LOCUS       NM_003882               5190 bp    mRNA    linear   PRI 17-SEP-2024
DEFINITION  Homo sapiens cellular communication network factor 4 (CCN4),
            transcript variant 1, mRNA.
ACCESSION   NM_003882
VERSION     NM_003882.4
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 5190)
  AUTHORS   Dropmann,A., Alex,S., Schorn,K., Tong,C., Caccamo,T., Godoy,P.,
            Ilkavets,I., Liebe,R., Gonzalez,D., Hengstler,J.G., Piiper,A.,
            Quagliata,L., Matter,M.S., Waidmann,O., Finkelmeier,F., Feng,T.,
            Weiss,T.S., Rahbari,N., Birgin,E., Rasbach,E., Roessler,S.,
            Breuhahn,K., Toth,M., Ebert,M.P., Dooley,S., Hammad,S. and
            Meindl-Beinker,N.M.
  TITLE     The TGF-beta1 target WISP1 is highly expressed in liver cirrhosis
            and cirrhotic HCC microenvironment and involved in pro- and
            anti-tumorigenic effects
  JOURNAL   Biochem Biophys Res Commun 732, 150409 (2024)
   PUBMED   39033550
  REMARK    GeneRIF: The TGF-beta1 target WISP1 is highly expressed in liver
            cirrhosis and cirrhotic HCC microenvironment and involved in pro-
            and anti-tumorigenic effects.
REFERENCE   2  (bases 1 to 5190)
  AUTHORS   Singh,K. and Oladipupo,S.S.
  TITLE     An overview of CCN4 (WISP1) role in human diseases
  JOURNAL   J Transl Med 22 (1), 601 (2024)
   PUBMED   38937782
  REMARK    GeneRIF: An overview of CCN4 (WISP1) role in human diseases.
            Review article
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 5190)
  AUTHORS   Christopoulou,M.E., Skandalis,S.S., Papakonstantinou,E., Stolz,D.
            and Aletras,A.J.
  TITLE     WISP1 induces the expression of macrophage migration inhibitory
            factor in human lung fibroblasts through Src kinases and
            EGFR-activated signaling pathways
  JOURNAL   Am J Physiol Cell Physiol 326 (3), C850-C865 (2024)
   PUBMED   38145300
  REMARK    GeneRIF: WISP1 induces the expression of macrophage migration
            inhibitory factor in human lung fibroblasts through Src kinases and
            EGFR-activated signaling pathways.
REFERENCE   4  (bases 1 to 5190)
  AUTHORS   Chen,Y., Li,P., Lin,M., Jiang,Y., Tan,G., Huang,L. and Song,D.
  TITLE     Silencing of METTL3 prevents the proliferation, migration,
            epithelial-mesenchymal transition, and renal fibrosis of high
            glucose-induced HK2 cells by mediating WISP1 in m6A-dependent
            manner
  JOURNAL   Aging (Albany NY) 16 (2), 1237-1248 (2024)
   PUBMED   38289593
  REMARK    GeneRIF: Silencing of METTL3 prevents the proliferation, migration,
            epithelial-mesenchymal transition, and renal fibrosis of high
            glucose-induced HK2 cells by mediating WISP1 in m6A-dependent
            manner.
REFERENCE   5  (bases 1 to 5190)
  AUTHORS   Liu,J., Lv,S., Ma,W., Yang,D. and Zhang,X.
  TITLE     Effect of WISP1 on paraquat-induced EMT
  JOURNAL   Toxicol In Vitro 93, 105693 (2023)
   PUBMED   37689312
  REMARK    GeneRIF: Effect of WISP1 on paraquat-induced EMT.
REFERENCE   6  (bases 1 to 5190)
  AUTHORS   Xie,D., Nakachi,K., Wang,H., Elashoff,R. and Koeffler,H.P.
  TITLE     Elevated levels of connective tissue growth factor, WISP-1, and
            CYR61 in primary breast cancers associated with more advanced
            features
  JOURNAL   Cancer Res 61 (24), 8917-8923 (2001)
   PUBMED   11751417
  REMARK    GeneRIF: Elevated levels of connective tissue growth factor,
            WISP-1, and CYR61 in primary breast cancers associated with more
            advanced features.
REFERENCE   7  (bases 1 to 5190)
  AUTHORS   Desnoyers,L., Arnott,D. and Pennica,D.
  TITLE     WISP-1 binds to decorin and biglycan
  JOURNAL   J Biol Chem 276 (50), 47599-47607 (2001)
   PUBMED   11598131
REFERENCE   8  (bases 1 to 5190)
  AUTHORS   Tanaka,S., Sugimachi,K., Saeki,H., Kinoshita,J., Ohga,T.,
            Shimada,M., Maehara,Y. and Sugimachi,K.
  TITLE     A novel variant of WISP1 lacking a Von Willebrand type C module
            overexpressed in scirrhous gastric carcinoma
  JOURNAL   Oncogene 20 (39), 5525-5532 (2001)
   PUBMED   11571650
REFERENCE   9  (bases 1 to 5190)
  AUTHORS   Xu,L., Corcoran,R.B., Welsh,J.W., Pennica,D. and Levine,A.J.
  TITLE     WISP-1 is a Wnt-1- and beta-catenin-responsive oncogene
  JOURNAL   Genes Dev 14 (5), 585-595 (2000)
   PUBMED   10716946
REFERENCE   10 (bases 1 to 5190)
  AUTHORS   Pennica,D., Swanson,T.A., Welsh,J.W., Roy,M.A., Lawrence,D.A.,
            Lee,J., Brush,J., Taneyhill,L.A., Deuel,B., Lew,M., Watanabe,C.,
            Cohen,R.L., Melhem,M.F., Finley,G.G., Quirke,P., Goddard,A.D.,
            Hillan,K.J., Gurney,A.L., Botstein,D. and Levine,A.J.
  TITLE     WISP genes are members of the connective tissue growth factor
            family that are up-regulated in wnt-1-transformed cells and
            aberrantly expressed in human colon tumors
  JOURNAL   Proc Natl Acad Sci U S A 95 (25), 14717-14722 (1998)
   PUBMED   9843955
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK293031.1, AF192304.6 and
            AI347990.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_003882.3.
            
            Summary: This gene encodes a member of the WNT1 inducible signaling
            pathway (WISP) protein subfamily, which belongs to the connective
            tissue growth factor (CTGF) family. WNT1 is a member of a family of
            cysteine-rich, glycosylated signaling proteins that mediate diverse
            developmental processes. The CTGF family members are characterized
            by four conserved cysteine-rich domains: insulin-like growth
            factor-binding domain, von Willebrand factor type C module,
            thrombospondin domain and C-terminal cystine knot-like domain. This
            gene may be downstream in the WNT1 signaling pathway that is
            relevant to malignant transformation. It is expressed at a high
            level in fibroblast cells, and overexpressed in colon tumors. The
            encoded protein binds to decorin and biglycan, two members of a
            family of small leucine-rich proteoglycans present in the
            extracellular matrix of connective tissue, and possibly prevents
            the inhibitory activity of decorin and biglycan in tumor cell
            proliferation. It also attenuates p53-mediated apoptosis in
            response to DNA damage through activation of the Akt kinase. It is
            83% identical to the mouse protein at the amino acid level.
            Multiple alternatively spliced transcript variants have been
            identified. [provided by RefSeq, Mar 2011].
            
            Transcript Variant: This variant (1) encodes the full length
            protein (isoform 1).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            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 :: AK315822.1, AF100779.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1966682, SAMEA1968189
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000250160.11/ ENSP00000250160.5
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1511              AK293031.1         1-1511
            1512-4914           AF192304.6         66135-69537
            4915-5190           AI347990.1         5-280               c
FEATURES             Location/Qualifiers
     source          1..5190
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="8"
                     /map="8q24.22"
     gene            1..5190
                     /gene="CCN4"
                     /gene_synonym="WISP1; WISP1-OT1; WISP1-UT1; WISP1c;
                     WISP1i; WISP1tc"
                     /note="cellular communication network factor 4"
                     /db_xref="GeneID:8840"
                     /db_xref="HGNC:HGNC:12769"
                     /db_xref="MIM:603398"
     exon            1..175
                     /gene="CCN4"
                     /gene_synonym="WISP1; WISP1-OT1; WISP1-UT1; WISP1c;
                     WISP1i; WISP1tc"
                     /inference="alignment:Splign:2.1.0"
     CDS             107..1210
                     /gene="CCN4"
                     /gene_synonym="WISP1; WISP1-OT1; WISP1-UT1; WISP1c;
                     WISP1i; WISP1tc"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; WNT1 inducible signaling pathway protein 1;
                     WNT1 induced secreted protein 1; CCN family member 4;
                     WISP1 3'UTR-associated RNA 1; WISP1 overlapping transcript
                     1 (non-protein coding)"
                     /codon_start=1
                     /product="CCN family member 4 isoform 1 precursor"
                     /protein_id="NP_003873.1"
                     /db_xref="CCDS:CCDS6371.1"
                     /db_xref="GeneID:8840"
                     /db_xref="HGNC:HGNC:12769"
                     /db_xref="MIM:603398"
                     /translation="MRWFLPWTLAAVTAAAASTVLATALSPAPTTMDFTPAPLEDTSS
                     RPQFCKWPCECPPSPPRCPLGVSLITDGCECCKMCAQQLGDNCTEAAICDPHRGLYCD
                     YSGDRPRYAIGVCAQVVGVGCVLDGVRYNNGQSFQPNCKYNCTCIDGAVGCTPLCLRV
                     RPPRLWCPHPRRVSIPGHCCEQWVCEDDAKRPRKTAPRDTGAFDAVGEVEAWHRNCIA
                     YTSPWSPCSTSCGLGVSTRISNVNAQCWPEQESRLCNLRPCDVDIHTLIKAGKKCLAV
                     YQPEASMNFTLAGCISTRSYQPKYCGVCMDNRCCIPYKSKTIDVSFQCPDGLGFSRQV
                     LWINACFCNLSCRNPNDIFADLESYPDFSEIAN"
     exon            176..455
                     /gene="CCN4"
                     /gene_synonym="WISP1; WISP1-OT1; WISP1-UT1; WISP1c;
                     WISP1i; WISP1tc"
                     /inference="alignment:Splign:2.1.0"
     exon            456..716
                     /gene="CCN4"
                     /gene_synonym="WISP1; WISP1-OT1; WISP1-UT1; WISP1c;
                     WISP1i; WISP1tc"
                     /inference="alignment:Splign:2.1.0"
     exon            717..910
                     /gene="CCN4"
                     /gene_synonym="WISP1; WISP1-OT1; WISP1-UT1; WISP1c;
                     WISP1i; WISP1tc"
                     /inference="alignment:Splign:2.1.0"
     exon            911..5190
                     /gene="CCN4"
                     /gene_synonym="WISP1; WISP1-OT1; WISP1-UT1; WISP1c;
                     WISP1i; WISP1tc"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5076..5081
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CCN4"
                     /gene_synonym="WISP1; WISP1-OT1; WISP1-UT1; WISP1c;
                     WISP1i; WISP1tc"
                     /note="hexamer: AATAAA"
     polyA_site      5096
                     /gene="CCN4"
                     /gene_synonym="WISP1; WISP1-OT1; WISP1-UT1; WISP1c;
                     WISP1i; WISP1tc"
                     /note="major polyA site"
     regulatory      5168..5173
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CCN4"
                     /gene_synonym="WISP1; WISP1-OT1; WISP1-UT1; WISP1c;
                     WISP1i; WISP1tc"
                     /note="hexamer: AATAAA"
     polyA_site      5190
                     /gene="CCN4"
                     /gene_synonym="WISP1; WISP1-OT1; WISP1-UT1; WISP1c;
                     WISP1i; WISP1tc"
ORIGIN      
        1 atatctggtg ctcctgatgg gccggccagt ctgggcccag ctcccccgag aggtggtcgg
       61 atcctctggg ctgctcggtc gatgcctgtg ccactgacgt ccaggcatga ggtggttcct
      121 gccctggacg ctggcagcag tgacagcagc agccgccagc accgtcctgg ccacggccct
      181 ctctccagcc cctacgacca tggactttac cccagctcca ctggaggaca cctcctcacg
      241 cccccaattc tgcaagtggc catgtgagtg cccgccatcc ccaccccgct gcccgctggg
      301 ggtcagcctc atcacagatg gctgtgagtg ctgtaagatg tgcgctcagc agcttgggga
      361 caactgcacg gaggctgcca tctgtgaccc ccaccggggc ctctactgtg actacagcgg
      421 ggaccgcccg aggtacgcaa taggagtgtg tgcacaggtg gtcggtgtgg gctgcgtcct
      481 ggatggggtg cgctacaaca acggccagtc cttccagcct aactgcaagt acaactgcac
      541 gtgcatcgac ggcgcggtgg gctgcacacc actgtgcctc cgagtgcgcc ccccgcgtct
      601 ctggtgcccc cacccgcggc gcgtgagcat acctggccac tgctgtgagc agtgggtatg
      661 tgaggacgac gccaagaggc cacgcaagac cgcaccccgt gacacaggag ccttcgatgc
      721 tgtgggtgag gtggaggcat ggcacaggaa ctgcatagcc tacacaagcc cctggagccc
      781 ttgctccacc agctgcggcc tgggggtctc cactcggatc tccaatgtta acgcccagtg
      841 ctggcctgag caagagagcc gcctctgcaa cttgcggcca tgcgatgtgg acatccatac
      901 actcattaag gcagggaaga agtgtctggc tgtgtaccag ccagaggcat ccatgaactt
      961 cacacttgcg ggctgcatca gcacacgctc ctatcaaccc aagtactgtg gagtttgcat
     1021 ggacaatagg tgctgcatcc cctacaagtc taagactatc gacgtgtcct tccagtgtcc
     1081 tgatgggctt ggcttctccc gccaggtcct atggattaat gcctgcttct gtaacctgag
     1141 ctgtaggaat cccaatgaca tctttgctga cttggaatcc taccctgact tctcagaaat
     1201 tgccaactag gcaggcacaa atcttgggtc ttggggacta acccaatgcc tgtgaagcag
     1261 tcagccctta tggccaataa cttttcacca atgagcctta gttaccctga tctggaccct
     1321 tggcctccat ttctgtctct aaccattcaa atgacgcctg atggtgctgc tcaggcccat
     1381 gctatgagtt ttctccttga tatcattcag catctactct aaagaaaaat gcctgtctct
     1441 agctgttctg gactacaccc aagcctgatc cagcctttcc aagtcactag aagtcctgct
     1501 ggatcttgcc taaatcccaa gaaatggaat caggtagact tttaatatca ctaatttctt
     1561 ctttagatgc caaaccacaa gactctttgg gtccattcag atgaatagat ggaatttgga
     1621 acaatagaat aatctattat ttggagcctg ccaagaggta ctgtaatggg taattctgac
     1681 gtcagcgcac caaaactatc ctgattccaa atatgtatgc acctcaaggt catcaaacat
     1741 ttgccaagtg agttgaatag ttgcttaatt ttgattttta atggaaagtt gtatccatta
     1801 acctgggcat tgttgaggtt aagtttctct tcacccctac actgtgaagg gtacagatta
     1861 ggtttgtccc agtcagaaat aaaatttgat aaacattcct gttgatggga aaagccccca
     1921 gttaatactc cagagacagg gaaaggtcag cccgtttcag aaggaccaat tgactctcac
     1981 actgaatcag ctgctgactg gcagggcttt gggcagttgg ccaggctctt ccttgaatct
     2041 tctcccttgt cctgcttggg gttcatagga attggtaagg cctctggact ggcctgtctg
     2101 gcccctgaga gtggtgccct ggaacactcc tctactctta cagagccttg agagacccag
     2161 ctgcagacca tgccagaccc actgaaatga ccaagacagg ttcaggtagg ggtgtgggtc
     2221 aaaccaagaa gtgggtgccc ttggtagcag cctggggtga cctctagagc tggaggctgt
     2281 gggactccag gggcccccgt gttcaggaca catctattgc agagactcat ttcacagcct
     2341 ttcgttctgc tgaccaaatg gccagttttc tggtaggaag atggaggttt accggttgtt
     2401 tagaaacaga aatagactta ataaaggttt aaagctgaag aggttgaagc taaaaggaaa
     2461 aggttgttgt taatgaatat caggctatta tttattgtat taggaaaata taatatttac
     2521 tgttagaatt cttttattta gggccttttc tgtgccagac attgctctca gtgctttgca
     2581 tgtattagct cactgaatct tcacgacaat gttgagaagt tcccattatt atttctgttc
     2641 ttacaaatgt gaaacggaag ctcatagagg tgagaaaact caaccagagt cacccagttg
     2701 gtgactggga aagttaggat tcagatcgaa attggactgt ctttataacc catattttcc
     2761 ccctgttttt agagcttcca aatgtgtcag aataggaaaa cattgcaata aatggcttga
     2821 ttttttaatg tcatttttcc ctcttatagt ctttctagct ccttttcaaa agacgagaat
     2881 atctgatttt ctgataattt aggtgcttaa gcatccaaaa tacatgggac acacaaaaat
     2941 ccaggaatcc cctgtagctt attccctctt tcccatcgga accagctctc atcacacatt
     3001 taaaagatga ttctgtttac ccaatgctgc atattgaatg ttgtgtagtt attcacaggg
     3061 aattctgtgc agtgtgcaga gagattccta aacgggaaaa ggactgggaa tacatcctcc
     3121 ttactgtgac ctccccaaaa cctagtccag tgcaaggtat acagtggtgc tcattaaata
     3181 cttgatgaat acaggaagct gtgcatgtgt tcctactttt attcgaagct ctcttcttcc
     3241 aaagctacat gaaaatagaa ttttaacagt caaaatttta tattaagtgc cttagcaaaa
     3301 gagacattta atatttcaaa gaaatgcata tgtatgtata catatatttg tgtatgcgta
     3361 tgcaagaatt cttgtataaa gagaattcac tccatgaatg atctcttctg taagtcagtg
     3421 tgaatcatgt tagattttct gagagtgaaa acacctgcca tctacaaatt acaaggctgg
     3481 ataacagctc actccatttg aaattcagtg gaaacccaag agctaggttc ttactgaatt
     3541 tgcatctcaa tttgggaaac tgaacttagc tttcaaagat cataggaagt ctggttggag
     3601 aaactaggga ttattctggc aatgggtgca ggaaggtggt cagaataacc cagtcgccat
     3661 tggttttgag aaacggaact atcttatgca gagcccggag ggcaagtctc agacccatgg
     3721 gttgaagcca tggagaagga aatttggatc caatgtaatg aagcgctttc taagtcagaa
     3781 tttccctgca atggtgtggc ctgattcaat aaaaattaag aataataaat ataatggaaa
     3841 aaaatctcca ctgattgagt gtttacttgg tgccaagcac tatgctaagt tgttcattat
     3901 tttatttaat tgttacagca attttgagta tgcatctttc actattttat aagtggaaaa
     3961 gagaagtgcc cccaaaaagt tagagctcaa acagcagctt attctaccag cccctgctct
     4021 tgcggaggcc tctggaaaag acctgaatga cacctattgg agaattacat ctacaagggg
     4081 cttcaaacag accaaataga tcatcacctc tgtggtccct tgttaactat atgttctgag
     4141 acaaaggaaa gctaccctaa gggttagtta acctttgctg aggaaattta cattcatact
     4201 tagagtgaat tactcaggtg tgcttaggtg tgcaaaaggg aaggagacct gaattcacca
     4261 agttaaatct tgctaaacct tatcataagc attttttgag cgcttagcat acaccaagcc
     4321 ttgtggaagg tgctttcctg ccatatctca tttaatcctc acagcaaacc tatagaatat
     4381 ggcattatca tctgagtctc acagaagttt agtcgtgtac tcaaggtctt accagctagt
     4441 gaacagcaga ccaagactgg aaacccagga tagtctgata cctgagccat ctcttcttgt
     4501 gctacgccta gttattctgt cccccaaatc aaaaggcatg acctttataa gaggcgcttt
     4561 actgacaata gctgcaattt taactttgaa aatgattcag aattatcaaa gatagtagat
     4621 tcgaatgaca tgattgtcta taatctcgct agccttgtac tgtgtgtgca tagcaattac
     4681 agggaagtaa tctagctcct gactattatg ttgaactatg tcgctgcttt ttacaaactt
     4741 gtcttgatcc aaagcagtca caatgataac cctgcatatc tgggaatcat aagtcaacta
     4801 tgtatccctg tgtgtgtata tatatgtatg tatgtatcta ttttcaaact gtgatttaat
     4861 atttaaatat tcctactgcc atttttgtga ctgaaaaact acacatgagg aaacgtctta
     4921 gaattttcca atagaggaaa aataacactt gggcaatctg tcatgtttca caacagttct
     4981 catttttctc atgatttgtg tagcgtggaa tgtgtttgct caatgtgaag ggttttcatt
     5041 gctcaatttc tctgtgtaag tcttttcctt aaggtaataa accatcagca aagtcacata
     5101 ctggagttgg tggcttttct tgtacaggca gttgttatga gacaatgatg gagcattgag
     5161 catgttcaat aaatgtgcag atggtggaaa
//
