DKK3_MOUSE
ID DKK3_MOUSE Reviewed; 349 AA.
AC Q9QUN9;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Dickkopf-related protein 3;
DE Short=Dickkopf-3;
DE Short=Dkk-3;
DE Short=mDkk-3;
DE Flags: Precursor;
GN Name=Dkk3;
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 [MRNA].
RX PubMed=10570958; DOI=10.1016/s0378-1119(99)00365-0;
RA Krupnik V.E., Sharp J.D., Jiang C., Robison K., Chickering T.W.,
RA Amaravadi L., Brown D.E., Guyot D., Mays G., Leiby K., Chang B., Duong T.,
RA Goodearl A.D.J., Gearing D.P., Sokol S.Y., McCarthy S.A.;
RT "Functional and structural diversity of the human Dickkopf gene family.";
RL Gene 238:301-313(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain, and Retina;
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 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 [6]
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).
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 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with LRP5 and LRP6. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Highest expression in brain, eye and heart.
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. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the dickkopf family. {ECO:0000305}.
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DR EMBL; AJ243964; CAB60111.1; -; mRNA.
DR EMBL; AF177400; AAF02680.1; -; mRNA.
DR EMBL; AK004853; BAB23617.1; -; mRNA.
DR EMBL; BC046304; AAH46304.1; -; mRNA.
DR EMBL; BC050934; AAH50934.1; -; mRNA.
DR CCDS; CCDS21752.1; -.
DR RefSeq; NP_056629.1; NM_015814.2.
DR RefSeq; XP_006508076.1; XM_006508013.1.
DR AlphaFoldDB; Q9QUN9; -.
DR IntAct; Q9QUN9; 1.
DR STRING; 10090.ENSMUSP00000033036; -.
DR GlyConnect; 2254; 3 N-Linked glycans (2 sites).
DR GlyGen; Q9QUN9; 4 sites, 3 N-linked glycans (2 sites).
DR iPTMnet; Q9QUN9; -.
DR PhosphoSitePlus; Q9QUN9; -.
DR MaxQB; Q9QUN9; -.
DR PaxDb; Q9QUN9; -.
DR PeptideAtlas; Q9QUN9; -.
DR PRIDE; Q9QUN9; -.
DR ProteomicsDB; 279779; -.
DR Antibodypedia; 2166; 642 antibodies from 41 providers.
DR DNASU; 50781; -.
DR Ensembl; ENSMUST00000033036; ENSMUSP00000033036; ENSMUSG00000030772.
DR GeneID; 50781; -.
DR KEGG; mmu:50781; -.
DR UCSC; uc009jgi.1; mouse.
DR CTD; 27122; -.
DR MGI; MGI:1354952; Dkk3.
DR VEuPathDB; HostDB:ENSMUSG00000030772; -.
DR eggNOG; KOG1218; Eukaryota.
DR GeneTree; ENSGT00390000000221; -.
DR HOGENOM; CLU_055300_0_0_1; -.
DR InParanoid; Q9QUN9; -.
DR OMA; QCQPHGR; -.
DR OrthoDB; 1139517at2759; -.
DR PhylomeDB; Q9QUN9; -.
DR TreeFam; TF337340; -.
DR BioGRID-ORCS; 50781; 4 hits in 70 CRISPR screens.
DR ChiTaRS; Dkk3; mouse.
DR PRO; PR:Q9QUN9; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9QUN9; protein.
DR Bgee; ENSMUSG00000030772; Expressed in epithelium of lens and 307 other tissues.
DR Genevisible; Q9QUN9; MM.
DR GO; GO:0005576; C:extracellular region; ISS:MGI.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0039706; F:co-receptor binding; IBA:GO_Central.
DR GO; GO:0048019; F:receptor antagonist activity; IBA:GO_Central.
DR GO; GO:0030325; P:adrenal gland development; IEA:Ensembl.
DR GO; GO:0032348; P:negative regulation of aldosterone biosynthetic process; ISO:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:MGI.
DR GO; GO:2000065; P:negative regulation of cortisol biosynthetic process; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; 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 2: Evidence at transcript level;
KW Coiled coil; Developmental protein; Disulfide bond; Glycoprotein;
KW Reference proteome; Secreted; Signal; Wnt signaling pathway.
FT SIGNAL 1..22
FT /evidence="ECO:0000250"
FT CHAIN 23..349
FT /note="Dickkopf-related protein 3"
FT /id="PRO_0000007223"
FT REGION 147..195
FT /note="DKK-type Cys-1"
FT REGION 208..284
FT /note="DKK-type Cys-2"
FT COILED 39..84
FT /evidence="ECO:0000255"
FT CARBOHYD 96
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 208..220
FT /evidence="ECO:0000250"
FT DISULFID 214..231
FT /evidence="ECO:0000250"
FT DISULFID 219..265
FT /evidence="ECO:0000250"
FT DISULFID 241..273
FT /evidence="ECO:0000250"
SQ SEQUENCE 349 AA; 38388 MW; 564CB3C4FB2EAB88 CRC64;
MQRLGGILLC TLLAAAVPTA PAPSPTVTWT PAEPGPALNY PQEEATLNEM FREVEELMED
TQHKLRSAVE EMEAEEAAAK TSSEVNLASL PPNYHNETST ETRVGNNTVH VHQEVHKITN
NQSGQVVFSE TVITSVGDEE GKRSHECIID EDCGPTRYCQ FSSFKYTCQP CRDQQMLCTR
DSECCGDQLC AWGHCTQKAT KGGNGTICDN QRDCQPGLCC AFQRGLLFPV CTPLPVEGEL
CHDPTSQLLD LITWELEPEG ALDRCPCASG LLCQPHSHSL VYMCKPAFVG SHDHSEESQL
PREAPDEYED VGFIGEVRQE LEDLERSLAQ EMAFEGPAPV ESLGGEEEI
