SH3GL2 (SH3-domain GRB2-like 2)

2009-03-01   Chinmay Kr Panda , Amlan Ghosh , Guru Prasad Maiti 

Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata 700026, India





10 exons; spans 217.93kb.


mRNA of 2483 and 2417bp (there are two transcripts).



352 amino acids; 39.96kDa and 330 amino acids; 37.51kDa.


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.


Cytoplasmic (diffuse cytoplasmic distribution in resting cells and a colocalization with EGF receptor in endocytic vesicles after EGF stimulation).


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.


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.



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

Implicated in

Entity name
Sporadic cancer
Reduced expressions of SH3GL2 due to different types of molecular alterations are involved in tumor formation in head and neck, breast and gastric tissues.
The prognostic significance of down regulation of SH3GL2 in sporadic tumors is not understood clearly.
Chromosomal deletions, chromosomal gain or amplification and chromosomal breakpoints are frequent.
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 name
Alzheimer 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.
SH3GL2 overexpression is now considered as a new indicator of the progression of Alzhemier disease.
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.


Pubmed IDLast YearTitleAuthors
145320012003Formation of an endophilin-Ca2+ channel complex is critical for clathrin-mediated synaptic vesicle endocytosis.Chen Y et al
190238822009SH3GL2 and CDKN2A/2B loci are independently altered in early dysplastic lesions of head and neck: correlation with HPV infection and tobacco habit.Ghosh A et al
91691421997A novel SH3-containing human gene family preferentially expressed in the central nervous system.Giachino C et al
126063382003Receptor-mediated chicken oocyte growth: differential expression of endophilin isoforms in developing follicles.Hirayama S et al
105313791999Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1.Howard L et al
110843152000Lipids, 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 et al
167635572006Endophilin BAR domain drives membrane curvature by two newly identified structure-based mechanisms.Masuda M et al
124777322003Neural Wiskott-Aldrich syndrome protein is recruited to rafts and associates with endophilin A in response to epidermal growth factor.Otsuki M et al
186706372008Genomic deletions correlate with underexpression of novel candidate genes at six loci in pediatric pilocytic astrocytoma.Potter N et al
113849862001Endophilin regulates JNK activation through its interaction with the germinal center kinase-like kinase.Ramjaun AR et al
181673512008Endophilin I expression is increased in the brains of Alzheimer disease patients.Ren Y et al
121275672002Endophilin-1: a multifunctional protein.Reutens AT et al
104900201999Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid.Schmidt A et al
173763082007Study of the SH3-domain GRB2-like 2 gene expression in laryngeal carcinoma.Shang C et al
182399742008Frequent deletion and methylation in SH3GL2 and CDKN2A loci are associated with early- and late-onset breast carcinoma.Sinha S et al
118940952002Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors.Soubeyran P et al
105359611999Identification of the endophilins (SH3p4/p8/p13) as novel binding partners for the beta1-adrenergic receptor.Tang Y et al
119554502002Endophilin mutations block clathrin-mediated endocytosis but not neurotransmitter release.Verstreken P et al

Other Information

Locus ID:

NCBI: 6456
MIM: 604465
HGNC: 10831
Ensembl: ENSG00000107295


dbSNP: 6456
ClinVar: 6456
TCGA: ENSG00000107295


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Infectious diseaseREACTOMER-HSA-5663205
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
MHC class II antigen presentationREACTOMER-HSA-2132295
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
EGFR downregulationREACTOMER-HSA-182971
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
Retrograde neurotrophin signallingREACTOMER-HSA-177504
Vesicle-mediated transportREACTOMER-HSA-5653656
Membrane TraffickingREACTOMER-HSA-199991
trans-Golgi Network Vesicle BuddingREACTOMER-HSA-199992
Clathrin derived vesicle buddingREACTOMER-HSA-421837
Golgi Associated Vesicle BiogenesisREACTOMER-HSA-432722
Lysosome Vesicle BiogenesisREACTOMER-HSA-432720
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
L1CAM interactionsREACTOMER-HSA-373760
Recycling pathway of L1REACTOMER-HSA-437239
Clathrin-mediated endocytosisREACTOMER-HSA-8856828
Cargo recognition for clathrin-mediated endocytosisREACTOMER-HSA-8856825
Signaling by METREACTOMER-HSA-6806834
Negative regulation of MET activityREACTOMER-HSA-6807004
Listeria monocytogenes entry into host cellsREACTOMER-HSA-8876384
InlB-mediated entry of Listeria monocytogenes into host cellREACTOMER-HSA-8875360

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
191655272009Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia.56
186024632008Ataxin-2 associates with the endocytosis complex and affects EGF receptor trafficking.40
230293642012MicroRNA-330 is an oncogenic factor in glioblastoma cells by regulating SH3GL2 gene.23
240766562013Endophilin, Lamellipodin, and Mena cooperate to regulate F-actin-dependent EGF-receptor endocytosis.23
182399742008Frequent deletion and methylation in SH3GL2 and CDKN2A loci are associated with early- and late-onset breast carcinoma.20
247367272014MiR-330-mediated regulation of SH3GL2 expression enhances malignant behaviors of glioblastoma stem cells by activating ERK and PI3K/AKT signaling pathways.18
236754852013Overexpression of EGFR in head and neck squamous cell carcinoma is associated with inactivation of SH3GL2 and CDC25A genes.17
248541212014Endophilin-1 regulates blood-brain barrier permeability by controlling ZO-1 and occludin expression via the EGFR-ERK1/2 pathway.13
196798472009Multi-ethnic genetic association study of carotid intima-media thickness using a targeted cardiovascular SNP microarray.12


Chinmay Kr Panda ; Amlan Ghosh ; Guru Prasad Maiti

SH3GL2 (SH3-domain GRB2-like 2)

Atlas Genet Cytogenet Oncol Haematol. 2009-03-01

Online version: