LOCUS       NM_001323                592 bp    mRNA    linear   PRI 20-SEP-2024
DEFINITION  Homo sapiens cystatin E/M (CST6), mRNA.
ACCESSION   NM_001323 XM_938803
VERSION     NM_001323.4
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 592)
  AUTHORS   Gai,D., Chen,J.R., Stewart,J.P., Nookaew,I., Habelhah,H., Ashby,C.,
            Sun,F., Cheng,Y., Li,C., Xu,H., Peng,B., Garg,T.K., Schinke,C.,
            Thanendrarajan,S., Zangari,M., Chen,F., Barlogie,B., van Rhee,F.,
            Tricot,G., Shaughnessy,J.D. Jr. and Zhan,F.
  TITLE     CST6 suppresses osteolytic bone disease in multiple myeloma by
            blocking osteoclast differentiation
  JOURNAL   J Clin Invest 132 (18), e159527 (2022)
   PUBMED   35881476
  REMARK    GeneRIF: CST6 suppresses osteolytic bone disease in multiple
            myeloma by blocking osteoclast differentiation.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 592)
  AUTHORS   Li,X., Liang,Y., Lian,C., Peng,F., Xiao,Y., He,Y., Ma,C., Wang,Y.,
            Zhang,P., Deng,Y., Su,Y., Luo,C., Kong,X., Yang,Q., Liu,T. and
            Hu,G.
  TITLE     CST6 protein and peptides inhibit breast cancer bone metastasis by
            suppressing CTSB activity and osteoclastogenesis
  JOURNAL   Theranostics 11 (20), 9821-9832 (2021)
   PUBMED   34815788
  REMARK    GeneRIF: CST6 protein and peptides inhibit breast cancer bone
            metastasis by suppressing CTSB activity and osteoclastogenesis.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 592)
  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   4  (bases 1 to 592)
  AUTHORS   van den Bogaard,E.H.J., van Geel,M., van Vlijmen-Willems,I.M.J.J.,
            Jansen,P.A.M., Peppelman,M., van Erp,P.E.J., Atalay,S.,
            Venselaar,H., Simon,M.E.H., Joosten,M., Schalkwijk,J. and
            Zeeuwen,P.L.J.M.
  TITLE     Deficiency of the human cysteine protease inhibitor cystatin M/E
            causes hypotrichosis and dry skin
  JOURNAL   Genet Med 21 (7), 1559-1567 (2019)
   PUBMED   30425301
  REMARK    GeneRIF: a loss-of-function variant in the human CST6 gene, which
            causes a novel autosomal recessive hypotrichosis syndrome
REFERENCE   5  (bases 1 to 592)
  AUTHORS   Li,Q., Zheng,Z.C., Ni,C.J., Jin,W.X., Jin,Y.X., Chen,Y.,
            Zhang,X.H., Chen,E.D. and Cai,Y.F.
  TITLE     Correlation of Cystatin E/M with Clinicopathological Features and
            Prognosis in Triple-Negative Breast Cancer
  JOURNAL   Ann Clin Lab Sci 48 (1), 40-44 (2018)
   PUBMED   29530995
  REMARK    GeneRIF: High CST6 expression is associated with lymph-node
            metastasis in Triple-Negative Breast Cancer.
REFERENCE   6  (bases 1 to 592)
  AUTHORS   Sotiropoulou,G., Anisowicz,A. and Sager,R.
  TITLE     Identification, cloning, and characterization of cystatin M, a
            novel cysteine proteinase inhibitor, down-regulated in breast
            cancer
  JOURNAL   J Biol Chem 272 (2), 903-910 (1997)
   PUBMED   8995380
REFERENCE   7  (bases 1 to 592)
  AUTHORS   Brown,W.M. and Dziegielewska,K.M.
  TITLE     Friends and relations of the cystatin superfamily--new members and
            their evolution
  JOURNAL   Protein Sci 6 (1), 5-12 (1997)
   PUBMED   9007972
  REMARK    Review article
REFERENCE   8  (bases 1 to 592)
  AUTHORS   Thiesse,M., Millar,S.J. and Dickinson,D.P.
  TITLE     The human type 2 cystatin gene family consists of eight to nine
            members, with at least seven genes clustered at a single locus on
            human chromosome 20
  JOURNAL   DNA Cell Biol 13 (2), 97-116 (1994)
   PUBMED   8179826
REFERENCE   9  (bases 1 to 592)
  AUTHORS   Barka,T., Asbell,P.A., van der Noen,H. and Prasad,A.
  TITLE     Cystatins in human tear fluid
  JOURNAL   Curr Eye Res 10 (1), 25-34 (1991)
   PUBMED   2029847
REFERENCE   10 (bases 1 to 592)
  AUTHORS   Saitoh,E., Isemura,S., Sanada,K., Kim,H.S., Smithies,O. and
            Maeda,N.
  TITLE     Cystatin superfamily. Evidence that family II cystatin genes are
            evolutionarily related to family III cystatin genes
  JOURNAL   Biol Chem Hoppe Seyler 369 Suppl, 191-197 (1988)
   PUBMED   3202964
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AI127639.1, U81233.1 and
            AA778147.1.
            
            On Nov 22, 2018 this sequence version replaced NM_001323.3.
            
            Summary: The cystatin superfamily encompasses proteins that contain
            multiple cystatin-like sequences. Some of the members are active
            cysteine protease inhibitors, while others have lost or perhaps
            never acquired this inhibitory activity. There are three inhibitory
            families in the superfamily, including the type 1 cystatins
            (stefins), type 2 cystatins and the kininogens. The type 2 cystatin
            proteins are a class of cysteine proteinase inhibitors found in a
            variety of human fluids and secretions, where they appear to
            provide protective functions. This gene encodes a cystatin from the
            type 2 family, which is down-regulated in metastatic breast tumor
            cells as compared to primary tumor cells. Loss of expression is
            likely associated with the progression of a primary tumor to a
            metastatic phenotype. [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 :: U81233.1, BQ685679.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1966682, SAMEA1968540
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000312134.3/ ENSP00000311313.2
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-112               AI127639.1         18-129
            113-542             U81233.1           94-523
            543-592             AA778147.1         10-59               c
FEATURES             Location/Qualifiers
     source          1..592
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11q13.1"
     gene            1..592
                     /gene="CST6"
                     /gene_synonym="ECTD15"
                     /note="cystatin E/M"
                     /db_xref="GeneID:1474"
                     /db_xref="HGNC:HGNC:2478"
                     /db_xref="MIM:601891"
     exon            1..277
                     /gene="CST6"
                     /gene_synonym="ECTD15"
                     /inference="alignment:Splign:2.1.0"
     CDS             38..487
                     /gene="CST6"
                     /gene_synonym="ECTD15"
                     /note="cystatin 6; cystatin-M; cystatin M/E; cysteine
                     proteinase inhibitor; cystatin-E"
                     /codon_start=1
                     /product="cystatin-M precursor"
                     /protein_id="NP_001314.1"
                     /db_xref="CCDS:CCDS8126.1"
                     /db_xref="GeneID:1474"
                     /db_xref="HGNC:HGNC:2478"
                     /db_xref="MIM:601891"
                     /translation="MARSNLPLALGLALVAFCLLALPRDARARPQERMVGELRDLSPD
                     DPQVQKAAQAAVASYNMGSNSIYYFRDTHIIKAQSQLVAGIKYFLTMEMGSTDCRKTR
                     VTGDHVDLTTCPLAAGAQQEKLRCDFEVLVVPWQNSSQLLKHNCVQM"
     exon            278..403
                     /gene="CST6"
                     /gene_synonym="ECTD15"
                     /inference="alignment:Splign:2.1.0"
     exon            404..592
                     /gene="CST6"
                     /gene_synonym="ECTD15"
                     /inference="alignment:Splign:2.1.0"
     regulatory      566..571
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CST6"
                     /gene_synonym="ECTD15"
                     /note="hexamer: AATAAA"
     polyA_site      592
                     /gene="CST6"
                     /gene_synonym="ECTD15"
                     /note="major polyA site"
ORIGIN      
        1 actcacggct ctgagggctc cgacggcact gacggccatg gcgcgttcga acctcccgct
       61 ggcgctgggc ctggccctgg tcgcattctg cctcctggcg ctgccacgcg acgcccgggc
      121 ccggccgcag gagcgcatgg tcggagaact ccgggacctg tcgcccgacg acccgcaggt
      181 gcagaaggcg gcgcaggcgg ccgtggccag ctacaacatg ggcagcaaca gcatctacta
      241 cttccgagac acgcacatca tcaaggcgca gagccagctg gtggccggca tcaagtactt
      301 cctgacgatg gagatgggga gcacagactg ccgcaagacc agggtcactg gagaccacgt
      361 cgacctcacc acttgccccc tggcagcagg ggcgcagcag gagaagctgc gctgtgactt
      421 tgaggtcctt gtggttccct ggcagaactc ctctcagctc ctaaagcaca actgtgtgca
      481 gatgtgataa gtccccgagg gcgaaggcca ttgggtttgg ggccatggtg gagggcactt
      541 caggtccgtg ggccgtatct gtcacaataa atggccagtg ctgcttcttg ca
//
