DAPLE_HUMAN
ID DAPLE_HUMAN Reviewed; 2028 AA.
AC Q9P219; Q69YK1; Q7L1M2; Q86SX7; Q8IYG8;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 3.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Protein Daple;
DE AltName: Full=Coiled-coil domain-containing protein 88C;
DE AltName: Full=Dvl-associating protein with a high frequency of leucine residues;
DE Short=hDaple;
DE AltName: Full=Hook-related protein 2;
DE Short=HkRP2;
GN Name=CCDC88C; Synonyms=DAPLE, KIAA1509 {ECO:0000312|HGNC:HGNC:19967};
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] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT PRO-1992.
RA Venter J.C., Adams M.C., Li P.W., Myers E.W.;
RT "Kits, such as nucleic acid arrays, comprising a majority of human exons or
RT transcripts, for detecting expression and other uses thereof.";
RL Patent number WO02068579, 06-SEP-2002.
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAH35914.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1658-2028, AND VARIANT PRO-1992.
RC TISSUE=Lymph {ECO:0000312|EMBL:AAH35914.1};
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 [4] {ECO:0000305, ECO:0000312|EMBL:CAD62629.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1748 (ISOFORM 3).
RC TISSUE=B-cell {ECO:0000312|EMBL:CAD62629.1};
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 707-2028 (ISOFORM 1), AND VARIANT PRO-1992.
RX PubMed=10819331; DOI=10.1093/dnares/7.2.143;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:143-150(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1687-2028, AND VARIANT PRO-1992.
RC TISSUE=Stomach;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7] {ECO:0000305}
RP IDENTIFICATION.
RX PubMed=15882442; DOI=10.1111/j.1600-0854.2005.00289.x;
RA Simpson F., Martin S., Evans T.M., Kerr M., James D.E., Parton R.G.,
RA Teasdale R.D., Wicking C.;
RT "A novel hook-related protein family and the characterization of hook-
RT related protein 1.";
RL Traffic 6:442-458(2005).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1806, 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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1444, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
RP INVOLVEMENT IN HYC1.
RX PubMed=21031079; DOI=10.1159/000319859;
RA Ekici A.B., Hilfinger D., Jatzwauk M., Thiel C.T., Wenzel D., Lorenz I.,
RA Boltshauser E., Goecke T.W., Staatz G., Morris-Rosendahl D.J., Sticht H.,
RA Hehr U., Reis A., Rauch A.;
RT "Disturbed Wnt signalling due to a mutation in CCDC88C causes an autosomal
RT recessive non-syndromic hydrocephalus with medial diverticulum.";
RL Mol. Syndromol. 1:99-112(2010).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [12]
RP INVOLVEMENT IN HYC1.
RX PubMed=23042809; DOI=10.1136/jmedgenet-2012-101190;
RA Drielsma A., Jalas C., Simonis N., Desir J., Simanovsky N., Pirson I.,
RA Elpeleg O., Abramowicz M., Edvardson S.;
RT "Two novel CCDC>88C mutations confirm the role of DAPLE in autosomal
RT recessive congenital hydrocephalus.";
RL J. Med. Genet. 49:708-712(2012).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-227; SER-239; SER-486;
RP SER-1601; SER-1806 AND THR-1954, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [14]
RP GBA MOTIF.
RX PubMed=30194280; DOI=10.1074/jbc.ra118.003580;
RA Maziarz M., Broselid S., DiGiacomo V., Park J.C., Luebbers A.,
RA Garcia-Navarrete L., Blanco-Canosa J.B., Baillie G.S., Garcia-Marcos M.;
RT "A biochemical and genetic discovery pipeline identifies PLCdelta4b as a
RT nonreceptor activator of heterotrimeric G-proteins.";
RL J. Biol. Chem. 293:16964-16983(2018).
RN [15]
RP FUNCTION, INTERACTION WITH DVL1; FZD7; GNAI1; GNAI2 AND GNAI3, SUBCELLULAR
RP LOCATION, GBA MOTIF, AND MUTAGENESIS OF PHE-1675.
RX PubMed=26126266; DOI=10.7554/elife.07091;
RA Aznar N., Midde K.K., Dunkel Y., Lopez-Sanchez I., Pavlova Y., Marivin A.,
RA Barbazan J., Murray F., Nitsche U., Janssen K.P., Willert K., Goel A.,
RA Abal M., Garcia-Marcos M., Ghosh P.;
RT "Daple is a novel non-receptor GEF required for trimeric G protein
RT activation in Wnt signaling.";
RL Elife 4:E07091-E07091(2015).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, ROLE OF PDZ DOMAIN, AND MUTAGENESIS OF
RP PHE-1675 AND 2025-GLY--VAL-2028.
RX PubMed=30948426; DOI=10.1083/jcb.201811174;
RA Marivin A., Morozova V., Walawalkar I., Leyme A., Kretov D.A.,
RA Cifuentes D., Dominguez I., Garcia-Marcos M.;
RT "GPCR-independent activation of G proteins promotes apical cell
RT constriction in vivo.";
RL J. Cell Biol. 218:1743-1763(2019).
RN [17]
RP INVOLVEMENT IN SCA40, VARIANT SCA40 HIS-464, CHARACTERIZATION OF VARIANT
RP SCA40 HIS-464, AND SUBCELLULAR LOCATION.
RX PubMed=25062847; DOI=10.1136/jmedgenet-2014-102333;
RA Tsoi H., Yu A.C., Chen Z.S., Ng N.K., Chan A.Y., Yuen L.Y., Abrigo J.M.,
RA Tsang S.Y., Tsui S.K., Tong T.M., Lo I.F., Lam S.T., Mok V.C., Wong L.K.,
RA Ngo J.C., Lau K.F., Chan T.F., Chan H.Y.;
RT "A novel missense mutation in CCDC88C activates the JNK pathway and causes
RT a dominant form of spinocerebellar ataxia.";
RL J. Med. Genet. 51:590-595(2014).
CC -!- FUNCTION: Required for activation of guanine nucleotide-binding
CC proteins (G-proteins) during non-canonical Wnt signaling
CC (PubMed:26126266). Binds to ligand-activated Wnt receptor FZD7,
CC displacing DVL1 from the FZD7 receptor and leading to inhibition of
CC canonical Wnt signaling (PubMed:26126266). Acts as a non-receptor
CC guanine nucleotide exchange factor by also binding to guanine
CC nucleotide-binding protein G(i) alpha (Gi-alpha) subunits, leading to
CC their activation (PubMed:26126266). Binding to Gi-alpha subunits
CC displaces the beta and gamma subunits from the heterotrimeric G-protein
CC complex, triggering non-canonical Wnt responses such as activation of
CC RAC1 and PI3K-AKT signaling (PubMed:26126266). Promotes apical
CC constriction of cells via ARHGEF18 (PubMed:30948426).
CC {ECO:0000269|PubMed:26126266, ECO:0000269|PubMed:30948426}.
CC -!- SUBUNIT: Homooligomer (By similarity). Interacts with DVL1 (via PDZ
CC domain); dissociates following initiation of non-canonical Wnt
CC signaling (PubMed:26126266). Interacts (via C-terminus) with ligand-
CC activated Wnt receptor FZD7; competes with DVL1 for binding to FZD7 and
CC displaces DVL1 from ligand-activated FZD7 (PubMed:26126266). Interacts
CC (via GBA motif) with guanine nucleotide-binding protein G(i) alpha
CC subunits GNAI1, GNAI2 and GNAI3 (inactive GDP-bound form); interacts
CC with higher affinity with GNAI1 and GNAI3 than with GNAI2 and
CC interaction leads to G(i) alpha subunit activation (PubMed:26126266).
CC Does not interact with GNAO1 (PubMed:26126266).
CC {ECO:0000250|UniProtKB:Q6VGS5, ECO:0000269|PubMed:26126266}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25062847,
CC ECO:0000269|PubMed:26126266}. Cell junction
CC {ECO:0000269|PubMed:30948426}. Note=Enriched at apical cell junctions.
CC {ECO:0000269|PubMed:30948426}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1 {ECO:0000269|PubMed:10819331, ECO:0000269|Ref.1};
CC IsoId=Q9P219-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:15489334};
CC IsoId=Q9P219-2; Sequence=VSP_052390, VSP_052391;
CC Name=3 {ECO:0000269|Ref.4};
CC IsoId=Q9P219-3; Sequence=VSP_052389, VSP_052392;
CC -!- DOMAIN: The GBA (G-alpha binding and activating) motif mediates binding
CC to the alpha subunits of guanine nucleotide-binding proteins (G
CC proteins). {ECO:0000269|PubMed:26126266, ECO:0000269|PubMed:30194280}.
CC -!- DOMAIN: The PDZ domain is required for localization to apical
CC junctions. {ECO:0000269|PubMed:30948426}.
CC -!- DISEASE: Hydrocephalus, congenital, 1 (HYC1) [MIM:236600]: A form of
CC congenital hydrocephalus, a disease characterized by onset in utero of
CC enlarged ventricles due to accumulation of ventricular cerebrospinal
CC fluid. Affected individuals may have neurologic impairment. HYC1
CC inheritance is autosomal recessive. {ECO:0000269|PubMed:21031079,
CC ECO:0000269|PubMed:23042809}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Spinocerebellar ataxia 40 (SCA40) [MIM:616053]: A form of
CC spinocerebellar ataxia, a clinically and genetically heterogeneous
CC group of cerebellar disorders. Patients show progressive incoordination
CC of gait and often poor coordination of hands, speech and eye movements,
CC due to degeneration of the cerebellum with variable involvement of the
CC brainstem and spinal cord. SCA40 is an autosomal dominant, slowly
CC progressive form. Brain MRI shows pontocerebellar atrophy along with a
CC global reduction in brain volume. {ECO:0000269|PubMed:25062847}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: [Isoform 3]: Due to intron retention. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the CCDC88 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA96033.2; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
CC Sequence=CAH10602.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; CQ719279; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL133153; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL135818; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC028565; AAH28565.2; -; mRNA.
DR EMBL; BC035914; AAH35914.1; -; mRNA.
DR EMBL; BX248302; CAD62629.1; -; mRNA.
DR EMBL; AB040942; BAA96033.2; ALT_SEQ; mRNA.
DR EMBL; AL833046; CAH10602.1; ALT_SEQ; mRNA.
DR CCDS; CCDS45151.1; -. [Q9P219-1]
DR RefSeq; NP_001073883.2; NM_001080414.3. [Q9P219-1]
DR AlphaFoldDB; Q9P219; -.
DR SMR; Q9P219; -.
DR BioGRID; 136368; 48.
DR IntAct; Q9P219; 20.
DR MINT; Q9P219; -.
DR STRING; 9606.ENSP00000374507; -.
DR GlyGen; Q9P219; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q9P219; -.
DR MetOSite; Q9P219; -.
DR PhosphoSitePlus; Q9P219; -.
DR BioMuta; CCDC88C; -.
DR DMDM; 308153605; -.
DR EPD; Q9P219; -.
DR jPOST; Q9P219; -.
DR MassIVE; Q9P219; -.
DR MaxQB; Q9P219; -.
DR PaxDb; Q9P219; -.
DR PeptideAtlas; Q9P219; -.
DR PRIDE; Q9P219; -.
DR ProteomicsDB; 83712; -. [Q9P219-1]
DR ProteomicsDB; 83713; -. [Q9P219-2]
DR ProteomicsDB; 83714; -. [Q9P219-3]
DR Antibodypedia; 105; 15 antibodies from 10 providers.
DR DNASU; 440193; -.
DR Ensembl; ENST00000389857.11; ENSP00000374507.6; ENSG00000015133.20. [Q9P219-1]
DR GeneID; 440193; -.
DR KEGG; hsa:440193; -.
DR MANE-Select; ENST00000389857.11; ENSP00000374507.6; NM_001080414.4; NP_001073883.2.
DR UCSC; uc010aty.4; human. [Q9P219-1]
DR CTD; 440193; -.
DR DisGeNET; 440193; -.
DR GeneCards; CCDC88C; -.
DR HGNC; HGNC:19967; CCDC88C.
DR HPA; ENSG00000015133; Tissue enhanced (bone marrow, lymphoid tissue).
DR MalaCards; CCDC88C; -.
DR MIM; 236600; phenotype.
DR MIM; 611204; gene.
DR MIM; 616053; phenotype.
DR neXtProt; NX_Q9P219; -.
DR OpenTargets; ENSG00000015133; -.
DR Orphanet; 269510; Congenital non-communicating hydrocephalus.
DR Orphanet; 423275; Spinocerebellar ataxia type 40.
DR PharmGKB; PA162381879; -.
DR VEuPathDB; HostDB:ENSG00000015133; -.
DR eggNOG; KOG4643; Eukaryota.
DR GeneTree; ENSGT00940000154785; -.
DR HOGENOM; CLU_001421_1_1_1; -.
DR InParanoid; Q9P219; -.
DR OMA; YRDELEC; -.
DR PhylomeDB; Q9P219; -.
DR TreeFam; TF320231; -.
DR PathwayCommons; Q9P219; -.
DR Reactome; R-HSA-5368598; Negative regulation of TCF-dependent signaling by DVL-interacting proteins.
DR SignaLink; Q9P219; -.
DR SIGNOR; Q9P219; -.
DR BioGRID-ORCS; 440193; 13 hits in 1084 CRISPR screens.
DR ChiTaRS; CCDC88C; human.
DR GenomeRNAi; 440193; -.
DR Pharos; Q9P219; Tbio.
DR PRO; PR:Q9P219; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9P219; protein.
DR Bgee; ENSG00000015133; Expressed in right uterine tube and 136 other tissues.
DR ExpressionAtlas; Q9P219; baseline and differential.
DR Genevisible; Q9P219; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0030054; C:cell junction; IMP:UniProtKB.
DR GO; GO:0005813; C:centrosome; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0051959; F:dynein light intermediate chain binding; IBA:GO_Central.
DR GO; GO:0005109; F:frizzled binding; IPI:UniProtKB.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; IPI:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; IBA:GO_Central.
DR GO; GO:0030165; F:PDZ domain binding; ISS:UniProtKB.
DR GO; GO:0043621; F:protein self-association; ISS:UniProtKB.
DR GO; GO:0003383; P:apical constriction; IDA:UniProtKB.
DR GO; GO:0031122; P:cytoplasmic microtubule organization; IBA:GO_Central.
DR GO; GO:0030705; P:cytoskeleton-dependent intracellular transport; IBA:GO_Central.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0035567; P:non-canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; ISS:UniProtKB.
DR GO; GO:0001932; P:regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IDA:UniProtKB.
DR GO; GO:0031098; P:stress-activated protein kinase signaling cascade; IMP:UniProtKB.
DR Gene3D; 1.10.418.10; -; 1.
DR InterPro; IPR001715; CH-domain.
DR InterPro; IPR036872; CH_dom_sf.
DR InterPro; IPR027719; Daple.
DR InterPro; IPR043936; HOOK_N.
DR PANTHER; PTHR18947:SF31; PTHR18947:SF31; 1.
DR Pfam; PF19047; HOOK_N; 1.
DR PROSITE; PS50021; CH; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Coiled coil; Cytoplasm;
KW Disease variant; Guanine-nucleotide releasing factor; Neurodegeneration;
KW Phosphoprotein; Reference proteome; Spinocerebellar ataxia;
KW Wnt signaling pathway.
FT CHAIN 1..2028
FT /note="Protein Daple"
FT /id="PRO_0000286864"
FT DOMAIN 11..131
FT /note="Calponin-homology (CH)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT REGION 222..250
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1011..1043
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1419..1724
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1736..1803
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1816..2021
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2026..2028
FT /note="DVL1-binding"
FT /evidence="ECO:0000250|UniProtKB:Q6VGS5"
FT COILED 247..428
FT /evidence="ECO:0000255"
FT COILED 456..1017
FT /evidence="ECO:0000255"
FT COILED 1045..1094
FT /evidence="ECO:0000255"
FT COILED 1139..1393
FT /evidence="ECO:0000255"
FT MOTIF 1661..1691
FT /note="GBA"
FT /evidence="ECO:0000269|PubMed:30194280"
FT MOTIF 2025..2028
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 225..249
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1013..1029
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1432..1461
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1486..1500
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1514..1537
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1565..1608
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1840..1854
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 227
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 239
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 486
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1444
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 1601
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1806
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1954
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..1550
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_052389"
FT VAR_SEQ 1..1476
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_052390"
FT VAR_SEQ 1477..1481
FT /note="SVGKG -> MSVLS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_052391"
FT VAR_SEQ 1551..1566
FT /note="LCEPSLEFEVPNHRQY -> MPSSTLPGWPGSSGGP (in isoform 3)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_052392"
FT VARIANT 464
FT /note="R -> H (in SCA40; no effect on subcellular location;
FT increases activation of the JNK signaling pathway; induces
FT apoptosis; dbSNP:rs587782989)"
FT /evidence="ECO:0000269|PubMed:25062847"
FT /id="VAR_071981"
FT VARIANT 637
FT /note="L -> V (in dbSNP:rs7160308)"
FT /id="VAR_057777"
FT VARIANT 811
FT /note="A -> E (in dbSNP:rs17127223)"
FT /id="VAR_046613"
FT VARIANT 1028
FT /note="A -> V (in dbSNP:rs1970911)"
FT /id="VAR_046614"
FT VARIANT 1992
FT /note="L -> P (in dbSNP:rs941920)"
FT /evidence="ECO:0000269|PubMed:10819331,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005,
FT ECO:0000269|Ref.1"
FT /id="VAR_046615"
FT MUTAGEN 1675
FT /note="F->A: Abolishes interaction with and activation of
FT GNAI3 and abolishes release of the beta and gamma subunits
FT from the heterotrimeric G-protein complex. Abolishes WNT5A-
FT mediated activation of RAC1. Failure to induce apical cell
FT constriction but does not affect localization to apical
FT cell junctions."
FT /evidence="ECO:0000269|PubMed:26126266,
FT ECO:0000269|PubMed:30948426"
FT MUTAGEN 2025..2028
FT /note="Missing: Failure to localize to apical cell
FT junctions and to induce apical cell constriction."
FT /evidence="ECO:0000269|PubMed:30948426"
FT CONFLICT 73
FT /note="L -> F (in Ref. 1; CQ719279)"
FT /evidence="ECO:0000305"
FT CONFLICT 1785..1830
FT /note="Missing (in Ref. 3; AAH35914)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2028 AA; 228230 MW; F4A1ED4929ABA076 CRC64;
MDVTVSELLE LFLQSPLVTW VKTFGPFGSG SQDNLTMYMD LVDGIFLNQI MLQIDPRPTN
QRINKHVNND VNLRIQNLTI LVRNIKTYYQ EVLQQLIVMN LPNVLMIGRD PLSGKSMEEI
KKVLLLVLGC AVQCERKEEF IERIKQLDIE TQAGIVAHIQ EVTHNQENVF DLQWLELPDV
APEELEALSR SMVLHLRRLI DQRDECTELI VDLTQERDYL QAQHPPSPIK SSSADSTPSP
TSSLSSEDKQ HLAVELADTK ARLRRVRQEL EDKTEQLVDT RHEVDQLVLE LQKVKQENIQ
LAADARSARA YRDELDSLRE KANRVERLEL ELTRCKEKLH DVDFYKARME ELREDNIILI
ETKAMLEEQL TAARARGDKV HELEKENLQL KSKLHDLELD RDTDKKRIEE LLEENMVLEI
AQKQSMNESA HLGWELEQLS KNADLSDASR KSFVFELNEC ASSRILKLEK ENQSLQSTIQ
GLRDASLVLE ESGLKCGELE KENHQLSKKI EKLQTQLERE KQSNQDLETL SEELIREKEQ
LQSDMETLKA DKARQIKDLE QEKDHLNRAM WSLRERSQVS SEARMKDVEK ENKALHQTVT
EANGKLSQLE FEKRQLHRDL EQAKEKGERA EKLERELQRL QEENGRLARK VTSLETATEK
VEALEHESQG LQLENRTLRK SLDTLQNVSL QLEGLERDNK QLDAENLELR RLVETMRFTS
TKLAQMEREN QQLEREKEEL RKNVDLLKAL GKKSERLELS YQSVSAENLR LQQSLESSSH
KTQTLESELG ELEAERQALR RDLEALRLAN AQLEGAEKDR KALEQEVAQL EKDKKLLEKE
AKRLWQQVEL KDAVLDDSTA KLSAVEKESR ALDKELARCR DAAGKLKELE KDNRDLTKQV
TVHARTLTTL REDLVLEKLK SQQLSSELDK LSQELEKVGL NRELLLQEDD SGSDTKYKIL
EGRNESALKT TLAMKEEKIV LLEAQMEEKA SLNRQLESEL QMLKKECETL RQNQGEGQHL
QNSFKHPAGK TAASHQGKEA WGPGHKEATM ELLRVKDRAI ELERNNAALQ AEKQLLKEQL
QHLETQNVTF SSQILTLQKQ SAFLQEHNTT LQTQTAKLQV ENSTLSSQSA ALTAQYTLLQ
NHHTAKETEN ESLQRQQEQL TAAYEALLQD HEHLGTLHER QSAEYEALIR QHSCLKTLHR
NLELEHKELG ERHGDMLKRK AELEEREKVL TTEREALQQE QRTNALAMGE NQRLRGELDR
VNFLHHQLKG EYEELHAHTK ELKTSLNNAQ LELNRWQARF DELKEQHQTM DISLTKLDNH
CELLSRLKGN LEEENHHLLS QIQLLSQQNQ MLLEQNMENK EQYHEEQKQY IDKLNALRRH
KEKLEEKIMD QYKFYDPPPK KKNHWIGAKA LVKLIKPKKE GSRERLKSTV DSPPWQLESS
DPASPAASQP LRSQAENPDT PALGSNCAEE RDAHNGSVGK GPGDLKPKRG SPHRGSLDRT
DASTDLAMRS WPSELGSRTC STSATTTAPS NSTPIARHPG RTKGYNSDDN LCEPSLEFEV
PNHRQYVSRP SSLESSRNTS SNSSPLNLKG SSEQLHGRSE SFSSEDLIPS RDLATLPREA
STPGRNALGR HEYPLPRNGP LPQEGAQKRG TAPPYVGVRP CSASPSSEMV TLEEFLEESN
RSSPTHDTPS CRDDLLSDYF RKASDPPAIG GQPGPPAKKE GAKMPTNFVA PTVKMAAPTS
EGRPLKPGQY VKPNFRLTEA EAPPSVAPRQ AQPPQSLSLG RPRQAPVPPA SHAPASRSAS
LSRAFSLASA DLLRASGPEA CKQESPQKLG APEALGGRET GSHTLQSPAP PSSHSLARER
TPLVGKAGSS CQGPGPRSRP LDTRRFSLAP PKEERLAPLH QSATAPAIAT AGAGAAAAGS
GSNSQLLHFS PAAAPAARTK PKAPPRSGEV ATITPVRAGL SLSEGDGVPG QGCSEGLPAK
SPGRSPDLAP HLGRALEDCS RGSVSKSSPA SPEPGGDPQT VWYEYGCV
