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AFAP1L2 (actin filament associated protein 1-like 2)

Written2014-01Xiaohui Bai, Serisha Moodley, Hae-Ra Cho, Mingyao Liu
Latner Thoracic Surgery Research Laboratoires, University Health Network, Toronto General Research Institute, University of Toronto, Toronto, Ontario, Canada

(Note : for Links provided by Atlas : click)

Identity

Alias_namesKIAA1914
KIAA1914
actin filament associated protein 1-like 2
Alias_symbol (synonym)FLJ14564
Em:AC005383.4
XB130
Other alias
HGNC (Hugo) AFAP1L2
LocusID (NCBI) 84632
Atlas_Id 52197
Location 10q25.3  [Link to chromosome band 10q25]
Location_base_pair Starts at 116054583 and ends at 116164537 bp from pter ( according to hg19-Feb_2009)  [Mapping AFAP1L2.png]
 
  Figure 1. XB130 chromosomal location and neighbour genes. A. xb130 gene is located on chromosome 10, at 10q25.3 by fluorescence in situ hybridization (FISH). B. Diagram of xb130 neighbour genes between 115939029 and 116450393.
Fusion genes
(updated 2016)
ABLIM1 (10q25.3) / AFAP1L2 (10q25.3)AFAP1L2 (10q25.3) / AFAP1L2 (10q25.3)AFAP1L2 (10q25.3) / GPX3 (5q33.1)
INPP5A (10q26.3) / AFAP1L2 (10q25.3)

DNA/RNA

Note Human XB130 was discovered in Dr. Mingyao Liu's laboratory (University of Toronto) in the process of cloning human actin filament associated protein (afap) gene. Using chicken AFAP protein sequence to search human cDNA library in GenBank, XB130 was found as an EST clone (GenBank accession number 1154093) with 34% sequence similarity to chicken AFAP protein. The clone contains partial coding sequence and 3' UTR. The upstream sequence was obtained using 5' rapid amplification of cDNA ends (RACE) from human lung alveolar epithelial cell mRNA. Western blot shows the protein molecular weight is 130 kD (Xu et al., 2007).
In 2003, the XB130 knockout mice were established through the collaboration of Drs. Mingyao Liu and Tak W. Mak at the University of Toronto.
Description Human xb130 genes contains 19 exons, which are covering the whole coding sequence.
Transcription The transcript size of xb130 is 3751 bp. There may be 7 splicing variants based on Ensembl data (www.ensembl.org). XB130 mRNA is highly expressed in the thyroid, parathyroid and spleen; moderately expressed in brain, pancreas, lung and kidney.

Protein

 
  Figure 2. XB130 functional domains and motifs. Human XB130 has 818 amino acids. It contains the following motif/domains: proline-rich region: residues 98-107; tyrosine phosphorylation motif: residues 54-57, 124-127; 148-151; 457-460; PH domain: residues 175-272; 353-445; coiled-coil region: residues 652-749.
Description XB130 is a novel adaptor protein, member of the actin filament associated protein (AFAP) family (Snyder et al., 2011). Accordingly, it is also known as AFAP1L2. The full length protein consists of 818 amino acids with a molecular weight of approximately 130 kDa by western blotting (Xu et al., 2007). As an adaptor protein, XB130 has no enzymatic domains or activity. Sequence structure analysis has revealed 23 putative tyrosine phosphorylation sites and 27 putative phosphorylation sites for serine/threonine kinases (Xu et al., 2007). The N-terminal of XB130 contains a proline rich, SH3 domain binding motif, three tyrosine containing SH2 domain binding sites (Xu et al., 2007), of which a YXXM motif is for PI3 kinase subunit p85 binding (Lodyga et al., 2009). In the middle region, there are two pleckstrin homology domains and another tyrosine binding motif (Xu et al., 2007). The C-terminal contains a coiled-coil region, which may be important for molecular trafficking or dimerization (Xu et al., 2007).
Expression In normal human tissue, the 4 kb mRNA transcript of XB130 is expressed highly in spleen and thyroid with lower expression in kidney, brain, lung and pancreas (Xu et al., 2007). Newer RNA sequencing by Illumina body map using RNA obtained from 16 normal human tissues shows high expression of XB130 in thyroid with lower expression in lymph nodes, brain, colon, adipocytes, kidney, lung, adrenal glands, breast, ovary, prostate and testis followed by whole blood, heart, skeletal muscles and liver (www.genecards.org).
XB130 protein is detected in normal tissues of thyroid, parathyroid, brain, kidney, skin and GI-tracks (www.proteinatlas.org).
XB130 protein expresses in human thyroid, colorectal, gastric and hepatocellular carcinomas (Shi et al., 2012; Shiozaki et al., 2013; Shiozaki et al., 2011; Zuo et al., 2012). Expression of XB130 has also been observed in a variety of cancer cell lines, including thyroid, lung, esophageal, pancreatic and colon cancers (Shi et al., 2012; Shiozaki et al., 2013; Zuo et al., 2012).
Localisation XB130 is distributed mainly in the cytoplasm and perinuclear region of lung epithelial BEAS-2B cells and several other cell types (Xu et al., 2007). Unlike AFAP, XB130 does not associate or co-localize with actin filament stress fibler (Lodyga et al., 2010). Stimulation of cells with EGF, PMA, or overexpression of constitutive Rac results in a translocation of XB130 to the cell periphery and leading edge of migrating cells (Lodyga et al., 2010).
Function XB130 is an adaptor protein that acts as a key mediator to drive signal transduction pathways. XB130 has been shown to bind to tyrosine kinase c-Src to enhance kinase activity and subsequently regulates Src-mediated AP-1/SRE transcription activation (Xu et al., 2007). XB130 is also highly involved in the PI3K/Akt pathway and effects cell proliferation, cell cycle progression and cell survival through binding to p85 alpha subunit of PI3K (Lodyga et al., 2009). XB130 may also play a role in the innate immune response, where knockdown of XB130 was shown to decrease IL-6 and IL-8 cytokine levels in human lung epithelial cells (Xu et al., 2007). XB130 is also involved in cell migration via association with Rac-GTPase and plays a significant role in lateral cell migration and cell invasion in both normal and cancer cell lines (Lodyga et al., 2010).
Yamanaka et al. reported phosphorylated XB130 affects cAMP-dependent DNA synthesis in rat thyroid cells (Yamanaka et al., 2012).
XB130 is aberrantly expressed in human cancers and has been shown to control tumour growth in vivo (Shiozaki et al., 2011). XB130 regulates thyroid cancer cell proliferation by controlling microRNA miR-33a, 149a and 193a expression to alter oncogenes Myc, FosL1, and SCL7A5 protein levels (Takeshita et al., 2013).
Homology XB130 shares similar sequence and domain structure cellular as AFAP and AFAP1L1 (Snyder et al., 2011).

Mutations

Somatic Somatic mutations of XB130 are reported in a variety of cancer tissues. Based on the data of Sanger Institute database (www.sanger.ac.uk), XB130 mutation sites have been identified in multiple tumor tissues, including lung, large intestine, ovary, skin, prostate, endometrium. Among these samples, 70% of identified cases are XB130 substitution missense mutation.

Implicated in

Note
  
Entity Various cancers
Note XB130 plays important roles in tumor progression by promoting cell proliferation, survival, motility and invasion in various cancer cells. Recently, XB130 has been identified in thyroid carcinoma (Shiozaki et al., 2011), esophageal squamous cell carcinoma (Shiozaki et al., 2013), and gastric cancer (Shi et al., 2012).
  
  
Entity Colorectal cancer
Note Tyrosine phosphorylated XB130 in colorectal cancer.
Prognosis Using mass spectrometry, Emaduddin et al. reported several proteins as tyrosine phosphorylated form are maintained at high level in colorectal cancer cells isolated from patients. XB130 is identified as one of these proteins. Therefore, tyrosine phosphorylated XB130 has a potential to be a biomarker of colorectal cancer (Emaduddin et al., 2008).
  
  
Entity Gastric cancer (GC)
Note XB130 expression level associates with the prognosis of gastric cancer.
Prognosis Based on the anlysis GC tissue samples from 411 patients with various stages, lower expression of XB130 mRNA as well as protein is significantly correlated with reduced patient survival time and shorter disease-free period (Shi et al., 2012).
  
  
Entity Thyroid cancer
Note XB130 as a tumor promoting gene, enhancing thyroid cancer cell growth.
Oncogenesis Knockdown XB130 using siRNA in thyroid cancer cell (WRO) is accompanied with an inhibition of G1-S phase cell cycle progression and enhanced apoptosis. The volume of tumors generated in nude mice after injecting these cells are smaller than those formed from cells with a normal XB130 expression (Shiozaki et al., 2011).
  
  
Entity Esophageal squamous cell carcinoma (ESCC)
Note XB130 protein is identified in ESCC primary cell lines and tumor samples.
Oncogenesis XB130 protein is highly expression in ESCC primary cells. XB130 protein is examined by immunohistochemistry staining from ESCC tissues collected from 52 patients. Positive XB130 staining is observed in 71% of ESCC samples, which indicates the association of XB130 protein and ESCC (Shiozaki et al., 2013).
  
  
Entity Soft tissue tumor
Note Decreased XB130 expression leads to a local aggressiveness of soft tissue tumor.
Oncogenesis Analysis of gene expression profile of 102 tumor samples with varying stages of soft tissue tumor shows a decreased XB130 expression in malignant mesenchymal tumors (Cunha et al., 2010).
  

Bibliography

Identification of genes associated with local aggressiveness and metastatic behavior in soft tissue tumors.
Cunha IW, Carvalho KC, Martins WK, Marques SM, Muto NH, Falzoni R, Rocha RM, Aguiar S, Simoes AC, Fahham L, Neves EJ, Soares FA, Reis LF.
Transl Oncol. 2010 Feb;3(1):23-32.
PMID 20165692
 
Odin (ANKS1A) is a Src family kinase target in colorectal cancer cells.
Emaduddin M, Edelmann MJ, Kessler BM, Feller SM.
Cell Commun Signal. 2008 Oct 9;6:7. doi: 10.1186/1478-811X-6-7.
PMID 18844995
 
Adaptor protein XB130 is a Rac-controlled component of lamellipodia that regulates cell motility and invasion.
Lodyga M, Bai XH, Kapus A, Liu M.
J Cell Sci. 2010 Dec 1;123(Pt 23):4156-69. doi: 10.1242/jcs.071050.
PMID 21084565
 
XB130, a tissue-specific adaptor protein that couples the RET/PTC oncogenic kinase to PI 3-kinase pathway.
Lodyga M, De Falco V, Bai XH, Kapus A, Melillo RM, Santoro M, Liu M.
Oncogene. 2009 Feb 19;28(7):937-49. doi: 10.1038/onc.2008.447. Epub 2008 Dec 8.
PMID 19060924
 
Silencing of XB130 is associated with both the prognosis and chemosensitivity of gastric cancer.
Shi M, Huang W, Lin L, Zheng D, Zuo Q, Wang L, Wang N, Wu Y, Liao Y, Liao W.
PLoS One. 2012;7(8):e41660. doi: 10.1371/journal.pone.0041660. Epub 2012 Aug 23.
PMID 22927913
 
XB130 as an independent prognostic factor in human esophageal squamous cell carcinoma.
Shiozaki A, Kosuga T, Ichikawa D, Komatsu S, Fujiwara H, Okamoto K, Iitaka D, Nakashima S, Shimizu H, Ishimoto T, Kitagawa M, Nakou Y, Kishimoto M, Liu M, Otsuji E.
Ann Surg Oncol. 2013 Sep;20(9):3140-50. doi: 10.1245/s10434-012-2474-4. Epub 2012 Jul 18.
PMID 22805860
 
AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes.
Snyder BN, Cho Y, Qian Y, Coad JE, Flynn DC, Cunnick JM.
Eur J Cell Biol. 2011 May;90(5):376-89. doi: 10.1016/j.ejcb.2010.11.016. Epub 2011 Feb 18.
PMID 21333378
 
XB130, a new adaptor protein, regulates expression of tumor suppressive microRNAs in cancer cells.
Takeshita H, Shiozaki A, Bai XH, Iitaka D, Kim H, Yang BB, Keshavjee S, Liu M.
PLoS One. 2013;8(3):e59057. doi: 10.1371/journal.pone.0059057. Epub 2013 Mar 19.
PMID 23527086
 
XB130, a novel adaptor protein for signal transduction.
Xu J, Bai XH, Lodyga M, Han B, Xiao H, Keshavjee S, Hu J, Zhang H, Yang BB, Liu M.
J Biol Chem. 2007 Jun 1;282(22):16401-12. Epub 2007 Apr 5.
PMID 17412687
 
Phosphatidylinositol 3-kinase-binding protein, PI3KAP/XB130, is required for cAMP-induced amplification of IGF mitogenic activity in FRTL-5 thyroid cells.
Yamanaka D, Akama T, Fukushima T, Nedachi T, Kawasaki C, Chida K, Minami S, Suzuki K, Hakuno F, Takahashi S.
Mol Endocrinol. 2012 Jun;26(6):1043-55. doi: 10.1210/me.2011-1349. Epub 2012 Apr 11.
PMID 22496359
 
Multivariate analysis of several molecular markers and clinicopathological features in postoperative prognosis of hepatocellular carcinoma.
Zuo Q, Huang H, Shi M, Zhang F, Sun J, Bin J, Liao Y, Liao W.
Anat Rec (Hoboken). 2012 Mar;295(3):423-31. doi: 10.1002/ar.21531. Epub 2011 Dec 20.
PMID 22190283
 

Citation

This paper should be referenced as such :
X Bai, S Moodley, HR Cho, M Liu
AFAP1L2 (actin filament associated protein 1-like 2)
Atlas Genet Cytogenet Oncol Haematol. 2014;18(9):628-631.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/AFAP1L2ID52197ch10q25.html


External links

Nomenclature
HGNC (Hugo)AFAP1L2   25901
Cards
AtlasAFAP1L2ID52197ch10q25
Entrez_Gene (NCBI)AFAP1L2  84632  actin filament associated protein 1 like 2
AliasesCTB-1144G6.4; KIAA1914; XB130
GeneCards (Weizmann)AFAP1L2
Ensembl hg19 (Hinxton)ENSG00000169129 [Gene_View]  chr10:116054583-116164537 [Contig_View]  AFAP1L2 [Vega]
Ensembl hg38 (Hinxton)ENSG00000169129 [Gene_View]  chr10:116054583-116164537 [Contig_View]  AFAP1L2 [Vega]
ICGC DataPortalENSG00000169129
TCGA cBioPortalAFAP1L2
AceView (NCBI)AFAP1L2
Genatlas (Paris)AFAP1L2
WikiGenes84632
SOURCE (Princeton)AFAP1L2
Genetics Home Reference (NIH)AFAP1L2
Genomic and cartography
GoldenPath hg19 (UCSC)AFAP1L2  -     chr10:116054583-116164537 -  10q26.11   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)AFAP1L2  -     10q26.11   [Description]    (hg38-Dec_2013)
EnsemblAFAP1L2 - 10q26.11 [CytoView hg19]  AFAP1L2 - 10q26.11 [CytoView hg38]
Mapping of homologs : NCBIAFAP1L2 [Mapview hg19]  AFAP1L2 [Mapview hg38]
OMIM612420   
Gene and transcription
Genbank (Entrez)AB067501 AF474151 AK123108 AK291712 AK294969
RefSeq transcript (Entrez)NM_001001936 NM_001287824 NM_032550
RefSeq genomic (Entrez)NC_000010 NC_018921 NT_030059 NW_004929376
Consensus coding sequences : CCDS (NCBI)AFAP1L2
Cluster EST : UnigeneHs.501106 [ NCBI ]
CGAP (NCI)Hs.501106
Alternative Splicing GalleryENSG00000169129
Gene ExpressionAFAP1L2 [ NCBI-GEO ]   AFAP1L2 [ EBI - ARRAY_EXPRESS ]   AFAP1L2 [ SEEK ]   AFAP1L2 [ MEM ]
Gene Expression Viewer (FireBrowse)AFAP1L2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)84632
GTEX Portal (Tissue expression)AFAP1L2
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8N4X5   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8N4X5  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8N4X5
Splice isoforms : SwissVarQ8N4X5
PhosPhoSitePlusQ8N4X5
Domaine pattern : Prosite (Expaxy)PH_DOMAIN (PS50003)   
Domains : Interpro (EBI)AFAP    AFAP1L2    PH_dom-like    PH_domain   
Domain families : Pfam (Sanger)PH (PF00169)   
Domain families : Pfam (NCBI)pfam00169   
Domain families : Smart (EMBL)PH (SM00233)  
Conserved Domain (NCBI)AFAP1L2
DMDM Disease mutations84632
Blocks (Seattle)AFAP1L2
PDB (SRS)2COF   
PDB (PDBSum)2COF   
PDB (IMB)2COF   
PDB (RSDB)2COF   
Structural Biology KnowledgeBase2COF   
SCOP (Structural Classification of Proteins)2COF   
CATH (Classification of proteins structures)2COF   
SuperfamilyQ8N4X5
Human Protein AtlasENSG00000169129
Peptide AtlasQ8N4X5
HPRD13902
IPIIPI00181905   IPI00455138   IPI00382615   IPI00902986   IPI00922153   IPI00514745   
Protein Interaction databases
DIP (DOE-UCLA)Q8N4X5
IntAct (EBI)Q8N4X5
FunCoupENSG00000169129
BioGRIDAFAP1L2
STRING (EMBL)AFAP1L2
ZODIACAFAP1L2
Ontologies - Pathways
QuickGOQ8N4X5
Ontology : AmiGOcytoplasm  plasma membrane  inflammatory response  regulation of mitotic cell cycle  SH3 domain binding  protein tyrosine kinase activator activity  regulation of interleukin-6 production  positive regulation of interleukin-8 production  signaling adaptor activity  SH2 domain binding  positive regulation of epidermal growth factor receptor signaling pathway  positive regulation of transcription, DNA-templated  positive regulation of protein tyrosine kinase activity  
Ontology : EGO-EBIcytoplasm  plasma membrane  inflammatory response  regulation of mitotic cell cycle  SH3 domain binding  protein tyrosine kinase activator activity  regulation of interleukin-6 production  positive regulation of interleukin-8 production  signaling adaptor activity  SH2 domain binding  positive regulation of epidermal growth factor receptor signaling pathway  positive regulation of transcription, DNA-templated  positive regulation of protein tyrosine kinase activity  
NDEx NetworkAFAP1L2
Atlas of Cancer Signalling NetworkAFAP1L2
Wikipedia pathwaysAFAP1L2
Orthology - Evolution
OrthoDB84632
GeneTree (enSembl)ENSG00000169129
Phylogenetic Trees/Animal Genes : TreeFamAFAP1L2
HOVERGENQ8N4X5
HOGENOMQ8N4X5
Homologs : HomoloGeneAFAP1L2
Homology/Alignments : Family Browser (UCSC)AFAP1L2
Gene fusions - Rearrangements
Fusion : MitelmanINPP5A/AFAP1L2 [10q26.3/10q25.3]  [t(10;10)(q25;q26)]  
Fusion: TCGAINPP5A 10q26.3 AFAP1L2 10q25.3 LGG
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerAFAP1L2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)AFAP1L2
dbVarAFAP1L2
ClinVarAFAP1L2
1000_GenomesAFAP1L2 
Exome Variant ServerAFAP1L2
ExAC (Exome Aggregation Consortium)AFAP1L2 (select the gene name)
Genetic variants : HAPMAP84632
Genomic Variants (DGV)AFAP1L2 [DGVbeta]
DECIPHER (Syndromes)10:116054583-116164537  ENSG00000169129
CONAN: Copy Number AnalysisAFAP1L2 
Mutations
ICGC Data PortalAFAP1L2 
TCGA Data PortalAFAP1L2 
Broad Tumor PortalAFAP1L2
OASIS PortalAFAP1L2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICAFAP1L2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDAFAP1L2
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 AFAP1L2
DgiDB (Drug Gene Interaction Database)AFAP1L2
DoCM (Curated mutations)AFAP1L2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)AFAP1L2 (select a term)
intoGenAFAP1L2
NCG5 (London)AFAP1L2
Cancer3DAFAP1L2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM612420   
Orphanet
MedgenAFAP1L2
Genetic Testing Registry AFAP1L2
NextProtQ8N4X5 [Medical]
TSGene84632
GENETestsAFAP1L2
Huge Navigator AFAP1L2 [HugePedia]
snp3D : Map Gene to Disease84632
BioCentury BCIQAFAP1L2
ClinGenAFAP1L2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD84632
Chemical/Pharm GKB GenePA162375773
Clinical trialAFAP1L2
Miscellaneous
canSAR (ICR)AFAP1L2 (select the gene name)
Probes
Litterature
PubMed24 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineAFAP1L2
EVEXAFAP1L2
GoPubMedAFAP1L2
iHOPAFAP1L2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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