LOCUS       NM_031443               1864 bp    mRNA    linear   PRI 12-OCT-2024
DEFINITION  Homo sapiens CCM2 scaffold protein (CCM2), transcript variant 2,
            mRNA.
ACCESSION   NM_031443
VERSION     NM_031443.4
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 1864)
  AUTHORS   Chaussenot,A., Ayrignac,X., Chatron,N., Granchon-Riolzir,T.,
            Labauge,P., Tournier-Lasserve,E. and Riant,F.
  TITLE     Loss of heterozygosity in CCM2 cDNA revealing a structural variant
            causing multiple cerebral cavernous malformations
  JOURNAL   Eur J Hum Genet 32 (7), 876-878 (2024)
   PUBMED   38755314
  REMARK    GeneRIF: Loss of heterozygosity in CCM2 cDNA revealing a structural
            variant causing multiple cerebral cavernous malformations.
REFERENCE   2  (bases 1 to 1864)
  AUTHORS   Gallione,C.J., Detter,M.R., Sheline,A., Christmas,H.M., Lee,C. and
            Marchuk,D.A.
  TITLE     Genetic genealogy uncovers a founder deletion mutation in the
            cerebral cavernous malformations 2 gene
  JOURNAL   Hum Genet 141 (11), 1761-1769 (2022)
   PUBMED   35488064
  REMARK    GeneRIF: Genetic genealogy uncovers a founder deletion mutation in
            the cerebral cavernous malformations 2 gene.
REFERENCE   3  (bases 1 to 1864)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Navarrete-Perea,J., Cannon,J.R.,
            Baltier,K., Gebreab,F., Gygi,M.P., Thornock,A., Zarraga,G., Tam,S.,
            Szpyt,J., Gassaway,B.M., Panov,A., Parzen,H., Fu,S., Golbazi,A.,
            Maenpaa,E., Stricker,K., Guha Thakurta,S., Zhang,T., Rad,R.,
            Pan,J., Nusinow,D.P., Paulo,J.A., Schweppe,D.K., Vaites,L.P.,
            Harper,J.W. and Gygi,S.P.
  TITLE     Dual proteome-scale networks reveal cell-specific remodeling of the
            human interactome
  JOURNAL   Cell 184 (11), 3022-3040 (2021)
   PUBMED   33961781
REFERENCE   4  (bases 1 to 1864)
  AUTHORS   Abou-Fadel,J., Qu,Y., Gonzalez,E.M., Smith,M. and Zhang,J.
  TITLE     Emerging roles of CCM genes during tumorigenesis with potential
            application as novel biomarkers across major types of cancers
  JOURNAL   Oncol Rep 43 (6), 1945-1963 (2020)
   PUBMED   32186778
  REMARK    GeneRIF: Emerging roles of CCM genes during tumorigenesis with
            potential application as novel biomarkers across major types of
            cancers.
REFERENCE   5  (bases 1 to 1864)
  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   6  (bases 1 to 1864)
  AUTHORS   Wan,D., Gong,Y., Qin,W., Zhang,P., Li,J., Wei,L., Zhou,X., Li,H.,
            Qiu,X., Zhong,F., He,L., Yu,J., Yao,G., Jiang,H., Qian,L., Yu,Y.,
            Shu,H., Chen,X., Xu,H., Guo,M., Pan,Z., Chen,Y., Ge,C., Yang,S. and
            Gu,J.
  TITLE     Large-scale cDNA transfection screening for genes related to cancer
            development and progression
  JOURNAL   Proc Natl Acad Sci U S A 101 (44), 15724-15729 (2004)
   PUBMED   15498874
  REMARK    Erratum:[Proc Natl Acad Sci U S A. 2004 Dec 14:101(50):17565]
REFERENCE   7  (bases 1 to 1864)
  AUTHORS   Denier,C., Goutagny,S., Labauge,P., Krivosic,V., Arnoult,M.,
            Cousin,A., Benabid,A.L., Comoy,J., Frerebeau,P., Gilbert,B.,
            Houtteville,J.P., Jan,M., Lapierre,F., Loiseau,H., Menei,P.,
            Mercier,P., Moreau,J.J., Nivelon-Chevallier,A., Parker,F.,
            Redondo,A.M., Scarabin,J.M., Tremoulet,M., Zerah,M., Maciazek,J.
            and Tournier-Lasserve,E.
  CONSRTM   Societe Francaise de Neurochirurgie
  TITLE     Mutations within the MGC4607 gene cause cerebral cavernous
            malformations
  JOURNAL   Am J Hum Genet 74 (2), 326-337 (2004)
   PUBMED   14740320
REFERENCE   8  (bases 1 to 1864)
  AUTHORS   Liquori,C.L., Berg,M.J., Siegel,A.M., Huang,E., Zawistowski,J.S.,
            Stoffer,T., Verlaan,D., Balogun,F., Hughes,L., Leedom,T.P.,
            Plummer,N.W., Cannella,M., Maglione,V., Squitieri,F., Johnson,E.W.,
            Rouleau,G.A., Ptacek,L. and Marchuk,D.A.
  TITLE     Mutations in a gene encoding a novel protein containing a
            phosphotyrosine-binding domain cause type 2 cerebral cavernous
            malformations
  JOURNAL   Am J Hum Genet 73 (6), 1459-1464 (2003)
   PUBMED   14624391
  REMARK    GeneRIF: MGC4607 encodes a protein with a phosphotyrosine-binding
            domain that may be part of the complex pathway of integrin
            signaling that, when perturbed, causes abnormal vascular
            morphogenesis in the brain, leading to CCM formation.
REFERENCE   9  (bases 1 to 1864)
  AUTHORS   Craig,H.D., Gunel,M., Cepeda,O., Johnson,E.W., Ptacek,L.,
            Steinberg,G.K., Ogilvy,C.S., Berg,M.J., Crawford,S.C., Scott,R.M.,
            Steichen-Gersdorf,E., Sabroe,R., Kennedy,C.T., Mettler,G.,
            Beis,M.J., Fryer,A., Awad,I.A. and Lifton,R.P.
  TITLE     Multilocus linkage identifies two new loci for a mendelian form of
            stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27
  JOURNAL   Hum Mol Genet 7 (12), 1851-1858 (1998)
   PUBMED   9811928
REFERENCE   10 (bases 1 to 1864)
  AUTHORS   Flemming,K.D., Smith,E., Marchuk,D. and Derry,W.B.
  TITLE     Familial Cerebral Cavernous Malformations
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301470
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AF370392.1 and BC004903.2.
            
            On Nov 30, 2019 this sequence version replaced NM_031443.3.
            
            Summary: This gene encodes a scaffold protein that functions in the
            stress-activated p38 Mitogen-activated protein kinase (MAPK)
            signaling cascade. The protein interacts with SMAD specific E3
            ubiquitin protein ligase 1 (also known as SMURF1) via a
            phosphotyrosine binding domain to promote RhoA degradation. The
            protein is required for normal cytoskeletal structure, cell-cell
            interactions, and lumen formation in endothelial cells. Mutations
            in this gene result in cerebral cavernous malformations. Multiple
            transcript variants encoding different isoforms have been found for
            this gene.[provided by RefSeq, Nov 2009].
            
            Transcript Variant: This variant (2) represents use of an alternate
            promoter and 5' UTR and uses a distinct start codon, compared to
            variant 1. The resulting isoform (2) has a shorter and distinct
            N-terminus, compared to isoform 1.
            
            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 :: BC008859.2, AF370392.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000258781.11/ ENSP00000258781.7
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-52                AF370392.1         14-65
            53-1864             BC004903.2         1-1812
FEATURES             Location/Qualifiers
     source          1..1864
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7p13"
     gene            1..1864
                     /gene="CCM2"
                     /gene_synonym="C7orf22; OSM; PP10187"
                     /note="CCM2 scaffold protein"
                     /db_xref="GeneID:83605"
                     /db_xref="HGNC:HGNC:21708"
                     /db_xref="MIM:607929"
     exon            1..163
                     /gene="CCM2"
                     /gene_synonym="C7orf22; OSM; PP10187"
                     /inference="alignment:Splign:2.1.0"
     CDS             134..1468
                     /gene="CCM2"
                     /gene_synonym="C7orf22; OSM; PP10187"
                     /note="isoform 2 is encoded by transcript variant 2;
                     malcavernin; cerebral cavernous malformations 2 protein;
                     cerebral cavernous malformation 2; osmosensing scaffold
                     for MEKK3; CCM2 scaffolding protein"
                     /codon_start=1
                     /product="cerebral cavernous malformations 2 protein
                     isoform 2"
                     /protein_id="NP_113631.1"
                     /db_xref="CCDS:CCDS5500.1"
                     /db_xref="GeneID:83605"
                     /db_xref="HGNC:HGNC:21708"
                     /db_xref="MIM:607929"
                     /translation="MEEEGKKGKKPGIVSPFKRVFLKGEKSRDKKAHEKVTERRPLHT
                     VVLSLPERVEPDRLLSDYIEKEVKYLGQLTSIPGYLNPSSRTEILHFIDNAKRAHQLP
                     GHLTQEHDAVLSLSAYNVKLAWRDGEDIILRVPIHDIAAVSYVRDDAAHLVVLKTAQD
                     PGISPSQSLCAESSRGLSAGSLSESAVGPVEACCLVILAAESKVAAEELCCLLGQVFQ
                     VVYTESTIDFLDRAIFDGASTPTHHLSLHSDDSSTKVDIKETYEVEASTFCFPESVDV
                     GGASPHSKTISESELSASATELLQDYMLTLRTKLSSQEIQQFAALLHEYRNGASIHEF
                     CINLRQLYGDSRKFLLLGLRPFIPEKDSQHFENFLETIGVKDGRGIITDSFGRHRRAL
                     STTSSSTTNGNRATGSSDDRSAPSEGDEWDRMISDISSDIEALGCSMDQDSA"
     exon            164..337
                     /gene="CCM2"
                     /gene_synonym="C7orf22; OSM; PP10187"
                     /inference="alignment:Splign:2.1.0"
     exon            338..421
                     /gene="CCM2"
                     /gene_synonym="C7orf22; OSM; PP10187"
                     /inference="alignment:Splign:2.1.0"
     exon            422..605
                     /gene="CCM2"
                     /gene_synonym="C7orf22; OSM; PP10187"
                     /inference="alignment:Splign:2.1.0"
     exon            606..742
                     /gene="CCM2"
                     /gene_synonym="C7orf22; OSM; PP10187"
                     /inference="alignment:Splign:2.1.0"
     exon            743..878
                     /gene="CCM2"
                     /gene_synonym="C7orf22; OSM; PP10187"
                     /inference="alignment:Splign:2.1.0"
     exon            879..936
                     /gene="CCM2"
                     /gene_synonym="C7orf22; OSM; PP10187"
                     /inference="alignment:Splign:2.1.0"
     exon            937..1048
                     /gene="CCM2"
                     /gene_synonym="C7orf22; OSM; PP10187"
                     /inference="alignment:Splign:2.1.0"
     exon            1049..1187
                     /gene="CCM2"
                     /gene_synonym="C7orf22; OSM; PP10187"
                     /inference="alignment:Splign:2.1.0"
     exon            1188..1864
                     /gene="CCM2"
                     /gene_synonym="C7orf22; OSM; PP10187"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1855..1860
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CCM2"
                     /gene_synonym="C7orf22; OSM; PP10187"
                     /note="hexamer: AATAAT"
     polyA_site      1864
                     /gene="CCM2"
                     /gene_synonym="C7orf22; OSM; PP10187"
                     /note="major polyA site"
ORIGIN      
        1 ggagacttcg ggcccggctg gcgggcggcg ccgggagcgc gggggcggcg ggcccgggtc
       61 gagcatgtag cggctgctgg cggcggggct cccggggcgg gccgggcggg ccgcgggagc
      121 cgcacgcggc gatatggaag aggagggcaa gaagggcaag aagcctggaa ttgtctcgcc
      181 atttaaacga gtattcctaa aaggtgaaaa gagtagagat aagaaagccc atgagaaggt
      241 gacagagagg cgccctctgc acactgtggt gttgtcattg cctgagcgcg tcgagccaga
      301 cagactgctg agcgactata ttgagaagga ggtaaagtat ttaggtcagt taacgtccat
      361 accaggatac ctgaatccct ccagtaggac tgaaatcctg catttcatag acaatgcaaa
      421 gagagcccac cagcttccgg gacacttgac tcaggagcac gatgctgtgc tcagcctgtc
      481 tgcgtacaac gtcaagctgg cctggaggga cggggaggat atcatcctca gggtgcccat
      541 ccatgacatc gccgccgtct cctatgttcg ggatgacgct gcacacctgg tggtcctgaa
      601 gacagcccag gacccaggga tctcccccag ccagagtctg tgtgcggaaa gttccagagg
      661 cctcagtgca ggctccctgt cggagagtgc agttgggccc gtggaggcat gctgcctggt
      721 catcctggct gcagagagca aggtcgctgc ggaggagctt tgctgtctgc taggccaggt
      781 cttccaggtt gtttacacgg agtccaccat cgactttctg gacagagcga tatttgatgg
      841 ggcctctacc ccgacccacc acctgtccct gcacagcgat gactcttcta caaaagtgga
      901 cattaaggag acctacgagg tggaagccag cactttctgc ttccctgaat ctgtggatgt
      961 gggtggtgca tcaccccaca gcaagaccat cagtgagagc gagctgagcg ccagcgccac
     1021 tgagctgctg caggactaca tgctgacgct gcgcaccaag ctgtcatcac aggagatcca
     1081 gcagtttgca gcactgctgc acgagtaccg caatggggcc tctatccacg agttctgcat
     1141 caacctgcgg cagctctacg gggacagccg caagttcctg ctgcttggtc tgaggccctt
     1201 catccctgag aaggacagcc agcacttcga gaacttcctg gagaccattg gcgtgaagga
     1261 tggccgcggc atcatcactg acagctttgg caggcaccgg cgggccctga gcaccacatc
     1321 cagttccacc accaatggga acagggccac gggcagctct gatgaccggt cggcaccctc
     1381 agagggggat gagtgggacc gcatgatctc ggacatcagc agcgacattg aggcgctggg
     1441 ctgcagcatg gaccaggact cagcatgatg gacagtggat gggggggcac ccacaccttc
     1501 cgcgcagtcg tcataggcct tcccagaagg agctgcccag acctgcgtgt cagcccttgg
     1561 tggtggccag ggagaggcgc ccggtgcaga tggccccggg cggcccaggt cctctactgt
     1621 gaaggagcag ggagctgccg agggacacga gcctcagtgc ggggtggaag gctctttgcc
     1681 ttgtccacca gggctcagcc aagccctgca gtgtgtcccc gctcggggag ggcccggccg
     1741 agcgggcagg gagagccagt cctgtcggct gggcccttgg acggctgtca gttttgcaca
     1801 tgatgttcct attgtaactc tcagagacct taaaaagaag tttactgcaa tgtgaataat
     1861 ttaa
//
