DAB2_HUMAN
ID DAB2_HUMAN Reviewed; 770 AA.
AC P98082; A6NES5; Q13598; Q9BTY0; Q9UK04;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 3.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Disabled homolog 2;
DE AltName: Full=Adaptor molecule disabled-2;
DE AltName: Full=Differentially expressed in ovarian carcinoma 2;
DE Short=DOC-2;
DE AltName: Full=Differentially-expressed protein 2;
GN Name=DAB2; Synonyms=DOC2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=8660969; DOI=10.1006/geno.1996.0185;
RA Albertsen H.M., Smith S.A., Melis R., Williams B., Holik P., Stevens J.,
RA White R.;
RT "Sequence, genomic structure, and chromosomal assignment of human DOC-2.";
RL Genomics 33:207-213(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND ALTERNATIVE
RP SPLICING.
RC TISSUE=Ovary;
RX PubMed=9620555; DOI=10.1038/sj.onc.1201769;
RA Mok S.C., Chan W.Y., Wong K.-K., Cheung K.K., Lau C.C., Ng S.W.,
RA Baldini A., Colitti C.V., Rock C.O., Berkowitz R.S.;
RT "DOC-2, a candidate tumor suppressor gene in human epithelial ovarian
RT cancer.";
RL Oncogene 16:2381-2387(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY.
RX PubMed=10340382; DOI=10.1038/sj.onc.1202649;
RA Fazili Z., Sun W., Mittelstaedt S., Cohen C., Xu X.-X.;
RT "Disabled-2 inactivation is an early step in ovarian tumorigenicity.";
RL Oncogene 18:3104-3113(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 3).
RX PubMed=11161789; DOI=10.1006/geno.2000.6383;
RA Sheng Z., He J., Tuppen J.A., Sun W., Fazili Z., Smith E.R., Dong F.B.,
RA Xu X.-X.;
RT "Structure, sequence, and promoter analysis of human disabled-2 gene
RT (DAB2).";
RL Genomics 70:381-386(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 44-304 (ISOFORM 1).
RC TISSUE=Ovary;
RX PubMed=8314147; DOI=10.1006/gyno.1994.1040;
RA Mok S.C., Wong K.-K., Chan R.K.W., Lau C.C., Tsao S.-W., Knapp R.C.,
RA Berkowitz R.S.;
RT "Molecular cloning of differentially expressed genes in human epithelial
RT ovarian cancer.";
RL Gynecol. Oncol. 52:247-252(1994).
RN [9]
RP INTERACTION WITH LRP2.
RX PubMed=10769163; DOI=10.1042/bj3470613;
RA Oleinikov A.V., Zhao J., Makker S.P.;
RT "Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic
RT receptor gp600/megalin.";
RL Biochem. J. 347:613-621(2000).
RN [10]
RP FUNCTION, INTERACTION WITH SMAD2; SMAD3; TGFBR1 AND TGFBR2, AND MUTAGENESIS
RP OF PHE-166.
RX PubMed=11387212; DOI=10.1093/emboj/20.11.2789;
RA Hocevar B.A., Smine A., Xu X.X., Howe P.H.;
RT "The adaptor molecule Disabled-2 links the transforming growth factor beta
RT receptors to the Smad pathway.";
RL EMBO J. 20:2789-2801(2001).
RN [11]
RP INTERACTION WITH MYO6, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 684-SER--PHE-686.
RX PubMed=11967127; DOI=10.1034/j.1600-0854.2002.30503.x;
RA Morris S.M., Arden S.D., Roberts R.C., Kendrick-Jones J., Cooper J.A.,
RA Luzio J.P., Buss F.;
RT "Myosin VI binds to and localises with Dab2, potentially linking receptor-
RT mediated endocytosis and the actin cytoskeleton.";
RL Traffic 3:331-341(2002).
RN [12]
RP FUNCTION, AND INTERACTION WITH DVL3 AND AXIN1.
RX PubMed=12805222; DOI=10.1093/emboj/cdg286;
RA Howe P.H.;
RT "Regulation of the Wnt signaling pathway by disabled-2 (Dab2).";
RL EMBO J. 22:3084-3094(2003).
RN [13]
RP INTERACTION WITH SH3KBP1, AND MUTAGENESIS OF ARG-720.
RX PubMed=14596919; DOI=10.1016/s0014-5793(03)01111-6;
RA Kowanetz K., Terzic J., Dikic I.;
RT "Dab2 links CIN85 with clathrin-mediated receptor internalization.";
RL FEBS Lett. 554:81-87(2003).
RN [14]
RP INTERACTION WITH LRP2, AND TISSUE SPECIFICITY.
RX PubMed=15134832; DOI=10.1016/j.biochi.2004.03.001;
RA Gallagher H., Oleinikov A.V., Fenske C., Newman D.J.;
RT "The adaptor disabled-2 binds to the third psi xNPxY sequence on the
RT cytoplasmic tail of megalin.";
RL Biochimie 86:179-182(2004).
RN [15]
RP FUNCTION.
RX PubMed=16267015; DOI=10.1158/0008-5472.can-05-1481;
RA Zhoul J., Hernandez G., Tu S.W., Huang C.L., Tseng C.P., Hsieh J.T.;
RT "The role of DOC-2/DAB2 in modulating androgen receptor-mediated cell
RT growth via the nongenomic c-Src-mediated pathway in normal prostatic
RT epithelium and cancer.";
RL Cancer Res. 65:9906-9913(2005).
RN [16]
RP FUNCTION.
RX PubMed=16984970; DOI=10.1242/jcs.03217;
RA Maurer M.E., Cooper J.A.;
RT "The adaptor protein Dab2 sorts LDL receptors into coated pits
RT independently of AP-2 and ARH.";
RL J. Cell Sci. 119:4235-4246(2006).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-401, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-401, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [20]
RP FUNCTION.
RX PubMed=19306879; DOI=10.1016/j.febslet.2009.03.037;
RA Chao W.T., Kunz J.;
RT "Focal adhesion disassembly requires clathrin-dependent endocytosis of
RT integrins.";
RL FEBS Lett. 583:1337-1343(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-401, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [23]
RP SUBCELLULAR LOCATION.
RX PubMed=21097498; DOI=10.1074/jbc.m110.161851;
RA Chetrit D., Barzilay L., Horn G., Bielik T., Smorodinsky N.I., Ehrlich M.;
RT "Negative regulation of the endocytic adaptor disabled-2 (Dab2) in
RT mitosis.";
RL J. Biol. Chem. 286:5392-5403(2011).
RN [24]
RP FUNCTION.
RX PubMed=21995445; DOI=10.1042/bj20111566;
RA Fu L., Rab A., Tang L.P., Rowe S.M., Bebok Z., Collawn J.F.;
RT "Dab2 is a key regulator of endocytosis and post-endocytic trafficking of
RT the cystic fibrosis transmembrane conductance regulator.";
RL Biochem. J. 441:633-643(2012).
RN [25]
RP FUNCTION, AND INTERACTION WITH LRP6.
RX PubMed=22491013; DOI=10.1038/emboj.2012.83;
RA Jiang Y., He X., Howe P.H.;
RT "Disabled-2 (Dab2) inhibits Wnt/beta-catenin signalling by binding LRP6 and
RT promoting its internalization through clathrin.";
RL EMBO J. 31:2336-2349(2012).
RN [26]
RP FUNCTION IN ENDOCYTOSIS, AND INTERACTION WITH FCHO2.
RX PubMed=22323290; DOI=10.1091/mbc.e11-09-0812;
RA Mulkearns E.E., Cooper J.A.;
RT "FCH domain only-2 organizes clathrin-coated structures and interacts with
RT Disabled-2 for low-density lipoprotein receptor endocytosis.";
RL Mol. Biol. Cell 23:1330-1342(2012).
RN [27]
RP INTERACTION WITH FCHO1.
RX PubMed=22484487; DOI=10.1038/ncb2473;
RA Umasankar P.K., Sanker S., Thieman J.R., Chakraborty S., Wendland B.,
RA Tsang M., Traub L.M.;
RT "Distinct and separable activities of the endocytic clathrin-coat
RT components Fcho1/2 and AP-2 in developmental patterning.";
RL Nat. Cell Biol. 14:488-501(2012).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-401; SER-675 AND SER-723, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-401, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Adapter protein that functions as clathrin-associated sorting
CC protein (CLASP) required for clathrin-mediated endocytosis of selected
CC cargo proteins. Can bind and assemble clathrin, and binds
CC simultaneously to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)
CC and cargos containing non-phosphorylated NPXY internalization motifs,
CC such as the LDL receptor, to recruit them to clathrin-coated pits. Can
CC function in clathrin-mediated endocytosis independently of the AP-2
CC complex. Involved in endocytosis of integrin beta-1; this function
CC seems to redundant with the AP-2 complex and seems to require DAB2
CC binding to endocytosis accessory EH domain-containing proteins such as
CC EPS15, EPS15L1 and ITSN1. Involved in endocytosis of cystic fibrosis
CC transmembrane conductance regulator/CFTR. Involved in endocytosis of
CC megalin/LRP2 lipoprotein receptor during embryonal development.
CC Required for recycling of the TGF-beta receptor. Involved in CFTR
CC trafficking to the late endosome. Involved in several receptor-mediated
CC signaling pathways. Involved in TGF-beta receptor signaling and
CC facilitates phosphorylation of the signal transducer SMAD2. Mediates
CC TFG-beta-stimulated JNK activation. May inhibit the canoniocal
CC Wnt/beta-catenin signaling pathway by stabilizing the beta-catenin
CC destruction complex through a competing association with axin
CC preventing its dephosphorylation through protein phosphatase 1 (PP1).
CC Sequesters LRP6 towards clathrin-mediated endocytosis, leading to
CC inhibition of Wnt/beta-catenin signaling. May activate non-canonical
CC Wnt signaling. In cell surface growth factor/Ras signaling pathways
CC proposed to inhibit ERK activation by interrupting the binding of GRB2
CC to SOS1 and to inhibit SRC by preventing its activating phosphorylation
CC at 'Tyr-419'. Proposed to be involved in modulation of androgen
CC receptor (AR) signaling mediated by SRC activation; seems to compete
CC with AR for interaction with SRC. Plays a role in the CSF-1 signal
CC transduction pathway. Plays a role in cellular differentiation.
CC Involved in cell positioning and formation of visceral endoderm (VE)
CC during embryogenesis and proposed to be required in the VE to respond
CC to Nodal signaling coming from the epiblast. Required for the
CC epithelial to mesenchymal transition, a process necessary for proper
CC embryonic development. May be involved in myeloid cell differentiation
CC and can induce macrophage adhesion and spreading. May act as a tumor
CC suppressor. {ECO:0000269|PubMed:11387212, ECO:0000269|PubMed:12805222,
CC ECO:0000269|PubMed:16267015, ECO:0000269|PubMed:16984970,
CC ECO:0000269|PubMed:19306879, ECO:0000269|PubMed:21995445,
CC ECO:0000269|PubMed:22323290, ECO:0000269|PubMed:22491013}.
CC -!- SUBUNIT: Interacts (via NPXY motif) with DAB2 (via PID domain). Can
CC interact (via PID domain) with LDLR, APP, APLP1 and APLP2, and weakly
CC with INPP5D (via NPXY motifs); the interaction is impaired by tyrosine
CC phosphorylation of the respective NPXY motifs. Can weakly interact (via
CC PID domain) with LRP1 (via NPXY motif); the interaction is enhanced by
CC tyrosine phosphorylation of the NPXY motif. Interacts with LRP2 (via
CC NPXY motif); the interaction is not affected by tyrosine
CC phosphorylation of the NPXY motif. Interacts with clathrin; in vitro
CC can assemble clathrin triskelia into polyhedral coats. Interacts with
CC AP2A2, ITGB1, ITGB3, ITGB5, PIAS2, DAB2IP, NOSTRIN, FCHO1, DVL3, EPS15,
CC ITSN1 and EPS15L1. Interacts with SH3KBP1 (via SH3 domains). Interacts
CC with GRB2; competes with SOS1 for binding to GRB2 and the interaction
CC is enhanced by EGF and NT-3 stimulation. Interacts with MAP3K7; the
CC interaction is induced by TGF-beta stimulation and may mediate TGF-beta
CC stimulated JNK activation. Interacts with AXIN1 and PPP1CA; the
CC interactions are mutually exclusive. Interacts with the globular tail
CC of MYO6. Interacts (via DPF motifs) with FCHO2; the interaction is
CC direct and required for DAB2-mediated LDLR endocytosis. Interacts with
CC LRP6; the interaction involves LRP6 phosphorylation by CK2 and
CC sequesters LRP6 towards clathrin-mediated endocytosis. Associates with
CC the TGF-beta receptor complex (Probable). Interacts with SMAD2 and
CC SMAD3; the interactions are enhanced upon TGF-beta stimulation.
CC Interacts with GRB2; the interaction is enhanced by EGF and NT-3
CC stimulation. Interacts with SRC; the interaction is enhanced by EGF
CC stimulation. {ECO:0000269|PubMed:10769163, ECO:0000269|PubMed:11387212,
CC ECO:0000269|PubMed:11967127, ECO:0000269|PubMed:12805222,
CC ECO:0000269|PubMed:14596919, ECO:0000269|PubMed:15134832,
CC ECO:0000269|PubMed:22323290, ECO:0000269|PubMed:22484487,
CC ECO:0000269|PubMed:22491013, ECO:0000305}.
CC -!- INTERACTION:
CC P98082; P05067: APP; NbExp=3; IntAct=EBI-1171238, EBI-77613;
CC P98082; P42566: EPS15; NbExp=2; IntAct=EBI-1171238, EBI-396684;
CC P98082; P62993: GRB2; NbExp=2; IntAct=EBI-1171238, EBI-401755;
CC P98082; O75581: LRP6; NbExp=20; IntAct=EBI-1171238, EBI-910915;
CC P98082; Q9UM54: MYO6; NbExp=3; IntAct=EBI-1171238, EBI-350606;
CC P98082; P16333: NCK1; NbExp=2; IntAct=EBI-1171238, EBI-389883;
CC P98082; Q15796: SMAD2; NbExp=4; IntAct=EBI-1171238, EBI-1040141;
CC P98082; P84022: SMAD3; NbExp=3; IntAct=EBI-1171238, EBI-347161;
CC P98082; P00441: SOD1; NbExp=3; IntAct=EBI-1171238, EBI-990792;
CC P98082-1; Q29122: MYO6; Xeno; NbExp=2; IntAct=EBI-15804617, EBI-15804516;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasmic vesicle, clathrin-coated
CC vesicle membrane. Membrane, clathrin-coated pit. Note=Colocalizes with
CC large insert-containing isoforms of MYO6 at clathrin-coated
CC pits/vesicles. During mitosis is progressively displaced from the
CC membrane and translocated to the cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P98082-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P98082-2; Sequence=VSP_004181;
CC Name=3;
CC IsoId=P98082-3; Sequence=VSP_038401;
CC -!- TISSUE SPECIFICITY: Expressed in deep invaginations, inclusion cysts
CC and the surface epithelial cells of the ovary. Also expressed in breast
CC epithelial cells, spleen, thymus, prostate, testis, macrophages,
CC fibroblasts, lung epithelial cells, placenta, brain stem, heart and
CC small intestine. Expressed in kidney proximal tubular epithelial cells
CC (at protein level). {ECO:0000269|PubMed:10340382,
CC ECO:0000269|PubMed:15134832, ECO:0000269|PubMed:9620555}.
CC -!- DOMAIN: The PID domain binds to predominantly non-phosphorylated NPXY
CC internalization motifs present in members of the LDLR and APP family;
CC it also mediates simultaneous binding to phosphatidylinositol 4,5-
CC bisphosphate. {ECO:0000250}.
CC -!- DOMAIN: The Asn-Pro-Phe (NPF) motifs, which are found in proteins
CC involved in the endocytic pathway, mediate the interaction with the EH
CC domain of EPS15, EPS15R and ITSN1. {ECO:0000250}.
CC -!- PTM: Phosphorylated. Phosphorylation during mitosis is leading to
CC membrane displacement (By similarity). {ECO:0000250}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/DAB2ID40258ch5p13.html";
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DR EMBL; U39050; AAC50824.1; -; mRNA.
DR EMBL; AH003698; AAB19032.1; -; Genomic_DNA.
DR EMBL; U53446; AAA98975.1; -; mRNA.
DR EMBL; AF188298; AAF05540.1; -; mRNA.
DR EMBL; AF205890; AAF23161.1; -; Genomic_DNA.
DR EMBL; AC008916; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471119; EAW55989.1; -; Genomic_DNA.
DR EMBL; BC003064; AAH03064.1; -; mRNA.
DR EMBL; L16886; AAA93195.1; -; mRNA.
DR CCDS; CCDS34149.1; -. [P98082-1]
DR CCDS; CCDS58946.1; -. [P98082-3]
DR PIR; G02228; G02228.
DR RefSeq; NP_001231800.1; NM_001244871.1. [P98082-3]
DR RefSeq; NP_001334.2; NM_001343.3. [P98082-1]
DR PDB; 2LSW; NMR; -; A=24-58.
DR PDB; 6O5O; X-ray; 1.75 A; A/B=31-191.
DR PDB; 6OVF; X-ray; 1.95 A; A/B=31-191.
DR PDBsum; 2LSW; -.
DR PDBsum; 6O5O; -.
DR PDBsum; 6OVF; -.
DR AlphaFoldDB; P98082; -.
DR BMRB; P98082; -.
DR SMR; P98082; -.
DR BioGRID; 107971; 141.
DR DIP; DIP-45617N; -.
DR ELM; P98082; -.
DR IntAct; P98082; 69.
DR MINT; P98082; -.
DR STRING; 9606.ENSP00000313391; -.
DR BindingDB; P98082; -.
DR GlyGen; P98082; 5 sites, 1 O-linked glycan (5 sites).
DR iPTMnet; P98082; -.
DR MetOSite; P98082; -.
DR PhosphoSitePlus; P98082; -.
DR BioMuta; DAB2; -.
DR DMDM; 145559465; -.
DR EPD; P98082; -.
DR jPOST; P98082; -.
DR MassIVE; P98082; -.
DR MaxQB; P98082; -.
DR PaxDb; P98082; -.
DR PeptideAtlas; P98082; -.
DR PRIDE; P98082; -.
DR ProteomicsDB; 57786; -. [P98082-1]
DR ProteomicsDB; 57787; -. [P98082-2]
DR ProteomicsDB; 57788; -. [P98082-3]
DR Antibodypedia; 3987; 317 antibodies from 35 providers.
DR DNASU; 1601; -.
DR Ensembl; ENST00000320816.11; ENSP00000313391.6; ENSG00000153071.15. [P98082-1]
DR Ensembl; ENST00000339788.10; ENSP00000345508.6; ENSG00000153071.15. [P98082-2]
DR Ensembl; ENST00000509337.5; ENSP00000426245.1; ENSG00000153071.15. [P98082-3]
DR Ensembl; ENST00000545653.5; ENSP00000439919.1; ENSG00000153071.15. [P98082-3]
DR GeneID; 1601; -.
DR KEGG; hsa:1601; -.
DR MANE-Select; ENST00000320816.11; ENSP00000313391.6; NM_001343.4; NP_001334.2.
DR UCSC; uc003jlw.4; human. [P98082-1]
DR CTD; 1601; -.
DR DisGeNET; 1601; -.
DR GeneCards; DAB2; -.
DR HGNC; HGNC:2662; DAB2.
DR HPA; ENSG00000153071; Tissue enhanced (kidney, placenta).
DR MIM; 601236; gene.
DR neXtProt; NX_P98082; -.
DR OpenTargets; ENSG00000153071; -.
DR PharmGKB; PA27132; -.
DR VEuPathDB; HostDB:ENSG00000153071; -.
DR eggNOG; KOG3535; Eukaryota.
DR GeneTree; ENSGT00940000155567; -.
DR HOGENOM; CLU_020747_1_0_1; -.
DR InParanoid; P98082; -.
DR OMA; DKMKLGV; -.
DR PhylomeDB; P98082; -.
DR TreeFam; TF316724; -.
DR PathwayCommons; P98082; -.
DR Reactome; R-HSA-190873; Gap junction degradation.
DR Reactome; R-HSA-196025; Formation of annular gap junctions.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR SignaLink; P98082; -.
DR SIGNOR; P98082; -.
DR BioGRID-ORCS; 1601; 9 hits in 1083 CRISPR screens.
DR ChiTaRS; DAB2; human.
DR GeneWiki; DAB2; -.
DR GenomeRNAi; 1601; -.
DR Pharos; P98082; Tbio.
DR PRO; PR:P98082; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P98082; protein.
DR Bgee; ENSG00000153071; Expressed in caput epididymis and 200 other tissues.
DR ExpressionAtlas; P98082; baseline and differential.
DR Genevisible; P98082; HS.
DR GO; GO:0005905; C:clathrin-coated pit; IDA:UniProtKB.
DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:UniProtKB.
DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0038024; F:cargo receptor activity; IMP:UniProtKB.
DR GO; GO:0035615; F:clathrin adaptor activity; IMP:UniProtKB.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IEA:Ensembl.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0046332; F:SMAD binding; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IEA:Ensembl.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl.
DR GO; GO:0048268; P:clathrin coat assembly; IEA:Ensembl.
DR GO; GO:0035026; P:leading edge cell differentiation; IMP:UniProtKB.
DR GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:BHF-UCL.
DR GO; GO:0030308; P:negative regulation of cell growth; IEA:Ensembl.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0032091; P:negative regulation of protein binding; IMP:BHF-UCL.
DR GO; GO:1903077; P:negative regulation of protein localization to plasma membrane; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0032349; P:positive regulation of aldosterone biosynthetic process; IEA:Ensembl.
DR GO; GO:2000860; P:positive regulation of aldosterone secretion; IEA:Ensembl.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
DR GO; GO:2000370; P:positive regulation of clathrin-dependent endocytosis; IMP:UniProtKB.
DR GO; GO:2000643; P:positive regulation of early endosome to late endosome transport; IMP:UniProtKB.
DR GO; GO:0045807; P:positive regulation of endocytosis; IMP:UniProtKB.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IDA:UniProtKB.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:BHF-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:BHF-UCL.
DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IDA:UniProtKB.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:2000096; P:positive regulation of Wnt signaling pathway, planar cell polarity pathway; IMP:BHF-UCL.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IBA:GO_Central.
DR GO; GO:2000298; P:regulation of Rho-dependent protein serine/threonine kinase activity; IEA:Ensembl.
DR GO; GO:1902074; P:response to salt; IEA:Ensembl.
DR GO; GO:0048545; P:response to steroid hormone; IEA:Ensembl.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006020; PTB/PI_dom.
DR Pfam; PF00640; PID; 1.
DR SMART; SM00462; PTB; 1.
DR PROSITE; PS01179; PID; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; Coated pit;
KW Cytoplasm; Cytoplasmic vesicle; Developmental protein; Differentiation;
KW Endocytosis; Membrane; Phosphoprotein; Protein transport;
KW Reference proteome; Transport; Tumor suppressor; Wnt signaling pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..770
FT /note="Disabled homolog 2"
FT /id="PRO_0000079770"
FT DOMAIN 45..196
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 230..447
FT /note="Required for localization to clathrin-coated pits"
FT /evidence="ECO:0000250"
FT REGION 284..482
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 604..732
FT /note="Sufficient for interaction with GRB2"
FT /evidence="ECO:0000250"
FT REGION 604..629
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 619..627
FT /note="Required for interaction with CSK"
FT /evidence="ECO:0000250"
FT REGION 649..770
FT /note="Required for interaction with MYO6"
FT /evidence="ECO:0000250"
FT REGION 663..671
FT /note="Required for interaction with GRB2 and CSK"
FT /evidence="ECO:0000250"
FT REGION 709..725
FT /note="Sufficient for interaction with SH3KBP1 SH3 domain"
FT /evidence="ECO:0000250"
FT REGION 742..770
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 293..295
FT /note="DPF 1"
FT MOTIF 298..300
FT /note="DPF 2"
FT COMPBIAS 1..18
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 21..38
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 300..335
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 344..397
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 407..430
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 466..482
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 615..629
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 742..760
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88797"
FT MOD_RES 170
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P98078"
FT MOD_RES 193
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P98078"
FT MOD_RES 326
FT /note="Phosphoserine; in mitosis"
FT /evidence="ECO:0000250|UniProtKB:O88797"
FT MOD_RES 328
FT /note="Phosphoserine; in mitosis"
FT /evidence="ECO:0000250|UniProtKB:O88797"
FT MOD_RES 401
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 675
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 723
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 729
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P98078"
FT VAR_SEQ 209..229
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10340382,
FT ECO:0000303|PubMed:11161789"
FT /id="VSP_038401"
FT VAR_SEQ 230..447
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_004181"
FT VARIANT 586
FT /note="T -> I (in dbSNP:rs700241)"
FT /id="VAR_031705"
FT VARIANT 634
FT /note="S -> N (in dbSNP:rs3733801)"
FT /id="VAR_050942"
FT MUTAGEN 166
FT /note="F->A: Impairs TGF-beta receptor signaling, no effect
FT on interaction with SMAD2."
FT /evidence="ECO:0000269|PubMed:11387212"
FT MUTAGEN 684..686
FT /note="SYF->AAA: Greatly reduced binding to MYO6."
FT /evidence="ECO:0000269|PubMed:11967127"
FT MUTAGEN 720
FT /note="R->A: Abolishes interaction with SH3KBP1."
FT /evidence="ECO:0000269|PubMed:14596919"
FT CONFLICT 44..47
FT /note="KGDG -> PRVC (in Ref. 8; AAA93195)"
FT /evidence="ECO:0000305"
FT CONFLICT 82
FT /note="A -> R (in Ref. 1; AAC50824/AAB19032, 2; AAA98975,
FT 4; AAF23161 and 8; AAA93195)"
FT /evidence="ECO:0000305"
FT CONFLICT 148
FT /note="A -> T (in Ref. 2; AAA98975)"
FT /evidence="ECO:0000305"
FT CONFLICT 197
FT /note="M -> R (in Ref. 2; AAA98975)"
FT /evidence="ECO:0000305"
FT CONFLICT 230..232
FT /note="ESK -> VCF (in Ref. 3; AAF05540 and 8; AAA93195)"
FT /evidence="ECO:0000305"
FT CONFLICT 275
FT /note="L -> S (in Ref. 1; AAC50824)"
FT /evidence="ECO:0000305"
FT CONFLICT 302..304
FT /note="QPD -> HTR (in Ref. 8; AAA93195)"
FT /evidence="ECO:0000305"
FT CONFLICT 498
FT /note="L -> Q (in Ref. 3; AAF05540)"
FT /evidence="ECO:0000305"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:2LSW"
FT HELIX 36..43
FT /evidence="ECO:0007829|PDB:6O5O"
FT TURN 44..46
FT /evidence="ECO:0007829|PDB:2LSW"
FT STRAND 48..59
FT /evidence="ECO:0007829|PDB:6O5O"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:6O5O"
FT HELIX 66..85
FT /evidence="ECO:0007829|PDB:6O5O"
FT STRAND 91..98
FT /evidence="ECO:0007829|PDB:6O5O"
FT STRAND 101..106
FT /evidence="ECO:0007829|PDB:6O5O"
FT TURN 107..109
FT /evidence="ECO:0007829|PDB:6O5O"
FT STRAND 112..116
FT /evidence="ECO:0007829|PDB:6O5O"
FT HELIX 118..120
FT /evidence="ECO:0007829|PDB:6O5O"
FT STRAND 121..126
FT /evidence="ECO:0007829|PDB:6O5O"
FT STRAND 133..138
FT /evidence="ECO:0007829|PDB:6O5O"
FT STRAND 145..153
FT /evidence="ECO:0007829|PDB:6O5O"
FT HELIX 156..180
FT /evidence="ECO:0007829|PDB:6O5O"
SQ SEQUENCE 770 AA; 82448 MW; 5B2F8B510A580A77 CRC64;
MSNEVETSAT NGQPDQQAAP KAPSKKEKKK GPEKTDEYLL ARFKGDGVKY KAKLIGIDDV
PDARGDKMSQ DSMMKLKGMA AAGRSQGQHK QRIWVNISLS GIKIIDEKTG VIEHEHPVNK
ISFIARDVTD NRAFGYVCGG EGQHQFFAIK TGQQAEPLVV DLKDLFQVIY NVKKKEEEKK
KIEEASKAVE NGSEALMILD DQTNKLKSGV DQMDLFGDMS TPPDLNSPTE SKDILLVDLN
SEIDTNQNSL RENPFLTNGI TSCSLPRPTP QASFLPENAF SANLNFFPTP NPDPFRDDPF
TQPDQSTPSS FDSLKSPDQK KENSSSSSTP LSNGPLNGDV DYFGQQFDQI SNRTGKQEAQ
AGPWPFSSSQ TQPAVRTQNG VSEREQNGFS VKSSPNPFVG SPPKGLSIQN GVKQDLESSV
QSSPHDSIAI IPPPQSTKPG RGRRTAKSSA NDLLASDIFA PPVSEPSGQA SPTGQPTALQ
PNPLDLFKTS APAPVGPLVG LGGVTVTLPQ AGPWNTASLV FNQSPSMAPG AMMGGQPSGF
SQPVIFGTSP AVSGWNQPSP FAASTPPPVP VVWGPSASVA PNAWSTTSPL GNPFQSNIFP
APAVSTQPPS MHSSLLVTPP QPPPRAGPPK DISSDAFTAL DPLGDKEIKD VKEMFKDFQL
RQPPAVPARK GEQTSSGTLS AFASYFNSKV GIPQENADHD DFDANQLLNK INEPPKPAPR
QVSLPVTKST DNAFENPFFK DSFGSSQASV ASSQPVSSEM YRDPFGNPFA
