SORBS2 (sorbin and SH3 domain containing 2)

2008-08-01   Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers; CHU Poitiers Hospital, F-86021 Poitiers, France

Identity

HGNC
LOCATION
4q35.1
LOCUSID
ALIAS
ARGBP2,PRO0618
FUSION GENES

DNA/RNA

Transcription

Various transcripts.

Proteins

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

Entity name
t(4;11)(q35;q23) in acute myeloid leukemia --> SORBS2 - KMT2A
Hybrid gene
5 MLL - 3 SORBS2
Entity name
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

Pubmed IDLast YearTitleAuthors
156595452005The Abl/Arg substrate ArgBP2/nArgBP2 coordinates the function of multiple regulatory mechanisms converging on the actin cytoskeleton.Cestra G et al
151288732004Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites.Haglund K et al
159496472005Human sorbin is generated via splicing of an alternative transcript from the ArgBP2 gene locus.Hand D et al
147291792004How do Abl family kinases regulate cell shape and movement?Hernández SE et al
105214851999nArgBP2, a novel neural member of ponsin/ArgBP2/vinexin family that interacts with synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP).Kawabe H et al
114814762001The sorbin homology domain: a motif for the targeting of proteins to lipid rafts.Kimura A et al
119377132002Vinexin, CAP/ponsin, ArgBP2: a novel adaptor protein family regulating cytoskeletal organization and signal transduction.Kioka N et al
166281912006ArgBP2, 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 et al
161251692005Involvement of palladin and alpha-actinin in targeting of the Abl/Arg kinase adaptor ArgBP2 to the actin cytoskeleton.Rönty M et al
124753932003Cbl-ArgBP2 complex mediates ubiquitination and degradation of c-Abl.Soubeyran P et al
185595032008ArgBP2-dependent signaling regulates pancreatic cell migration, adhesion, and tumorigenicity.Taieb D et al
19153771991Isolation and characterisation of porcine sorbin.Vagne-Descroix M et al
9211901977[Natural transmission of Schistosoma mansoni in Guadeloupe (French Antilles). Preliminary note (author's transl)].Golvan YJ et al
157846222005ArgBP2gamma interacts with Akt and p21-activated kinase-1 and promotes cell survival.Yuan ZQ et al

Other Information

Locus ID:

NCBI: 8470
MIM: 616349
HGNC: 24098
Ensembl: ENSG00000154556

Variants:

dbSNP: 8470
ClinVar: 8470
TCGA: ENSG00000154556
COSMIC: SORBS2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000154556ENST00000284776O94875
ENSG00000154556ENST00000319454H7BXR3
ENSG00000154556ENST00000319471O94875
ENSG00000154556ENST00000355634O94875
ENSG00000154556ENST00000393523A0A1D5RMN3
ENSG00000154556ENST00000393528O94875
ENSG00000154556ENST00000414724C9JDX2
ENSG00000154556ENST00000415274C9JBB0
ENSG00000154556ENST00000418609O94875
ENSG00000154556ENST00000419063C9JN77
ENSG00000154556ENST00000420158C9J4Z9
ENSG00000154556ENST00000421420C9JWC3
ENSG00000154556ENST00000421639C9J9D3
ENSG00000154556ENST00000425679C9JC90
ENSG00000154556ENST00000428330C9JM25
ENSG00000154556ENST00000429056C9JI79
ENSG00000154556ENST00000430503C9J348
ENSG00000154556ENST00000431902C9JBB0
ENSG00000154556ENST00000432655C9JZ60
ENSG00000154556ENST00000435480C9JBB0
ENSG00000154556ENST00000437304O94875
ENSG00000154556ENST00000438278H7BZK1
ENSG00000154556ENST00000439049C9JFS9
ENSG00000154556ENST00000439914C9JL62
ENSG00000154556ENST00000444771C9J3W4
ENSG00000154556ENST00000444781C9JEA9
ENSG00000154556ENST00000445115C9J7Q5
ENSG00000154556ENST00000445343C9IZ89
ENSG00000154556ENST00000445625H7BZX1
ENSG00000154556ENST00000448662O94875
ENSG00000154556ENST00000449407O94875
ENSG00000154556ENST00000450341C9JBR8
ENSG00000154556ENST00000451701C9JG84
ENSG00000154556ENST00000451958C9J620
ENSG00000154556ENST00000451974H7C1R7
ENSG00000154556ENST00000452351C9IZT7
ENSG00000154556ENST00000456060C9JLD6
ENSG00000154556ENST00000456596C9J8E3
ENSG00000154556ENST00000457247C9J4K2
ENSG00000154556ENST00000457934C9J372
ENSG00000154556ENST00000650145A0A3B3ITL8

Expression (GTEx)

0
50
100
150
200

References

Pubmed IDYearTitleCitations
192400612009Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.75
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
124753932003Cbl-ArgBP2 complex mediates ubiquitination and degradation of c-Abl.26
263592332015SORBS2 transcription is activated by telomere position effect-over long distance upon telomere shortening in muscle cells from patients with facioscapulohumeral dystrophy.24
185595032008ArgBP2-dependent signaling regulates pancreatic cell migration, adhesion, and tumorigenicity.19
243429962013Sorbin and SH3 domain-containing protein 2 is released from infarcted heart in the very early phase: proteomic analysis of cardiac tissues from patients.18
262142762015Genetic Modifiers of Age at Onset in Carriers of the G206A Mutation in PSEN1 With Familial Alzheimer Disease Among Caribbean Hispanics.15
196314502010CIP4 is a new ArgBP2 interacting protein that modulates the ArgBP2 mediated control of WAVE1 phosphorylation and cancer cell migration.11
254291092015Arg kinase-binding protein 2 (ArgBP2) interaction with α-actinin and actin stress fibers inhibits cell migration.10
208866122010Arg/Abl-binding protein, a Z-body and Z-band protein, binds sarcomeric, costameric, and signaling molecules.9

Citation

Jean-Loup Huret

SORBS2 (sorbin and SH3 domain containing 2)

Atlas Genet Cytogenet Oncol Haematol. 2008-08-01

Online version: http://atlasgeneticsoncology.org/gene/693/sorbs2