CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-014123
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Disabled homolog 2-interacting protein 
Protein Synonyms/Alias
 DAB2 interaction protein; DAB2-interacting protein; ASK-interacting protein 1; AIP-1; DOC-2/DAB-2 interactive protein 
Gene Name
 DAB2IP 
Gene Synonyms/Alias
 AF9Q34; AIP1; KIAA1743 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
223KLWVIEAKDLPAKKKacetylation[1]
1136KIIDAQEKRIASLDAubiquitination[2]
Reference
 [1] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 101 202 PH.
 DOMAIN 200 295 C2.
 DOMAIN 371 563 Ras-GAP.
 REGION 646 943 Necessary for interaction with AKT1.
 MOD_RES 702 702 Phosphoserine (By similarity).
 MOD_RES 728 728 Phosphoserine; by MAP3K5 and RIPK1.
 MOD_RES 978 978 Phosphoserine.  
Keyword
 Alternative splicing; Angiogenesis; Apoptosis; Cell cycle; Cell membrane; Cell projection; Chromosomal rearrangement; Coiled coil; Complete proteome; Cytoplasm; Developmental protein; Growth regulation; GTPase activation; Immunity; Inflammatory response; Innate immunity; Membrane; Phosphoprotein; Polymorphism; Reference proteome; Stress response; Tumor suppressor; Unfolded protein response. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1189 AA 
Protein Sequence
MSAGGSARKS TGRSSYYYRL LRRPRLQRQR SRSRSRTRPA RESPQERPGS RRSLPGSLSE 60
KSPSMEPSAA TPFRVTGFLS RRLKGSIKRT KSQPKLDRNH SFRHILPGFR SAAAAAADNE 120
RSHLMPRLKE SRSHESLLSP SSAVEALDLS MEEEVVIKPV HSSILGQDYC FEVTTSSGSK 180
CFSCRSAAER DKWMENLRRA VHPNKDNSRR VEHILKLWVI EAKDLPAKKK YLCELCLDDV 240
LYARTTGKLK TDNVFWGEHF EFHNLPPLRT VTVHLYRETD KKKKKERNSY LGLVSLPAAS 300
VAGRQFVEKW YPVVTPNPKG GKGPGPMIRI KARYQTITIL PMEMYKEFAE HITNHYLGLC 360
AALEPILSAK TKEEMASALV HILQSTGKVK DFLTDLMMSE VDRCGDNEHL IFRENTLATK 420
AIEEYLKLVG QKYLQDALGE FIKALYESDE NCEVDPSKCS AADLPEHQGN LKMCCELAFC 480
KIINSYCVFP RELKEVFASW RQECSSRGRP DISERLISAS LFLRFLCPAI MSPSLFNLLQ 540
EYPDDRTART LTLIAKVTQN LANFAKFGSK EEYMSFMNQF LEHEWTNMQR FLLEISNPET 600
LSNTAGFEGY IDLGRELSSL HSLLWEAVSQ LEQSIVSKLG PLPRILRDVH TALSTPGSGQ 660
LPGTNDLAST PGSGSSSISA GLQKMVIEND LSGLIDFTRL PSPTPENKDL FFVTRSSGVQ 720
PSPARSSSYS EANEPDLQMA NGGKSLSMVD LQDARTLDGE AGSPAGPDVL PTDGQAAAAQ 780
LVAGWPARAT PVNLAGLATV RRAGQTPTTP GTSEGAPGRP QLLAPLSFQN PVYQMAAGLP 840
LSPRGLGDSG SEGHSSLSSH SNSEELAAAA KLGSFSTAAE ELARRPGELA RRQMSLTEKG 900
GQPTVPRQNS AGPQRRIDQP PPPPPPPPPA PRGRTPPNLL STLQYPRPSS GTLASASPDW 960
VGPSTRLRQQ SSSSKGDSPE LKPRAVHKQG PSPVSPNALD RTAAWLLTMN AQLLEDEGLG 1020
PDPPHRDRLR SKDELSQAEK DLAVLQDKLR ISTKKLEEYE TLFKCQEETT QKLVLEYQAR 1080
LEEGEERLRR QQEDKDIQMK GIISRLMSVE EELKKDHAEM QAAVDSKQKI IDAQEKRIAS 1140
LDAANARLMS ALTQLKERYS MQARNGISPT NPTKLQITEN GEFRNSSNC 1189 
Gene Ontology
 GO:0044300; C:cerebellar mossy fiber; ISS:UniProtKB.
 GO:0044301; C:climbing fiber; ISS:UniProtKB.
 GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
 GO:0030139; C:endocytic vesicle; IDA:UniProtKB.
 GO:0031235; C:intrinsic to internal side of plasma membrane; IBA:RefGenome.
 GO:0032809; C:neuronal cell body membrane; ISS:UniProtKB.
 GO:1990032; C:parallel fiber; ISS:UniProtKB.
 GO:0071889; F:14-3-3 protein binding; IDA:BHF-UCL.
 GO:0036312; F:phosphatidylinositol 3-kinase regulatory subunit binding; IDA:UniProtKB.
 GO:0032266; F:phosphatidylinositol-3-phosphate binding; IDA:UniProtKB.
 GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:UniProtKB.
 GO:0032403; F:protein complex binding; IDA:UniProtKB.
 GO:0051721; F:protein phosphatase 2A binding; IDA:BHF-UCL.
 GO:0005099; F:Ras GTPase activator activity; ISS:BHF-UCL.
 GO:0017124; F:SH3 domain binding; IDA:UniProtKB.
 GO:0035591; F:signaling adaptor activity; IDA:BHF-UCL.
 GO:0007257; P:activation of JUN kinase activity; IDA:BHF-UCL.
 GO:0000185; P:activation of MAPKKK activity; IDA:UniProtKB.
 GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
 GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
 GO:0021814; P:cell motility involved in cerebral cortex radial glia guided migration; ISS:UniProtKB.
 GO:0044257; P:cellular protein catabolic process; IDA:UniProtKB.
 GO:0071364; P:cellular response to epidermal growth factor stimulus; ISS:BHF-UCL.
 GO:0071347; P:cellular response to interleukin-1; IDA:UniProtKB.
 GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
 GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB.
 GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IDA:UniProtKB.
 GO:0072577; P:endothelial cell apoptotic process; TAS:BHF-UCL.
 GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IMP:BHF-UCL.
 GO:0007252; P:I-kappaB phosphorylation; ISS:UniProtKB.
 GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
 GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
 GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISS:BHF-UCL.
 GO:0021819; P:layer formation in cerebral cortex; ISS:UniProtKB.
 GO:0016525; P:negative regulation of angiogenesis; IDA:UniProtKB.
 GO:0090090; P:negative regulation of canonical Wnt receptor signaling pathway; IMP:BHF-UCL.
 GO:0035414; P:negative regulation of catenin import into nucleus; ISS:BHF-UCL.
 GO:2000599; P:negative regulation of cyclin catabolic process; IDA:UniProtKB.
 GO:0010596; P:negative regulation of endothelial cell migration; IMP:UniProtKB.
 GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; ISS:BHF-UCL.
 GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:BHF-UCL.
 GO:0010719; P:negative regulation of epithelial to mesenchymal transition; IDA:UniProtKB.
 GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
 GO:0048147; P:negative regulation of fibroblast proliferation; ISS:BHF-UCL.
 GO:0070317; P:negative regulation of G0 to G1 transition; IDA:UniProtKB.
 GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB cascade; IDA:UniProtKB.
 GO:0043407; P:negative regulation of MAP kinase activity; IDA:BHF-UCL.
 GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:BHF-UCL.
 GO:0043553; P:negative regulation of phosphatidylinositol 3-kinase activity; IDA:UniProtKB.
 GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase cascade; IDA:UniProtKB.
 GO:0034261; P:negative regulation of Ras GTPase activity; IMP:BHF-UCL.
 GO:0046580; P:negative regulation of Ras protein signal transduction; IC:BHF-UCL.
 GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; IDA:UniProtKB.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
 GO:0030948; P:negative regulation of vascular endothelial growth factor receptor signaling pathway; IMP:UniProtKB.
 GO:1900747; P:negative regulation of vascular endothelial growth factor signaling pathway; ISS:UniProtKB.
 GO:0048812; P:neuron projection morphogenesis; ISS:UniProtKB.
 GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
 GO:2001235; P:positive regulation of apoptotic signaling pathway; IDA:UniProtKB.
 GO:0071158; P:positive regulation of cell cycle arrest; IDA:UniProtKB.
 GO:1900006; P:positive regulation of dendrite development; ISS:UniProtKB.
 GO:0046330; P:positive regulation of JNK cascade; IDA:UniProtKB.
 GO:2001224; P:positive regulation of neuron migration; ISS:UniProtKB.
 GO:1901800; P:positive regulation of proteasomal protein catabolic process; IMP:UniProtKB.
 GO:0090129; P:positive regulation of synapse maturation; ISS:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0032312; P:regulation of ARF GTPase activity; ISS:UniProtKB.
 GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
 GO:1900744; P:regulation of p38MAPK cascade; ISS:UniProtKB.
 GO:0043254; P:regulation of protein complex assembly; IDA:UniProtKB.
 GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
 GO:0006927; P:transformed cell apoptotic process; TAS:BHF-UCL.
 GO:0035148; P:tube formation; IMP:UniProtKB.
 GO:0036324; P:vascular endothelial growth factor receptor-2 signaling pathway; ISS:UniProtKB. 
Interpro
 IPR000008; C2_Ca-dep.
 IPR008973; C2_Ca/lipid-bd_dom_CaLB.
 IPR021887; DUF3498.
 IPR011993; PH_like_dom.
 IPR001849; Pleckstrin_homology.
 IPR001936; RasGAP.
 IPR023152; RasGAP_CS.
 IPR008936; Rho_GTPase_activation_prot. 
Pfam
 PF00168; C2
 PF12004; DUF3498
 PF00616; RasGAP 
SMART
 SM00239; C2
 SM00233; PH
 SM00323; RasGAP 
PROSITE
 PS50004; C2
 PS50003; PH_DOMAIN
 PS00509; RAS_GTPASE_ACTIV_1
 PS50018; RAS_GTPASE_ACTIV_2 
PRINTS