DAB2IP is a Ras GTPase-activating protein (GAP) that acts as a tumor suppressor gene and is inactivated by methylation in prostate and breast cancers. It also interacts with MAP3K5 to disrupt the association of MAP3K5 with the inhibitory 14-3-3 complex.
Function:
Functions as a Ras GTPase-activating protein (By similarity). Through its interaction with MAP3K5 disrupts the association of MAP3K5 with the inhibitory 14-3-3 complex. Mediates TNF/TRAF2-induced MAP3K5-JNK activation, while it inhibits CHUK-NF-kappa-B signaling. May act as a tumor suppressor gene.
Subunit:
Interacts with MAP3K5, preferentially with its 'Ser-966' dephosphorylated form. On plasma membrane, exists in an inactive form complexed with TNFR1. In response to TNF, dissociates from TNFR1 complex, tranlocates to cytoplasm and forms part of an intracellular signaling complex comprising TRADD, RALBP1, TRAF2 and MAP3K5. Binding to MAP3K5 is induced by TNF. Interacts with DAB1 and DAB2 (By similarity). Part of a cytoplasmic complex made of HIPK1, DAB2IP and MAP3K5 in response to TNF. This complex formation promotes MAP3K5-JNK activation and subsequent apoptosis.
Subcellular Location:
Membrane. Cytoplasm. Note=Translocates to the cytoplasm in response to TNF.
Tissue Specificity:
Low expression in prostate. Down-regulated in prostate cancer.
DISEASE:
Note=A chromosomal aberration involving DAB2IP is found in a patient with acute myeloid leukemia (AML). Translocation t(9;11)(q34;q23) with MLL. May give rise to a MLL-DAB2IP fusion protein lacking the PH domain.
Similarity:
Contains 1 C2 domain.
Contains 1 PH domain.
Contains 1 Ras-GAP domain.
SWISS:
Q5VWQ8
Gene ID:
153090
Database links:
Entrez Gene: 153090 Human
Entrez Gene: 69601 Mouse
Entrez Gene: 192126 Rat
Omim: 609205 Human
SwissProt: Q5VWQ8 Human
SwissProt: Q3UHC7 Mouse
SwissProt: Q6P730 Rat
Unigene: 522378 Human
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