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SORBS2 (sorbin and SH3 domain containing 2)

Written2008-08Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)ARGBP2
KIAA0777
Other aliasARGBP2 (Arg/Abl-interacting protein 2)
FLJ93447
PRO0618
HGNC (Hugo) SORBS2
LocusID (NCBI) 8470
Atlas_Id 693
Location 4q35.1  [Link to chromosome band 4q35]
Location_base_pair Starts at 185585444 and ends at 185812256 bp from pter ( according to hg19-Feb_2009)  [Mapping SORBS2.png]
Fusion genes
(updated 2016)
AGAP1 (2q37.2) / SORBS2 (4q35.1)C6orf106 (6p21.31) / SORBS2 (4q35.1)KMT2A (11q23.3) / SORBS2 (4q35.1)
NUDT3 (6p21.31) / SORBS2 (4q35.1)PDLIM3 (4q35.1) / SORBS2 (4q35.1)R3HDM2 (12q13.3) / SORBS2 (4q35.1)
RAI14 (5p13.2) / SORBS2 (4q35.1)SORBS2 (4q35.1) / AIF1 (6p21.33)SORBS2 (4q35.1) / ARHGAP27 (17q21.31)
SORBS2 (4q35.1) / CCDC34 (11p14.1)SORBS2 (4q35.1) / CKB (14q32.32)SORBS2 (4q35.1) / PDLIM5 (4q22.3)
SORBS2 (4q35.1) / PHLPP2 (16q22.2)SORBS2 (4q35.1) / PLAGL1 (6q24.2)SORBS2 (4q35.1) / RP11-487E13.1 ()
SORBS2 (4q35.1) / SORBS2 (4q35.1)SORBS2 (4q35.1) / TNRC6A (16p12.1)

DNA/RNA

Transcription Various transcripts.

Protein

Description The N-term region of the protein contains a sorbin homology (SoHo) domain. Sorbin, a 153 amino acid peptide, was isolated from porcine intestine (Vagne-Descroix et al., 1991). As a matter of fact, human sorbin is spliced from an alternative transcript from the SORBS2/ArgBP2 gene locus (Hand and Eiden, 2005). The sorbin homology domain is a motif for the targeting of proteins to lipid rafts (Kimura et al., 2001); 3 proteins present the SoHo domain: SORBS2/ArgBP2, SORBS1 (also called c-Cbl-associated protein (CAP), or ponsin) (10q24), and SORBS3 (vinexin) (8p21). The C-term region of the three SORBS genes contains 3 SH3 domains. The three genes share the same structural organization and present overlapping functions.
Expression Widely expressed; very abundant in heart.
Localisation Cytoplasm and nucleus (like its partner ABL1).
Function Adaptor protein.
Signaling proteins like ABL1 and ABL2 (ARG) (1q25) associate with and phosphorylate SORBS2 (Wang et al., 1997).
SORBS2 negatively regulates ABL1 and ABL2 by recruiting CBL (11q23.3) in a complex with ABL1, facilitating phosphorylation of CBL by ABL1 and promoting CBL-directed ubiquitination and degradation of ABL1 and SORBS2 in the proteasome (Soubeyran et al., 2003).
Role in AKT/PAK1 cell survival pathway: ArgBP2gamma (another SORBS2 splice) interacts with AKT and PAK1. Expression of ArgBP2gamma induces PAK1 activity and overrides apoptosis induced by ectopic expression of BAD or DNA damage (Yuan et al., 2005).
Cytoskeletal proteins: SORBS2 also binds VCL (vinculin) (10q22) a protein which plays an important role in cell adhesion and migration, and MLLT4 (also called AF6 or afadin) (6q27), another component of cell membranes at specialized sites of cell-cell contact (Kawabe et al., 1999).
SORBS2 has been found to localize at the Z-disks of cardiac myofibrils, indicating that ArgBP2 has a specialized function associated with the contractile apparatus of cardiac muscle (Wang et al., 1997). SORBS2 binds alpha actinin, an actin crosslinking protein and a major component of the Z-disks, and PALLD (palladin) (4q32), a protein associated with the alpha actinin network.
SORBS2 co-localize with ABL1 in actin stress fibers (bundles of actin filaments which appear/disappear upon stimuli) (Wang et al., 1997).
nArgBP2, a spliced form of SORB2 with a zinc finger motif in the central part of the protein, is found in the post-synaptic densities and binds DLGAP1 (SAPAP, 18p11) (Kawabe et al., 1999).
SORBS2 also interacts with SPTAN1 (alpha 2-spectrin) (9q34), another component of the membrane-associated cytoskeleton, DNM1 (9q34) and DNM2 (19p13) (dynamins) (GTPases implicated in the regulation of actin dynamics and abundantly found in the brain), WASF2 (1p36), and SYNJ2 (synaptojanin 2) (6q25), the last two undergo ubiquitination and ABL1-dependent tyrosine phosphorylation (Cestra et al., 2005).
ABL1 plays an important role in axonogenesis; ABL1 and ABL2 localize to the pre- and postsynaptic compartments of synapses.
SORBS2 binds WASF1 (also called WAVE1) (6q21) and PTPN12 (7q11). PTPN12, a protein tyrosine phosphatase, prevents SORBS2 phosphorylation by ABL1. Phosphorylation of WASF1 induced by the overexpression of ABL1 was enhanced in the presence of SORBS2, and overexpression of PTPN12 abolished the ABL1-mediated phosphorylation of WASF1 (Taieb et al., 2008).
SORBS2 inhibits adhesion and migration of pancreatic cells (Taieb et al., 2008).
Lipid rafts: SORBS2 links via its SH3 domains with proline-rich motifs of CBL and that of PTK2B (PYK2) (8p21) in a complex that is recruited to lipid rafts (via its SoHo domain) following growth factor stimulation, partially co-localizing with actin, which appears to be critical for cytoskeletal rearrangements in growing neurites (Haglund et al., 2004).
Homology SORBS1 and SORBS3.

Implicated in

Note
  
Entity t(4;11)(q35;q23) in acute myeloid leukemia --> SORBS2 - MLL
Hybrid/Mutated Gene 5' MLL - 3' SORBS2
  
  
Entity Pancreas cancer
Oncogenesis SORBS2 is repressed during pancreas carcinogenesis and during progression of the disease. The antitumoral potential of SORBS2 appears to be linked to the control of cell adhesion and migration (inhibition of cell migration) rather than to the regulation of cell proliferation or sensitivity to apoptosis (Taieb et al., 2008).
  

Bibliography

The Abl/Arg substrate ArgBP2/nArgBP2 coordinates the function of multiple regulatory mechanisms converging on the actin cytoskeleton.
Cestra G, Toomre D, Chang S, De Camilli P.
Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1731-6.
PMID 15659545
 
Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites.
Haglund K, Ivankovic-Dikic I, Shimokawa N, Kruh GD, Dikic I.
J Cell Sci. 2004 May 15;117(Pt 12):2557-68.
PMID 15128873
 
Human sorbin is generated via splicing of an alternative transcript from the ArgBP2 gene locus.
Hand D, Eiden LE.
Peptides. 2005 Jul;26(7):1278-82.
PMID 15949647
 
How do Abl family kinases regulate cell shape and movement?
Hernandez SE, Krishnaswami M, Miller AL, Koleske AJ.
Trends Cell Biol. 2004 Jan;14(1):36-44. (Review)
PMID 14729179
 
nArgBP2, a novel neural member of ponsin/ArgBP2/vinexin family that interacts with synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP).
Kawabe H, Hata Y, Takeuchi M, Ide N, Mizoguchi A, Takai Y.
J Biol Chem. 1999 Oct 22;274(43):30914-8.
PMID 10521485
 
The sorbin homology domain: a motif for the targeting of proteins to lipid rafts.
Kimura A, Baumann CA, Chiang SH, Saltiel AR.
Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9098-103.
PMID 11481476
 
Vinexin, CAP/ponsin, ArgBP2: a novel adaptor protein family regulating cytoskeletal organization and signal transduction.
Kioka N, Ueda K, Amachi T.
Cell Struct Funct. 2002 Feb;27(1):1-7. (Review)
PMID 11937713
 
ArgBP2, encoding a negative regulator of ABL, is fused to MLL in a case of infant M5 acute myeloid leukemia involving 4q35 and 11q23.
Pession A, Lo Nigro L, Montemurro L, Serravalle S, Fazzina R, Izzi G, Nucifora G, Slany R, Tonelli R.
Leukemia. 2006 Jul;20(7):1310-3.
PMID 16628191
 
Involvement of palladin and alpha-actinin in targeting of the Abl/Arg kinase adaptor ArgBP2 to the actin cytoskeleton.
Ronty M, Taivainen A, Moza M, Kruh GD, Ehler E, Carpen O.
Exp Cell Res. 2005 Oct 15;310(1):88-98.
PMID 16125169
 
Cbl-ArgBP2 complex mediates ubiquitination and degradation of c-Abl.
Soubeyran P, Barac A, Szymkiewicz I, Dikic I.
Biochem J. 2003 Feb 15;370(Pt 1):29-34.
PMID 12475393
 
ArgBP2-dependent signaling regulates pancreatic cell migration, adhesion, and tumorigenicity.
Taieb D, Roignot J, Andre F, Garcia S, Masson B, Pierres A, Iovanna JL, Soubeyran P.
Cancer Res. 2008 Jun 15;68(12):4588-96.
PMID 18559503
 
Isolation and characterisation of porcine sorbin.
Vagne-Descroix M, Pansu D, Jornvall H, Carlquist M, Guignard H, Jourdan G, Desvigne A, Collinet M, Caillet C, Mutt V.
Eur J Biochem. 1991 Oct 1;201(1):53-9.
PMID 1915377
 
ArgBP2, a multiple Src homology 3 domain-containing, Arg/Abl-interacting protein, is phosphorylated in v-Abl-transformed cells and localized in stress fibers and cardiocyte Z-disks.
Wang B, Golemis EA, Kruh GD.
J Biol Chem. 1997 Jul 11;272(28):17542-50.
PMID 921190
 
ArgBP2gamma interacts with Akt and p21-activated kinase-1 and promotes cell survival.
Yuan ZQ, Kim D, Kaneko S, Sussman M, Bokoch GM, Kruh GD, Nicosia SV, Testa JR, Cheng JQ.
J Biol Chem. 2005 Jun 3;280(22):21483-90.
PMID 15784622
 

Citation

This paper should be referenced as such :
Huret, JL
SORBS2 (sorbin, SH3 domain containing 2)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(7):497-498.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/SORBS2ID693ch4q35.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(4;11)(q35;q23) KMT2A/SORBS2


External links

Nomenclature
HGNC (Hugo)SORBS2   24098
Cards
AtlasSORBS2ID693ch4q35
Entrez_Gene (NCBI)SORBS2  8470  sorbin and SH3 domain containing 2
AliasesARGBP2; PRO0618
GeneCards (Weizmann)SORBS2
Ensembl hg19 (Hinxton)ENSG00000154556 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000154556 [Gene_View]  chr4:185585444-185812256 [Contig_View]  SORBS2 [Vega]
ICGC DataPortalENSG00000154556
TCGA cBioPortalSORBS2
AceView (NCBI)SORBS2
Genatlas (Paris)SORBS2
WikiGenes8470
SOURCE (Princeton)SORBS2
Genetics Home Reference (NIH)SORBS2
Genomic and cartography
GoldenPath hg38 (UCSC)SORBS2  -     chr4:185585444-185812256 -  4q35.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SORBS2  -     4q35.1   [Description]    (hg19-Feb_2009)
EnsemblSORBS2 - 4q35.1 [CytoView hg19]  SORBS2 - 4q35.1 [CytoView hg38]
Mapping of homologs : NCBISORBS2 [Mapview hg19]  SORBS2 [Mapview hg38]
OMIM616349   
Gene and transcription
Genbank (Entrez)###############################################################################################################################################################################################################################################################
RefSeq transcript (Entrez)NM_001145670 NM_001145671 NM_001145672 NM_001145673 NM_001145674 NM_001145675 NM_001270771 NM_003603 NM_021069
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)SORBS2
Cluster EST : UnigeneHs.655143 [ NCBI ]
CGAP (NCI)Hs.655143
Alternative Splicing GalleryENSG00000154556
Gene ExpressionSORBS2 [ NCBI-GEO ]   SORBS2 [ EBI - ARRAY_EXPRESS ]   SORBS2 [ SEEK ]   SORBS2 [ MEM ]
Gene Expression Viewer (FireBrowse)SORBS2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)8470
GTEX Portal (Tissue expression)SORBS2
Protein : pattern, domain, 3D structure
UniProt/SwissProtO94875   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO94875  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO94875
Splice isoforms : SwissVarO94875
PhosPhoSitePlusO94875
Domaine pattern : Prosite (Expaxy)SH3 (PS50002)    SOHO (PS50831)   
Domains : Interpro (EBI)ArgBP2    SH3_domain    SoHo_dom    Znf_C2H2   
Domain families : Pfam (Sanger)SH3_1 (PF00018)    SH3_9 (PF14604)    Sorb (PF02208)   
Domain families : Pfam (NCBI)pfam00018    pfam14604    pfam02208   
Domain families : Smart (EMBL)SH3 (SM00326)  Sorb (SM00459)  
Conserved Domain (NCBI)SORBS2
DMDM Disease mutations8470
Blocks (Seattle)SORBS2
PDB (SRS)4IGZ   
PDB (PDBSum)4IGZ   
PDB (IMB)4IGZ   
PDB (RSDB)4IGZ   
Structural Biology KnowledgeBase4IGZ   
SCOP (Structural Classification of Proteins)4IGZ   
CATH (Classification of proteins structures)4IGZ   
SuperfamilyO94875
Human Protein AtlasENSG00000154556
Peptide AtlasO94875
HPRD12473
IPI###############################################################################################################################################################################################################################################################   
Protein Interaction databases
DIP (DOE-UCLA)O94875
IntAct (EBI)O94875
FunCoupENSG00000154556
BioGRIDSORBS2
STRING (EMBL)SORBS2
ZODIACSORBS2
Ontologies - Pathways
QuickGOO94875
Ontology : AmiGORNA binding  structural constituent of cytoskeleton  protein binding  nucleus  focal adhesion  actin filament organization  cell adhesion  cytoskeletal adaptor activity  biological_process  structural constituent of muscle  actin cytoskeleton  apical plasma membrane  cell migration  Z disc  lamellipodium  perinuclear region of cytoplasm  cell growth involved in cardiac muscle cell development  
Ontology : EGO-EBIRNA binding  structural constituent of cytoskeleton  protein binding  nucleus  focal adhesion  actin filament organization  cell adhesion  cytoskeletal adaptor activity  biological_process  structural constituent of muscle  actin cytoskeleton  apical plasma membrane  cell migration  Z disc  lamellipodium  perinuclear region of cytoplasm  cell growth involved in cardiac muscle cell development  
NDEx NetworkSORBS2
Atlas of Cancer Signalling NetworkSORBS2
Wikipedia pathwaysSORBS2
Orthology - Evolution
OrthoDB8470
GeneTree (enSembl)ENSG00000154556
Phylogenetic Trees/Animal Genes : TreeFamSORBS2
HOVERGENO94875
HOGENOMO94875
Homologs : HomoloGeneSORBS2
Homology/Alignments : Family Browser (UCSC)SORBS2
Gene fusions - Rearrangements
Fusion : MitelmanPDLIM3/SORBS2 [4q35.1/4q35.1]  [t(4;4)(q35;q35)]  
Fusion : MitelmanR3HDM2/SORBS2 [12q13.3/4q35.1]  [t(4;12)(q35;q13)]  
Fusion : MitelmanSORBS2/AIF1 [4q35.1/6p21.33]  [t(4;6)(q35;p21)]  
Fusion : MitelmanSORBS2/ARHGAP27 [4q35.1/17q21.31]  [t(4;17)(q35;q21)]  
Fusion : COSMICKMT2A [11q23.3]  -  SORBS2 [4q35.1]  [fusion_1839]  [fusion_1840]  
Fusion: TCGAPDLIM3 4q35.1 SORBS2 4q35.1 BRCA
Fusion: TCGAR3HDM2 12q13.3 SORBS2 4q35.1 GBM
Fusion: TCGASORBS2 4q35.1 AIF1 6p21.33 BRCA
Fusion: TCGASORBS2 4q35.1 ARHGAP27 17q21.31 PRAD
Fusion: TCGASORBS2 4q35.1 RP11-487E13.1 LUAD
Fusion : TICdbKMT2A [11q23.3]  -  SORBS2 [4q35.1]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSORBS2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SORBS2
dbVarSORBS2
ClinVarSORBS2
1000_GenomesSORBS2 
Exome Variant ServerSORBS2
ExAC (Exome Aggregation Consortium)SORBS2 (select the gene name)
Genetic variants : HAPMAP8470
Genomic Variants (DGV)SORBS2 [DGVbeta]
DECIPHERSORBS2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSORBS2 
Mutations
ICGC Data PortalSORBS2 
TCGA Data PortalSORBS2 
Broad Tumor PortalSORBS2
OASIS PortalSORBS2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSORBS2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSORBS2
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 SORBS2
DgiDB (Drug Gene Interaction Database)SORBS2
DoCM (Curated mutations)SORBS2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SORBS2 (select a term)
intoGenSORBS2
NCG5 (London)SORBS2
Cancer3DSORBS2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM616349   
Orphanet
MedgenSORBS2
Genetic Testing Registry SORBS2
NextProtO94875 [Medical]
TSGene8470
GENETestsSORBS2
Target ValidationSORBS2
Huge Navigator SORBS2 [HugePedia]
snp3D : Map Gene to Disease8470
BioCentury BCIQSORBS2
ClinGenSORBS2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD8470
Chemical/Pharm GKB GenePA142670890
Clinical trialSORBS2
Miscellaneous
canSAR (ICR)SORBS2 (select the gene name)
Probes
Litterature
PubMed56 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSORBS2
EVEXSORBS2
GoPubMedSORBS2
iHOPSORBS2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Jun 7 12:15:13 CEST 2017

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