DACT1_HUMAN
ID DACT1_HUMAN Reviewed; 836 AA.
AC Q9NYF0; A8MYJ2; Q86TY0;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 15-AUG-2003, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Dapper homolog 1;
DE Short=hDPR1;
DE AltName: Full=Dapper antagonist of catenin 1;
DE AltName: Full=Hepatocellular carcinoma novel gene 3 protein;
GN Name=DACT1; Synonyms=DPR1, HNG3;
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 212-836 (ISOFORM 1).
RC TISSUE=Placenta;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 248-836 (ISOFORM 1), AND VARIANT VAL-464.
RA Gong S., Qian X., Fu W., Chen W.;
RT "Cloning of a murine cDNA and its human homolog encoding transcription
RT factor-like proteins.";
RL Zhongguo Sheng Wu Hua Xue Yu Fen Zi Sheng Wu Xue Bao 17:280-287(2001).
RN [4]
RP IDENTIFICATION.
RX PubMed=11970895; DOI=10.1016/s1534-5807(02)00140-5;
RA Cheyette B.N.R., Waxman J.S., Miller J.R., Takemaru K., Sheldahl L.C.,
RA Khlebtsova N., Fox E.P., Earnest T.N., Moon R.T.;
RT "Dapper, a Dishevelled-associated antagonist of beta-catenin and JNK
RT signaling, is required for notochord formation.";
RL Dev. Cell 2:449-461(2002).
RN [5]
RP FUNCTION, AND ALTERNATIVE SPLICING (ISOFORM 2).
RX PubMed=15580286; DOI=10.1038/sj.onc.1208340;
RA Yau T.O., Chan C.Y., Chan K.L., Lee M.F., Wong C.M., Fan S.T., Ng I.O.;
RT "HDPR1, a novel inhibitor of the WNT/beta-catenin signaling, is frequently
RT downregulated in hepatocellular carcinoma: involvement of methylation-
RT mediated gene silencing.";
RL Oncogene 24:1607-1614(2005).
RN [6]
RP FUNCTION, AND INTERACTION WITH DVL2.
RX PubMed=16446366; DOI=10.1074/jbc.m600274200;
RA Zhang L., Gao X., Wen J., Ning Y., Chen Y.G.;
RT "Dapper 1 antagonizes Wnt signaling by promoting dishevelled degradation.";
RL J. Biol. Chem. 281:8607-8612(2006).
RN [7]
RP FUNCTION.
RX PubMed=17197390; DOI=10.1096/fj.06-6246com;
RA Su Y., Zhang L., Gao X., Meng F., Wen J., Zhou H., Meng A., Chen Y.-G.;
RT "The evolutionally conserved activity of Dapper2 in antagonizing TGF-beta
RT signaling.";
RL FASEB J. 21:682-690(2007).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CTNNB1 AND HDAC1, AND
RP MUTAGENESIS OF LEU-132; ILE-136 AND 622-LYS-LYS-623.
RX PubMed=18936100; DOI=10.1074/jbc.m804088200;
RA Gao X., Wen J., Zhang L., Li X., Ning Y., Meng A., Chen Y.G.;
RT "Dapper1 is a nucleocytoplasmic shuttling protein that negatively modulates
RT Wnt signaling in the nucleus.";
RL J. Biol. Chem. 283:35679-35688(2008).
RN [9]
RP INTERACTION WITH HDAC1 AND GSK3A.
RX PubMed=21718540; DOI=10.1186/1471-2091-12-33;
RA Kivimae S., Yang X.Y., Cheyette B.N.;
RT "All Dact (Dapper/Frodo) scaffold proteins dimerize and exhibit conserved
RT interactions with Vangl, Dvl, and serine/threonine kinases.";
RL BMC Biochem. 12:33-33(2011).
RN [10]
RP PHOSPHORYLATION AT SER-237 AND SER-827, AND INTERACTION WITH YWHAB.
RX PubMed=21262972; DOI=10.1074/jbc.m110.211607;
RA Chen H., Liu L., Ma B., Ma T.M., Hou J.J., Xie G.M., Wu W., Yang F.Q.,
RA Chen Y.G.;
RT "Protein kinase A-mediated 14-3-3 association impedes human Dapper1 to
RT promote dishevelled degradation.";
RL J. Biol. Chem. 286:14870-14880(2011).
RN [11]
RP FUNCTION, AND INTERACTION WITH GSK3B AND CTNNB1.
RX PubMed=22470507; DOI=10.1371/journal.pone.0034004;
RA Yuan G., Wang C., Ma C., Chen N., Tian Q., Zhang T., Fu W.;
RT "Oncogenic function of DACT1 in colon cancer through the regulation of
RT beta-catenin.";
RL PLoS ONE 7:E34004-E34004(2012).
RN [12]
RP SUBCELLULAR LOCATION, INTERACTION WITH DVL2, POSSIBLE INVOLVEMENT IN NTD,
RP VARIANTS NTD TRP-45 AND LYS-356, VARIANTS GLY-142; GLY-702; GLY-800 AND
RP LYS-808, AND CHARACTERIZATION OF VARIANTS NTD TRP-45 AND LYS-356.
RX PubMed=22610794; DOI=10.1002/humu.22121;
RA Shi Y., Ding Y., Lei Y.P., Yang X.Y., Xie G.M., Wen J., Cai C.Q., Li H.,
RA Chen Y., Zhang T., Wu B.L., Jin L., Chen Y.G., Wang H.Y.;
RT "Identification of novel rare mutations of DACT1 in human neural tube
RT defects.";
RL Hum. Mutat. 33:1450-1455(2012).
RN [13]
RP INVOLVEMENT IN TBS2, VARIANT TBS2 419-TRP--VAL-836 DEL, AND
RP CHARACTERIZATION OF VARIANT TBS2 419-TRP--VAL-836 DEL.
RX PubMed=28054444; DOI=10.1002/humu.23171;
RA Webb B.D., Metikala S., Wheeler P.G., Sherpa M.D., Houten S.M., Horb M.E.,
RA Schadt E.E.;
RT "Heterozygous pathogenic variant in DACT1 causes an autosomal-dominant
RT syndrome with features overlapping Townes-Brocks syndrome.";
RL Hum. Mutat. 38:373-377(2017).
RN [14]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-124 AND LEU-682.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Involved in regulation of intracellular signaling pathways
CC during development. Specifically thought to play a role in canonical
CC and/or non-canonical Wnt signaling pathways through interaction with
CC DSH (Dishevelled) family proteins. The activation/inhibition of Wnt
CC signaling may depend on the phosphorylation status. Proposed to
CC regulate the degradation of CTNNB1/beta-catenin, thereby modulating the
CC transcriptional activation of target genes of the Wnt signaling
CC pathway. Its function in stabilizing CTNNB1 may involve inhibition of
CC GSK3B activity. Promotes the membrane localization of CTNNB1. The
CC cytoplasmic form can induce DVL2 degradation via a lysosome-dependent
CC mechanism; the function is inhibited by PKA-induced binding to 14-3-3
CC proteins, such as YWHAB. Seems to be involved in morphogenesis at the
CC primitive streak by regulating VANGL2 and DVL2; the function seems to
CC be independent of canonical Wnt signaling and rather involves the non-
CC canonical Wnt/planar cell polarity (PCP) pathway (By similarity). The
CC nuclear form may prevent the formation of LEF1:CTNNB1 complex and
CC recruit HDAC1 to LEF1 at target gene promoters to repress transcription
CC thus antagonizing Wnt signaling. May be involved in positive regulation
CC of fat cell differentiation. During neuronal differentiation may be
CC involved in excitatory synapse organization, and dendrite formation and
CC establishment of spines. {ECO:0000250, ECO:0000269|PubMed:15580286,
CC ECO:0000269|PubMed:16446366, ECO:0000269|PubMed:17197390,
CC ECO:0000269|PubMed:18936100, ECO:0000269|PubMed:22470507}.
CC -!- SUBUNIT: Can form homodimers and heterodimers with DACT2 or DACT3.
CC Interacts with CSNK1D, PKA catalytic subunit, PKC-type kinase, CSNK2A1,
CC CSNK2B, DVL1, DVL3, VANGL1, VANGL2, CTNND1 and HDAC1 (By similarity).
CC Interacts with DVL2. Interacts with YWHAB; the interaction is enhanced
CC by PKA phosphorylating DACT1 at Ser-237 and Ser-827. Interacts with
CC CTNNB1 and HDAC1. Interacts with GSK3B; the interaction is indicative
CC for an association of DACT1 with the beta-catenin destruction complex.
CC Interacts with GSK3A. {ECO:0000250, ECO:0000269|PubMed:16446366,
CC ECO:0000269|PubMed:18936100, ECO:0000269|PubMed:21262972,
CC ECO:0000269|PubMed:21718540, ECO:0000269|PubMed:22470507,
CC ECO:0000269|PubMed:22610794}.
CC -!- INTERACTION:
CC Q9NYF0; P35222: CTNNB1; NbExp=3; IntAct=EBI-3951744, EBI-491549;
CC Q9NYF0; O14641: DVL2; NbExp=6; IntAct=EBI-3951744, EBI-740850;
CC Q9NYF0; P49841: GSK3B; NbExp=3; IntAct=EBI-3951744, EBI-373586;
CC Q9NYF0; P31946: YWHAB; NbExp=4; IntAct=EBI-3951744, EBI-359815;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Synapse {ECO:0000250}.
CC Note=Shuttles between the nucleus and the cytoplasm. Seems to be
CC nuclear in the absence of Wnt signaling and to translocate to the
CC cytoplasm in its presence.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Alpha, Long;
CC IsoId=Q9NYF0-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta, Short;
CC IsoId=Q9NYF0-2; Sequence=VSP_044198;
CC -!- DOMAIN: The C-terminal PDZ-binding motif mediates interaction with the
CC PDZ domains of DSH (Dishevelled) family proteins.
CC {ECO:0000250|UniProtKB:Q8R4A3}.
CC -!- DISEASE: Neural tube defects (NTD) [MIM:182940]: Congenital
CC malformations of the central nervous system and adjacent structures
CC related to defective neural tube closure during the first trimester of
CC pregnancy. Failure of neural tube closure can occur at any level of the
CC embryonic axis. Common NTD forms include anencephaly, myelomeningocele
CC and spina bifida, which result from the failure of fusion in the
CC cranial and spinal region of the neural tube. NTDs have a
CC multifactorial etiology encompassing both genetic and environmental
CC components. {ECO:0000269|PubMed:22610794}. Note=Disease susceptibility
CC is associated with variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Townes-Brocks syndrome 2 (TBS2) [MIM:617466]: A form of
CC Townes-Brocks syndrome, a rare autosomal dominant disease characterized
CC by the triad of imperforate anus, dysplastic ears, and thumb
CC malformations. Minor features of the condition include hearing loss,
CC foot malformations, renal impairment with or without renal
CC malformations, genitourinary malformations, and congenital heart
CC disease. {ECO:0000269|PubMed:28054444}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the dapper family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF65569.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAD61905.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Dapper antagonist of beta-catenin homolog 1 (Xenopus
CC laevis) (DACT1); Note=Leiden Open Variation Database (LOVD);
CC URL="https://databases.lovd.nl/shared/genes/DACT1";
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DR EMBL; AL133312; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX161433; CAD61905.1; ALT_INIT; mRNA.
DR EMBL; AF251079; AAF65569.1; ALT_INIT; mRNA.
DR EMBL; BK000256; DAA00310.1; -; mRNA.
DR CCDS; CCDS41961.1; -. [Q9NYF0-2]
DR CCDS; CCDS9736.1; -. [Q9NYF0-1]
DR RefSeq; NP_001072988.1; NM_001079520.1. [Q9NYF0-2]
DR RefSeq; NP_057735.2; NM_016651.5. [Q9NYF0-1]
DR RefSeq; XP_006720230.1; XM_006720167.3.
DR AlphaFoldDB; Q9NYF0; -.
DR BioGRID; 119486; 35.
DR IntAct; Q9NYF0; 23.
DR MINT; Q9NYF0; -.
DR STRING; 9606.ENSP00000337439; -.
DR iPTMnet; Q9NYF0; -.
DR PhosphoSitePlus; Q9NYF0; -.
DR BioMuta; DACT1; -.
DR DMDM; 34098740; -.
DR jPOST; Q9NYF0; -.
DR MassIVE; Q9NYF0; -.
DR PaxDb; Q9NYF0; -.
DR PeptideAtlas; Q9NYF0; -.
DR PRIDE; Q9NYF0; -.
DR ProteomicsDB; 2406; -.
DR ProteomicsDB; 83217; -. [Q9NYF0-1]
DR Antibodypedia; 66; 160 antibodies from 24 providers.
DR DNASU; 51339; -.
DR Ensembl; ENST00000335867.4; ENSP00000337439.4; ENSG00000165617.15. [Q9NYF0-1]
DR Ensembl; ENST00000395153.8; ENSP00000378582.3; ENSG00000165617.15. [Q9NYF0-2]
DR GeneID; 51339; -.
DR KEGG; hsa:51339; -.
DR MANE-Select; ENST00000395153.8; ENSP00000378582.3; NM_001079520.2; NP_001072988.1. [Q9NYF0-2]
DR UCSC; uc001xdw.4; human. [Q9NYF0-1]
DR CTD; 51339; -.
DR DisGeNET; 51339; -.
DR GeneCards; DACT1; -.
DR HGNC; HGNC:17748; DACT1.
DR HPA; ENSG00000165617; Low tissue specificity.
DR MalaCards; DACT1; -.
DR MIM; 182940; phenotype.
DR MIM; 607861; gene.
DR MIM; 617466; phenotype.
DR neXtProt; NX_Q9NYF0; -.
DR OpenTargets; ENSG00000165617; -.
DR Orphanet; 63260; Craniorachischisis.
DR Orphanet; 268823; Occipital encephalocele.
DR Orphanet; 857; Townes-Brocks syndrome.
DR PharmGKB; PA134957283; -.
DR VEuPathDB; HostDB:ENSG00000165617; -.
DR eggNOG; ENOG502QVXB; Eukaryota.
DR GeneTree; ENSGT00950000183181; -.
DR HOGENOM; CLU_021211_1_0_1; -.
DR InParanoid; Q9NYF0; -.
DR OMA; VADVHPK; -.
DR OrthoDB; 674318at2759; -.
DR PhylomeDB; Q9NYF0; -.
DR TreeFam; TF331300; -.
DR PathwayCommons; Q9NYF0; -.
DR Reactome; R-HSA-4641258; Degradation of DVL.
DR SignaLink; Q9NYF0; -.
DR SIGNOR; Q9NYF0; -.
DR BioGRID-ORCS; 51339; 10 hits in 1075 CRISPR screens.
DR ChiTaRS; DACT1; human.
DR GenomeRNAi; 51339; -.
DR Pharos; Q9NYF0; Tbio.
DR PRO; PR:Q9NYF0; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9NYF0; protein.
DR Bgee; ENSG00000165617; Expressed in cortical plate and 133 other tissues.
DR ExpressionAtlas; Q9NYF0; baseline and differential.
DR Genevisible; Q9NYF0; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0008013; F:beta-catenin binding; IDA:UniProtKB.
DR GO; GO:0070097; F:delta-catenin binding; ISS:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0051018; F:protein kinase A binding; IDA:UniProtKB.
DR GO; GO:0005080; F:protein kinase C binding; ISS:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0048619; P:embryonic hindgut morphogenesis; ISS:UniProtKB.
DR GO; GO:1904864; P:negative regulation of beta-catenin-TCF complex assembly; IDA:ParkinsonsUK-UCL.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0046329; P:negative regulation of JNK cascade; IDA:UniProtKB.
DR GO; GO:0032091; P:negative regulation of protein binding; IGI:ParkinsonsUK-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0021915; P:neural tube development; IMP:ParkinsonsUK-UCL.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; IGI:ParkinsonsUK-UCL.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; IDA:UniProtKB.
DR GO; GO:2000095; P:regulation of Wnt signaling pathway, planar cell polarity pathway; ISS:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR024848; Dact1.
DR InterPro; IPR024843; Dapper.
DR PANTHER; PTHR15919; PTHR15919; 1.
DR PANTHER; PTHR15919:SF12; PTHR15919:SF12; 1.
DR Pfam; PF15268; Dapper; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Cytoplasm; Developmental protein;
KW Disease variant; Neurogenesis; Nucleus; Phosphoprotein; Reference proteome;
KW Synapse; Wnt signaling pathway.
FT CHAIN 1..836
FT /note="Dapper homolog 1"
FT /id="PRO_0000191353"
FT REGION 1..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 92..156
FT /note="Required for self-association"
FT /evidence="ECO:0000250"
FT REGION 316..335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 350..374
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 401..521
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 588..679
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 92..156
FT /evidence="ECO:0000255"
FT MOTIF 132..141
FT /note="Nuclear export signal"
FT MOTIF 610..623
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000305"
FT MOTIF 826..836
FT /note="PDZ-binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 23..47
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 401..421
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 473..487
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 504..521
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 604..625
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 656..670
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 237
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:21262972"
FT MOD_RES 827
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:21262972"
FT VAR_SEQ 213..249
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_044198"
FT VARIANT 45
FT /note="R -> W (in NTD; uncertain pathological significance;
FT does not affect interaction with DVL2; does not affect
FT subcellular location; increases RHOA activation but
FT decreases the ability to activate JNK; dbSNP:rs778976254)"
FT /evidence="ECO:0000269|PubMed:22610794"
FT /id="VAR_068427"
FT VARIANT 124
FT /note="G -> C (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036461"
FT VARIANT 142
FT /note="D -> G (found in a patient with craniorachischisis;
FT sporadic case; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:22610794"
FT /id="VAR_068428"
FT VARIANT 356
FT /note="N -> K (in NTD; does not affect interaction with
FT DVL2; does not affect subcellular location; results in
FT reduced RHOA and JNK activation)"
FT /evidence="ECO:0000269|PubMed:22610794"
FT /id="VAR_068429"
FT VARIANT 419..836
FT /note="Missing (in TBS2; the mutant protein is stable and
FT expressed)"
FT /evidence="ECO:0000269|PubMed:28054444"
FT /id="VAR_080125"
FT VARIANT 446
FT /note="D -> N (in dbSNP:rs34015825)"
FT /id="VAR_053057"
FT VARIANT 464
FT /note="A -> V (in dbSNP:rs17832998)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_053058"
FT VARIANT 628
FT /note="S -> A (in dbSNP:rs17094821)"
FT /id="VAR_053059"
FT VARIANT 682
FT /note="S -> L (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs1198900887)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036462"
FT VARIANT 697
FT /note="G -> S (in dbSNP:rs698025)"
FT /id="VAR_053060"
FT VARIANT 702
FT /note="V -> G (found in a patient with closed spina bifida;
FT sporadic case; unknown pathological significance;
FT dbSNP:rs1028180302)"
FT /evidence="ECO:0000269|PubMed:22610794"
FT /id="VAR_068430"
FT VARIANT 800
FT /note="D -> G (in dbSNP:rs773720154)"
FT /evidence="ECO:0000269|PubMed:22610794"
FT /id="VAR_068431"
FT VARIANT 808
FT /note="T -> K (found in a patient with encephalocele;
FT sporadic case; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:22610794"
FT /id="VAR_068432"
FT MUTAGEN 132
FT /note="L->A: Abolishes nuclear export; when associated with
FT A-136."
FT /evidence="ECO:0000269|PubMed:18936100"
FT MUTAGEN 136
FT /note="I->A: Abolishes nuclear export; when associated with
FT A-132."
FT /evidence="ECO:0000269|PubMed:18936100"
FT MUTAGEN 237
FT /note="S->A: Impairs interaction with YWHAB. Abolishes
FT interaction with YWHAB; when associated with A-827."
FT MUTAGEN 622..623
FT /note="KK->AA: Partial nuclear accumulation upon LMB
FT treatment."
FT /evidence="ECO:0000269|PubMed:18936100"
FT MUTAGEN 827
FT /note="S->A: Abolishes interaction with YWHAB; when
FT associated with A-237."
SQ SEQUENCE 836 AA; 90174 MW; 10B77DC5B7C73485 CRC64;
MKPSPAGTAK ELEPPAPARG EQRTAEPEGR WREKGEADTE RQRTRERQEA TLAGLAELEY
LRQRQELLVR GALRGAGGAG AAAPRAGELL GEAAQRSRLE EKFLEENILL LRKQLNCLRR
RDAGLLNQLQ ELDKQISDLR LDVEKTSEEH LETDSRPSSG FYELSDGASG SLSNSSNSVF
SECLSSCHSS TCFCSPLEAT LSLSDGCPKS ADLIGLLEYK EGHCEDQASG AVCRSLSTPQ
FNSLDVIADV NPKYQCDLVS KNGNDVYRYP SPLHAVAVQS PMFLLCLTGN PLREEDRLGN
HASDICGGSE LDAVKTDSSL PSPSSLWSAS HPSSSKKMDG YILSLVQKKT HPVRTNKPRT
SVNADPTKGL LRNGSVCVRA PGGVSQGNSV NLKNSKQACL PSGGIPSLNN GTFSPPKQWS
KESKAEQAES KRVPLPEGCP SGAASDLQSK HLPKTAKPAS QEHARCSAIG TGESPKESAQ
LSGASPKESP SRGPAPPQEN KVVQPLKKMS QKNSLQGVPP ATPPLLSTAF PVEERPALDF
KSEGSSQSLE EAHLVKAQFI PGQQPSVRLH RGHRNMGVVK NSSLKHRGPA LQGLENGLPT
VREKTRAGSK KCRFPDDLDT NKKLKKASSK GRKSGGGPEA GVPGRPAGGG HRAGSRAHGH
GREAVVAKPK HKRTDYRRWK SSAEISYEEA LRRARRGRRE NVGLYPAPVP LPYASPYAYV
ASDSEYSAEC ESLFHSTVVD TSEDEQSNYT TNCFGDSESS VSEGEFVGES TTTSDSEESG
GLIWSQFVQT LPIQTVTAPD LHNHPAKTFV KIKASHNLKK KILRFRSGSL KLMTTV
