LOCUS       NM_139279               4120 bp    mRNA    linear   PRI 21-SEP-2024
DEFINITION  Homo sapiens multiple coagulation factor deficiency 2, ER cargo
            receptor complex subunit (MCFD2), transcript variant 1, mRNA.
ACCESSION   NM_139279
VERSION     NM_139279.6
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 4120)
  AUTHORS   Zhang,Y., Zhu,M., Zheng,C., Wei,W., Emmer,B.T. and Zhang,B.
  TITLE     LMAN1-MCFD2 complex is a cargo receptor for the ER-Golgi transport
            of alpha1-antitrypsin
  JOURNAL   Biochem J 479 (7), 839-855 (2022)
   PUBMED   35322856
  REMARK    GeneRIF: LMAN1-MCFD2 complex is a cargo receptor for the ER-Golgi
            transport of alpha1-antitrypsin.
REFERENCE   2  (bases 1 to 4120)
  AUTHORS   Cho,N.H., Cheveralls,K.C., Brunner,A.D., Kim,K., Michaelis,A.C.,
            Raghavan,P., Kobayashi,H., Savy,L., Li,J.Y., Canaj,H., Kim,J.Y.S.,
            Stewart,E.M., Gnann,C., McCarthy,F., Cabrera,J.P., Brunetti,R.M.,
            Chhun,B.B., Dingle,G., Hein,M.Y., Huang,B., Mehta,S.B.,
            Weissman,J.S., Gomez-Sjoberg,R., Itzhak,D.N., Royer,L.A., Mann,M.
            and Leonetti,M.D.
  TITLE     OpenCell: Endogenous tagging for the cartography of human cellular
            organization
  JOURNAL   Science 375 (6585), eabi6983 (2022)
   PUBMED   35271311
REFERENCE   3  (bases 1 to 4120)
  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 4120)
  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   5  (bases 1 to 4120)
  AUTHORS   Guy,J.E., Wigren,E., Svard,M., Hard,T. and Lindqvist,Y.
  TITLE     New insights into multiple coagulation factor deficiency from the
            solution structure of human MCFD2
  JOURNAL   J Mol Biol 381 (4), 941-955 (2008)
   PUBMED   18590741
  REMARK    GeneRIF: These results provide an explanation for the previously
            observed calcium dependence of the MCFD2-ERGIC-53 interaction.
REFERENCE   6  (bases 1 to 4120)
  AUTHORS   Mohanty,D., Ghosh,K., Shetty,S., Spreafico,M., Garagiola,I. and
            Peyvandi,F.
  TITLE     Mutations in the MCFD2 gene and a novel mutation in the LMAN1 gene
            in Indian families with combined deficiency of factor V and VIII
  JOURNAL   Am J Hematol 79 (4), 262-266 (2005)
   PUBMED   16044454
  REMARK    GeneRIF: Mutations in (LMAN1) and (MCFD2), have been found to be
            responsible for the dual deficiency of FV and FVIII.
REFERENCE   7  (bases 1 to 4120)
  AUTHORS   Zhang,B., Cunningham,M.A., Nichols,W.C., Bernat,J.A., Seligsohn,U.,
            Pipe,S.W., McVey,J.H., Schulte-Overberg,U., de Bosch,N.B.,
            Ruiz-Saez,A., White,G.C., Tuddenham,E.G., Kaufman,R.J. and
            Ginsburg,D.
  TITLE     Bleeding due to disruption of a cargo-specific ER-to-Golgi
            transport complex
  JOURNAL   Nat Genet 34 (2), 220-225 (2003)
   PUBMED   12717434
  REMARK    GeneRIF: inactivating mutations in MCFD2 cause combined deficiency
            of factor V and factor VIII with a phenotype indistinguishable from
            that caused by mutations in LMAN1
REFERENCE   8  (bases 1 to 4120)
  AUTHORS   Nichols,W.C., Terry,V.H., Wheatley,M.A., Yang,A., Zivelin,A.,
            Ciavarella,N., Stefanile,C., Matsushita,T., Saito,H., de
            Bosch,N.B., Ruiz-Saez,A., Torres,A., Thompson,A.R., Feinstein,D.I.,
            White,G.C., Negrier,C., Vinciguerra,C., Aktan,M., Kaufman,R.J.,
            Ginsburg,D. and Seligsohn,U.
  TITLE     ERGIC-53 gene structure and mutation analysis in 19 combined
            factors V and VIII deficiency families
  JOURNAL   Blood 93 (7), 2261-2266 (1999)
   PUBMED   10090935
REFERENCE   9  (bases 1 to 4120)
  AUTHORS   Neerman-Arbez,M., Johnson,K.M., Morris,M.A., McVey,J.H.,
            Peyvandi,F., Nichols,W.C., Ginsburg,D., Rossier,C.,
            Antonarakis,S.E. and Tuddenham,E.G.
  TITLE     Molecular analysis of the ERGIC-53 gene in 35 families with
            combined factor V-factor VIII deficiency
  JOURNAL   Blood 93 (7), 2253-2260 (1999)
   PUBMED   10090934
REFERENCE   10 (bases 1 to 4120)
  AUTHORS   Deka,N., Wong,E., Matera,A.G., Kraft,R., Leinwand,L.A. and
            Schmid,C.W.
  TITLE     Repetitive nucleotide sequence insertions into a novel
            calmodulin-related gene and its processed pseudogene
  JOURNAL   Gene 71 (1), 123-134 (1988)
   PUBMED   2463956
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA330030.1, AF537214.1 and
            AI371370.1.
            
            On Aug 31, 2019 this sequence version replaced NM_139279.5.
            
            Summary: This gene encodes a soluble luminal protein with two
            calmodulin-like EF-hand motifs at its C-terminus. This protein
            forms a complex with LMAN1 (lectin mannose binding protein 1; also
            known as ERGIC-53) that facilitates the transport of coagulation
            factors V (FV) and VIII (FVIII) from the endoplasmic reticulum to
            the Golgi apparatus via an endoplasmic reticulum Golgi intermediate
            compartment (ERGIC). Mutations in this gene cause combined
            deficiency of FV and FVIII (F5F8D); a rare autosomal recessive
            bleeding disorder characterized by mild to moderate bleeding and
            coordinate reduction in plasma FV and FVIII levels. This protein
            has also been shown to maintain stem cell potential in adult
            central nervous system and is a marker for testicular germ cell
            tumors. The 3' UTR of this gene contains a transposon-like human
            repeat element named 'THE 1'. A processed RNA pseudogene of this
            gene is on chromosome 6p22.1. Alternative splicing results in
            multiple transcript variants encoding distinct isoforms. [provided
            by RefSeq, Apr 2016].
            
            Transcript Variant: This variant (1) encodes isoform A. Variants 1,
            2, 3 and 4 encode the same isoform (A).
            
            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 :: AL833900.1, BC040357.2 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968189, SAMEA2145245
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000319466.9/ ENSP00000317271.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1                 DA330030.1         19-19
            2-4116              AF537214.1         1-4115
            4117-4120           AI371370.1         16-19               c
FEATURES             Location/Qualifiers
     source          1..4120
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2p21"
     gene            1..4120
                     /gene="MCFD2"
                     /gene_synonym="F5F8D; F5F8D2; LMAN1IP; SDNSF"
                     /note="multiple coagulation factor deficiency 2, ER cargo
                     receptor complex subunit"
                     /db_xref="GeneID:90411"
                     /db_xref="HGNC:HGNC:18451"
                     /db_xref="MIM:607788"
     exon            1..84
                     /gene="MCFD2"
                     /gene_synonym="F5F8D; F5F8D2; LMAN1IP; SDNSF"
                     /inference="alignment:Splign:2.1.0"
     exon            85..239
                     /gene="MCFD2"
                     /gene_synonym="F5F8D; F5F8D2; LMAN1IP; SDNSF"
                     /inference="alignment:Splign:2.1.0"
     CDS             91..531
                     /gene="MCFD2"
                     /gene_synonym="F5F8D; F5F8D2; LMAN1IP; SDNSF"
                     /note="isoform A precursor is encoded by transcript
                     variant 1; neural stem cell-derived neuronal survival
                     protein"
                     /codon_start=1
                     /product="multiple coagulation factor deficiency protein 2
                     isoform A precursor"
                     /protein_id="NP_644808.1"
                     /db_xref="CCDS:CCDS33192.1"
                     /db_xref="GeneID:90411"
                     /db_xref="HGNC:HGNC:18451"
                     /db_xref="MIM:607788"
                     /translation="MTMRSLLRTPFLCGLLWAFCAPGARAEEPAASFSQPGSMGLDKN
                     TVHDQEHIMEHLEGVINKPEAEMSPQELQLHYFKMHDYDGNNLLDGLELSTAITHVHK
                     EEGSEQAPLMSEDELINIIDGVLRDDDKNNDGYIDYAEFAKSLQ"
     exon            240..399
                     /gene="MCFD2"
                     /gene_synonym="F5F8D; F5F8D2; LMAN1IP; SDNSF"
                     /inference="alignment:Splign:2.1.0"
     exon            400..4120
                     /gene="MCFD2"
                     /gene_synonym="F5F8D; F5F8D2; LMAN1IP; SDNSF"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4100..4105
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MCFD2"
                     /gene_synonym="F5F8D; F5F8D2; LMAN1IP; SDNSF"
                     /note="hexamer: AATAAA"
     polyA_site      4120
                     /gene="MCFD2"
                     /gene_synonym="F5F8D; F5F8D2; LMAN1IP; SDNSF"
                     /note="major polyA site"
ORIGIN      
        1 cgaagccgag gaagagcgtt ttggggacgg gggctggtga ggctcacgtt ggagggcttc
       61 gcgtctgctt cggagaccgt aaggatattg atgaccatga gatccctgct cagaaccccc
      121 ttcctgtgtg gcctgctctg ggccttttgt gccccaggcg ccagggctga ggagcctgca
      181 gccagcttct cccaacccgg cagcatgggc ctggataaga acacagtgca cgaccaagag
      241 catatcatgg agcatctaga aggtgtcatc aacaaaccag aggcggagat gtcgccacaa
      301 gaattgcagc tccattactt caaaatgcat gattatgatg gcaataattt gcttgatggc
      361 ttagaactct ccacagccat cactcatgtc cataaggagg aagggagtga acaggcacca
      421 ctaatgagtg aagatgaact gattaacata atagatggtg ttttgagaga tgatgacaag
      481 aacaatgatg gatacattga ctatgctgaa tttgcaaaat cactgcagta gatgttattt
      541 ggccatctcc tggttatata caaatgtgac ccgtgataat gtgattgaac actttagtaa
      601 tgcaaaataa ctcatttcca actactgctg cagcattttg gtaaaaacct gtagcgattc
      661 gttacactgg ggtgagaaga gataagagaa atgaaagaga agagaaatgg gacatctaat
      721 agtccctaag tgctattaaa taccttattg gacaagggct tgcttcaagc atctgtatta
      781 gtctgtatta atgctgctga taaagacgta cccgagactg ggaagaaaaa gaggtttact
      841 tggacttaca gttccacatg gctggggagg cctcagaatc atggcgggag gtgaaaggca
      901 cttcttacat ggcagcaaga gaaaatgagg aagaagcaaa agtggaaacc cctgataagc
      961 catcagatct tgtgaaactt attcactatc acaagaatag catgggaaag actggccccc
     1021 atgattcaat tacctcccct tgggtctctc ccacaacacg tgggaattct ggtagataca
     1081 atttcaagtt gagatttggg tggggacata gccaaaccat atcattctac ccctggcccc
     1141 tccaaatctc atgtcctcac tattcaaaac caatcatgcc ttcctaacag tcccccaaag
     1201 tcttaactct tttcagcatt aacgcaaaaa tccacagtcc aaagtctcat ctgagacaag
     1261 gcaagtccct tccacctatg agcctgtaaa atcaaaagca agctagttac ttcctagata
     1321 ccaacagggg tacaggtatt gattaaagac ggctgttcca aatgggagaa attggccaaa
     1381 ataaaggggt tacagggccc atgcaagtcc gaaatccagc agggctgtca aattttaaag
     1441 ttccagaata atctcctttg actccaggtc tcacatccag gtcatactga tgcaagaagt
     1501 gggttcccat ggtcttgggc agctctgccc ctgtggcttt gtagggtaca gcctccctcc
     1561 tggctgcttt cacggctgtt gttcagtgcc tgcggctttt ccaggtgcac ggtgcaagct
     1621 gttggtggat ctaccattct ggggtctgga ggacggtggc cctcttctca cagctccact
     1681 aggcagtgcc ccagtaggga ctctgtgtgg gggctcccac accacatttc ccttctgcac
     1741 tgccctagca gaggttctct cccctgccgc tgagagggcc tctcccctgc agcaaacgtt
     1801 tgcctgggca ttgaggcatt tccatacatc ttctgaaaac taggcggagg tttccaaatc
     1861 tcaattcttg acttctgtgc acctgcaggc ttaacagcac atagaagctg ccaaggcttg
     1921 gggcttccac tctgaagcca cagcccgagc tgtatgttgg cccctttcag ccatggctgg
     1981 agtggctggg acacaagaca ccaagtccct aggctgcaca cacatgtcag gggctgccct
     2041 gacatggcct ggagacattt tccccatggt gttggggatt aacattaggc tccttgctac
     2101 ttatgcaaat ttctgcagct ggcttgaatt tctccccaga aaatgggttt ttcttttcta
     2161 ttgcatagtc aggctgcaaa tttccaaact tttatgcttt gcttccctta tttataaggg
     2221 aatgccttta aaagcaccca agtcacctgt tgaacacttt gctgcttaga aatttcttcc
     2281 gctagttaac ctaaatcatc tctctcaagt tcaaagttcc acaaatccct atggaagggg
     2341 caaaatgctg ccagtctctt tgctaaaaca taacaagagt cacctttact ccagttccca
     2401 acaagttcct catcttcatc tgaggccacc tcagcctgga ctttgttgtc catattgcta
     2461 tcagcatttg gggcaaagcc attcaacaag tctgtaggaa gttccaaact ttcccacatt
     2521 ttcctgtttt cttctgagcc ctccaaactg ttccagcctc tgcctgttac ccagttccaa
     2581 agtcacttcc acattttggg tatttcttca gcaggtccca atctactggt accaatttac
     2641 tgtattagtc cgttttcacg ctgctgataa agacataccc gagactggga agaaaaagtg
     2701 gtttaattgg acttaaagtt ccacatggct ggggaggcct cagaatcatg gtgggaggca
     2761 aaagacactt cttacattgt ggcaagaaaa aatgaggaag aagcaaaagc agaaacccct
     2821 gataaactga tcagatctca tgagacttat tcactgtcac gagaatagca cgggaaagac
     2881 tggcccccat gattcaatta cctccccctg ggtctgtccc acaacacgtg ggaattctgg
     2941 gagatacaat tcaagttgag atttgtgggg ggacacaacc aaaccatatc agcatccttt
     3001 caagaatatt agataattgg agctgagtac tcaggaactt gactgtagta gaatactgct
     3061 agtttcttaa ttttaattca catcacctga aaagtaaaac aacaggcttt gccaagtgga
     3121 tgcttttcag taacagtgaa gtggagtgaa taccaaatgt ttgccctggt ggttcctatc
     3181 tcttcaggca aacatggtca gtattctgta aagttcccct ggcctaaatg attacttgct
     3241 ctgggcaagt ggatatttat taggctattt caaagccaca gcataagaat gtcagcctag
     3301 ccacagagtc tgagattctg agttcagcct agccacagag tctaagattc tgtatcctct
     3361 gacattttgg aaatgataca ctactggctt aagtgatgac tctttcagat tttcagtatt
     3421 ttatacaact actgccacat ccttatactt tattgctttt ctgtcttctt caacctggga
     3481 gagaccctga atttgagtgt gttctctaat caatagtggt ttagctttct tttctatttc
     3541 actcgtttct agggtttttt atttgcagtt taggaactat taggaatgtc aggactttat
     3601 cagcaggggt aaaactacca cctggcctag cctaagtagg aagtgaaaag ataattcacc
     3661 aaacaatgat taatcagata gaagttctag tcaagaggga tattgttgaa gttacctctt
     3721 ttagcctaga tacatggatt cttttcaaat caggaaagat tagaaaagga acccaaaaaa
     3781 ccctttaaca gtgtgaatct ttatagtatt tgaaaatgag aagaagcagc agattgtaat
     3841 ttggtttatt ggatgtgatg gacgttctgt aatagaaaac ctgaaacgat gattgaatgg
     3901 gaaaaagaga ctacaaaatt tgtcgtagga tgtatacaga cttattttct ttattacagt
     3961 attataagaa aacatatgta tttgtaaaaa tggtttcctg tgtcaagtat ttgtgcagtc
     4021 agagctgact tgtaaactat tcttgtaata gctcattatt ttgaaagatt tatatatgat
     4081 gaattctgga tatatgacca ataaaactga tgaagcaaaa
//
