Atlas of Genetics and Cytogenetics in Oncology and Haematology

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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)


Alias_namesSH3 domain containing GRB2 like 2
Alias_symbol (synonym)SH3P4
Other aliasEndophilin-1
HGNC (Hugo) SH3GL2
LocusID (NCBI) 6456
Atlas_Id 44345
Location 9p22.2  [Link to chromosome band 9p22]
Location_base_pair Starts at 17578954 and ends at 17797128 bp from pter ( according to hg19-Feb_2009)  [Mapping SH3GL2.png]
Local_order Next to ADAMTSL1 and FAN154A.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ARFGAP2 (11p11.2) / SH3GL2 (9p22.2)SH3GL2 (9p22.2) / SH3GL2 (9p22.2)


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


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.


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

Implicated in

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.


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


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 :

External links

HGNC (Hugo)SH3GL2   10831
Entrez_Gene (NCBI)SH3GL2  6456  SH3 domain containing GRB2 like 2, endophilin A1
AliasesCNSA2; EEN-B1; SH3D2A; SH3P4
GeneCards (Weizmann)SH3GL2
Ensembl hg19 (Hinxton)ENSG00000107295 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000107295 [Gene_View]  chr9:17578954-17797128 [Contig_View]  SH3GL2 [Vega]
ICGC DataPortalENSG00000107295
TCGA cBioPortalSH3GL2
AceView (NCBI)SH3GL2
Genatlas (Paris)SH3GL2
SOURCE (Princeton)SH3GL2
Genetics Home Reference (NIH)SH3GL2
Genomic and cartography
GoldenPath hg38 (UCSC)SH3GL2  -     chr9:17578954-17797128 +  9p22.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SH3GL2  -     9p22.2   [Description]    (hg19-Feb_2009)
EnsemblSH3GL2 - 9p22.2 [CytoView hg19]  SH3GL2 - 9p22.2 [CytoView hg38]
Mapping of homologs : NCBISH3GL2 [Mapview hg19]  SH3GL2 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AB206840 AF036268 AK057744 AK293546 AK293592
RefSeq transcript (Entrez)NM_003026
RefSeq genomic (Entrez)
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]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6456
GTEX Portal (Tissue expression)SH3GL2
Human Protein AtlasENSG00000107295-SH3GL2 [pathology]   [cell]   [tissue]
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
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   
Human Protein Atlas [tissue]ENSG00000107295-SH3GL2 [tissue]
Peptide AtlasQ99962
IPIIPI00019171   IPI00922749   IPI00651733   IPI01012435   IPI01009303   
Protein Interaction databases
IntAct (EBI)Q99962
Ontologies - Pathways
Ontology : AmiGOGolgi membrane  regulation of receptor internalization  protein binding  early endosome  cytosol  plasma membrane  microtubule-based movement  signal transduction  central nervous system development  lipid binding  synaptic vesicle uncoating  antigen processing and presentation of exogenous peptide antigen via MHC class II  clathrin-coated endocytic vesicle membrane  neuron projection development  negative regulation of epidermal growth factor receptor signaling pathway  identical protein binding  synapse  membrane organization  extracellular exosome  dendrite extension  cellular response to brain-derived neurotrophic factor stimulus  
Ontology : EGO-EBIGolgi membrane  regulation of receptor internalization  protein binding  early endosome  cytosol  plasma membrane  microtubule-based movement  signal transduction  central nervous system development  lipid binding  synaptic vesicle uncoating  antigen processing and presentation of exogenous peptide antigen via MHC class II  clathrin-coated endocytic vesicle membrane  neuron projection development  negative regulation of epidermal growth factor receptor signaling pathway  identical protein binding  synapse  membrane organization  extracellular exosome  dendrite extension  cellular response to brain-derived neurotrophic factor stimulus  
REACTOMEQ99962 [protein]
REACTOME PathwaysR-HSA-8875360 [pathway]   
NDEx NetworkSH3GL2
Atlas of Cancer Signalling NetworkSH3GL2
Wikipedia pathwaysSH3GL2
Orthology - Evolution
GeneTree (enSembl)ENSG00000107295
Phylogenetic Trees/Animal Genes : TreeFamSH3GL2
Homologs : HomoloGeneSH3GL2
Homology/Alignments : Family Browser (UCSC)SH3GL2
Gene fusions - Rearrangements
Fusion : QuiverSH3GL2
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSH3GL2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SH3GL2
Exome Variant ServerSH3GL2
ExAC (Exome Aggregation Consortium)ENSG00000107295
GNOMAD BrowserENSG00000107295
Genetic variants : HAPMAP6456
Genomic Variants (DGV)SH3GL2 [DGVbeta]
DECIPHERSH3GL2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSH3GL2 
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)
NCG5 (London)SH3GL2
Cancer3DSH3GL2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry SH3GL2
NextProtQ99962 [Medical]
Target ValidationSH3GL2
Huge Navigator SH3GL2 [HugePedia]
snp3D : Map Gene to Disease6456
BioCentury BCIQSH3GL2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6456
Chemical/Pharm GKB GenePA35737
Clinical trialSH3GL2
canSAR (ICR)SH3GL2 (select the gene name)
PubMed87 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Jan 5 12:45:10 CET 2018

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