DKK2_HUMAN
ID DKK2_HUMAN Reviewed; 259 AA.
AC Q9UBU2; A0AVE9; B2R6S7; Q9UIU3;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Dickkopf-related protein 2;
DE Short=Dickkopf-2;
DE Short=Dkk-2;
DE Short=hDkk-2;
DE Flags: Precursor;
GN Name=DKK2; ORFNames=UNQ682/PRO1316;
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 [MRNA].
RC TISSUE=Fetal lung;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Tanaka S., Sugimachi K., Sugimachi K.;
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-146.
RC TISSUE=Brain, and Testis;
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 75-259.
RA Tate G., Suzuki T., Mitsuya T.;
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [8]
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).
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 -!- INTERACTION:
CC Q9UBU2; P60371: KRTAP10-6; NbExp=3; IntAct=EBI-13274770, EBI-12012928;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed in heart, brain, skeletal muscle and
CC lung.
CC -!- DOMAIN: The C-terminal cysteine-rich domain mediates interaction with
CC LRP5 and LRP6. {ECO:0000250}.
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; AF177395; AAF02675.1; -; mRNA.
DR EMBL; AB033208; BAA85465.1; -; mRNA.
DR EMBL; AY358414; AAQ88780.1; -; mRNA.
DR EMBL; AK312695; BAG35574.1; -; mRNA.
DR EMBL; CH471057; EAX06209.1; -; Genomic_DNA.
DR EMBL; BC075077; AAH75077.1; -; mRNA.
DR EMBL; BC075078; AAH75078.1; -; mRNA.
DR EMBL; BC126328; AAI26329.1; -; mRNA.
DR EMBL; BC126330; AAI26331.1; -; mRNA.
DR EMBL; AB035181; BAA87056.1; -; Genomic_DNA.
DR CCDS; CCDS3675.1; -.
DR RefSeq; NP_055236.1; NM_014421.2.
DR AlphaFoldDB; Q9UBU2; -.
DR SMR; Q9UBU2; -.
DR BioGRID; 118014; 49.
DR DIP; DIP-59408N; -.
DR IntAct; Q9UBU2; 2.
DR STRING; 9606.ENSP00000285311; -.
DR GlyGen; Q9UBU2; 1 site.
DR iPTMnet; Q9UBU2; -.
DR PhosphoSitePlus; Q9UBU2; -.
DR BioMuta; DKK2; -.
DR DMDM; 13124093; -.
DR jPOST; Q9UBU2; -.
DR MassIVE; Q9UBU2; -.
DR MaxQB; Q9UBU2; -.
DR PaxDb; Q9UBU2; -.
DR PeptideAtlas; Q9UBU2; -.
DR PRIDE; Q9UBU2; -.
DR ABCD; Q9UBU2; 2 sequenced antibodies.
DR Antibodypedia; 4050; 334 antibodies from 39 providers.
DR DNASU; 27123; -.
DR Ensembl; ENST00000285311.8; ENSP00000285311.3; ENSG00000155011.9.
DR GeneID; 27123; -.
DR KEGG; hsa:27123; -.
DR MANE-Select; ENST00000285311.8; ENSP00000285311.3; NM_014421.3; NP_055236.1.
DR UCSC; uc003hyi.4; human.
DR CTD; 27123; -.
DR DisGeNET; 27123; -.
DR GeneCards; DKK2; -.
DR HGNC; HGNC:2892; DKK2.
DR HPA; ENSG00000155011; Tissue enhanced (cervix).
DR MIM; 605415; gene.
DR neXtProt; NX_Q9UBU2; -.
DR OpenTargets; ENSG00000155011; -.
DR PharmGKB; PA27346; -.
DR VEuPathDB; HostDB:ENSG00000155011; -.
DR eggNOG; KOG1218; Eukaryota.
DR GeneTree; ENSGT00940000162188; -.
DR HOGENOM; CLU_080459_2_0_1; -.
DR InParanoid; Q9UBU2; -.
DR OrthoDB; 1139517at2759; -.
DR PhylomeDB; Q9UBU2; -.
DR TreeFam; TF330916; -.
DR PathwayCommons; Q9UBU2; -.
DR Reactome; R-HSA-201681; TCF dependent signaling in response to WNT.
DR Reactome; R-HSA-3772470; Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
DR Reactome; R-HSA-5339717; Signaling by LRP5 mutants.
DR SignaLink; Q9UBU2; -.
DR BioGRID-ORCS; 27123; 10 hits in 1068 CRISPR screens.
DR ChiTaRS; DKK2; human.
DR GeneWiki; DKK2; -.
DR GenomeRNAi; 27123; -.
DR Pharos; Q9UBU2; Tbio.
DR PRO; PR:Q9UBU2; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9UBU2; protein.
DR Bgee; ENSG00000155011; Expressed in upper leg skin and 122 other tissues.
DR ExpressionAtlas; Q9UBU2; baseline and differential.
DR Genevisible; Q9UBU2; HS.
DR GO; GO:0005615; C:extracellular space; IDA: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:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:BHF-UCL.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:BHF-UCL.
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 Developmental protein; Disulfide bond; Glycoprotein; Reference proteome;
KW 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_0000007220"
FT REGION 78..127
FT /note="DKK-type Cys-1"
FT REGION 183..256
FT /note="DKK-type Cys-2"
FT CARBOHYD 52
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 183..195
FT /evidence="ECO:0000250"
FT DISULFID 189..204
FT /evidence="ECO:0000250"
FT DISULFID 194..231
FT /evidence="ECO:0000250"
FT DISULFID 214..239
FT /evidence="ECO:0000250"
FT DISULFID 233..256
FT /evidence="ECO:0000250"
FT VARIANT 146
FT /note="R -> Q (in dbSNP:rs17037102)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_021966"
SQ SEQUENCE 259 AA; 28447 MW; 39DDA3FA8975E87F CRC64;
MAALMRSKDS SCCLLLLAAV LMVESSQIGS SRAKLNSIKS SLGGETPGQA ANRSAGMYQG
LAFGGSKKGK NLGQAYPCSS DKECEVGRYC HSPHQGSSAC MVCRRKKKRC HRDGMCCPST
RCNNGICIPV TESILTPHIP ALDGTRHRDR NHGHYSNHDL GWQNLGRPHT KMSHIKGHEG
DPCLRSSDCI EGFCCARHFW TKICKPVLHQ GEVCTKQRKK GSHGLEIFQR CDCAKGLSCK
VWKDATYSSK ARLHVCQKI
