SH3GL2 (SH3-domain GRB2-like 2)
2009-03-01 Chinmay Kr Panda , Amlan Ghosh , Guru Prasad Maiti AffiliationDepartment of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata 700026, India
Identity
HGNC
LOCATION
9p22.2
LOCUSID
ALIAS
CNSA2,EEN-B1,SH3D2A,SH3P4
FUSION GENES
DNA/RNA
Description
10 exons; spans 217.93kb.
Transcription
mRNA of 2483 and 2417bp (there are two transcripts).
Proteins
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.
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.
Mutations
Somatic
In SH3GL2, mutation in SH3 domain has only been reported.
Implicated in
Entity name
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 name
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 14532001 | 2003 | Formation of an endophilin-Ca2+ channel complex is critical for clathrin-mediated synaptic vesicle endocytosis. | Chen Y et al |
| 19023882 | 2009 | 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 et al |
| 9169142 | 1997 | A novel SH3-containing human gene family preferentially expressed in the central nervous system. | Giachino C et al |
| 12606338 | 2003 | Receptor-mediated chicken oocyte growth: differential expression of endophilin isoforms in developing follicles. | Hirayama S et al |
| 10531379 | 1999 | Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1. | Howard L et al |
| 11084315 | 2000 | 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 et al |
| 16763557 | 2006 | Endophilin BAR domain drives membrane curvature by two newly identified structure-based mechanisms. | Masuda M et al |
| 12477732 | 2003 | Neural Wiskott-Aldrich syndrome protein is recruited to rafts and associates with endophilin A in response to epidermal growth factor. | Otsuki M et al |
| 18670637 | 2008 | Genomic deletions correlate with underexpression of novel candidate genes at six loci in pediatric pilocytic astrocytoma. | Potter N et al |
| 11384986 | 2001 | Endophilin regulates JNK activation through its interaction with the germinal center kinase-like kinase. | Ramjaun AR et al |
| 18167351 | 2008 | Endophilin I expression is increased in the brains of Alzheimer disease patients. | Ren Y et al |
| 12127567 | 2002 | Endophilin-1: a multifunctional protein. | Reutens AT et al |
| 10490020 | 1999 | Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid. | Schmidt A et al |
| 17376308 | 2007 | Study of the SH3-domain GRB2-like 2 gene expression in laryngeal carcinoma. | Shang C et al |
| 18239974 | 2008 | Frequent deletion and methylation in SH3GL2 and CDKN2A loci are associated with early- and late-onset breast carcinoma. | Sinha S et al |
| 11894095 | 2002 | Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors. | Soubeyran P et al |
| 10535961 | 1999 | Identification of the endophilins (SH3p4/p8/p13) as novel binding partners for the beta1-adrenergic receptor. | Tang Y et al |
| 11955450 | 2002 | Endophilin 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
Variants:
dbSNP: 6456
ClinVar: 6456
TCGA: ENSG00000107295
COSMIC: SH3GL2
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000107295 | ENST00000380607 | Q99962 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36827984 | 2023 | EndophilinA-dependent coupling between activity-induced calcium influx and synaptic autophagy is disrupted by a Parkinson-risk mutation. | 8 |
| 36827984 | 2023 | EndophilinA-dependent coupling between activity-induced calcium influx and synaptic autophagy is disrupted by a Parkinson-risk mutation. | 8 |
| 31960967 | 2020 | Reduction of nuclear Y654-p-β-catenin expression through SH3GL2-meditated downregulation of EGFR in chemotolerance TNBC: Clinical and prognostic importance. | 4 |
| 32367751 | 2020 | A family of fuchs endothelial corneal dystrophy and anterior polar cataract with an analysis of whole exome sequencing. | 0 |
| 31960967 | 2020 | Reduction of nuclear Y654-p-β-catenin expression through SH3GL2-meditated downregulation of EGFR in chemotolerance TNBC: Clinical and prognostic importance. | 4 |
| 32367751 | 2020 | A family of fuchs endothelial corneal dystrophy and anterior polar cataract with an analysis of whole exome sequencing. | 0 |
| 31375213 | 2019 | miR-424-5p maybe regulate blood-brain barrier permeability in a model in vitro with Abeta incubated endothelial cells. | 10 |
| 31406142 | 2019 | Cancer Testis Antigen Promotes Triple Negative Breast Cancer Metastasis and is Traceable in the Circulating Extracellular Vesicles. | 15 |
| 31663854 | 2019 | A proline-rich motif on VGLUT1 reduces synaptic vesicle super-pool and spontaneous release frequency. | 10 |
| 31375213 | 2019 | miR-424-5p maybe regulate blood-brain barrier permeability in a model in vitro with Abeta incubated endothelial cells. | 10 |
| 31406142 | 2019 | Cancer Testis Antigen Promotes Triple Negative Breast Cancer Metastasis and is Traceable in the Circulating Extracellular Vesicles. | 15 |
| 31663854 | 2019 | A proline-rich motif on VGLUT1 reduces synaptic vesicle super-pool and spontaneous release frequency. | 10 |
| 29481784 | 2018 | Endophilin A1 mediates seizure activity via regulation of AMPARs in a PTZ-kindled epileptic mouse model. | 7 |
| 29481784 | 2018 | Endophilin A1 mediates seizure activity via regulation of AMPARs in a PTZ-kindled epileptic mouse model. | 7 |
| 28470949 | 2017 | Loss of SH3GL2 promotes the migration and invasion behaviours of glioblastoma cells through activating the STAT3/MMP2 signalling. | 14 |
Citation
Chinmay Kr Panda ; Amlan Ghosh ; Guru Prasad Maiti
SH3GL2 (SH3-domain GRB2-like 2)
Atlas Genet Cytogenet Oncol Haematol. 2009-03-01
Online version: http://atlasgeneticsoncology.org/gene/44345/sh3gl2
