SwissVarQ8IWZ3
PhosPhoSitePlusQ8IWZ3
Domaine pattern : Prosite (Expaxy)ANK_REP_REGION (PS50297)    ANK_REPEAT (PS50088)    KH_TYPE_1 (PS50084)   
Domains : Interpro (EBI)Ankyrin_rpt    Ankyrin_rpt-contain_dom    KH_dom    KH_dom_type_1   
Domain families : Pfam (Sanger)Ank_2 (PF12796)    KH_1 (PF00013)   
Domain families : Pfam (NCBI)pfam12796    pfam00013   
Domain families : Smart (EMBL)ANK (SM00248)  KH (SM00322)  
Conserved Domain (NCBI)ANKHD1
DMDM Disease mutations54882
Blocks (Seattle)ANKHD1
SuperfamilyQ8IWZ3
Human Protein AtlasENSG00000131503
Peptide AtlasQ8IWZ3
HPRD16489
Protein Interaction databases
DIP (DOE-UCLA)Q8IWZ3
IntAct (EBI)Q8IWZ3
FunCoupENSG00000131503
BioGRIDANKHD1
STRING (EMBL)ANKHD1
ZODIACANKHD1
Ontologies - Pathways
QuickGOQ8IWZ3
Ontology : AmiGOprotein binding  nucleoplasm  cytoplasm  cytoplasm  poly(A) RNA binding  innate immune response  
Ontology : EGO-EBIprotein binding  nucleoplasm  cytoplasm  cytoplasm  poly(A) RNA binding  innate immune response  
NDEx NetworkANKHD1
Atlas of Cancer Signalling NetworkANKHD1
Wikipedia pathwaysANKHD1
Orthology - Evolution
OrthoDB54882
GeneTree (enSembl)ENSG00000131503
Phylogenetic Trees/Animal Genes : TreeFamANKHD1
HOVERGENQ8IWZ3
HOGENOMQ8IWZ3
Homologs : HomoloGeneANKHD1
Homology/Alignments : Family Browser (UCSC)ANKHD1
Gene fusions - Rearrangements
Fusion : MitelmanANKHD1/CYSTM1 [5q31.3/5q31.3]  
Fusion : MitelmanANKHD1/PCDH1 [5q31.3/5q31.3]  [t(5;5)(q31;q31)]  
Fusion : MitelmanANKHD1/TIAM2 [5q31.3/6q25.3]  [t(5;6)(q31;q25)]  
Fusion : MitelmanITGAV/ANKHD1 [2q32.1/5q31.3]  [t(2;5)(q32;q31)]  
Fusion : MitelmanPCDHA11/ANKHD1 [5q31.3/5q31.3]  [t(5;5)(q31;q31)]  
Fusion: TCGAANKHD1 5q31.3 C5orf32 BRCA
Fusion: TCGAANKHD1 5q31.3 TIAM2 6q25.3 BRCA
Fusion: TCGAPCDHA11 5q31.3 ANKHD1 5q31.3 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerANKHD1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ANKHD1
dbVarANKHD1
ClinVarANKHD1
1000_GenomesANKHD1 
Exome Variant ServerANKHD1
ExAC (Exome Aggregation Consortium)ANKHD1 (select the gene name)
Genetic variants : HAPMAP54882
Genomic Variants (DGV)ANKHD1 [DGVbeta]
DECIPHER (Syndromes)5:139781399-139852062  ENSG00000131503
CONAN: Copy Number AnalysisANKHD1 
Mutations
ICGC Data PortalANKHD1 
TCGA Data PortalANKHD1 
Broad Tumor PortalANKHD1
OASIS PortalANKHD1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICANKHD1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDANKHD1
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 ANKHD1
DgiDB (Drug Gene Interaction Database)ANKHD1
DoCM (Curated mutations)ANKHD1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ANKHD1 (select a term)
intoGenANKHD1
NCG5 (London)ANKHD1
Cancer3DANKHD1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM610500   
Orphanet
MedgenANKHD1
Genetic Testing Registry ANKHD1
NextProtQ8IWZ3 [Medical]
TSGene54882
GENETestsANKHD1
Huge Navigator ANKHD1 [HugePedia]
snp3D : Map Gene to Disease54882
BioCentury BCIQANKHD1
ClinGenANKHD1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD54882
Chemical/Pharm GKB GenePA134947858
Clinical trialANKHD1
Miscellaneous
canSAR (ICR)ANKHD1 (select the gene name)
Probes
Litterature
PubMed30 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineANKHD1
EVEXANKHD1
GoPubMedANKHD1
iHOPANKHD1
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 : Sat Jan 21 16:31:42 CET 2017

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.