LOCUS       NM_000506               1990 bp    mRNA    linear   PRI 05-OCT-2024
DEFINITION  Homo sapiens coagulation factor II, thrombin (F2), mRNA.
ACCESSION   NM_000506
VERSION     NM_000506.5
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 1990)
  AUTHORS   Aleksandrowicz,K., Hempel,D., Politynska,B., Wojtukiewicz,A.M.,
            Honn,K.V., Tang,D.G. and Wojtukiewicz,M.Z.
  TITLE     The Complex Role of Thrombin in Cancer and Metastasis: Focus on
            Interactions with the Immune System
  JOURNAL   Semin Thromb Hemost 50 (3), 462-473 (2024)
   PUBMED   37984359
  REMARK    GeneRIF: The Complex Role of Thrombin in Cancer and Metastasis:
            Focus on Interactions with the Immune System.
REFERENCE   2  (bases 1 to 1990)
  AUTHORS   Biswas,I., Giri,H., Panicker,S.R. and Rezaie,A.R.
  TITLE     Thrombomodulin Switches Signaling and Protease-Activated Receptor 1
            Cleavage Specificity of Thrombin
  JOURNAL   Arterioscler Thromb Vasc Biol 44 (3), 603-616 (2024)
   PUBMED   38174561
  REMARK    GeneRIF: Thrombomodulin Switches Signaling and Protease-Activated
            Receptor 1 Cleavage Specificity of Thrombin.
REFERENCE   3  (bases 1 to 1990)
  AUTHORS   Risman,R.A., Belcher,H.A., Ramanujam,R.K., Weisel,J.W., Hudson,N.E.
            and Tutwiler,V.
  TITLE     Comprehensive Analysis of the Role of Fibrinogen and Thrombin in
            Clot Formation and Structure for Plasma and Purified Fibrinogen
  JOURNAL   Biomolecules 14 (2), 230 (2024)
   PUBMED   38397467
  REMARK    GeneRIF: Comprehensive Analysis of the Role of Fibrinogen and
            Thrombin in Clot Formation and Structure for Plasma and Purified
            Fibrinogen.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 1990)
  AUTHORS   Ha,G.H., Yeon,J.Y., Kim,K.H., Lee,D.M., Chae,H.Y., Nam,H., Lee,K.,
            Kim,D.O., Kim,C.K. and Joo,K.M.
  TITLE     Thrombin Priming Promotes the Neuroprotective Effects of Human
            Wharton's Jelly-Derived Mesenchymal Stem Cells Via the
            HGF/AKT/STAT3 Signaling Pathway
  JOURNAL   Stem Cells Dev 33 (3-4), 89-103 (2024)
   PUBMED   38164089
  REMARK    GeneRIF: Thrombin Priming Promotes the Neuroprotective Effects of
            Human Wharton's Jelly-Derived Mesenchymal Stem Cells Via the
            HGF/AKT/STAT3 Signaling Pathway.
REFERENCE   5  (bases 1 to 1990)
  AUTHORS   Papareddy,P., Rydengard,V., Pasupuleti,M., Walse,B., Morgelin,M.,
            Chalupka,A., Malmsten,M. and Schmidtchen,A.
  TITLE     Proteolysis of human thrombin generates novel host defense peptides
  JOURNAL   PLoS Pathog 6 (4), e1000857 (2010)
   PUBMED   20421939
  REMARK    GeneRIF: C-terminal peptides of thrombin display antimicrobial
            activity against Gram-positive and Gram-negative bacteria.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 1990)
  AUTHORS   Kujovich,J.L.
  TITLE     Prothrombin Thrombophilia
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301327
REFERENCE   7  (bases 1 to 1990)
  AUTHORS   Iwahana,H., Yoshimoto,K., Shigekiyo,T., Shirakami,A., Saito,S. and
            Itakura,M.
  TITLE     Molecular and genetic analysis of a compound heterozygote for
            dysprothrombinemia of prothrombin Tokushima and hypoprothrombinemia
  JOURNAL   Am J Hum Genet 51 (6), 1386-1395 (1992)
   PUBMED   1334372
REFERENCE   8  (bases 1 to 1990)
  AUTHORS   Owen,C.A. Jr., Henriksen,R.A., McDuffie,F.C. and Mann,K.G.
  TITLE     Prothrombin Quick. A newly identified dysprothrombinemia
  JOURNAL   Mayo Clin Proc 53 (1), 29-33 (1978)
   PUBMED   625142
REFERENCE   9  (bases 1 to 1990)
  AUTHORS   Butkowski,R.J., Elion,J., Downing,M.R. and Mann,K.G.
  TITLE     Primary structure of human prethrombin 2 and alpha-thrombin
  JOURNAL   J Biol Chem 252 (14), 4942-4957 (1977)
   PUBMED   873923
REFERENCE   10 (bases 1 to 1990)
  AUTHORS   Walz,D.A., Hewett-Emmett,D. and Seegers,W.H.
  TITLE     Amino acid sequence of human prothrombin fragments 1 and 2
  JOURNAL   Proc Natl Acad Sci U S A 74 (5), 1969-1972 (1977)
   PUBMED   266717
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK312965.1, AK303747.1 and
            BC051332.1.
            
            On Aug 31, 2019 this sequence version replaced NM_000506.4.
            
            Summary: This gene encodes the prothrombin protein (also known as
            coagulation factor II). This protein is proteolytically cleaved in
            multiple steps to form the activated serine protease thrombin. The
            activated thrombin enzyme plays an important role in thrombosis and
            hemostasis by converting fibrinogen to fibrin during blood clot
            formation, by stimulating platelet aggregation, and by activating
            additional coagulation factors. Thrombin also plays a role in cell
            proliferation, tissue repair, and angiogenesis as well as
            maintaining vascular integrity during development and postnatal
            life. Peptides derived from the C-terminus of this protein have
            antimicrobial activity against E. coli and P. aeruginosa. Mutations
            in this gene lead to various forms of thrombosis and
            dysprothrombinemia. Rapid increases in cytokine levels following
            coronavirus infections can dysregulate the coagulation cascade and
            produce thrombosis, compromised blood supply, and organ failure.
            [provided by RefSeq, May 2020].
            
            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 :: AK222775.1, BC051332.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2145122, SAMEA2155590
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            coronavirus related                :: relevant for disease process
            MANE Ensembl match                 :: ENST00000311907.10/
                                                  ENSP00000308541.5
            Protein has antimicrobial activity :: PMID: 20421939
            RefSeq Select criteria             :: based on single
                                                  protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-516               AK312965.1         13-528
            517-1985            AK303747.1         478-1946
            1986-1990           BC051332.1         1974-1978
FEATURES             Location/Qualifiers
     source          1..1990
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11p11.2"
     gene            1..1990
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /note="coagulation factor II, thrombin"
                     /db_xref="GeneID:2147"
                     /db_xref="HGNC:HGNC:3535"
                     /db_xref="MIM:176930"
     exon            1..102
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /inference="alignment:Splign:2.1.0"
     CDS             24..1892
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /EC_number="3.4.21.5"
                     /note="prothrombin B-chain; prepro-coagulation factor II;
                     thrombin factor II"
                     /codon_start=1
                     /product="prothrombin preproprotein"
                     /protein_id="NP_000497.1"
                     /db_xref="CCDS:CCDS31476.1"
                     /db_xref="GeneID:2147"
                     /db_xref="HGNC:HGNC:3535"
                     /db_xref="MIM:176930"
                     /translation="MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRA
                     NTFLEEVRKGNLERECVEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAA
                     CLEGNCAEGLGTNYRGHVNITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNP
                     DSSTTGPWCYTTDPTVRRQECSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRG
                     QQYQGRLAVTTHGLPCLAWASAQAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYV
                     AGKPGDFGYCDLNYCEEAVEEETGDGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEA
                     DCGLRPLFEKKSLEDKTERELLESYIDGRIVEGSDAEIGMSPWQVMLFRKSPQELLCG
                     ASLISDRWVLTAAHCLLYPPWDKNFTENDLLVRIGKHSRTRYERNIEKISMLEKIYIH
                     PRYNWRENLDRDIALMKLKKPVAFSDYIHPVCLPDRETAASLLQAGYKGRVTGWGNLK
                     ETWTANVGKGQPSVLQVVNLPIVERPVCKDSTRIRITDNMFCAGYKPDEGKRGDACEG
                     DSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKYGFYTHVFRLKKWIQKVIDQFGE"
     exon            103..263
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /inference="alignment:Splign:2.1.0"
     exon            264..288
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /inference="alignment:Splign:2.1.0"
     exon            289..339
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /inference="alignment:Splign:2.1.0"
     exon            340..445
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /inference="alignment:Splign:2.1.0"
     exon            446..582
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /inference="alignment:Splign:2.1.0"
     exon            583..897
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /inference="alignment:Splign:2.1.0"
     exon            898..1026
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /inference="alignment:Splign:2.1.0"
     exon            1027..1153
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /inference="alignment:Splign:2.1.0"
     exon            1154..1321
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /inference="alignment:Splign:2.1.0"
     exon            1322..1495
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /inference="alignment:Splign:2.1.0"
     exon            1496..1677
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /inference="alignment:Splign:2.1.0"
     exon            1678..1748
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /inference="alignment:Splign:2.1.0"
     exon            1749..1990
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1970..1975
                     /regulatory_class="polyA_signal_sequence"
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /note="hexamer: AATAAA"
     polyA_site      1990
                     /gene="F2"
                     /gene_synonym="PT; RPRGL2; THPH1"
                     /note="major polyA site"
ORIGIN      
        1 agtgacccag gagctgacac actatggcgc acgtccgagg cttgcagctg cctggctgcc
       61 tggccctggc tgccctgtgt agccttgtgc acagccagca tgtgttcctg gctcctcagc
      121 aagcacggtc gctgctccag cgggtccggc gagccaacac cttcttggag gaggtgcgca
      181 agggcaacct ggagcgagag tgcgtggagg agacgtgcag ctacgaggag gccttcgagg
      241 ctctggagtc ctccacggct acggatgtgt tctgggccaa gtacacagct tgtgagacag
      301 cgaggacgcc tcgagataag cttgctgcat gtctggaagg taactgtgct gagggtctgg
      361 gtacgaacta ccgagggcat gtgaacatca cccggtcagg cattgagtgc cagctatgga
      421 ggagtcgcta cccacataag cctgaaatca actccactac ccatcctggg gccgacctac
      481 aggagaattt ctgccgcaac cccgacagca gcaccacggg accctggtgc tacactacag
      541 accccaccgt gaggaggcag gaatgcagca tccctgtctg tggccaggat caagtcactg
      601 tagcgatgac tccacgctcc gaaggctcca gtgtgaatct gtcacctcca ttggagcagt
      661 gtgtccctga tcgggggcag cagtaccagg ggcgcctggc ggtgaccaca catgggctcc
      721 cctgcctggc ctgggccagc gcacaggcca aggccctgag caagcaccag gacttcaact
      781 cagctgtgca gctggtggag aacttctgcc gcaacccaga cggggatgag gagggcgtgt
      841 ggtgctatgt ggccgggaag cctggcgact ttgggtactg cgacctcaac tattgtgagg
      901 aggccgtgga ggaggagaca ggagatgggc tggatgagga ctcagacagg gccatcgaag
      961 ggcgtaccgc caccagtgag taccagactt tcttcaatcc gaggaccttt ggctcgggag
     1021 aggcagactg tgggctgcga cctctgttcg agaagaagtc gctggaggac aaaaccgaaa
     1081 gagagctcct ggaatcctac atcgacgggc gcattgtgga gggctcggat gcagagatcg
     1141 gcatgtcacc ttggcaggtg atgcttttcc ggaagagtcc ccaggagctg ctgtgtgggg
     1201 ccagcctcat cagtgaccgc tgggtcctca ccgccgccca ctgcctcctg tacccgccct
     1261 gggacaagaa cttcaccgag aatgaccttc tggtgcgcat tggcaagcac tcccgcacca
     1321 ggtacgagcg aaacattgaa aagatatcca tgttggaaaa gatctacatc caccccaggt
     1381 acaactggcg ggagaacctg gaccgggaca ttgccctgat gaagctgaag aagcctgttg
     1441 ccttcagtga ctacattcac cctgtgtgtc tgcccgacag ggagacggca gccagcttgc
     1501 tccaggctgg atacaagggg cgggtgacag gctggggcaa cctgaaggag acgtggacag
     1561 ccaacgttgg taaggggcag cccagtgtcc tgcaggtggt gaacctgccc attgtggagc
     1621 ggccggtctg caaggactcc acccggatcc gcatcactga caacatgttc tgtgctggtt
     1681 acaagcctga tgaagggaaa cgaggggatg cctgtgaagg tgacagtggg ggaccctttg
     1741 tcatgaagag cccctttaac aaccgctggt atcaaatggg catcgtctca tggggtgaag
     1801 gctgtgaccg ggatgggaaa tatggcttct acacacatgt gttccgcctg aagaagtgga
     1861 tacagaaggt cattgatcag tttggagagt agggggccac tcatattctg ggctcctgga
     1921 accaatcccg tgaaagaatt atttttgtgt ttctaaaact atggttccca ataaaagtga
     1981 ctctcagcga
//
