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SH3GL2 (SH3-domain GRB2-like 2)

Written2009-03Chinmay Kr Panda, Amlan Ghosh, Guru Prasad Maiti
Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata 700026, India

(Note : for Links provided by Atlas : click)

Identity

Alias_namesSH3 domain containing GRB2 like 2
Alias_symbol (synonym)SH3P4
SH3D2A
CNSA2
EEN-B1
Other aliasEndophilin-1
FLJ20276
FLJ25015
OTTHUMP00000021084
HGNC (Hugo) SH3GL2
LocusID (NCBI) 6456
Atlas_Id 44345
Location 9p22.2  [Link to chromosome band 9p22]
Location_base_pair Starts at 17578952 and ends at 17797126 bp from pter ( according to hg19-Feb_2009)  [Mapping SH3GL2.png]
Local_order Next to ADAMTSL1 and FAN154A.
Fusion genes
(updated 2016)
ARFGAP2 (11p11.2) / SH3GL2 (9p22.2)SH3GL2 (9p22.2) / SH3GL2 (9p22.2)

DNA/RNA

Description 10 exons; spans 217.93kb.
Transcription mRNA of 2483 and 2417bp (there are two transcripts).

Protein

Description 352 amino acids; 39.96kDa and 330 amino acids; 37.51kDa.
Expression Highest expression found in brain followed by pituitary gland and kidney. Expression has also been reported in bladder, eye, heart, cervix, breast, head and neck tissues etc.
Localisation Cytoplasmic (diffuse cytoplasmic distribution in resting cells and a colocalization with EGF receptor in endocytic vesicles after EGF stimulation).
Function SH3GL2 is a presynaptic protein that binds to dynamin, a GTPase that is implicated in endocytosis and recycling of synaptic vesicles. SH3GL2 by its LPAAT activity may induce negative membrane curvature by converting an inverted cone shaped lipid to a cone shaped lipid in the cytoplasmic leaflet of the bilayer. Through this action, SH3GL2 works with dynamin to mediate synaptic vesicle invagination from the plasma membrane and fission.
SH3GL2 in complex with CBL and CIN85 participates in activated EGF receptor (Stimulated by EGF) endocytosis from the membrane surface and its subsequent lysosomal degradation.
The SH3 domain of SH3GL2 binds to a 24 amino acid proline rich domain (PRD) in the third intracellular loop of the G-protein coupled-1-adrenergic receptor. SH3GL2 overexpression increased isoproterenol-induced receptor internalization by 25% and decreased coupling of receptor to the G-protein.
The SH3 domain of SH3GL2 also binds to a proline rich domain within the cytoplasmic tail of metalloprotease disintegrins, transmembrane glycoproteins acting in cell adhesion and growth factor signaling. SH3GL2 binds preferentially to the pro-form found in the trans-Golgi network. Therefore SH3GL2 binding may regulate intracellular transit and maturation of metalloprotease disintegrin.
Rat germinal centre kinse-like kinase (rGLK), a serine/threonine cytosolic kinase, interacted with SH3GL2. rGLK modulated c-Jun N-terminal kinase (JNK) activity by phosphorylation and binds to the SH3 domain of SH3GL2 through a C-terminal proline rich domain. Coexpression of rGLK and full length SH3GL2 increased JNK activity two fold, whereas coexpression with the SH3 domain of SH3GL2 abrogated rGLK-induced JNK activation. SH3GL2, therefore, modulated the mitogen-activated protein kinase pathway through physical association with rGLK.
Homology SH3GL2 contains a C-terminal SH3 domain, which shares 92% and 84% amino acid sequence homology with the SH3 domain of SH3GL3 and SH3GL1, respectively. The SH3 domain of SH3GL2 also shows high homology to the C-terminal SH3 domain of GRB2.

Mutations

Somatic In SH3GL2, mutation in SH3 domain has only been reported.

Implicated in

Note
  
Entity Sporadic cancer
Disease Reduced expressions of SH3GL2 due to different types of molecular alterations are involved in tumor formation in head and neck, breast and gastric tissues.
Prognosis The prognostic significance of down regulation of SH3GL2 in sporadic tumors is not understood clearly.
Cytogenetics Chromosomal deletions, chromosomal gain or amplification and chromosomal breakpoints are frequent.
Oncogenesis LOH on 9p22 is one of the most frequent events identified in head and neck tumor, breast carcinoma, pituitary adenoma, neuroblastoma etc. However, promoter methylation appears to be another common mechanism of SH3GL2 inactivation.
  
  
Entity Alzheimer disease
Disease The increased expression level of SH3GL2 in neuron is linked to an increase in the activation of the stress kinase c-Jun N-terminal kinase with the subsequent death of the neuron.
Prognosis SH3GL2 overexpression is now considered as a new indicator of the progression of Alzhemier disease.
Cytogenetics Increase in aneuploidy or aberration, but chromosomal loss or gain in aneuploid cell was not specific. In some forms of Alzheimer disease, a specific type of aneuploidy-trisomy 21 mosaicism has been reported.
  

Bibliography

Formation of an endophilin-Ca2+ channel complex is critical for clathrin-mediated synaptic vesicle endocytosis.
Chen Y, Deng L, Maeno-Hikichi Y, Lai M, Chang S, Chen G, Zhang JF.
Cell. 2003 Oct 3;115(1):37-48.
PMID 14532001
 
SH3GL2 and CDKN2A/2B loci are independently altered in early dysplastic lesions of head and neck: correlation with HPV infection and tobacco habit.
Ghosh A, Ghosh S, Maiti GP, Sabbir MG, Alam N, Sikdar N, Roy B, Roychoudhury S, Panda CK.
J Pathol. 2009 Feb;217(3):408-19.
PMID 19023882
 
A novel SH3-containing human gene family preferentially expressed in the central nervous system.
Giachino C, Lantelme E, Lanzetti L, Saccone S, Bella Valle G, Migone N.
Genomics. 1997 May 1;41(3):427-34.
PMID 9169142
 
Receptor-mediated chicken oocyte growth: differential expression of endophilin isoforms in developing follicles.
Hirayama S, Bajari TM, Nimpf J, Schneider WJ.
Biol Reprod. 2003 May;68(5):1850-60. Epub 2002 Dec 11.
PMID 12606338
 
Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1.
Howard L, Nelson KK, Maciewicz RA, Blobel CP.
J Biol Chem. 1999 Oct 29;274(44):31693-9.
PMID 10531379
 
Lipids, lipid modification and lipid-protein interaction in membrane budding and fission--insights from the roles of endophilin A1 and synaptophysin in synaptic vesicle endocytosis.
Huttner WB, Schmidt A.
Curr Opin Neurobiol. 2000 Oct;10(5):543-51. (REVIEW)
PMID 11084315
 
Endophilin BAR domain drives membrane curvature by two newly identified structure-based mechanisms.
Masuda M, Takeda S, Sone M, Ohki T, Mori H, Kamioka Y, Mochizuki N.
EMBO J. 2006 Jun 21;25(12):2889-97. Epub 2006 Jun 8.
PMID 16763557
 
Neural Wiskott-Aldrich syndrome protein is recruited to rafts and associates with endophilin A in response to epidermal growth factor.
Otsuki M, Itoh T, Takenawa T.
J Biol Chem. 2003 Feb 21;278(8):6461-9. Epub 2002 Dec 10.
PMID 12477732
 
Genomic deletions correlate with underexpression of novel candidate genes at six loci in pediatric pilocytic astrocytoma.
Potter N, Karakoula A, Phipps KP, Harkness W, Hayward R, Thompson DN, Jacques TS, Harding B, Thomas DG, Palmer RW, Rees J, Darling J, Warr TJ.
Neoplasia. 2008 Aug;10(8):757-72.
PMID 18670637
 
Endophilin regulates JNK activation through its interaction with the germinal center kinase-like kinase.
Ramjaun AR, Angers A, Legendre-Guillemin V, Tong XK, McPherson PS.
J Biol Chem. 2001 Aug 3;276(31):28913-9. Epub 2001 May 30.
PMID 11384986
 
Endophilin I expression is increased in the brains of Alzheimer disease patients.
Ren Y, Xu HW, Davey F, Taylor M, Aiton J, Coote P, Fang F, Yao J, Chen D, Chen JX, Yan SD, Gunn-Moore FJ.
J Biol Chem. 2008 Feb 29;283(9):5685-91. Epub 2007 Dec 31.
PMID 18167351
 
Endophilin-1: a multifunctional protein.
Reutens AT, Begley CG.
Int J Biochem Cell Biol. 2002 Oct;34(10):1173-7. (REVIEW)
PMID 12127567
 
Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid.
Schmidt A, Wolde M, Thiele C, Fest W, Kratzin H, Podtelejnikov AV, Witke W, Huttner WB, Soling HD.
Nature. 1999 Sep 9;401(6749):133-41.
PMID 10490020
 
Study of the SH3-domain GRB2-like 2 gene expression in laryngeal carcinoma.
Shang C, Fu WN, Guo Y, Huang DF, Sun KL.
Chin Med J (Engl). 2007 Mar 5;120(5):385-8.
PMID 17376308
 
Frequent deletion and methylation in SH3GL2 and CDKN2A loci are associated with early- and late-onset breast carcinoma.
Sinha S, Chunder N, Mukherjee N, Alam N, Roy A, Roychoudhury S, Kumar Panda C.
Ann Surg Oncol. 2008 Apr;15(4):1070-80. Epub 2008 Feb 1.
PMID 18239974
 
Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors.
Soubeyran P, Kowanetz K, Szymkiewicz I, Langdon WY, Dikic I.
Nature. 2002 Mar 14;416(6877):183-7.
PMID 11894095
 
Identification of the endophilins (SH3p4/p8/p13) as novel binding partners for the beta1-adrenergic receptor.
Tang Y, Hu LA, Miller WE, Ringstad N, Hall RA, Pitcher JA, DeCamilli P, Lefkowitz RJ.
Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12559-64.
PMID 10535961
 
Endophilin mutations block clathrin-mediated endocytosis but not neurotransmitter release.
Verstreken P, Kjaerulff O, Lloyd TE, Atkinson R, Zhou Y, Meinertzhagen IA, Bellen HJ.
Cell. 2002 Apr 5;109(1):101-12.
PMID 11955450
 

Citation

This paper should be referenced as such :
Panda, CK ; Ghosh, A ; Maiti, GP
SH3GL2 (SH3-domain GRB2-like 2)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(3):305-304.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/SH3GL2ID44345ch9p22.html


External links

Nomenclature
HGNC (Hugo)SH3GL2   10831
Cards
AtlasSH3GL2ID44345ch9p22
Entrez_Gene (NCBI)SH3GL2  6456  SH3-domain GRB2-like 2
AliasesCNSA2; EEN-B1; SH3D2A; SH3P4
GeneCards (Weizmann)SH3GL2
Ensembl hg19 (Hinxton)ENSG00000107295 [Gene_View]  chr9:17578952-17797126 [Contig_View]  SH3GL2 [Vega]
Ensembl hg38 (Hinxton)ENSG00000107295 [Gene_View]  chr9:17578952-17797126 [Contig_View]  SH3GL2 [Vega]
ICGC DataPortalENSG00000107295
TCGA cBioPortalSH3GL2
AceView (NCBI)SH3GL2
Genatlas (Paris)SH3GL2
WikiGenes6456
SOURCE (Princeton)SH3GL2
Genetics Home Reference (NIH)SH3GL2
Genomic and cartography
GoldenPath hg19 (UCSC)SH3GL2  -     chr9:17578952-17797126 +  9p22   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)SH3GL2  -     9p22   [Description]    (hg38-Dec_2013)
EnsemblSH3GL2 - 9p22 [CytoView hg19]  SH3GL2 - 9p22 [CytoView hg38]
Mapping of homologs : NCBISH3GL2 [Mapview hg19]  SH3GL2 [Mapview hg38]
OMIM604465   
Gene and transcription
Genbank (Entrez)AB206840 AF036268 AK057744 AK293546 AK293592
RefSeq transcript (Entrez)NM_003026
RefSeq genomic (Entrez)NC_000009 NC_018920 NT_008413 NW_004929342
Consensus coding sequences : CCDS (NCBI)SH3GL2
Cluster EST : UnigeneHs.743740 [ NCBI ]
CGAP (NCI)Hs.743740
Alternative Splicing GalleryENSG00000107295
Gene ExpressionSH3GL2 [ NCBI-GEO ]   SH3GL2 [ EBI - ARRAY_EXPRESS ]   SH3GL2 [ SEEK ]   SH3GL2 [ MEM ]
Gene Expression Viewer (FireBrowse)SH3GL2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6456
GTEX Portal (Tissue expression)SH3GL2
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ99962   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ99962  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ99962
Splice isoforms : SwissVarQ99962
PhosPhoSitePlusQ99962
Domaine pattern : Prosite (Expaxy)BAR (PS51021)    SH3 (PS50002)   
Domains : Interpro (EBI)AH/BAR-dom    BAR_dom    SH3_2    SH3_domain    Spectrin_alpha_SH3   
Domain families : Pfam (Sanger)BAR (PF03114)    SH3_2 (PF07653)   
Domain families : Pfam (NCBI)pfam03114    pfam07653   
Domain families : Smart (EMBL)BAR (SM00721)  SH3 (SM00326)  
Conserved Domain (NCBI)SH3GL2
DMDM Disease mutations6456
Blocks (Seattle)SH3GL2
PDB (SRS)1X03    1X04    2D4C    2DBM   
PDB (PDBSum)1X03    1X04    2D4C    2DBM   
PDB (IMB)1X03    1X04    2D4C    2DBM   
PDB (RSDB)1X03    1X04    2D4C    2DBM   
Structural Biology KnowledgeBase1X03    1X04    2D4C    2DBM   
SCOP (Structural Classification of Proteins)1X03    1X04    2D4C    2DBM   
CATH (Classification of proteins structures)1X03    1X04    2D4C    2DBM   
SuperfamilyQ99962
Human Protein AtlasENSG00000107295
Peptide AtlasQ99962
HPRD05125
IPIIPI00019171   IPI00922749   IPI00651733   IPI01012435   IPI01009303   
Protein Interaction databases
DIP (DOE-UCLA)Q99962
IntAct (EBI)Q99962
FunCoupENSG00000107295
BioGRIDSH3GL2
STRING (EMBL)SH3GL2
ZODIACSH3GL2
Ontologies - Pathways
QuickGOQ99962
Ontology : AmiGOGolgi membrane  regulation of receptor internalization  protein binding  cytosol  plasma membrane  microtubule-based movement  signal transduction  central nervous system development  lipid binding  antigen processing and presentation of exogenous peptide antigen via MHC class II  clathrin-coated endocytic vesicle membrane  negative regulation of epidermal growth factor receptor signaling pathway  identical protein binding  synaptic vesicle endocytosis  extracellular exosome  
Ontology : EGO-EBIGolgi membrane  regulation of receptor internalization  protein binding  cytosol  plasma membrane  microtubule-based movement  signal transduction  central nervous system development  lipid binding  antigen processing and presentation of exogenous peptide antigen via MHC class II  clathrin-coated endocytic vesicle membrane  negative regulation of epidermal growth factor receptor signaling pathway  identical protein binding  synaptic vesicle endocytosis  extracellular exosome  
Pathways : KEGGEndocytosis   
REACTOMEQ99962 [protein]
REACTOME Pathways177504 [pathway]   182971 [pathway]   2132295 [pathway]   432720 [pathway]   432722 [pathway]   437239 [pathway]   6807004 [pathway]   8856825 [pathway]   8856828 [pathway]   8875360 [pathway]   
NDEx NetworkSH3GL2
Atlas of Cancer Signalling NetworkSH3GL2
Wikipedia pathwaysSH3GL2
Orthology - Evolution
OrthoDB6456
GeneTree (enSembl)ENSG00000107295
Phylogenetic Trees/Animal Genes : TreeFamSH3GL2
HOVERGENQ99962
HOGENOMQ99962
Homologs : HomoloGeneSH3GL2
Homology/Alignments : Family Browser (UCSC)SH3GL2
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSH3GL2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SH3GL2
dbVarSH3GL2
ClinVarSH3GL2
1000_GenomesSH3GL2 
Exome Variant ServerSH3GL2
ExAC (Exome Aggregation Consortium)SH3GL2 (select the gene name)
Genetic variants : HAPMAP6456
Genomic Variants (DGV)SH3GL2 [DGVbeta]
DECIPHER (Syndromes)9:17578952-17797126  ENSG00000107295
CONAN: Copy Number AnalysisSH3GL2 
Mutations
ICGC Data PortalSH3GL2 
TCGA Data PortalSH3GL2 
Broad Tumor PortalSH3GL2
OASIS PortalSH3GL2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSH3GL2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSH3GL2
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 SH3GL2
DgiDB (Drug Gene Interaction Database)SH3GL2
DoCM (Curated mutations)SH3GL2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SH3GL2 (select a term)
intoGenSH3GL2
NCG5 (London)SH3GL2
Cancer3DSH3GL2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM604465   
Orphanet
MedgenSH3GL2
Genetic Testing Registry SH3GL2
NextProtQ99962 [Medical]
TSGene6456
GENETestsSH3GL2
Huge Navigator SH3GL2 [HugePedia]
snp3D : Map Gene to Disease6456
BioCentury BCIQSH3GL2
ClinGenSH3GL2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6456
Chemical/Pharm GKB GenePA35737
Clinical trialSH3GL2
Miscellaneous
canSAR (ICR)SH3GL2 (select the gene name)
Probes
Litterature
PubMed84 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSH3GL2
EVEXSH3GL2
GoPubMedSH3GL2
iHOPSH3GL2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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