LOCUS       NM_000505               2036 bp    mRNA    linear   PRI 17-SEP-2024
DEFINITION  Homo sapiens coagulation factor XII (F12), mRNA.
ACCESSION   NM_000505
VERSION     NM_000505.4
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 2036)
  AUTHORS   Elwakiel,A., Gupta,D., Rana,R., Manoharan,J., Al-Dabet,M.M.,
            Ambreen,S., Fatima,S., Zimmermann,S., Mathew,A., Li,Z., Singh,K.,
            Gupta,A., Pal,S., Sulaj,A., Kopf,S., Schwab,C., Baber,R.,
            Geffers,R., Gotze,T., Alo,B., Lamers,C., Kluge,P., Kuenze,G.,
            Kohli,S., Renne,T., Shahzad,K. and Isermann,B.
  TITLE     Factor XII signaling via uPAR-integrin beta1 axis promotes tubular
            senescence in diabetic kidney disease
  JOURNAL   Nat Commun 15 (1), 7963 (2024)
   PUBMED   39261453
  REMARK    GeneRIF: Factor XII signaling via uPAR-integrin beta1 axis promotes
            tubular senescence in diabetic kidney disease.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 2036)
  AUTHORS   Dominguez-Reyes,V.M., Hernandez-Juarez,J., Arreola-Diaz,R.,
            Majluf-Cruz,K., Reyes-Maldonado,E., Alvarado-Moreno,J.A.,
            Ruiz,L.A.M. and Majluf-Cruz,A.
  TITLE     Factor XII Deficiency in Mexico: High Prevalence in the General
            Population and Patients with Venous Thromboembolic Disease
  JOURNAL   Arch Med Res 55 (1), 102913 (2024)
   PUBMED   38065013
  REMARK    GeneRIF: Factor XII Deficiency in Mexico: High Prevalence in the
            General Population and Patients with Venous Thromboembolic Disease.
REFERENCE   3  (bases 1 to 2036)
  AUTHORS   Ji,W., Lin,S., Chen,J., Jin,C., Lin,X., Ye,Z., Qiu,L. and Qian,D.
  TITLE     [Genetic analysis of a Chinese pedigree affected with Congenital
            coagulation factor XII deficiency due to a c.1A>G start codon
            variant of F12 gene]
  JOURNAL   Zhonghua Yi Xue Yi Chuan Xue Za Zhi 40 (5), 547-551 (2023)
   PUBMED   37102287
  REMARK    GeneRIF: [Genetic analysis of a Chinese pedigree affected with
            Congenital coagulation factor XII deficiency due to a c.1A>G start
            codon variant of F12 gene].
REFERENCE   4  (bases 1 to 2036)
  AUTHORS   Fang,S., Yang,J., Zhang,X., Yang,L. and Wang,G.
  TITLE     [Analysis of F12 gene variants and molecular mechanisms in patients
            with coagulation factor deficiency]
  JOURNAL   Zhonghua Yi Xue Yi Chuan Xue Za Zhi 40 (4), 429-434 (2023)
   PUBMED   36972937
  REMARK    GeneRIF: [Analysis of F12 gene variants and molecular mechanisms in
            patients with coagulation factor deficiency].
REFERENCE   5  (bases 1 to 2036)
  AUTHORS   Calvo,S.E., Pagliarini,D.J. and Mootha,V.K.
  TITLE     Upstream open reading frames cause widespread reduction of protein
            expression and are polymorphic among humans
  JOURNAL   Proc Natl Acad Sci U S A 106 (18), 7507-7512 (2009)
   PUBMED   19372376
  REMARK    GeneRIF: Includes the study of a polymorphic upstream ORF in this
            gene, and shows that it functions to reduce protein levels by ~50%.
REFERENCE   6  (bases 1 to 2036)
  AUTHORS   Harris,R.J., Ling,V.T. and Spellman,M.W.
  TITLE     O-linked fucose is present in the first epidermal growth factor
            domain of factor XII but not protein C
  JOURNAL   J Biol Chem 267 (8), 5102-5107 (1992)
   PUBMED   1544894
REFERENCE   7  (bases 1 to 2036)
  AUTHORS   McMullen,B.A., Fujikawa,K. and Davie,E.W.
  TITLE     Location of the disulfide bonds in human plasma prekallikrein: the
            presence of four novel apple domains in the amino-terminal portion
            of the molecule
  JOURNAL   Biochemistry 30 (8), 2050-2056 (1991)
   PUBMED   1998666
REFERENCE   8  (bases 1 to 2036)
  AUTHORS   Miyata,T., Kawabata,S., Iwanaga,S., Takahashi,I., Alving,B. and
            Saito,H.
  TITLE     Coagulation factor XII (Hageman factor) Washington D.C.: inactive
            factor XIIa results from Cys-571----Ser substitution
  JOURNAL   Proc Natl Acad Sci U S A 86 (21), 8319-8322 (1989)
   PUBMED   2510163
REFERENCE   9  (bases 1 to 2036)
  AUTHORS   Fujikawa,K. and McMullen,B.A.
  TITLE     Amino acid sequence of human beta-factor XIIa
  JOURNAL   J Biol Chem 258 (18), 10924-10933 (1983)
   PUBMED   6604055
REFERENCE   10 (bases 1 to 2036)
  AUTHORS   Mandle,R.J. Jr. and Kaplan,A.P.
  TITLE     Hageman-factor-dependent fibrinolysis: generation of fibrinolytic
            activity by the interaction of human activated factor XI and
            plasminogen
  JOURNAL   Blood 54 (4), 850-862 (1979)
   PUBMED   89876
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC145098.2, AB095845.1,
            M11723.1 and BE139501.1.
            
            On Feb 27, 2020 this sequence version replaced NM_000505.3.
            
            Summary: This gene encodes coagulation factor XII which circulates
            in blood as a zymogen. This single chain zymogen is converted to a
            two-chain serine protease with an heavy chain (alpha-factor XIIa)
            and a light chain. The heavy chain contains two fibronectin-type
            domains, two epidermal growth factor (EGF)-like domains, a kringle
            domain and a proline-rich domain, whereas the light chain contains
            only a catalytic domain. On activation, further cleavages takes
            place in the heavy chain, resulting in the production of
            beta-factor XIIa light chain and the alpha-factor XIIa light chain
            becomes beta-factor XIIa heavy chain. Prekallikrein is cleaved by
            factor XII to form kallikrein, which then cleaves factor XII first
            to alpha-factor XIIa and then to beta-factor XIIa. The active
            factor XIIa participates in the initiation of blood coagulation,
            fibrinolysis, and the generation of bradykinin and angiotensin. It
            activates coagulation factors VII and XI. Defects in this gene do
            not cause any clinical symptoms and the sole effect is that
            whole-blood clotting time is prolonged. [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 :: M11723.1, AB095845.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1968540 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000253496.4/ ENSP00000253496.3
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            regulatory uORF        :: PMID: 19372376
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-34                AC145098.2         46711-46744         c
            35-655              AB095845.1         47-667
            656-671             AC145098.2         41990-42005         c
            672-1551            AB095845.1         684-1563
            1552-2035           M11723.1           1476-1959
            2036-2036           BE139501.1         13-13               c
FEATURES             Location/Qualifiers
     source          1..2036
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="5"
                     /map="5q35.3"
     gene            1..2036
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /note="coagulation factor XII"
                     /db_xref="GeneID:2161"
                     /db_xref="HGNC:HGNC:3530"
                     /db_xref="MIM:610619"
     exon            1..94
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /inference="alignment:Splign:2.1.0"
     regulatory      33..41
                     /regulatory_class="uORF"
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /experiment="DESCRIPTION:regulatory uORF[PMID:19372376]"
                     /note="this uORF is predicted to encode a 2 aa peptide
                     (PMID:19372376)"
     CDS             38..1885
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /EC_number="3.4.21.38"
                     /note="Hageman factor; coagulation factor XIIa heavy
                     chain; beta-factor XIIa part 1; beta-factor XIIa part 2;
                     coagulation factor XIIa light chain; Plasma coagulation
                     Factor XIIa"
                     /codon_start=1
                     /product="coagulation factor XII preproprotein"
                     /protein_id="NP_000496.2"
                     /db_xref="CCDS:CCDS34302.1"
                     /db_xref="GeneID:2161"
                     /db_xref="HGNC:HGNC:3530"
                     /db_xref="MIM:610619"
                     /translation="MRALLLLGFLLVSLESTLSIPPWEAPKEHKYKAEEHTVVLTVTG
                     EPCHFPFQYHRQLYHKCTHKGRPGPQPWCATTPNFDQDQRWGYCLEPKKVKDHCSKHS
                     PCQKGGTCVNMPSGPHCLCPQHLTGNHCQKEKCFEPQLLRFFHKNEIWYRTEQAAVAR
                     CQCKGPDAHCQRLASQACRTNPCLHGGRCLEVEGHRLCHCPVGYTGAFCDVDTKASCY
                     DGRGLSYRGLARTTLSGAPCQPWASEATYRNVTAEQARNWGLGGHAFCRNPDNDIRPW
                     CFVLNRDRLSWEYCDLAQCQTPTQAAPPTPVSPRLHVPLMPAQPAPPKPQPTTRTPPQ
                     SQTPGALPAKREQPPSLTRNGPLSCGQRLRKSLSSMTRVVGGLVALRGAHPYIAALYW
                     GHSFCAGSLIAPCWVLTAAHCLQDRPAPEDLTVVLGQERRNHSCEPCQTLAVRSYRLH
                     EAFSPVSYQHDLALLRLQEDADGSCALLSPYVQPVCLPSGAARPSETTLCQVAGWGHQ
                     FEGAEEYASFLQEAQVPFLSLERCSAPDVHGSSILPGMLCAGFLEGGTDACQGDSGGP
                     LVCEDQAAERRLTLQGIISWGSGCGDRNKPGVYTDVAYYLAWIREHTVS"
     exon            95..152
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /inference="alignment:Splign:2.1.0"
     exon            153..252
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /inference="alignment:Splign:2.1.0"
     exon            253..323
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /inference="alignment:Splign:2.1.0"
     exon            324..434
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /inference="alignment:Splign:2.1.0"
     exon            435..566
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /inference="alignment:Splign:2.1.0"
     exon            567..671
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /inference="alignment:Splign:2.1.0"
     exon            672..837
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /inference="alignment:Splign:2.1.0"
     exon            838..1055
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /inference="alignment:Splign:2.1.0"
     exon            1056..1287
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /inference="alignment:Splign:2.1.0"
     exon            1288..1424
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /inference="alignment:Splign:2.1.0"
     exon            1425..1568
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /inference="alignment:Splign:2.1.0"
     exon            1569..1717
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /inference="alignment:Splign:2.1.0"
     exon            1718..2036
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2013..2018
                     /regulatory_class="polyA_signal_sequence"
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /note="hexamer: AATAAA"
     polyA_site      2036
                     /gene="F12"
                     /gene_synonym="HAE3; HAEX; HAF"
                     /note="major polyA site"
ORIGIN      
        1 actcctggat aggcagctgg accaacggac ggatgccatg agggctctgc tgctcctggg
       61 gttcctgctg gtgagcttgg agtcaacact ttcgattcca ccttgggaag cccccaagga
      121 gcataagtac aaagctgaag agcacacagt cgttctcact gtcaccgggg agccctgcca
      181 cttccccttc cagtaccacc ggcagctgta ccacaaatgt acccacaagg gccggccagg
      241 ccctcagccc tggtgtgcta ccacccccaa ctttgatcag gaccagcgat ggggatactg
      301 tttggagccc aagaaagtga aagaccactg cagcaaacac agcccctgcc agaaaggagg
      361 gacctgtgtg aacatgccaa gcggccccca ctgtctctgt ccacaacacc tcactggaaa
      421 ccactgccag aaagagaagt gctttgagcc tcagcttctc cggtttttcc acaagaatga
      481 gatatggtat agaactgagc aagcagctgt ggccagatgc cagtgcaagg gtcctgatgc
      541 ccactgccag cggctggcca gccaggcctg ccgcaccaac ccgtgcctcc atgggggtcg
      601 ctgcctagag gtggagggcc accgcctgtg ccactgcccg gtgggctaca ccggagcctt
      661 ctgcgacgtg gacaccaagg caagctgcta tgatggccgc gggctcagct accgcggcct
      721 ggccaggacc acgctctcgg gtgcgccctg tcagccgtgg gcctcggagg ccacctaccg
      781 gaacgtgact gccgagcaag cgcggaactg gggactgggc ggccacgcct tctgccggaa
      841 cccggacaac gacatccgcc cgtggtgctt cgtgctgaac cgcgaccggc tgagctggga
      901 gtactgcgac ctggcacagt gccagacccc aacccaggcg gcgcctccga ccccggtgtc
      961 ccctaggctt catgtcccac tcatgcccgc gcagccggca ccgccgaagc ctcagcccac
     1021 gacccggacc ccgcctcagt cccagacccc gggagccttg ccggcgaagc gggagcagcc
     1081 gccttccctg accaggaacg gcccactgag ctgcgggcag cggctccgca agagtctgtc
     1141 ttcgatgacc cgcgtcgttg gcgggctggt ggcgctacgc ggggcgcacc cctacatcgc
     1201 cgcgctgtac tggggccaca gtttctgcgc cggcagcctc atcgccccct gctgggtgct
     1261 gacggccgct cactgcctgc aggaccggcc cgcacccgag gatctgacgg tggtgctcgg
     1321 ccaggaacgc cgtaaccaca gctgtgagcc gtgccagacg ttggccgtgc gctcctaccg
     1381 cttgcacgag gccttctcgc ccgtcagcta ccagcacgac ctggctctgt tgcgccttca
     1441 ggaggatgcg gacggcagct gcgcgctcct gtcgccttac gttcagccgg tgtgcctgcc
     1501 aagcggcgcc gcgcgaccct ccgagaccac gctctgccag gtggccggct ggggccacca
     1561 gttcgagggg gcggaggaat atgccagctt cctgcaggag gcgcaggtac cgttcctctc
     1621 cctggagcgc tgctcagccc cggacgtgca cggatcctcc atcctccccg gcatgctctg
     1681 cgcagggttc ctcgagggcg gcaccgatgc gtgccagggt gattccggag gcccgctggt
     1741 gtgtgaggac caagctgcag agcgccggct caccctgcaa ggcatcatca gctggggatc
     1801 gggctgtggt gaccgcaaca agccaggcgt ctacaccgat gtggcctact acctggcctg
     1861 gatccgggag cacaccgttt cctgattgct cagggactca tctttccctc cttggtgatt
     1921 ccgcagtgag agagtggctg gggcatggaa ggcaagattg tgtcccattc ccccagtgcg
     1981 gccagctccg cgccaggatg gcgcaggaac tcaataaagt gctttgaaaa tgctga
//
