Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q5VWQ8 (DAB2P_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Disabled homolog 2-interacting protein

Short name=DAB2 interaction protein
Short name=DAB2-interacting protein
Alternative name(s):
ASK-interacting protein 1
Short name=AIP-1
DOC-2/DAB-2 interactive protein
Gene names
Name:DAB2IP
Synonyms:AF9Q34, AIP1, KIAA1743
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1189 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Functions as a scaffold protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Involved in several processes such as innate immune response, inflammation and cell growth inhibition, apoptosis, cell survival, angiogenesis, cell migration and maturation. Plays also a role in cell cycle checkpoint control; reduces G1 phase cyclin levels resulting in G0/G1 cell cycle arrest. Mediates signal transduction by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF), interferon (IFN) or lipopolysaccharide (LPS). Modulates the balance between phosphatidylinositol 3-kinase (PI3K)-AKT-mediated cell survival and apoptosis stimulated kinase (MAP3K5)-JNK signaling pathways; sequesters both AKT1 and MAP3K5 and counterbalances the activity of each kinase by modulating their phosphorylation status in response to proinflammatory stimuli. Acts as a regulator of the endoplasmic reticulum (ER) unfolded protein response (UPR) pathway; specifically involved in transduction of the ER stress-response to the JNK cascade through ERN1. Mediates TNF-alpha-induced apoptosis activation by facilitating dissociation of inhibitor 14-3-3 from MAP3K5; recruits the PP2A phosphatase complex which dephosphorylates MAP3K5 on 'Ser-966', leading to the dissociation of 13-3-3 proteins and activation of the MAP3K5-JNK signaling pathway in endothelial cells. Mediates also TNF/TRAF2-induced MAP3K5-JNK activation, while it inhibits CHUK-NF-kappa-B signaling. Acts a negative regulator in the IFN-gamma-mediated JAK-STAT signaling cascade by inhibiting smooth muscle cell (VSMCs) proliferation and intimal expansion, and thus, prevents graft arteriosclerosis (GA). Acts as a GTPase-activating protein (GAP) for the ADP ribosylation factor 6 (ARF6) and Ras. Promotes hydrolysis of the ARF6-bound GTP and thus, negatively regulates phosphatidylinositol 4,5-bisphosphate (PIP2)-dependent TLR4-TIRAP-MyD88 and NF-kappa-B signaling pathways in endothelial cells in response to lipopolysaccharides (LPS). Binds specifically to phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 3-phosphate (PtdIns3P). In response to vascular endothelial growth factor (VEGFA), acts as a negative regulator of the VEGFR2-PI3K-mediated angiogenic signaling pathway by inhibiting endothelial cell migration and tube formation. In the developing brain, promotes both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex in a glial-dependent locomotion process. Probable downstream effector of the Reelin signaling pathway; promotes Purkinje cell (PC) dendrites development and formation of cerebellar synapses. Functions also as a tumor suppressor protein in prostate cancer progression; prevents cell proliferation and epithelial-to-mesenchymal transition (EMT) through activation of the glycogen synthase kinase-3 beta (GSK3B)-induced beta-catenin and inhibition of PI3K-AKT and Ras-MAPK survival downstream signaling cascades, respectively. Ref.8 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 Ref.22

Subunit structure

On plasma membrane, exists in an inactive form complexed with TNFR1; in response to TNF-alpha, dissociates from TNFR1 complex, tranlocates to cytoplasm and forms part of an intracellular signaling complex comprising TRADD, RALBP1, TRAF2 and MAP3K5. Interacts with DAB1. Interacts (via NPXY motif) with DAB2 (via PID domain). Interacts (via PH domain) with ERN1 By similarity. Part of a cytoplasmic complex made of HIPK1, DAB2IP and MAP3K5 in response to TNF-alpha; this complex formation promotes MAP3K5-JNK activation and subsequent apoptosis. Interacts (via N-terminal domain) with JAK2; the interaction occurs in a IFNG/IFN-gamma-dependent manner and inhibits JAK2 autophosphorylation activity. Interacts (via C2 domain) with GSK3B; the interaction stimulates GSK3B kinase activation. Interacts (via C2 domain) with PPP2CA. Interacts (via proline-rich motif) with a regulatory p85 subunit (via SH3 domain) of the PI3K complex; the interaction inhibits the PI3K-AKT complex activity in a TNF-alpha-dependent manner in prostate cancer (PCa) cells. Interacts with AKT1; the interaction is increased in a TNF-alpha-induced manner. Interacts (via C2 domain and active form preferentially) with KDR/VEGFR2 (tyrosine-phosphorylated active form preferentially); the interaction occurs at the late phase of VEGFA response and inhibits KDR/VEGFR2 activity. Interacts (via N-terminus C2 domain) with MAP3K5 ('Ser-966' dephosphorylated form preferentially); the interaction occurs in a TNF-alpha-induced manner. Interacts (via Ras-GAP domain) with the catalytic subunit of protein phosphatase PP2A; the interaction occurs in resting endothelial cells, is further enhanced by TNF-alpha stimulation and is required to bridge PP2A to MAP3K5. Interacts (via C-terminus PER domain) with TRAF2 (via zinc fingers); the interaction occurs in a TNF-alpha-dependent manner. Interacts with 14-3-3 proteins; the interaction occurs in a TNF-alpha-dependent manner. Interacts (via Ras-GAP domain) with RIPK1 (via kinase domain); the interaction occurs in a TNF-alpha-dependent manner. Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.15 Ref.16 Ref.18 Ref.20

Subcellular location

Cytoplasm. Cell membrane; Peripheral membrane protein Potential. Membrane. Cell projectiondendrite By similarity. Note: Localized in soma and dendrites of Purkinje cells as well as in scattered cell bodies in the molecular layer of the cerebellum By similarity. Colocalizes with TIRAP at the plasma membrane. Colocalizes with ARF6 at the plasma membrane and endocytic vesicles. Translocates from the plasma membrane to the cytoplasm in response to TNF-alpha. Phosphatidylinositol 4-phosphate (PtdIns4P) binding is essential for plasma membrane localization. Ref.9 Ref.10 Ref.16

Tissue specificity

Expressed in endothelial and vascular smooth muscle cells (VSMCs). Expressed in prostate epithelial but poorly in prostate cancer cells. Poorly expressed in medulloblastoma cells compared to cerebellar precursor proliferating progenitor cells (at protein level). Low expression in prostate. Down-regulated in prostate cancer. Ref.1 Ref.11 Ref.20 Ref.22

Induction

Down-regulated in prostate cancer and medulloblastoma. Ref.17 Ref.22

Domain

The C2 and Ras-GAP domains constitutively bind to MAP3K5 and facilitate the release of 14-3-3 proteins from MAP3K5. The PH and Ras-GAP domains, but not the NPXY motif, are crucial for its cell membrane localization and neuronal migration function. The PH domain is necessary but not sufficient to activate the JNK signaling pathway through ERN1 By similarity. Exists in a closed inactive form by an intramolecular interaction between the N- and the C-terminal domains. The proline-rich motif is critical both for PI3K-AKT activity inhibition and MAP3K5 activation. The PH and C2 domains are necessary for the binding to phosphatidylinositol phosphate. The Ras-GAP domain is necessary for its tumor-suppressive function.

Post-translational modification

In response to TNF-alpha-induction, phosphorylated at Ser-728; phosphorylation leads to a conformational change, and thus, increases its association with 14-3-3 proteins, MAP3K5, RIPK1 and TRAF2 in endothelial cells; also stimulates regulatory p85 subunit sequestring and PI3K-p85 complex activity inhibition. Ref.11 Ref.15

Involvement in disease

A chromosomal aberration involving DAB2IP is found in a patient with acute myeloid leukemia (AML). Translocation t(9;11)(q34;q23) with KMT2A/MLL1. May give rise to a KMT2A/MLL1-DAB2IP fusion protein lacking the PH domain.

Miscellaneous

The DAB2IP gene is found epigenetically silenced in numerous aggressive cancers, like prostate cancers and medulloblastoma tumors. Epigenetic suppression of DAB2IP by EZH2 is a major mechanism of DAB2IP inactivation in human prostate cancer and increases metastatic potential (Ref.17, Ref.22).

Sequence similarities

Contains 1 C2 domain.

Contains 1 PH domain.

Contains 1 Ras-GAP domain.

Sequence caution

The sequence CAH72155.3 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Biological processAngiogenesis
Apoptosis
Cell cycle
Growth regulation
Immunity
Inflammatory response
Innate immunity
Stress response
Unfolded protein response
   Cellular componentCell membrane
Cell projection
Cytoplasm
Membrane
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
Polymorphism
   DiseaseTumor suppressor
   DomainCoiled coil
   Molecular functionDevelopmental protein
GTPase activation
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processI-kappaB phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

activation of JUN kinase activity

Inferred from direct assay Ref.8. Source: BHF-UCL

activation of MAPKKK activity

Inferred from direct assay Ref.15. Source: UniProtKB

angiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

cell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

cell motility involved in cerebral cortex radial glia guided migration

Inferred from sequence or structural similarity. Source: UniProtKB

cellular protein catabolic process

Inferred from direct assay Ref.11. Source: UniProtKB

cellular response to epidermal growth factor stimulus

Inferred from sequence or structural similarity PubMed 11812785. Source: BHF-UCL

cellular response to interleukin-1

Inferred from direct assay Ref.16. Source: UniProtKB

cellular response to lipopolysaccharide

Inferred from direct assay Ref.16. Source: UniProtKB

cellular response to tumor necrosis factor

Inferred from direct assay Ref.11. Source: UniProtKB

cellular response to vascular endothelial growth factor stimulus

Inferred from direct assay Ref.13. Source: UniProtKB

endothelial cell apoptotic process

Traceable author statement Ref.15. Source: BHF-UCL

extrinsic apoptotic signaling pathway via death domain receptors

Inferred from mutant phenotype Ref.15. Source: BHF-UCL

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress

Inferred from sequence or structural similarity PubMed 18281285. Source: BHF-UCL

layer formation in cerebral cortex

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of ERK1 and ERK2 cascade

Inferred from direct assay Ref.15. Source: UniProtKB

negative regulation of G0 to G1 transition

Inferred from direct assay Ref.15. Source: UniProtKB

negative regulation of GTPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from direct assay Ref.11. Source: UniProtKB

negative regulation of MAP kinase activity

Inferred from direct assay Ref.8. Source: BHF-UCL

negative regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype Ref.17. Source: BHF-UCL

negative regulation of Ras GTPase activity

Inferred from mutant phenotype Ref.17. Source: BHF-UCL

negative regulation of Ras protein signal transduction

Inferred by curator Ref.17. Source: BHF-UCL

negative regulation of angiogenesis

Inferred from direct assay Ref.13. Source: UniProtKB

negative regulation of canonical Wnt signaling pathway

Inferred from mutant phenotype Ref.18. Source: BHF-UCL

negative regulation of catenin import into nucleus

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from direct assay Ref.15. Source: UniProtKB

negative regulation of cyclin catabolic process

Inferred from direct assay Ref.15. Source: UniProtKB

negative regulation of endothelial cell migration

Inferred from mutant phenotype Ref.13. Source: UniProtKB

negative regulation of epidermal growth factor receptor signaling pathway

Inferred from sequence or structural similarity PubMed 11812785. Source: BHF-UCL

negative regulation of epithelial cell migration

Inferred from mutant phenotype Ref.18. Source: UniProtKB

negative regulation of epithelial cell proliferation

Inferred from mutant phenotype Ref.17. Source: BHF-UCL

negative regulation of epithelial to mesenchymal transition

Inferred from direct assay Ref.17. Source: UniProtKB

negative regulation of fibroblast proliferation

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of phosphatidylinositol 3-kinase activity

Inferred from direct assay Ref.15. Source: UniProtKB

negative regulation of phosphatidylinositol 3-kinase signaling

Inferred from direct assay Ref.15. Source: UniProtKB

negative regulation of protein phosphorylation

Inferred from mutant phenotype Ref.18. Source: UniProtKB

negative regulation of protein serine/threonine kinase activity

Inferred from direct assay Ref.15. Source: UniProtKB

negative regulation of toll-like receptor 4 signaling pathway

Inferred from direct assay Ref.16. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.9. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from mutant phenotype Ref.18. Source: UniProtKB

negative regulation of vascular endothelial growth factor receptor signaling pathway

Inferred from mutant phenotype Ref.13. Source: UniProtKB

negative regulation of vascular endothelial growth factor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

neuron projection morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of JNK cascade

Inferred from direct assay Ref.11Ref.15. Source: UniProtKB

positive regulation of JUN kinase activity

Inferred from direct assay Ref.9. Source: BHF-UCL

positive regulation of MAPK cascade

Inferred from direct assay Ref.15. Source: UniProtKB

positive regulation of Ras GTPase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of apoptotic process

Inferred from direct assay Ref.11Ref.15. Source: UniProtKB

positive regulation of apoptotic signaling pathway

Inferred from direct assay Ref.15. Source: UniProtKB

positive regulation of cell cycle arrest

Inferred from direct assay Ref.15. Source: UniProtKB

positive regulation of dendrite development

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neuron migration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of proteasomal protein catabolic process

Inferred from mutant phenotype Ref.18. Source: UniProtKB

positive regulation of protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein serine/threonine kinase activity

Inferred from direct assay Ref.15. Source: UniProtKB

positive regulation of synapse maturation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.11. Source: UniProtKB

regulation of ARF GTPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of p38MAPK cascade

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of protein complex assembly

Inferred from direct assay Ref.16. Source: UniProtKB

response to unfolded protein

Inferred from electronic annotation. Source: UniProtKB-KW

transformed cell apoptotic process

Traceable author statement Ref.15. Source: BHF-UCL

tube formation

Inferred from mutant phenotype Ref.13. Source: UniProtKB

vascular endothelial growth factor receptor-2 signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentaxon

Inferred from sequence or structural similarity. Source: UniProtKB

cerebellar mossy fiber

Inferred from sequence or structural similarity. Source: UniProtKB

climbing fiber

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.16. Source: UniProtKB

dendrite

Inferred from electronic annotation. Source: UniProtKB-SubCell

endocytic vesicle

Inferred from direct assay Ref.16. Source: UniProtKB

intrinsic component of the cytoplasmic side of the plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

neuronal cell body

Inferred from sequence or structural similarity. Source: UniProtKB

neuronal cell body membrane

Inferred from sequence or structural similarity. Source: UniProtKB

parallel fiber

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.16. Source: UniProtKB

   Molecular_function14-3-3 protein binding

Inferred from direct assay Ref.11. Source: BHF-UCL

Ras GTPase activator activity

Inferred from sequence or structural similarity. Source: BHF-UCL

SH3 domain binding

Inferred from direct assay Ref.13Ref.15. Source: UniProtKB

death receptor binding

Inferred from physical interaction Ref.9. Source: BHF-UCL

identical protein binding

Inferred from physical interaction Ref.8. Source: IntAct

kinase binding

Inferred from physical interaction Ref.11. Source: UniProtKB

mitogen-activated protein kinase kinase binding

Inferred from physical interaction Ref.11. Source: UniProtKB

mitogen-activated protein kinase kinase kinase binding

Inferred from physical interaction Ref.8. Source: BHF-UCL

phosphatidylinositol 3-kinase binding

Inferred from direct assay Ref.13. Source: UniProtKB

phosphatidylinositol 3-kinase regulatory subunit binding

Inferred from direct assay Ref.15. Source: UniProtKB

phosphatidylinositol-3-phosphate binding

Inferred from direct assay Ref.16. Source: UniProtKB

phosphatidylinositol-4-phosphate binding

Inferred from direct assay Ref.16. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.11Ref.15Ref.18. Source: UniProtKB

protein complex binding

Inferred from direct assay Ref.15. Source: UniProtKB

protein homodimerization activity

Inferred from physical interaction Ref.8. Source: BHF-UCL

protein kinase binding

Inferred from physical interaction Ref.18. Source: BHF-UCL

protein phosphatase 2A binding

Inferred from direct assay Ref.18. Source: BHF-UCL

signaling adaptor activity

Inferred from direct assay Ref.18. Source: BHF-UCL

vascular endothelial growth factor receptor 2 binding

Inferred from physical interaction Ref.13. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself2EBI-2871881,EBI-2871881
MAP3K5Q996832EBI-2871881,EBI-476263

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q5VWQ8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Note: Gene prediction based on EST data.
Isoform 2 (identifier: Q5VWQ8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-124: Missing.
Isoform 3 (identifier: Q5VWQ8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-193: Missing.
     1158-1189: RYSMQARNGISPTNPTKLQITENGEFRNSSNC → SMH
Isoform 4 (identifier: Q5VWQ8-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-124: Missing.
     1158-1189: RYSMQARNGISPTNPTKLQITENGEFRNSSNC → SMH
Isoform 5 (identifier: Q5VWQ8-5)

The sequence of this isoform differs from the canonical sequence as follows:
     2-41: SAGGSARKSTGRSSYYYRLLRRPRLQRQRSRSRSRTRPAR → EPDSLLDQDDSY
     1158-1189: RYSMQARNGISPTNPTKLQITENGEFRNSSNC → SMH
Note: Gene prediction based on EST data.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11891189Disabled homolog 2-interacting protein
PRO_0000252407

Regions

Domain101 – 202102PH
Domain200 – 29596C2
Domain371 – 563193Ras-GAP
Region646 – 943298Necessary for interaction with AKT1
Coiled coil1026 – 1159134 Potential
Compositional bias8 – 5245Arg-rich
Compositional bias112 – 1176Poly-Ala
Compositional bias867 – 8704Poly-Ala
Compositional bias903 – 94846Pro-rich

Sites

Site172 – 1732Breakpoint for translocation to form KMT2A/MLL1-DAB2IP

Amino acid modifications

Modified residue7281Phosphoserine; by MAP3K5 and RIPK1 Ref.11 Ref.15
Modified residue9781Phosphoserine Ref.21

Natural variations

Alternative sequence1 – 193193Missing in isoform 3.
VSP_020952
Alternative sequence1 – 124124Missing in isoform 2 and isoform 4.
VSP_020953
Alternative sequence2 – 4140SAGGS…TRPAR → EPDSLLDQDDSY in isoform 5.
VSP_047361
Alternative sequence1158 – 118932RYSMQ…NSSNC → SMH in isoform 3, isoform 4 and isoform 5.
VSP_020954
Natural variant591S → F.
Corresponds to variant rs7027492 [ dbSNP | Ensembl ].
VAR_056858

Experimental info

Mutagenesis228 – 2303KKK → AAA: Reduces interaction with KDR/VEGFR2. Does not inhibit interaction with MAP3K5. Ref.8 Ref.13
Mutagenesis281 – 2844KKKK → AAAA: Significantly reduces interaction with MAP3K5. Does not reduce interaction with KDR/VEGFR2. Ref.8 Ref.13
Mutagenesis4131R → L: Does not inhibit interaction with MAP3K5. Does not reduce GSK3B-induced beta-catenin transcription activity, TNF-alpha-induced apoptosis, ARF6-mediated TLR4-TIRAP-MyD88 signaling inhibition, Ras and NF-kappa-B activities and tumor development. Does not suppress tumor development; when associated with A-728. Ref.8 Ref.15 Ref.16 Ref.17
Mutagenesis7281S → A: Inhibits phosphorylation and TNF-alpha-induced MAP3K5 dephosphorylation. Reduces interaction with 14-3-3 proteins, AKT1, a regulatory p85 subunit, MAP3K5, RIPK1, TRAF2 and TNF-alpha-induced MAP3K5-JNK signaling and apoptosis. Reduces RAS activity. Does not reduce GSK3B-induced beta catenin-mediated transcription activity. Does not reduce NF-kappa-B activity, cell invasion, epithelial-to-mesenchymal transition (EMT) and tumor development. Does not suppress tumor development; when associated with R-413. Ref.11 Ref.12 Ref.15 Ref.17
Mutagenesis920 – 92910PPPPPPPPPP → AAAAAAAAAA: Reduces interaction with a regulatory p85 subunit of the PI3K complex. Inhibits MAP3K5 active form increase, AKT1 active form decrease, PI3K-p85 complex activity inhibition and TNF-induced apoptosis. Ref.15
Mutagenesis9351T → A: Does not reduce interaction with 14-3-3 proteins. Ref.11
Sequence conflict4821I → T in AAM00371. Ref.1
Sequence conflict9211P → S in AAM00371. Ref.1
Sequence conflict1091 – 10922QQ → HE in AAM00371. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 17, 2006. Version 2.
Checksum: 7494FF05AACF3320

FASTA1,189131,625
        10         20         30         40         50         60 
MSAGGSARKS TGRSSYYYRL LRRPRLQRQR SRSRSRTRPA RESPQERPGS RRSLPGSLSE 

        70         80         90        100        110        120 
KSPSMEPSAA TPFRVTGFLS RRLKGSIKRT KSQPKLDRNH SFRHILPGFR SAAAAAADNE 

       130        140        150        160        170        180 
RSHLMPRLKE SRSHESLLSP SSAVEALDLS MEEEVVIKPV HSSILGQDYC FEVTTSSGSK 

       190        200        210        220        230        240 
CFSCRSAAER DKWMENLRRA VHPNKDNSRR VEHILKLWVI EAKDLPAKKK YLCELCLDDV 

       250        260        270        280        290        300 
LYARTTGKLK TDNVFWGEHF EFHNLPPLRT VTVHLYRETD KKKKKERNSY LGLVSLPAAS 

       310        320        330        340        350        360 
VAGRQFVEKW YPVVTPNPKG GKGPGPMIRI KARYQTITIL PMEMYKEFAE HITNHYLGLC 

       370        380        390        400        410        420 
AALEPILSAK TKEEMASALV HILQSTGKVK DFLTDLMMSE VDRCGDNEHL IFRENTLATK 

       430        440        450        460        470        480 
AIEEYLKLVG QKYLQDALGE FIKALYESDE NCEVDPSKCS AADLPEHQGN LKMCCELAFC 

       490        500        510        520        530        540 
KIINSYCVFP RELKEVFASW RQECSSRGRP DISERLISAS LFLRFLCPAI MSPSLFNLLQ 

       550        560        570        580        590        600 
EYPDDRTART LTLIAKVTQN LANFAKFGSK EEYMSFMNQF LEHEWTNMQR FLLEISNPET 

       610        620        630        640        650        660 
LSNTAGFEGY IDLGRELSSL HSLLWEAVSQ LEQSIVSKLG PLPRILRDVH TALSTPGSGQ 

       670        680        690        700        710        720 
LPGTNDLAST PGSGSSSISA GLQKMVIEND LSGLIDFTRL PSPTPENKDL FFVTRSSGVQ 

       730        740        750        760        770        780 
PSPARSSSYS EANEPDLQMA NGGKSLSMVD LQDARTLDGE AGSPAGPDVL PTDGQAAAAQ 

       790        800        810        820        830        840 
LVAGWPARAT PVNLAGLATV RRAGQTPTTP GTSEGAPGRP QLLAPLSFQN PVYQMAAGLP 

       850        860        870        880        890        900 
LSPRGLGDSG SEGHSSLSSH SNSEELAAAA KLGSFSTAAE ELARRPGELA RRQMSLTEKG 

       910        920        930        940        950        960 
GQPTVPRQNS AGPQRRIDQP PPPPPPPPPA PRGRTPPNLL STLQYPRPSS GTLASASPDW 

       970        980        990       1000       1010       1020 
VGPSTRLRQQ SSSSKGDSPE LKPRAVHKQG PSPVSPNALD RTAAWLLTMN AQLLEDEGLG 

      1030       1040       1050       1060       1070       1080 
PDPPHRDRLR SKDELSQAEK DLAVLQDKLR ISTKKLEEYE TLFKCQEETT QKLVLEYQAR 

      1090       1100       1110       1120       1130       1140 
LEEGEERLRR QQEDKDIQMK GIISRLMSVE EELKKDHAEM QAAVDSKQKI IDAQEKRIAS 

      1150       1160       1170       1180 
LDAANARLMS ALTQLKERYS MQARNGISPT NPTKLQITEN GEFRNSSNC 

« Hide

Isoform 2 [UniParc].

Checksum: 4787F41F02108AA3
Show »

FASTA1,065117,651
Isoform 3 [UniParc].

Checksum: E69CEB1FB00A2219
Show »

FASTA967106,764
Isoform 4 [UniParc].

Checksum: 1B07D8D3B9DEA76A
Show »

FASTA1,036114,410
Isoform 5 [UniParc].

Checksum: 85C487CD98660B19
Show »

FASTA1,132125,041

References

« Hide 'large scale' references
[1]"Differential regulation of the human gene DAB2IP in normal and malignant prostatic epithelia: cloning and characterization."
Chen H., Pong R.-C., Wang Z., Hsieh J.-T.
Genomics 79:573-581(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY.
[2]"Identification of a novel RAS GTPase-activating protein (RASGAP) gene at 9q34 as an MLL fusion partner in a patient with de novo acute myeloid leukemia."
von Bergh A.R.M., Wijers P.M., Groot A.J., van Zelderen-Bhola S., Falkenburg J.H.F., Kluin P.M., Schuuring E.
Genes Chromosomes Cancer 39:324-334(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), CHROMOSOMAL TRANSLOCATION WITH KMT2A/MLL1.
[3]"Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.
DNA Res. 7:347-355(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Tissue: Brain.
[4]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[5]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
[8]"AIP1 mediates TNF-alpha-induced ASK1 activation by facilitating dissociation of ASK1 from its inhibitor 14-3-3."
Zhang R., He X., Liu W., Lu M., Hsieh J.-T., Min W.
J. Clin. Invest. 111:1933-1943(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MAP3K5, MUTAGENESIS OF 228-LYS--LYS-230; 281-LYS--LYS-284 AND ARG-413.
[9]"AIP1/DAB2IP, a novel member of the Ras-GAP family, transduces TRAF2-induced ASK1-JNK activation."
Zhang H., Zhang R., Luo Y., D'Alessio A., Pober J.S., Min W.
J. Biol. Chem. 279:44955-44965(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH TNFR1; MAP3K5; TRADD; RALBP1 AND TRAF2.
[10]"Tumor necrosis factor alpha-induced desumoylation and cytoplasmic translocation of homeodomain-interacting protein kinase 1 are critical for apoptosis signal-regulating kinase 1-JNK/p38 activation."
Li X., Zhang R., Luo D., Park S.-J., Wang Q., Kim Y., Min W.
J. Biol. Chem. 280:15061-15070(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIPK1, SUBCELLULAR LOCATION.
[11]"RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site is critical for tumor necrosis factor-induced ASK1-JNK/p38 activation."
Zhang H., Zhang H., Lin Y., Li J., Pober J.S., Min W.
J. Biol. Chem. 282:14788-14796(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH 14-3-3 PROTEINS; MAP3K5; RIPK1 AND TRAF2, PHOSPHORYLATION AT SER-728, MUTAGENESIS OF SER-728 AND THR-935, TISSUE SPECIFICITY.
[12]"AIP1 recruits phosphatase PP2A to ASK1 in tumor necrosis factor-induced ASK1-JNK activation."
Min W., Lin Y., Tang S., Yu L., Zhang H., Wan T., Luhn T., Fu H., Chen H.
Circ. Res. 102:840-848(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF SER-728.
[13]"AIP1 functions as an endogenous inhibitor of VEGFR2-mediated signaling and inflammatory angiogenesis in mice."
Zhang H., He Y., Dai S., Xu Z., Luo Y., Wan T., Luo D., Jones D., Tang S., Chen H., Sessa W.C., Min W.
J. Clin. Invest. 118:3904-3916(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH KDR AND P85 SUBUNIT OF PI3K, MUTAGENESIS OF 228-LYS--LYS-230 AND 281-LYS--LYS-284.
[14]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell survival and apoptosis."
Xie D., Gore C., Zhou J., Pong R.C., Zhang H., Yu L., Vessella R.L., Min W., Hsieh J.T.
Proc. Natl. Acad. Sci. U.S.A. 106:19878-19883(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH AKT1 AND P85 SUBUNIT OF PI3K, PHOSPHORYLATION AT SER-728, MUTAGENESIS OF ARG-413; SER-728 AND 920-PRO--PRO-929.
[16]"AIP1 functions as Arf6-GAP to negatively regulate TLR4 signaling."
Wan T., Liu T., Zhang H., Tang S., Min W.
J. Biol. Chem. 285:3750-3757(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PHOSPHATIDYLINOSITOL, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-413.
[17]"An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-kappaB."
Min J., Zaslavsky A., Fedele G., McLaughlin S.K., Reczek E.E., De Raedt T., Guney I., Strochlic D.E., Macconaill L.E., Beroukhim R., Bronson R.T., Ryeom S., Hahn W.C., Loda M., Cichowski K.
Nat. Med. 16:286-294(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PROSTATE CANCER, INDUCTION, MUTAGENESIS OF ARG-413 AND SER-728.
[18]"Role of DAB2IP in modulating epithelial-to-mesenchymal transition and prostate cancer metastasis."
Xie D., Gore C., Liu J., Pong R.C., Mason R., Hao G., Long M., Kabbani W., Yu L., Zhang H., Chen H., Sun X., Boothman D.A., Min W., Hsieh J.T.
Proc. Natl. Acad. Sci. U.S.A. 107:2485-2490(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PROSTATE CANCER, INTERACTION WITH GSK3B AND PPP2CA.
[19]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"AIP1 prevents graft arteriosclerosis by inhibiting interferon-gamma-dependent smooth muscle cell proliferation and intimal expansion."
Yu L., Qin L., Zhang H., He Y., Chen H., Pober J.S., Tellides G., Min W.
Circ. Res. 109:418-427(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH JAK2, TISSUE SPECIFICITY.
[21]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-978, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]"EZH2-regulated DAB2IP is a medulloblastoma tumor suppressor and a positive marker for survival."
Smits M., van Rijn S., Hulleman E., Biesmans D., van Vuurden D.G., Kool M., Haberler C., Aronica E., Vandertop W.P., Noske D.P., Wurdinger T.
Clin. Cancer Res. 18:4048-4058(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MEDULLOBLASTOMA DEVELOPMENT, INDUCTION, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF367051 mRNA. Translation: AAM00371.1.
AY032952 mRNA. Translation: AAK50336.1.
AB051530 mRNA. Translation: BAB21834.2.
AL357936 Genomic DNA. No translation available.
AL365274 Genomic DNA. Translation: CAH72155.3. Sequence problems.
AL365274 Genomic DNA. Translation: CAQ10385.1.
AL365274 Genomic DNA. Translation: CAH72158.1.
CH471090 Genomic DNA. Translation: EAW87503.1.
CH471090 Genomic DNA. Translation: EAW87504.1.
BC146762 mRNA. Translation: AAI46763.1.
CCDSCCDS6832.1. [Q5VWQ8-2]
CCDS6833.2. [Q5VWQ8-5]
RefSeqNP_115941.2. NM_032552.3. [Q5VWQ8-5]
NP_619723.1. NM_138709.2. [Q5VWQ8-2]
XP_005251776.1. XM_005251719.2. [Q5VWQ8-1]
UniGeneHs.522378.

3D structure databases

ProteinModelPortalQ5VWQ8.
SMRQ5VWQ8. Positions 329-662.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid127478. 13 interactions.
DIPDIP-41721N.
IntActQ5VWQ8. 3 interactions.
MINTMINT-268247.
STRING9606.ENSP00000259371.

PTM databases

PhosphoSiteQ5VWQ8.

Polymorphism databases

DMDM116247768.

Proteomic databases

MaxQBQ5VWQ8.
PaxDbQ5VWQ8.
PRIDEQ5VWQ8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000259371; ENSP00000259371; ENSG00000136848. [Q5VWQ8-5]
ENST00000309989; ENSP00000310827; ENSG00000136848. [Q5VWQ8-2]
ENST00000408936; ENSP00000386183; ENSG00000136848. [Q5VWQ8-1]
GeneID153090.
KEGGhsa:153090.
UCSCuc004bln.3. human.
uc004blo.3. human. [Q5VWQ8-1]

Organism-specific databases

CTD153090.
GeneCardsGC09P124329.
HGNCHGNC:17294. DAB2IP.
HPAHPA036977.
MIM609205. gene.
neXtProtNX_Q5VWQ8.
PharmGKBPA27133.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG245428.
HOVERGENHBG006492.
InParanoidQ5VWQ8.
OMAEKGGQPT.
OrthoDBEOG74XS5P.
PhylomeDBQ5VWQ8.
TreeFamTF105303.

Gene expression databases

ArrayExpressQ5VWQ8.
BgeeQ5VWQ8.
CleanExHS_DAB2IP.
GenevestigatorQ5VWQ8.

Family and domain databases

Gene3D1.10.506.10. 1 hit.
2.30.29.30. 1 hit.
2.60.40.150. 1 hit.
InterProIPR000008. C2_dom.
IPR021887. DUF3498.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR001936. RasGAP.
IPR023152. RasGAP_CS.
IPR008936. Rho_GTPase_activation_prot.
[Graphical view]
PfamPF00168. C2. 1 hit.
PF12004. DUF3498. 1 hit.
PF00616. RasGAP. 1 hit.
[Graphical view]
SMARTSM00239. C2. 1 hit.
SM00233. PH. 1 hit.
SM00323. RasGAP. 1 hit.
[Graphical view]
SUPFAMSSF48350. SSF48350. 1 hit.
SSF49562. SSF49562. 1 hit.
PROSITEPS50003. PH_DOMAIN. 1 hit.
PS00509. RAS_GTPASE_ACTIV_1. 1 hit.
PS50018. RAS_GTPASE_ACTIV_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDAB2IP. human.
GeneWikiDAB2IP.
GenomeRNAi153090.
NextBio87071.
PROQ5VWQ8.
SOURCESearch...

Entry information

Entry nameDAB2P_HUMAN
AccessionPrimary (citable) accession number: Q5VWQ8
Secondary accession number(s): A6H8V2 expand/collapse secondary AC list , A6NHI9, B0QZB1, G3XA90, Q8TDL2, Q96SE1, Q9C0C0
Entry history
Integrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: October 17, 2006
Last modified: July 9, 2014
This is version 101 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM