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disabled homolog 2-interacting protein (DAB2-interacting protein, DAB2 interaction protein, ASK-interacting protein 1, DAB2IP, AF9Q34, AIP1, KIAA1743)
Function:
1) Ras GTPase-activating protein
2) on plasma membrane, exists in an inactive form complexed with TNFR1
- in response to TNF, dissociates from TNFR1 complex, tranlocates to cytoplasm & forms part of intracellular signaling complex comprising TRADD, RALBP1, TRAF2 & MAP3K5
- binding to MAP3K5 is induced by TNF
- preferentially binds Ser-966 dephosphorylated MAP3K5, & disrupts association of MAP3K5 with inhibitory 14-3-3 complex
- mediates TNF/TRAF2-induced MAP3K5-JNK activation
3) inhibits CHUK-NF-kappa-B signaling
4) tumor suppressor (putative)
5) interacts with DAB1 & DAB2
Structure:
- contains 1 C2 domain
- contains 1 PH domain
- contains 1 Ras-GAP domain
- C2 domain & Ras-GAP domain are required for interaction with MAP3K5
Compartment:
- membrane, cytoplasm
- translocates to cytoplasm in response to TNF
Alternative splicing: named isoforms=3
Expression:
- low expression in prostate
Pathology:
- down-regulated in prostate cancer
- chromosomal translocation t(9;11)(q34;q23) involving DAB2IP with MLL is found in a patient with acute myeloid leukemia
- gives rise to a MLL-DAB2IP fusion protein lacking the PH domain (putative)
General
ras GTPase activator protein (Ras p21 protein activator, p120, rasGAP, RASA1)
Properties
SIZE: MW = 132 kD
entity length = 1189 aa
COMPARTMENT: cytoplasm
MOTIF: arginine-rich region {8-52}
MOTIF: arginine residue (SEVERAL)
PH domain {101-202}
MOTIF: alanine-rich region {112-117}
MOTIF: alanine residue (SEVERAL)
Breakpoint for translocation to form MLL- DAB2IP {172-173}
C2 domain {200-295}
MOTIF: binding site
FOR-BINDING-OF: phospholipid
Ca+2-binding site
ras-GAP domain
NAME: ras-GAP domain
SITE: 371-563
Ser phosphorylation site {S702}
alanine-rich region {867-870}
MOTIF: alanine residue (SEVERAL)
proline-rich region
SITE: 903-948
MOTIF: proline residue (SEVERAL)
coiled coil {1026-1159}
Database Correlations
UniProt Q5VWQ8
References
- UniProt :accession Q5VWQ8
- Atlas of Genetics and Cytogenetics in Oncology and Haematology
http://atlasgeneticsoncology.org/Genes/AF9q34ID316.html