LOCUS       NM_000312               1769 bp    mRNA    linear   PRI 05-AUG-2024
DEFINITION  Homo sapiens protein C, inactivator of coagulation factors Va and
            VIIIa (PROC), transcript variant 10, mRNA.
ACCESSION   NM_000312
VERSION     NM_000312.4
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 1769)
  AUTHORS   Lai,Z., Li,J., Zhou,S., Wu,X., Yuan,J., Li,F., Wu,W., Ding,Q.,
            Dai,J., Wang,X., Lu,Y. and Cai,X.
  TITLE     Mutation Ter462GlnextTer17 introduces a tail to C-terminus of
            protein C and causes venous thrombosis
  JOURNAL   Thromb Res 240, 109044 (2024)
   PUBMED   38824799
  REMARK    GeneRIF: Mutation Ter462GlnextTer17 introduces a tail to C-terminus
            of protein C and causes venous thrombosis.
REFERENCE   2  (bases 1 to 1769)
  AUTHORS   Guo,H., Liu,D., Gelbard,H., Cheng,T., Insalaco,R., Fernandez,J.A.,
            Griffin,J.H. and Zlokovic,B.V.
  TITLE     Activated Protein C Prevents Neuronal Apoptosis via Protease
            Activated Receptors 1 and 3
  JOURNAL   Neuron 111 (24), 4116 (2023)
   PUBMED   38135361
  REMARK    GeneRIF: Activated Protein C Prevents Neuronal Apoptosis via
            Protease Activated Receptors 1 and 3.
REFERENCE   3  (bases 1 to 1769)
  AUTHORS   Witt,I., Beck,S., Seydewitz,H.H., Tasangil,C. and Schenck,W.
  TITLE     A novel homozygous missense mutation (Val 325-->Ala) in the protein
            C gene causing neonatal purpura fulminans
  JOURNAL   Blood Coagul Fibrinolysis 5 (4), 651-653 (1994)
   PUBMED   7841324
REFERENCE   4  (bases 1 to 1769)
  AUTHORS   Grundy,C.B., Chisholm,M., Kakkar,V.V. and Cooper,D.N.
  TITLE     A novel homozygous missense mutation in the protein C (PROC) gene
            causing recurrent venous thrombosis
  JOURNAL   Hum Genet 89 (6), 683-684 (1992)
   PUBMED   1511988
REFERENCE   5  (bases 1 to 1769)
  AUTHORS   Patracchini,P., Aiello,V., Palazzi,P., Calzolari,E. and Bernardi,F.
  TITLE     Sublocalization of the human protein C gene on chromosome 2q13-q14
  JOURNAL   Hum Genet 81 (2), 191-192 (1989)
   PUBMED   2912888
REFERENCE   6  (bases 1 to 1769)
  AUTHORS   Romeo,G., Hassan,H.J., Staempfli,S., Roncuzzi,L., Cianetti,L.,
            Leonardi,A., Vicente,V., Mannucci,P.M., Bertina,R., Peschle,C. et
            al.
  TITLE     Hereditary thrombophilia: identification of nonsense and missense
            mutations in the protein C gene
  JOURNAL   Proc Natl Acad Sci U S A 84 (9), 2829-2832 (1987)
   PUBMED   2437584
REFERENCE   7  (bases 1 to 1769)
  AUTHORS   Beckmann,R.J., Schmidt,R.J., Santerre,R.F., Plutzky,J.,
            Crabtree,G.R. and Long,G.L.
  TITLE     The structure and evolution of a 461 amino acid human protein C
            precursor and its messenger RNA, based upon the DNA sequence of
            cloned human liver cDNAs
  JOURNAL   Nucleic Acids Res 13 (14), 5233-5247 (1985)
   PUBMED   2991859
REFERENCE   8  (bases 1 to 1769)
  AUTHORS   Foster,D.C., Yoshitake,S. and Davie,E.W.
  TITLE     The nucleotide sequence of the gene for human protein C
  JOURNAL   Proc Natl Acad Sci U S A 82 (14), 4673-4677 (1985)
   PUBMED   2991887
REFERENCE   9  (bases 1 to 1769)
  AUTHORS   Kisiel,W.
  TITLE     Human plasma protein C: isolation, characterization, and mechanism
            of activation by alpha-thrombin
  JOURNAL   J Clin Invest 64 (3), 761-769 (1979)
   PUBMED   468991
REFERENCE   10 (bases 1 to 1769)
  AUTHORS   Esmon,C.T., Stenflo,J. and Suttie,J.W.
  TITLE     A new vitamin K-dependent protein. A phospholipid-binding zymogen
            of a serine esterase
  JOURNAL   J Biol Chem 251 (10), 3052-3056 (1976)
   PUBMED   1270437
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA642156.1 and BC034377.1.
            
            On Dec 4, 2019 this sequence version replaced NM_000312.3.
            
            Summary: This gene encodes a vitamin K-dependent plasma
            glycoprotein. The encoded protein is cleaved to its activated form
            by the thrombin-thrombomodulin complex. This activated form
            contains a serine protease domain and functions in degradation of
            the activated forms of coagulation factors V and VIII. Mutations in
            this gene have been associated with thrombophilia due to protein C
            deficiency, neonatal purpura fulminans, and recurrent venous
            thrombosis.[provided by RefSeq, Dec 2009].
            
            Transcript Variant: This variant (10), as well as variants 11 and
            12, encodes isoform 10.
            
            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 :: BC034377.1, X02750.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1970526, SAMEA2145122
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000234071.8/ ENSP00000234071.4
            RefSeq Select criteria :: based on manual assertion, conservation
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-32                DA642156.1         8-39
            33-509              BC034377.1         1-477
            510-510             DA642156.1         513-513
            511-1769            BC034377.1         479-1737
FEATURES             Location/Qualifiers
     source          1..1769
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2q14.3"
     gene            1..1769
                     /gene="PROC"
                     /gene_synonym="APC; PC; PROC1; THPH3; THPH4"
                     /note="protein C, inactivator of coagulation factors Va
                     and VIIIa"
                     /db_xref="GeneID:5624"
                     /db_xref="HGNC:HGNC:9451"
                     /db_xref="MIM:612283"
     exon            1..66
                     /gene="PROC"
                     /gene_synonym="APC; PC; PROC1; THPH3; THPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            67..157
                     /gene="PROC"
                     /gene_synonym="APC; PC; PROC1; THPH3; THPH4"
                     /inference="alignment:Splign:2.1.0"
     CDS             88..1473
                     /gene="PROC"
                     /gene_synonym="APC; PC; PROC1; THPH3; THPH4"
                     /EC_number="3.4.21.69"
                     /note="isoform 10 preproprotein is encoded by transcript
                     variant 10; vitamin K-dependent protein C; autoprothrombin
                     IIA; anticoagulant protein C; blood coagulation factor
                     XIV; prepro-protein C; type I protein C; Protein C-Nagoya;
                     activated protein C"
                     /codon_start=1
                     /product="vitamin K-dependent protein C isoform 10
                     preproprotein"
                     /protein_id="NP_000303.1"
                     /db_xref="CCDS:CCDS2145.1"
                     /db_xref="GeneID:5624"
                     /db_xref="HGNC:HGNC:9451"
                     /db_xref="MIM:612283"
                     /translation="MWQLTSLLLFVATWGISGTPAPLDSVFSSSERAHQVLRIRKRAN
                     SFLEELRHSSLERECIEEICDFEEAKEIFQNVDDTLAFWSKHVDGDQCLVLPLEHPCA
                     SLCCGHGTCIDGIGSFSCDCRSGWEGRFCQREVSFLNCSLDNGGCTHYCLEEVGWRRC
                     SCAPGYKLGDDLLQCHPAVKFPCGRPWKRMEKKRSHLKRDTEDQEDQVDPRLIDGKMT
                     RRGDSPWQVVLLDSKKKLACGAVLIHPSWVLTAAHCMDESKKLLVRLGEYDLRRWEKW
                     ELDLDIKEVFVHPNYSKSTTDNDIALLHLAQPATLSQTIVPICLPDSGLAERELNQAG
                     QETLVTGWGYHSSREKEAKRNRTFVLNFIKIPVVPHNECSEVMSNMVSENMLCAGILG
                     DRQDACEGDSGGPMVASFHGTWFLVGLVSWGEGCGLLHNYGVYTKVSRYLDWIHGHIR
                     DKEAPQKSWAP"
     exon            158..324
                     /gene="PROC"
                     /gene_synonym="APC; PC; PROC1; THPH3; THPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            325..349
                     /gene="PROC"
                     /gene_synonym="APC; PC; PROC1; THPH3; THPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            350..487
                     /gene="PROC"
                     /gene_synonym="APC; PC; PROC1; THPH3; THPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            488..622
                     /gene="PROC"
                     /gene_synonym="APC; PC; PROC1; THPH3; THPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            623..765
                     /gene="PROC"
                     /gene_synonym="APC; PC; PROC1; THPH3; THPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            766..883
                     /gene="PROC"
                     /gene_synonym="APC; PC; PROC1; THPH3; THPH4"
                     /inference="alignment:Splign:2.1.0"
     exon            884..1769
                     /gene="PROC"
                     /gene_synonym="APC; PC; PROC1; THPH3; THPH4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1520..1525
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PROC"
                     /gene_synonym="APC; PC; PROC1; THPH3; THPH4"
                     /note="hexamer: ATTAAA"
     polyA_site      1542
                     /gene="PROC"
                     /gene_synonym="APC; PC; PROC1; THPH3; THPH4"
                     /note="major polyA site"
     regulatory      1749..1754
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PROC"
                     /gene_synonym="APC; PC; PROC1; THPH3; THPH4"
                     /note="hexamer: AATAAA"
     polyA_site      1769
                     /gene="PROC"
                     /gene_synonym="APC; PC; PROC1; THPH3; THPH4"
                     /note="major polyA site"
ORIGIN      
        1 aactcgaact ccaggctgtc atggcggcag gacggcgaac ttgcagtatc tccacgaccc
       61 gcccctacag gtgccagtgc ctccagaatg tggcagctca caagcctcct gctgttcgtg
      121 gccacctggg gaatttccgg cacaccagct cctcttgact cagtgttctc cagcagcgag
      181 cgtgcccacc aggtgctgcg gatccgcaaa cgtgccaact ccttcctgga ggagctccgt
      241 cacagcagcc tggagcggga gtgcatagag gagatctgtg acttcgagga ggccaaggaa
      301 attttccaaa atgtggatga cacactggcc ttctggtcca agcacgtcga cggtgaccag
      361 tgcttggtct tgcccttgga gcacccgtgc gccagcctgt gctgcgggca cggcacgtgc
      421 atcgacggca tcggcagctt cagctgcgac tgccgcagcg gctgggaggg ccgcttctgc
      481 cagcgcgagg tgagcttcct caattgctcg ctggacaacg gcggctgcac gcattactgc
      541 ctagaggagg tgggctggcg gcgctgtagc tgtgcgcctg gctacaagct gggggacgac
      601 ctcctgcagt gtcaccccgc agtgaagttc ccttgtggga ggccctggaa gcggatggag
      661 aagaagcgca gtcacctgaa acgagacaca gaagaccaag aagaccaagt agatccgcgg
      721 ctcattgatg ggaagatgac caggcgggga gacagcccct ggcaggtggt cctgctggac
      781 tcaaagaaga agctggcctg cggggcagtg ctcatccacc cctcctgggt gctgacagcg
      841 gcccactgca tggatgagtc caagaagctc cttgtcaggc ttggagagta tgacctgcgg
      901 cgctgggaga agtgggagct ggacctggac atcaaggagg tcttcgtcca ccccaactac
      961 agcaagagca ccaccgacaa tgacatcgca ctgctgcacc tggcccagcc cgccaccctc
     1021 tcgcagacca tagtgcccat ctgcctcccg gacagcggcc ttgcagagcg cgagctcaat
     1081 caggccggcc aggagaccct cgtgacgggc tggggctacc acagcagccg agagaaggag
     1141 gccaagagaa accgcacctt cgtcctcaac ttcatcaaga ttcccgtggt cccgcacaat
     1201 gagtgcagcg aggtcatgag caacatggtg tctgagaaca tgctgtgtgc gggcatcctc
     1261 ggggaccggc aggatgcctg cgagggcgac agtggggggc ccatggtcgc ctccttccac
     1321 ggcacctggt tcctggtggg cctggtgagc tggggtgagg gctgtgggct ccttcacaac
     1381 tacggcgttt acaccaaagt cagccgctac ctcgactgga tccatgggca catcagagac
     1441 aaggaagccc cccagaagag ctgggcacct tagcgaccct ccctgcaggg ctgggctttt
     1501 gcatggcaat ggatgggaca ttaaagggac atgtaacaag cacaccggcc tgctgttctg
     1561 tccttccatc cctcttttgg gctcttctgg agggaagtaa catttactga gcacctgttg
     1621 tatgtcacat gccttatgaa tagaatctta actcctagag caactctgtg gggtggggag
     1681 gagcagatcc aagttttgcg gggtctaaag ctgtgtgtgt tgagggggat actctgttta
     1741 tgaaaaagaa taaaaaacac aaccacgaa
//
