DAAM2_MOUSE
ID DAAM2_MOUSE Reviewed; 1115 AA.
AC Q80U19; E9QNU9; Q6TAB7; Q810J5;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 4.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Disheveled-associated activator of morphogenesis 2 {ECO:0000303|PubMed:15533824};
GN Name=Daam2 {ECO:0000303|PubMed:15533824, ECO:0000312|MGI:MGI:1923691};
GN Synonyms=Kiaa0381 {ECO:0000303|PubMed:12693553};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=15533824; DOI=10.1016/j.modgep.2004.06.001;
RA Nakaya M.-A., Habas R., Biris K., Dunty W.C. Jr., Kato Y., He X.,
RA Yamaguchi T.P.;
RT "Identification and comparative expression analyses of Daam genes in mouse
RT and Xenopus.";
RL Gene Expr. Patterns 5:97-105(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Pancreas;
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 [5]
RP TISSUE SPECIFICITY.
RX PubMed=15464228; DOI=10.1016/j.devbrainres.2004.07.014;
RA Kida Y., Shiraishi T., Ogura T.;
RT "Identification of chick and mouse Daam1 and Daam2 genes and their
RT expression patterns in the central nervous system.";
RL Brain Res. Dev. Brain Res. 153:143-150(2004).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, AND INTERACTION WITH DVL3.
RX PubMed=22227309; DOI=10.1016/j.devcel.2011.10.025;
RA Lee H.K., Deneen B.;
RT "Daam2 is required for dorsal patterning via modulation of canonical Wnt
RT signaling in the developing spinal cord.";
RL Dev. Cell 22:183-196(2012).
RN [8]
RP FUNCTION.
RX PubMed=24091014; DOI=10.1016/j.devcel.2013.07.019;
RA Welsh I.C., Thomsen M., Gludish D.W., Alfonso-Parra C., Bai Y.,
RA Martin J.F., Kurpios N.A.;
RT "Integration of left-right Pitx2 transcription and Wnt signaling drives
RT asymmetric gut morphogenesis via Daam2.";
RL Dev. Cell 26:629-644(2013).
RN [9]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=26526197; DOI=10.1016/j.ydbio.2015.10.003;
RA Ajima R., Bisson J.A., Helt J.C., Nakaya M.A., Habas R., Tessarollo L.,
RA He X., Morrisey E.E., Yamaguchi T.P., Cohen E.D.;
RT "DAAM1 and DAAM2 are co-required for myocardial maturation and sarcomere
RT assembly.";
RL Dev. Biol. 408:126-139(2015).
RN [10]
RP FUNCTION.
RX PubMed=25754822; DOI=10.1016/j.neuron.2015.02.024;
RA Lee H.K., Chaboub L.S., Zhu W., Zollinger D., Rasband M.N., Fancy S.P.,
RA Deneen B.;
RT "Daam2-PIP5K is a regulatory pathway for Wnt signaling and therapeutic
RT target for remyelination in the CNS.";
RL Neuron 85:1227-1243(2015).
CC -!- FUNCTION: Key regulator of the Wnt signaling pathway, which is required
CC for various processes during development, such as dorsal patterning,
CC determination of left/right symmetry or myelination in the central
CC nervous system (PubMed:22227309, PubMed:24091014, PubMed:25754822).
CC Acts downstream of Wnt ligands and upstream of beta-catenin (CTNNB1)
CC (PubMed:22227309, PubMed:25754822). Required for canonical Wnt
CC signaling pathway during patterning in the dorsal spinal cord by
CC promoting the aggregation of Disheveled (Dvl) complexes, thereby
CC clustering and formation of Wnt receptor signalosomes and potentiating
CC Wnt activity (PubMed:22227309). During dorsal patterning of the spinal
CC cord, inhibits oligodendrocytes differentiation via interaction with
CC PIP5K1A (PubMed:25754822). Also regulates non-canonical Wnt signaling
CC pathway (PubMed:24091014). Acts downstream of PITX2 in the developing
CC gut and is required for left/right asymmetry within dorsal mesentery:
CC affects mesenchymal condensation by lengthening cadherin-based
CC junctions through WNT5A and non-canonical Wnt signaling, inducing
CC polarized condensation in the left dorsal mesentery necessary to
CC initiate gut rotation (PubMed:24091014). Together with DAAM1, required
CC for myocardial maturation and sarcomere assembly (PubMed:26526197). Is
CC a regulator of actin nucleation and elongation, filopodia formation and
CC podocyte migration (By similarity). {ECO:0000250|UniProtKB:Q86T65,
CC ECO:0000269|PubMed:22227309, ECO:0000269|PubMed:24091014,
CC ECO:0000269|PubMed:25754822, ECO:0000269|PubMed:26526197}.
CC -!- SUBUNIT: Interacts with DVL3. Interacts with INF2 (By similarity).
CC {ECO:0000250|UniProtKB:Q86T65, ECO:0000269|PubMed:22227309}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q80U19-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q80U19-2; Sequence=VSP_008005, VSP_008006;
CC -!- TISSUE SPECIFICITY: In early embryogenesis, expression is confined to
CC embryonic ectoderm. Highly dynamic expression in later stages of
CC gastrulation. In early somite stages, detected in posterior node and
CC persists until 9-10 somites have developed when expression is
CC concentrated in the chordoneural hinge. During organogenesis, expressed
CC in the CNS, PNS, liver primordia, limb buds and genital tubercle.
CC {ECO:0000269|PubMed:15464228, ECO:0000269|PubMed:15533824}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the embryonic myocardium: not
CC expressed in the myocardium at 9.5 dpc but is present in epicardial
CC cells. At 10.5 dpc, expressed in the mesenchyme surrounding the ventral
CC foregut and in regions enriched in cardiac progenitors, as well as the
CC epicardium and lining of the pericardial cavity. By 12.5 dpc, expressed
CC throughout the myocardium and ventricular trabeculae.
CC {ECO:0000269|PubMed:26526197}.
CC -!- DOMAIN: The DAD domain regulates activation via by an autoinhibitory
CC interaction with the GBD/FH3 domain. This autoinhibition is released
CC upon competitive binding of an activated GTPase. The release of DAD
CC allows the FH2 domain to then nucleate and elongate nonbranched actin
CC filaments (By similarity). {ECO:0000250|UniProtKB:O08808}.
CC -!- DISRUPTION PHENOTYPE: Conditional knockout mice lacking Daam2 in
CC myocardial cells do not show any heart defects. Conditional knockout
CC mice lacking Daam1 and Daam2 in myocardial cells show cardiomyopathy,
CC which is stronger than with a single Daam1 deletion.
CC {ECO:0000269|PubMed:26526197}.
CC -!- SIMILARITY: Belongs to the formin homology family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC65548.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC65548.2; Type=Miscellaneous discrepancy; Note=Partially unspliced pre-RNA.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY426536; AAR05119.1; -; mRNA.
DR EMBL; AK122266; BAC65548.2; ALT_SEQ; Transcribed_RNA.
DR EMBL; AC124748; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC165258; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC050043; AAH50043.1; -; mRNA.
DR CCDS; CCDS37648.1; -. [Q80U19-1]
DR RefSeq; NP_001008232.2; NM_001008231.2. [Q80U19-1]
DR AlphaFoldDB; Q80U19; -.
DR SMR; Q80U19; -.
DR BioGRID; 218129; 10.
DR STRING; 10090.ENSMUSP00000052085; -.
DR iPTMnet; Q80U19; -.
DR PhosphoSitePlus; Q80U19; -.
DR SwissPalm; Q80U19; -.
DR EPD; Q80U19; -.
DR jPOST; Q80U19; -.
DR MaxQB; Q80U19; -.
DR PaxDb; Q80U19; -.
DR PeptideAtlas; Q80U19; -.
DR PRIDE; Q80U19; -.
DR ProteomicsDB; 279262; -. [Q80U19-1]
DR ProteomicsDB; 279263; -. [Q80U19-2]
DR Antibodypedia; 53613; 216 antibodies from 28 providers.
DR DNASU; 76441; -.
DR Ensembl; ENSMUST00000057610; ENSMUSP00000052085; ENSMUSG00000040260. [Q80U19-1]
DR Ensembl; ENSMUST00000224595; ENSMUSP00000153095; ENSMUSG00000040260. [Q80U19-2]
DR GeneID; 76441; -.
DR KEGG; mmu:76441; -.
DR UCSC; uc008cyl.1; mouse. [Q80U19-1]
DR UCSC; uc008cyn.1; mouse. [Q80U19-2]
DR CTD; 23500; -.
DR MGI; MGI:1923691; Daam2.
DR VEuPathDB; HostDB:ENSMUSG00000040260; -.
DR eggNOG; KOG1922; Eukaryota.
DR GeneTree; ENSGT00940000157801; -.
DR HOGENOM; CLU_002356_1_0_1; -.
DR InParanoid; Q80U19; -.
DR OMA; PCFGMGL; -.
DR OrthoDB; 1204639at2759; -.
DR PhylomeDB; Q80U19; -.
DR TreeFam; TF314602; -.
DR BioGRID-ORCS; 76441; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Daam2; mouse.
DR PRO; PR:Q80U19; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q80U19; protein.
DR Bgee; ENSMUSG00000040260; Expressed in lumbar subsegment of spinal cord and 264 other tissues.
DR Genevisible; Q80U19; MM.
DR GO; GO:0003779; F:actin binding; IEA:InterPro.
DR GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:InterPro.
DR GO; GO:0007368; P:determination of left/right symmetry; IMP:MGI.
DR GO; GO:0021516; P:dorsal spinal cord development; IMP:UniProtKB.
DR GO; GO:0048715; P:negative regulation of oligodendrocyte differentiation; IDA:UniProtKB.
DR GO; GO:0090521; P:podocyte cell migration; ISO:MGI.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0030833; P:regulation of actin filament polymerization; ISO:MGI.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0051489; P:regulation of filopodium assembly; ISO:MGI.
DR GO; GO:2000050; P:regulation of non-canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 1.20.58.2220; -; 1.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR014767; DAD_dom.
DR InterPro; IPR015425; FH2_Formin.
DR InterPro; IPR042201; FH2_Formin_sf.
DR InterPro; IPR010472; FH3_dom.
DR InterPro; IPR014768; GBD/FH3_dom.
DR InterPro; IPR010473; GTPase-bd.
DR Pfam; PF06367; Drf_FH3; 1.
DR Pfam; PF06371; Drf_GBD; 1.
DR Pfam; PF02181; FH2; 1.
DR SMART; SM01139; Drf_FH3; 1.
DR SMART; SM01140; Drf_GBD; 1.
DR SMART; SM00498; FH2; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS51231; DAD; 1.
DR PROSITE; PS51444; FH2; 1.
DR PROSITE; PS51232; GBD_FH3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Reference proteome;
KW Wnt signaling pathway.
FT CHAIN 1..1115
FT /note="Disheveled-associated activator of morphogenesis 2"
FT /id="PRO_0000194910"
FT DOMAIN 40..416
FT /note="GBD/FH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00579"
FT DOMAIN 518..694
FT /note="FH1"
FT DOMAIN 595..1042
FT /note="FH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00774"
FT DOMAIN 1065..1095
FT /note="DAD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00577"
FT REGION 510..605
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 655..697
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 434..515
FT /evidence="ECO:0000255"
FT COMPBIAS 538..580
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 516..524
FT /note="TGPVSSPPP -> VRGHHPHPI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008005"
FT VAR_SEQ 525..1115
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008006"
FT CONFLICT 994
FT /note="G -> R (in Ref. 1; AAR05119)"
FT /evidence="ECO:0000305"
FT CONFLICT 997
FT /note="E -> D (in Ref. 1; AAR05119)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1115 AA; 128370 MW; EC327BF7CFD5A889 CRC64;
MALRKRSPHG LGFLCCFGGS DLPEIDLRDS HPLQYLEFSG PIPNPEELNV RFAELVDELD
LTDKNREAVF ALPPEKKWQI YCSKRKEQED PNKLATSWPE YYIDRINAMA AMQNLYETED
EETDKRNQVV EDLKTALRTQ PMRFVTRFID LEGLTCLLNF LRGMDHTTCE SRIHTSLIGC
IKALMNNSQG RAHVLAQPEA ISIIAQSLRT ENSKTKVAVL EILGAVCLVP GGHKKVLQAM
LHYQAYAAER TRFQTLLNEL DRSLGRYRDE VNLKTAIMSF INAVLNAGAG EDNLEFRLHL
RYEFLMLGIQ PVIDKLRQHE NAILDKHLDF FEMVRNEDDL ELARRFDMVH IDTKSASQMF
ELIHKKLKHT EAYPCLLSVL HHCLQMPYKR NGGYFQQWQL LDRILQQIVL QDERGVDPDL
APLENFNVKN IVNMLINENE VKQWRDQAEK FRKEHMELMS RLERKERECE TKTLEKEEMM
RTLNKMKDKL ARESQELRQA RGQVAELVAR HNESSTGPVS SPPPPGGPLT LSSSRTTNDL
PPPPPPLPFD SCPPPPAPPL PPGGPPIPPG APPCFSSGPP PSHDPFSSNE APLRKKRIPQ
PSHPLKSFNW VKLNEERVSG TVWNEIDDSQ VFRILDLEDF EKMFSAYQRH QACMQEGPQR
ERGNVRDGGA ASRPLPAVEA SAHRTEKASR SMVSATGAKK ELGSTEDIYI TSRKVKELSV
IDGRRAQNCI ILLSKLKLSN DEIRQAILRM DEQEDLAKDM LEQLLKFIPE KSDIDLLEEH
KHEIERMARA DRFLYEMSRI DHYQQRLQAL FFKKKFQERL AEAKPKVEAI LLASRELTLS
QRLKQMLEVV LAIGNFMNKG QRGGAYGFRV ASLNKIADTK SSIDRNISLL HYLIMILEKH
FPDILNMPSE LKHLSEAAKV NLAELEKEVS ILRRGLRAVE VELEYQRHQA RDPNDKFVPV
MSDFITVSSF SFSELEDQLN EARDKFAKAL THFGEQESKM QPDEFFGIFD TFLQAFLEAR
QDLEAMRRRK EEDERRARME FMLKEQREKE RWQRQRKVLA GGALEESGEF DDLVSALRSG
EVFDKDLSKF KRNRKRPGSQ VPEVTRERAI NRLNY
