DKK2_MOUSE
ID DKK2_MOUSE Reviewed; 259 AA.
AC Q9QYZ8; Q8BFW0;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Dickkopf-related protein 2;
DE Short=Dickkopf-2;
DE Short=Dkk-2;
DE Short=mDkk-2;
DE Flags: Precursor;
GN Name=Dkk2;
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].
RX PubMed=10495270; DOI=10.1016/s0925-4773(99)00138-0;
RA Monaghan P.A., Kioschis P., Wu W., Zuniga A., Bock D., Poustka A.,
RA Delius H., Niehrs C.;
RT "Dickkopf genes are co-ordinately expressed in mesodermal lineages.";
RL Mech. Dev. 87:45-56(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
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 GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Olfactory epithelium;
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 [6]
RP REVIEW OF THE DKK FAMILY.
RX PubMed=17143291; DOI=10.1038/sj.onc.1210054;
RA Niehrs C.;
RT "Function and biological roles of the Dickkopf family of Wnt modulators.";
RL Oncogene 25:7469-7481(2006).
RN [7]
RP DEVELOPMENTAL STAGE.
RX PubMed=27550540; DOI=10.1038/srep31668;
RA Mulvaney J.F., Thompkins C., Noda T., Nishimura K., Sun W.W., Lin S.Y.,
RA Coffin A., Dabdoub A.;
RT "Kremen1 regulates mechanosensory hair cell development in the mammalian
RT cochlea and the zebrafish lateral line.";
RL Sci. Rep. 6:31668-31668(2016).
RN [8]
RP STRUCTURE BY NMR OF 172-259, SUBUNIT, FUNCTION, INTERACTION WITH LRP5 AND
RP LRP6, AND DISULFIDE BONDS.
RX PubMed=18524778; DOI=10.1074/jbc.m802375200;
RA Chen L., Wang K., Shao Y., Huang J., Li X., Shan J., Wu D., Zheng J.J.;
RT "Structural insight into the mechanisms of Wnt signaling antagonism by
RT Dkk.";
RL J. Biol. Chem. 283:23364-23370(2008).
CC -!- FUNCTION: Antagonizes canonical Wnt signaling by inhibiting LRP5/6
CC interaction with Wnt and by forming a ternary complex with the
CC transmembrane protein KREMEN that promotes internalization of LRP5/6.
CC DKKs play an important role in vertebrate development, where they
CC locally inhibit Wnt regulated processes such as antero-posterior axial
CC patterning, limb development, somitogenesis and eye formation. In the
CC adult, Dkks are implicated in bone formation and bone disease, cancer
CC and Alzheimer disease. {ECO:0000269|PubMed:18524778}.
CC -!- SUBUNIT: Interacts with LRP5 and LRP6. {ECO:0000269|PubMed:18524778}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- DEVELOPMENTAL STAGE: Expressed in the developing cochlea.
CC {ECO:0000269|PubMed:27550540}.
CC -!- DOMAIN: The C-terminal cysteine-rich domain mediates interaction with
CC LRP5 and LRP6.
CC -!- PTM: May be proteolytically processed by a furin-like protease.
CC -!- SIMILARITY: Belongs to the dickkopf family. {ECO:0000305}.
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DR EMBL; AJ243963; CAB60110.1; -; mRNA.
DR EMBL; AK028225; BAC25824.1; -; mRNA.
DR EMBL; AK031749; BAC27536.1; -; mRNA.
DR EMBL; AC127260; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466532; EDL12195.1; -; Genomic_DNA.
DR EMBL; BC096448; AAH96448.1; -; mRNA.
DR CCDS; CCDS17844.1; -.
DR RefSeq; NP_064661.2; NM_020265.4.
DR PDB; 2JTK; NMR; -; A=172-259.
DR PDBsum; 2JTK; -.
DR AlphaFoldDB; Q9QYZ8; -.
DR SMR; Q9QYZ8; -.
DR STRING; 10090.ENSMUSP00000029665; -.
DR GlyGen; Q9QYZ8; 1 site.
DR PhosphoSitePlus; Q9QYZ8; -.
DR MaxQB; Q9QYZ8; -.
DR PaxDb; Q9QYZ8; -.
DR PRIDE; Q9QYZ8; -.
DR ProteomicsDB; 279718; -.
DR Antibodypedia; 4050; 334 antibodies from 39 providers.
DR DNASU; 56811; -.
DR Ensembl; ENSMUST00000029665; ENSMUSP00000029665; ENSMUSG00000028031.
DR GeneID; 56811; -.
DR KEGG; mmu:56811; -.
DR UCSC; uc008rjw.2; mouse.
DR CTD; 27123; -.
DR MGI; MGI:1890663; Dkk2.
DR VEuPathDB; HostDB:ENSMUSG00000028031; -.
DR eggNOG; KOG1218; Eukaryota.
DR GeneTree; ENSGT00940000162188; -.
DR HOGENOM; CLU_080459_2_0_1; -.
DR InParanoid; Q9QYZ8; -.
DR OMA; SNYICVP; -.
DR OrthoDB; 1139517at2759; -.
DR PhylomeDB; Q9QYZ8; -.
DR TreeFam; TF330916; -.
DR Reactome; R-MMU-3772470; Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
DR BioGRID-ORCS; 56811; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Dkk2; mouse.
DR EvolutionaryTrace; Q9QYZ8; -.
DR PRO; PR:Q9QYZ8; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9QYZ8; protein.
DR Bgee; ENSMUSG00000028031; Expressed in vestibular membrane of cochlear duct and 183 other tissues.
DR Genevisible; Q9QYZ8; MM.
DR GO; GO:0005576; C:extracellular region; ISS:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0039706; F:co-receptor binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0048019; F:receptor antagonist activity; IBA:GO_Central.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:MGI.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:ParkinsonsUK-UCL.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR006796; Dickkopf_N.
DR InterPro; IPR039863; DKK-like.
DR PANTHER; PTHR12113; PTHR12113; 1.
DR Pfam; PF04706; Dickkopf_N; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Developmental protein; Disulfide bond; Glycoprotein;
KW Reference proteome; Secreted; Signal; Wnt signaling pathway.
FT SIGNAL 1..33
FT /evidence="ECO:0000255"
FT CHAIN 34..259
FT /note="Dickkopf-related protein 2"
FT /id="PRO_0000007221"
FT REGION 42..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 78..127
FT /note="DKK-type Cys-1"
FT REGION 183..256
FT /note="DKK-type Cys-2"
FT COMPBIAS 42..59
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 52
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 183..195
FT /evidence="ECO:0000269|PubMed:18524778"
FT DISULFID 189..204
FT /evidence="ECO:0000269|PubMed:18524778"
FT DISULFID 194..231
FT /evidence="ECO:0000269|PubMed:18524778"
FT DISULFID 214..239
FT /evidence="ECO:0000269|PubMed:18524778"
FT DISULFID 233..256
FT /evidence="ECO:0000269|PubMed:18524778"
FT CONFLICT 35
FT /note="L -> P (in Ref. 1; CAB60110)"
FT /evidence="ECO:0000305"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:2JTK"
FT STRAND 193..196
FT /evidence="ECO:0007829|PDB:2JTK"
FT STRAND 199..201
FT /evidence="ECO:0007829|PDB:2JTK"
FT STRAND 203..206
FT /evidence="ECO:0007829|PDB:2JTK"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:2JTK"
FT STRAND 222..224
FT /evidence="ECO:0007829|PDB:2JTK"
FT STRAND 237..241
FT /evidence="ECO:0007829|PDB:2JTK"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:2JTK"
FT STRAND 254..258
FT /evidence="ECO:0007829|PDB:2JTK"
SQ SEQUENCE 259 AA; 28432 MW; E649ED8E3BC7E8E4 CRC64;
MAALMRVKDS SRCLLLLAAV LMVESSQLGS SRAKLNSIKS SLGGETPAQS ANRSAGMNQG
LAFGGSKKGK SLGQAYPCSS DKECEVGRYC HSPHQGSSAC MLCRRKKKRC HRDGMCCPGT
RCNNGICIPV TESILTPHIP ALDGTRHRDR NHGHYSNHDL GWQNLGRPHS KMPHIKGHEG
DPCLRSSDCI DGFCCARHFW TKICKPVLHQ GEVCTKQRKK GSHGLEIFQR CDCAKGLSCK
VWKDATYSSK ARLHVCQKI
