LOCUS       NM_014420                896 bp    mRNA    linear   PRI 04-APR-2024
DEFINITION  Homo sapiens dickkopf WNT signaling pathway inhibitor 4 (DKK4),
            mRNA.
ACCESSION   NM_014420
VERSION     NM_014420.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 896)
  AUTHORS   Haenig,C., Atias,N., Taylor,A.K., Mazza,A., Schaefer,M.H., Russ,J.,
            Riechers,S.P., Jain,S., Coughlin,M., Fontaine,J.F., Freibaum,B.D.,
            Brusendorf,L., Zenkner,M., Porras,P., Stroedicke,M., Schnoegl,S.,
            Arnsburg,K., Boeddrich,A., Pigazzini,L., Heutink,P., Taylor,J.P.,
            Kirstein,J., Andrade-Navarro,M.A., Sharan,R. and Wanker,E.E.
  TITLE     Interactome Mapping Provides a Network of Neurodegenerative Disease
            Proteins and Uncovers Widespread Protein Aggregation in Affected
            Brains
  JOURNAL   Cell Rep 32 (7), 108050 (2020)
   PUBMED   32814053
REFERENCE   2  (bases 1 to 896)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   3  (bases 1 to 896)
  AUTHORS   Chouhan,S., Singh,S., Athavale,D., Ramteke,P., Vanuopadath,M.,
            Nair,B.G., Nair,S.S. and Bhat,M.K.
  TITLE     Sensitization of hepatocellular carcinoma cells towards doxorubicin
            and sorafenib is facilitated by glucosedependent alterations in
            reactive oxygen species, P-glycoprotein and DKK4
  JOURNAL   J Biosci 45 (2020)
   PUBMED   32713860
  REMARK    GeneRIF: Sensitization of hepatocellular carcinoma cells towards
            doxorubicin and sorafenib is facilitated by glucosedependent
            alterations in reactive oxygen species, P-glycoprotein and DKK4.
REFERENCE   4  (bases 1 to 896)
  AUTHORS   Sun,S., Yu,M., Fan,Z., Yeh,I.T., Feng,H., Liu,H. and Han,D.
  TITLE     DLX3 regulates osteogenic differentiation of bone marrow
            mesenchymal stem cells via Wnt/beta-catenin pathway mediated
            histone methylation of DKK4
  JOURNAL   Biochem Biophys Res Commun 516 (1), 171-176 (2019)
   PUBMED   31202458
  REMARK    GeneRIF: The data implied that DLX3 regulated Wnt/beta-catenin
            pathway through histone modification of DKK4 during the osteogenic
            differentiation of bone marrow mesenchymal stem cells.
REFERENCE   5  (bases 1 to 896)
  AUTHORS   Patel,S., Barkell,A.M., Gupta,D., Strong,S.L., Bruton,S.,
            Muskett,F.W., Addis,P.W., Renshaw,P.S., Slocombe,P.M., Doyle,C.,
            Clargo,A., Taylor,R.J., Prosser,C.E., Henry,A.J., Robinson,M.K.,
            Waters,L.C., Holdsworth,G. and Carr,M.D.
  TITLE     Structural and functional analysis of Dickkopf 4 (Dkk4): New
            insights into Dkk evolution and regulation of Wnt signaling by Dkk
            and Kremen proteins
  JOURNAL   J Biol Chem 293 (31), 12149-12166 (2018)
   PUBMED   29925589
  REMARK    GeneRIF: Dkk4 CRD2 mediates high-affinity binding to both the E1E2
            region of low-density lipoprotein receptor-related protein 6 (LRP6
            E1E2) and the Kremen1 (Krm1) extracellular domain.
REFERENCE   6  (bases 1 to 896)
  AUTHORS   Proitsi,P., Li,T., Hamilton,G., Di Forti,M., Collier,D.,
            Killick,R., Chen,R., Sham,P., Murray,R., Powell,J. and Lovestone,S.
  TITLE     Positional pathway screen of wnt signaling genes in schizophrenia:
            association with DKK4
  JOURNAL   Biol Psychiatry 63 (1), 13-16 (2008)
   PUBMED   17553464
  REMARK    GeneRIF: DKK4 may play a role in schizophrenia pathogenesis
            GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   7  (bases 1 to 896)
  AUTHORS   Zhang,Z. and Henzel,W.J.
  TITLE     Signal peptide prediction based on analysis of experimentally
            verified cleavage sites
  JOURNAL   Protein Sci 13 (10), 2819-2824 (2004)
   PUBMED   15340161
REFERENCE   8  (bases 1 to 896)
  AUTHORS   Mao,B. and Niehrs,C.
  TITLE     Kremen2 modulates Dickkopf2 activity during Wnt/LRP6 signaling
  JOURNAL   Gene 302 (1-2), 179-183 (2003)
   PUBMED   12527209
REFERENCE   9  (bases 1 to 896)
  AUTHORS   Yoshida,S., Satoh,H., Mitsuya,T. and Tate,G.
  TITLE     Assignment of the human dickkopf (Xenopus) homolog 4 (DKK4) to
            chromosome 8p11.2-->p11.1 by fluorescence in situ hybridization
  JOURNAL   Cytogenet Cell Genet 94 (1-2), 88-89 (2001)
   PUBMED   11701963
  REMARK    GeneRIF: chromosome 8 mapping by FISH
REFERENCE   10 (bases 1 to 896)
  AUTHORS   Krupnik,V.E., Sharp,J.D., Jiang,C., Robison,K., Chickering,T.W.,
            Amaravadi,L., Brown,D.E., Guyot,D., Mays,G., Leiby,K., Chang,B.,
            Duong,T., Goodearl,A.D., Gearing,D.P., Sokol,S.Y. and McCarthy,S.A.
  TITLE     Functional and structural diversity of the human Dickkopf gene
            family
  JOURNAL   Gene 238 (2), 301-313 (1999)
   PUBMED   10570958
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC107885.5, BX105775.1 and
            AF177397.1.
            
            On Nov 22, 2018 this sequence version replaced NM_014420.2.
            
            Summary: This gene encodes a protein that is a member of the
            dickkopf family. The secreted protein contains two cysteine rich
            regions and is involved in embryonic development through its
            interactions with the Wnt signaling pathway. Activity of this
            protein is modulated by binding to the Wnt co-receptor and the
            co-factor kremen 2. [provided by RefSeq, Jul 2008].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: CX167283.1, CX163996.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968968, SAMEA2144335
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000220812.3/ ENSP00000220812.2
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-73                AC107885.5         72188-72260         c
            74-574              BX105775.1         1-501
            575-891             AF177397.1         508-824
            892-896             AC107885.5         69094-69098         c
FEATURES             Location/Qualifiers
     source          1..896
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="8"
                     /map="8p11.21"
     gene            1..896
                     /gene="DKK4"
                     /gene_synonym="DKK-4"
                     /note="dickkopf WNT signaling pathway inhibitor 4"
                     /db_xref="GeneID:27121"
                     /db_xref="HGNC:HGNC:2894"
                     /db_xref="MIM:605417"
     exon            1..295
                     /gene="DKK4"
                     /gene_synonym="DKK-4"
                     /inference="alignment:Splign:2.1.0"
     CDS             185..859
                     /gene="DKK4"
                     /gene_synonym="DKK-4"
                     /note="dickkopf-related protein 4; hDkk-4; dickkopf-4"
                     /codon_start=1
                     /product="dickkopf-related protein 4 precursor"
                     /protein_id="NP_055235.1"
                     /db_xref="CCDS:CCDS6130.1"
                     /db_xref="GeneID:27121"
                     /db_xref="HGNC:HGNC:2894"
                     /db_xref="MIM:605417"
                     /translation="MVAAVLLGLSWLCSPLGALVLDFNNIRSSADLHGARKGSQCLSD
                     TDCNTRKFCLQPRDEKPFCATCRGLRRRCQRDAMCCPGTLCVNDVCTTMEDATPILER
                     QLDEQDGTHAEGTTGHPVQENQPKRKPSIKKSQGRKGQEGESCLRTFDCGPGLCCARH
                     FWTKICKPVLLEGQVCSRRGHKDTAQAPEIFQRCDCGPGLLCRSQLTSNRQHARLRVC
                     QKIEKL"
     exon            296..446
                     /gene="DKK4"
                     /gene_synonym="DKK-4"
                     /inference="alignment:Splign:2.1.0"
     exon            447..599
                     /gene="DKK4"
                     /gene_synonym="DKK-4"
                     /inference="alignment:Splign:2.1.0"
     exon            600..896
                     /gene="DKK4"
                     /gene_synonym="DKK-4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      869..874
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DKK4"
                     /gene_synonym="DKK-4"
                     /note="hexamer: AATAAA"
     polyA_site      896
                     /gene="DKK4"
                     /gene_synonym="DKK-4"
                     /note="major polyA site"
ORIGIN      
        1 agactttgct cagccgattt cacgcacctt actcagacta aggtttactt ctttcagaaa
       61 aagcagtgac aaacagacga cgtgctgagc tgccagctta gtggaagctc tgctctgggt
      121 ggagagcagc ctcgctttgg tgacgcacag tgctgggacc ctccaggagc cccgggattg
      181 aaggatggtg gcggccgtcc tgctggggct gagctggctc tgctctcccc tgggagctct
      241 ggtcctggac ttcaacaaca tcaggagctc tgctgacctg catggggccc ggaagggctc
      301 acagtgcctg tctgacacgg actgcaatac cagaaagttc tgcctccagc cccgcgatga
      361 gaagccgttc tgtgctacat gtcgtgggtt gcggaggagg tgccagcgag atgccatgtg
      421 ctgccctggg acactctgtg tgaacgatgt ttgtactacg atggaagatg caaccccaat
      481 attagaaagg cagcttgatg agcaagatgg cacacatgca gaaggaacaa ctgggcaccc
      541 agtccaggaa aaccaaccca aaaggaagcc aagtattaag aaatcacaag gcaggaaggg
      601 acaagaggga gaaagttgtc tgagaacttt tgactgtggc cctggacttt gctgtgctcg
      661 tcatttttgg acgaaaattt gtaagccagt ccttttggag ggacaggtct gctccagaag
      721 agggcataaa gacactgctc aagctccaga aatcttccag cgttgcgact gtggccctgg
      781 actactgtgt cgaagccaat tgaccagcaa tcggcagcat gctcgattaa gagtatgcca
      841 aaaaatagaa aagctataaa tatttcaaaa taaagaagaa tccacattgc atttga
//
