LOCUS       NM_173517               6087 bp    mRNA    linear   PRI 19-SEP-2024
DEFINITION  Homo sapiens vitamin K epoxide reductase complex subunit 1 like 1
            (VKORC1L1), transcript variant 1, mRNA.
ACCESSION   NM_173517
VERSION     NM_173517.6
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 6087)
  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   2  (bases 1 to 6087)
  AUTHORS   Haenig,C., Atias,N., Taylor,A.K., Mazza,A., Schaefer,M.H., Russ,J.,
            Riechers,S.P., Jain,S., Coughlin,M., Fontaine,J.F., Freibaum,B.D.,
            Brusendorf,L., Zenkner,M., Porras,P., Stroedicke,M., Schnoegl,S.,
            Arnsburg,K., Boeddrich,A., Pigazzini,L., Heutink,P., Taylor,J.P.,
            Kirstein,J., Andrade-Navarro,M.A., Sharan,R. and Wanker,E.E.
  TITLE     Interactome Mapping Provides a Network of Neurodegenerative Disease
            Proteins and Uncovers Widespread Protein Aggregation in Affected
            Brains
  JOURNAL   Cell Rep 32 (7), 108050 (2020)
   PUBMED   32814053
REFERENCE   3  (bases 1 to 6087)
  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 6087)
  AUTHORS   Wu,S., Chen,X., Jin,D.Y., Stafford,D.W., Pedersen,L.G. and Tie,J.K.
  TITLE     Warfarin and vitamin K epoxide reductase: a molecular accounting
            for observed inhibition
  JOURNAL   Blood 132 (6), 647-657 (2018)
   PUBMED   29743176
  REMARK    GeneRIF: The disputed loop sequence between the 1st and 2d
            transmembrane domain of VKOR in the cytoplasm. Using molecular
            dynamics simulations, a T-shaped stacking interaction between
            warfarin and Tyr 139, within the proposed TY139A warfarin-binding
            motif, was seen. Y25, A26, and Y139) were essential for warfarin
            binding to VKOR, with a reversible dynamic warfarin-binding pocket
            opening and conformational changes .
REFERENCE   5  (bases 1 to 6087)
  AUTHORS   Czogalla,K.J., Liphardt,K., Honing,K., Hornung,V., Biswas,A.,
            Watzka,M. and Oldenburg,J.
  TITLE     VKORC1 and VKORC1L1 have distinctly different oral anticoagulant
            dose-response characteristics and binding sites
  JOURNAL   Blood Adv 2 (6), 691-702 (2018)
   PUBMED   29581108
  REMARK    GeneRIF: we have established KO HEK 293T cell lines that express
            either endogenously VKORC1 or VKORC1L1, and found that VKORC1 is
            more sensitive to OACs than VKORC1L1, whereas rodenticides
            apparently inhibit both VKOR enzymes equally
REFERENCE   6  (bases 1 to 6087)
  AUTHORS   Oldenburg,J., Watzka,M. and Bevans,C.G.
  TITLE     VKORC1 and VKORC1L1: Why do Vertebrates Have Two Vitamin K
            2,3-Epoxide Reductases?
  JOURNAL   Nutrients 7 (8), 6250-6280 (2015)
   PUBMED   26264021
  REMARK    Review article
            Publication Status: Online-Only
REFERENCE   7  (bases 1 to 6087)
  AUTHORS   Westhofen,P., Watzka,M., Marinova,M., Hass,M., Kirfel,G.,
            Muller,J., Bevans,C.G., Muller,C.R. and Oldenburg,J.
  TITLE     Human vitamin K 2,3-epoxide reductase complex subunit 1-like 1
            (VKORC1L1) mediates vitamin K-dependent intracellular antioxidant
            function
  JOURNAL   J Biol Chem 286 (17), 15085-15094 (2011)
   PUBMED   21367861
  REMARK    GeneRIF: VKORC1L1 is responsible for driving vitamin K-mediated
            intracellular antioxidation pathways critical to cell survival.
REFERENCE   8  (bases 1 to 6087)
  AUTHORS   Yin,T., Hanada,H., Miyashita,K., Kokubo,Y., Akaiwa,Y., Otsubo,R.,
            Nagatsuka,K., Otsuki,T., Okayama,A., Minematsu,K., Naritomi,H.,
            Tomoike,H. and Miyata,T.
  TITLE     No association between vitamin K epoxide reductase complex subunit
            1-like 1 (VKORC1L1) and the variability of warfarin dose
            requirement in a Japanese patient population
  JOURNAL   Thromb Res 122 (2), 179-184 (2008)
   PUBMED   17996924
  REMARK    GeneRIF: VKORC1L1 does not affect the variability of warfarin dose
            requirement in a Japanese patient population
REFERENCE   9  (bases 1 to 6087)
  AUTHORS   Girard,A., Sachidanandam,R., Hannon,G.J. and Carmell,M.A.
  TITLE     A germline-specific class of small RNAs binds mammalian Piwi
            proteins
  JOURNAL   Nature 442 (7099), 199-202 (2006)
   PUBMED   16751776
REFERENCE   10 (bases 1 to 6087)
  AUTHORS   Rost,S., Fregin,A., Ivaskevicius,V., Conzelmann,E., Hortnagel,K.,
            Pelz,H.J., Lappegard,K., Seifried,E., Scharrer,I., Tuddenham,E.G.,
            Muller,C.R., Strom,T.M. and Oldenburg,J.
  TITLE     Mutations in VKORC1 cause warfarin resistance and multiple
            coagulation factor deficiency type 2
  JOURNAL   Nature 427 (6974), 537-541 (2004)
   PUBMED   14765194
  REMARK    GeneRIF: molecular cloning
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC093582.3, HY064992.1,
            AK289522.1, AC073261.8 and BM991935.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_173517.5.
            
            Summary: This gene encodes an enzyme important in the vitamin K
            cycle, which is involved in the carboxylation of glutamate residues
            present in vitamin K-dependent proteins. The encoded enzyme
            catalyzes the de-epoxidation of vitamin K 2,3-epoxide. Oxidative
            stress may upregulate expression of this gene and the encoded
            protein may protect cells and membrane proteins form oxidative
            damage. This gene and a related gene (Gene ID: 79001) may have
            arisen by gene duplication of an ancestral gene. [provided by
            RefSeq, Oct 2016].
            
            Transcript Variant: This variant (1) represents the longer
            transcript but encodes the shorter isoform (1).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            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 :: SRR1803612.245096.1,
                                           SRR1803617.280945.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            CDS uses downstream in-frame AUG :: community standard
                                                (PMID:26264021)
            MANE Ensembl match               :: ENST00000360768.5/
                                                ENSP00000353998.2
            RefSeq Select criteria           :: based on conservation,
                                                expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-25                AC093582.3         53384-53408
            26-283              HY064992.1         1-258
            284-710             AK289522.1         1-427
            711-6025            AC073261.8         28070-33384
            6026-6087           BM991935.1         23-84               c
FEATURES             Location/Qualifiers
     source          1..6087
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7q11.21"
     gene            1..6087
                     /gene="VKORC1L1"
                     /note="vitamin K epoxide reductase complex subunit 1 like
                     1"
                     /db_xref="GeneID:154807"
                     /db_xref="HGNC:HGNC:21492"
                     /db_xref="MIM:608838"
     exon            1..492
                     /gene="VKORC1L1"
                     /inference="alignment:Splign:2.1.0"
     CDS             299..829
                     /gene="VKORC1L1"
                     /EC_number="1.17.4.4"
                     /note="isoform 1 is encoded by transcript variant 1;
                     VKORC1-like protein 1"
                     /codon_start=1
                     /product="vitamin K epoxide reductase complex subunit
                     1-like protein 1 isoform 1"
                     /protein_id="NP_775788.2"
                     /db_xref="CCDS:CCDS5529.1"
                     /db_xref="GeneID:154807"
                     /db_xref="HGNC:HGNC:21492"
                     /db_xref="MIM:608838"
                     /translation="MAAPVLLRVSVPRWERVARYAVCAAGILLSIYAYHVEREKERDP
                     EHRALCDLGPWVKCSAALASRWGRGFGLLGSIFGKDGVLNQPNSVFGLIFYILQLLLG
                     MTASAVAALILMTSSIMSVVGSLYLAYILYFVLKEFCIICIVTYVLNFLLLIINYKRL
                     VYLNEAWKRQLQPKQD"
     exon            493..602
                     /gene="VKORC1L1"
                     /inference="alignment:Splign:2.1.0"
     exon            603..6087
                     /gene="VKORC1L1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5052..5057
                     /regulatory_class="polyA_signal_sequence"
                     /gene="VKORC1L1"
                     /note="hexamer: AATAAA"
     polyA_site      5077
                     /gene="VKORC1L1"
     regulatory      6067..6072
                     /regulatory_class="polyA_signal_sequence"
                     /gene="VKORC1L1"
                     /note="hexamer: AATAAA"
     polyA_site      6087
                     /gene="VKORC1L1"
                     /note="major polyA site"
ORIGIN      
        1 agtctccgcc cgccgatccg gcctcttcgg ccgttgcgca ctccaccccc tccctccgcg
       61 cccgcgcgcg ccttccccgc cccgtccgcc tcactccttt tggggcggtt gggccgcgcg
      121 cctgtggggg cggggcccgg agcaggccac cgagccaatg gggcgcggcg gcggcggcgg
      181 cggtggtggc ggcggcggcg gaggcggcgg tggcggcggt ggcggctggg tcgggccccg
      241 acgggcggcg gcggctgagg tggaggcgga gggaggcggc ggcggcggcg gcgggaagat
      301 ggcggctccc gtcctgctaa gagtgtcggt gccgcggtgg gagcgggtgg cccggtatgc
      361 agtgtgcgct gccggaatcc tgctctccat ctacgcctac cacgtggagc gggagaagga
      421 gcgggacccc gagcaccggg ccctctgcga cctggggccc tgggtgaagt gctccgccgc
      481 ccttgcctcc agatggggtc gaggatttgg tcttttgggt tccatttttg gaaaggatgg
      541 tgtattaaac cagccaaaca gtgtctttgg acttatattt tatatactac agttattact
      601 tggcatgaca gcaagcgctg tggcggcttt gatcctcatg acgtcctcca tcatgtcggt
      661 cgtggggtcc ctgtacctgg cctacattct gtactttgtg ctgaaggagt tctgcatcat
      721 ctgcatcgtc acgtacgtgc tgaacttcct tcttctcatt atcaactaca aacgactagt
      781 ttacttgaac gaggcctgga agcggcagct gcaacccaag caggactgac gcccgacaga
      841 ctccacccta acagtctcaa gcccctttcc attcagttta ttttgcagca ggtttttatt
      901 attattatta ttattattat tcacaacaga cactttccct aagaatctca aactgatttt
      961 taaaaatccg gtaaattaga aggggccctc gctattttct gtgtcagtct tcattttaaa
     1021 tatggataca aaaaggatac gccgagccaa tcaaagacaa gctttaactt tactttgaag
     1081 tgtttctgaa atgataaaat gtagccctag ccccctgccc tcaattgtaa agtgagcaac
     1141 cattgctagt aattctttaa tgtgtataaa ttcaatttca ggtataacaa atgtgatcat
     1201 gacatgaaaa tattctagaa tagatactgt attaaatatt gccatgttta caatatgtaa
     1261 tatgttttta gccgatggat ttaaacatgt agattcaact agaatccatt tgtgatattt
     1321 gtaaataaag gtagaaatat tagatccatt tctgcagaac ttactgtaca gtttagttgg
     1381 agtgtagcac tgaagaactg tcagctcagc gttgactgag gagatagtga aaatagccta
     1441 tacacagcat cttgtgaaaa gtactggcag ccgtggttgc agcaaataat agggcaaaaa
     1501 aaataataat agggtggtcg gttccctttc atctccctct tctgaaagga aaaaattgaa
     1561 ttggaacgtt caagtccagt ttgtgttcag tcataaaact gggccagttg ttaaccttac
     1621 agaatgagtc atgtggccag accttcaagt ccaaggcctt cagacactaa ggatgggaaa
     1681 atgggtattt ttctttggag aaaagctgga aatataaaca tggcattttt aggtaaagtt
     1741 tcttccacta gttgaatttt catgcagata tttttcctta acgttggtgc cagtcaagca
     1801 aagagtatta tgatggaaaa gaccagtcca agccccatcg ctccggagtg ggagccagtg
     1861 ttcttgctaa ttgtttcttt ctgcactaac cactcagatg tctaatttaa ttgttttgca
     1921 gtcaaatact ggatttgtaa ccttcagggc tgacatgctg cccagtttgc ttcatcggga
     1981 gaatagcaac aggtagacac atctcaaggc taaatctgct catgtcgcca ctgctctcat
     2041 aatgacacac atgcagtaag aagacttttg taaggggatt tgagtacacc caaatgaaat
     2101 tgtgacagga tgtttgtatg gttaacatct gatatcagaa tgttaaaagt gccttctgtc
     2161 ttaaatctca aaccaaatat tttgtgtgtt gaccttgggc agaagaagtg tccttccctc
     2221 ctttcttcac cgtcaggtag aaaacctgca ctctgcagaa gggtcctgtg tgatcactta
     2281 atcctctggt tgagaagcag cagtaatgtt tttgcttcca acctgattaa tcattttatg
     2341 ttgaaaatag tcaatgagac cagtatctct tgagtgcttt atttgccttc tctttgaagg
     2401 gaggggacgg gctctgctct gtaaactcaa atgtgtagag tcagcaacaa ttccgtagct
     2461 tccaactgac tcagaattga tgcaacgtag gtcttctggc ccgaggcagg tatcaagtcc
     2521 aaatcataat gaacttttca ccagtttcaa ccagtttctt aaaagagagc ttaagtcaag
     2581 atttcatcaa gacttgtgtt ttcccatgaa tgtgaatctt tcaatggctg ttggagtatg
     2641 tatgtactgt tcttgcattc tgaagtagtt aaagaactct agaaagtact gattggccat
     2701 ctggtgtcta tggagaaaga agtcctcacg tttgagggct gtacagtgag gccatcttgt
     2761 agcagcgcat ccagctctac caaggcagtc ctctggttct tttttctaag ctacagtgga
     2821 aatggcctaa tggttaaaac tgtggtatac atgacatcgg ttgtgctaaa caagttcctc
     2881 gtgtcccaat atccaatggt ttttcatcct attttgtatc aatcaacaga gtatagttaa
     2941 agcttgtctt gatgttgcat tcttgcaaat gtcttcaact cttacctgag aaaacatggc
     3001 aaaatggtca gccagaccct tccagttttt cctttgcttt tctaagcctc ggggaaacca
     3061 ctgtttcagt tgtataaaaa cttttgccac attcctatgg cccagtcgaa ttaataccct
     3121 ttttctcact gagagaggaa cacgtactgc ctgtcataac agcattgtaa tgccagtgtc
     3181 tcagtaacag aatcctggtg ggtgttaatt gggtgttttt tgccctggag aattcagatt
     3241 cctttctata cctccgattc tgcccagaag agggggggaa tcaccagtgt tacaaaatta
     3301 gaagattgtt ttgcctgttt tagactgaat atttgaacac tgcagcatta ctagccacca
     3361 gtgttaaagg acagatgagg ggaaacattt gtttttagca gtaattccat gcctcatctt
     3421 ttttaagtga tttgttccaa atgaagccat ttattgactt gatgttcaca aatatcattt
     3481 gaagaaataa caggaattgg ggttagatga taaattctag ggaatctagg tgatttggag
     3541 gatttcattt gttttgcatt acagctagtt gctctcacta aaggtaaatt tccggtgaaa
     3601 taactcaggt ttaactagct gtgtgcccag aatcactgtt ccttcataca tgtgtcctct
     3661 ccttaaattc attactttca aatgatgttc aaagcattga ctattttcat tcaaagaaac
     3721 tacattcggc cgggcacggt ggctcacgcc tataatccca gcactttggg aggccgaggc
     3781 gggtggatta cctaaggtca ggagttcaag accagcctgg ccagcatagt gaaaccccat
     3841 ctctactaaa aatacaaaaa ttagccaggc gcagtggcac acccctgtaa tcccagctac
     3901 tcgggaggct gagggaggag aattgcttga gcccgggaga cagaggttgc agtgagtcaa
     3961 gatcatgcca ctgcactcca gcctggccaa cagagcgaga ctgtcccccc cccaaaaaaa
     4021 aaagagagag actgcattca aagaggacca agactacagt gaaattaaaa ctgtttgctg
     4081 gctgggcatg gtggctcaca cctgtaatcc cagcactttg ggaggccgag gcggttggat
     4141 cacctgaggt cagaagttcg agatcagcct gaccgacata gtggaaccct gtctttacta
     4201 aaaatacaaa aattagctgg gcatggtggc ggcacctgta atgccagctc ctccagaggc
     4261 tgaggcagga gaattgcttg aacccagtag gtggaggttg cagtgagcca cagttgcgcc
     4321 attgcactcc agcctgggca atgagtgaaa ctctgtctca aataaaaaaa taaaaataaa
     4381 aactatttgt tgacttttgt ttttcattta gttttggaaa agactatttg caaaagtaca
     4441 gagttatctt cagcaattac ttcacaactt agattggtac caagagtgac aggagatctt
     4501 gtcttggaag atcattatta gatgccaaca aggagaccca ctgtgatttc tggtaaccta
     4561 tttggggaaa aagacctaat gacctaatat gcaatttctg tcctcgtgtc tttttctcta
     4621 acacacagtc atgggtgaaa catttcagac acctcaggca gcacttatgg tttctaattg
     4681 tgagaactac ccttccatca aacaaaaagg gcaagggtgg gagccccggc tacttggtta
     4741 aacatttttt actacaaatt cgcccagaaa aggtgaaata ttttgttata aaactgtatt
     4801 aagcatggcc taagtattta ttaggtatat gatctgtgta gtatgttcca tcagaaatat
     4861 ttcttactag tgctttaagc tccagagtaa acagtcattt aaaatggagt tcactgggca
     4921 ggtttcccct ttaatctaga tagaaatact ctttatcaga gatttaaggc actgttttgc
     4981 taactggtaa ataaaaccaa atgtaaatat gtaagaatgt ttatttgttg cacataactt
     5041 ttttggtata aaataaatgt agaagttacc tgtggaagtt gtgctcccat tattcttaaa
     5101 ctgcagggtt gcattccaaa agaactgaaa cgaagtcttt ttagactcag taggagcctt
     5161 atattcttga agtcaatact gtaacctcat ttctaaggta tacagggttg attctttttc
     5221 tcttaaatca tatgtaactt gcagaagatt cagagtcctc agacctctag ttcttggaat
     5281 tcctgtaggt ttacggtgta tgtgattgtc aagaattaat gacaaaaatg tgtcactgcc
     5341 tacagttctg tgaacactca gaatgtatta atgagctgtt tttccatagt tttactttag
     5401 cttaccttga atactccctg tataatcctc taaaaaggta gcatcggcaa gaaagatgaa
     5461 tccgttggaa atacagctga gccatacttc acggaataga acaagtgtgt tctgtgctgg
     5521 agctcaagac ctgtggaaag ggactgcccc cactgggtgc aatggctcat gcctgtaatc
     5581 ccagcacttt gggaggtaga ggcgggtgga tcacttgagg tcaggagttc aagaccagcc
     5641 tggccaacat ggtgaaacct gcctctactg aaaaatacag aaaaattagc caggattgtg
     5701 gtgtgcgcct gtaatcccag ctattcagga agctgaggca ggagaattgc ttgaaccagg
     5761 gaggcggagg ttgcagtgag acgagatcac gccactgcac tgcagcctag gcgacagagg
     5821 aagactccag ctcaagaaaa aaaacaatgg actgccccta atttgtaaac catttaaatg
     5881 tgtctattac atttaacttt tcttaatgtt tgtcaactaa aagttttatt cattatactt
     5941 tgacatactg gaacacaaaa cttgattcct ttgaaaaact aaagagaagt tgataaaaaa
     6001 aatacagaag ctctagattc ctaattggaa ctgactacac tcatttttaa aaaatggacg
     6061 atgcctaata aaaccacatg aaattaa
//
