LOCUS       NM_004341               7286 bp    mRNA    linear   PRI 19-SEP-2024
DEFINITION  Homo sapiens carbamoyl-phosphate synthetase 2, aspartate
            transcarbamylase, and dihydroorotase (CAD), transcript variant 1,
            mRNA.
ACCESSION   NM_004341
VERSION     NM_004341.5
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 7286)
  AUTHORS   Del Cano-Ochoa,F., Ng,B.G., Rubio-Del-Campo,A., Mahajan,S.,
            Wilson,M.P., Vilar,M., Rymen,D., Sanchez-Pintos,P., Kenny,J., Ley
            Martos,M., Campos,T., Wortmann,S.B., Freeze,H.H. and
            Ramon-Maiques,S.
  TITLE     Beyond genetics: Deciphering the impact of missense variants in CAD
            deficiency
  JOURNAL   J Inherit Metab Dis 46 (6), 1170-1185 (2023)
   PUBMED   37540500
  REMARK    GeneRIF: Beyond genetics: Deciphering the impact of missense
            variants in CAD deficiency.
REFERENCE   2  (bases 1 to 7286)
  AUTHORS   O'Neill,A.C., Uzbas,F., Antognolli,G., Merino,F., Draganova,K.,
            Jack,A., Zhang,S., Pedini,G., Schessner,J.P., Cramer,K.,
            Schepers,A., Metzger,F., Esgleas,M., Smialowski,P., Guerrini,R.,
            Falk,S., Feederle,R., Freytag,S., Wang,Z., Bahlo,M., Jungmann,R.,
            Bagni,C., Borner,G.H.H., Robertson,S.P., Hauck,S.M. and Gotz,M.
  TITLE     Spatial centrosome proteome of human neural cells uncovers
            disease-relevant heterogeneity
  JOURNAL   Science 376 (6599), eabf9088 (2022)
   PUBMED   35709258
REFERENCE   3  (bases 1 to 7286)
  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   4  (bases 1 to 7286)
  AUTHORS   Del Cano-Ochoa,F. and Ramon-Maiques,S.
  TITLE     Deciphering CAD: Structure and function of a mega-enzymatic
            pyrimidine factory in health and disease
  JOURNAL   Protein Sci 30 (10), 1995-2008 (2021)
   PUBMED   34288185
  REMARK    GeneRIF: Deciphering CAD: Structure and function of a
            mega-enzymatic pyrimidine factory in health and disease.
            Review article
REFERENCE   5  (bases 1 to 7286)
  AUTHORS   Russo,R., Marra,R., Andolfo,I., Manna,F., De Rosa,G., Rosato,B.E.,
            Radhakrishnan,K., Fahey,M. and Iolascon,A.
  TITLE     Uridine treatment normalizes the congenital dyserythropoietic
            anemia type II-like hematological phenotype in a patient with
            homozygous mutation in the CAD gene
  JOURNAL   Am J Hematol 95 (11), 1423-1426 (2020)
   PUBMED   32720728
  REMARK    GeneRIF: Uridine treatment normalizes the congenital
            dyserythropoietic anemia type II-like hematological phenotype in a
            patient with homozygous mutation in the CAD gene.
REFERENCE   6  (bases 1 to 7286)
  AUTHORS   Iwahana,H., Fujimura,M., Ii,S., Kondo,M., Moritani,M.,
            Takahashi,Y., Yamaoka,T., Yoshimoto,K. and Itakura,M.
  TITLE     Molecular cloning of a human cDNA encoding a trifunctional enzyme
            of carbamoyl-phosphate synthetase-aspartate
            transcarbamoylase-dihydroorotase in de Novo pyrimidine synthesis
  JOURNAL   Biochem Biophys Res Commun 219 (1), 249-255 (1996)
   PUBMED   8619816
REFERENCE   7  (bases 1 to 7286)
  AUTHORS   Davidson,J.N., Rao,G.N., Niswander,L., Andreano,C., Tamer,C. and
            Chen,K.C.
  TITLE     Organization and nucleotide sequence of the 3' end of the human CAD
            gene
  JOURNAL   DNA Cell Biol 9 (9), 667-676 (1990)
   PUBMED   1979741
REFERENCE   8  (bases 1 to 7286)
  AUTHORS   Chen,K.C., Vannais,D.B., Jones,C., Patterson,D. and Davidson,J.N.
  TITLE     Mapping of the gene encoding the multifunctional protein carrying
            out the first three steps of pyrimidine biosynthesis to human
            chromosome 2
  JOURNAL   Hum Genet 82 (1), 40-44 (1989)
   PUBMED   2565865
REFERENCE   9  (bases 1 to 7286)
  AUTHORS   Rao,G.N., Buford,E.S. and Davidson,J.N.
  TITLE     Transcriptional regulation of the human CAD gene during myeloid
            differentiation
  JOURNAL   Mol Cell Biol 7 (5), 1961-1966 (1987)
   PUBMED   2885743
REFERENCE   10 (bases 1 to 7286)
  AUTHORS   Carrey,E.A., Campbell,D.G. and Hardie,D.G.
  TITLE     Phosphorylation and activation of hamster carbamyl phosphate
            synthetase II by cAMP-dependent protein kinase. A novel mechanism
            for regulation of pyrimidine nucleotide biosynthesis
  JOURNAL   EMBO J 4 (13B), 3735-3742 (1985)
   PUBMED   4092695
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC013403.9, BC065510.1,
            D78586.1, BU541191.1, BM927624.1, BU558264.1, BQ447516.1 and
            AC013413.6.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_004341.4.
            
            Summary: The de novo synthesis of pyrimidine nucleotides is
            required for mammalian cells to proliferate. This gene encodes a
            trifunctional protein which is associated with the enzymatic
            activities of the first 3 enzymes in the 6-step pathway of
            pyrimidine biosynthesis: carbamoylphosphate synthetase (CPS II),
            aspartate transcarbamoylase, and dihydroorotase. This protein is
            regulated by the mitogen-activated protein kinase (MAPK) cascade,
            which indicates a direct link between activation of the MAPK
            cascade and de novo biosynthesis of pyrimidine nucleotides.
            Alternative splicing results in multiple transcript variants
            encoding different isoforms. [provided by RefSeq, Apr 2015].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            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 :: BC065510.1, D78586.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000264705.9/ ENSP00000264705.3
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-21                AC013403.9         158069-158089
            22-305              BC065510.1         1-284
            306-307             D78586.1           149-150
            308-3956            BC065510.1         287-3935
            3957-4555           BU541191.1         200-798
            4556-5043           BM927624.1         275-762
            5044-5712           BU558264.1         25-693
            5713-7129           BC065510.1         5692-7108
            7130-7135           BQ447516.1         18-23               c
            7136-7286           AC013413.6         26786-26936
FEATURES             Location/Qualifiers
     source          1..7286
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2p23.3"
     gene            1..7286
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /note="carbamoyl-phosphate synthetase 2, aspartate
                     transcarbamylase, and dihydroorotase"
                     /db_xref="GeneID:790"
                     /db_xref="HGNC:HGNC:1424"
                     /db_xref="MIM:114010"
     exon            1..265
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     CDS             184..6861
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /EC_number="2.1.3.2"
                     /EC_number="3.5.2.3"
                     /EC_number="6.3.4.16"
                     /EC_number="6.3.5.5"
                     /EC_number="3.5.1.2"
                     /note="isoform 1 is encoded by transcript variant 1;
                     multifunctional protein CAD; CAD trifunctional protein;
                     carbamoyl phosphate synthetase 2-aspartate
                     transcarbamylase-dihydroorotase"
                     /codon_start=1
                     /product="multifunctional protein CAD isoform 1"
                     /protein_id="NP_004332.2"
                     /db_xref="CCDS:CCDS1742.1"
                     /db_xref="GeneID:790"
                     /db_xref="HGNC:HGNC:1424"
                     /db_xref="MIM:114010"
                     /translation="MAALVLEDGSVLRGQPFGAAVSTAGEVVFQTGMVGYPEALTDPS
                     YKAQILVLTYPLIGNYGIPPDEMDEFGLCKWFESSGIHVAALVVGECCPTPSHWSATR
                     TLHEWLQQHGIPGLQGVDTRELTKKLREQGSLLGKLVQNGTEPSSLPFLDPNARPLVP
                     EVSIKTPRVFNTGGAPRILALDCGLKYNQIRCLCQRGAEVTVVPWDHALDSQEYEGLF
                     LSNGPGDPASYPSVVSTLSRVLSEPNPRPVFGICLGHQLLALAIGAKTYKMRYGNRGH
                     NQPCLLVGSGRCFLTSQNHGFAVETDSLPADWAPLFTNANDGSNEGIVHNSLPFFSVQ
                     FHPEHQAGPSDMELLFDIFLETVKEATAGNPGGQTVRERLTERLCPPGIPTPGSGLPP
                     PRKVLILGSGGLSIGQAGEFDYSGSQAIKALKEENIQTLLINPNIATVQTSQGLADKV
                     YFLPITPHYVTQVIRNERPDGVLLTFGGQTALNCGVELTKAGVLARYGVRVLGTPVET
                     IELTEDRRAFAARMAEIGEHVAPSEAANSLEQAQAAAERLGYPVLVRAAFALGGLGSG
                     FASNREELSALVAPAFAHTSQVLVDKSLKGWKEIEYEVVRDAYGNCVTVCNMENLDPL
                     GIHTGESIVVAPSQTLNDREYQLLRQTAIKVTQHLGIVGECNVQYALNPESEQYYIIE
                     VNARLSRSSALASKATGYPLAYVAAKLALGIPLPELRNSVTGGTAAFEPSVDYCVVKI
                     PRWDLSKFLRVSTKIGSCMKSVGEVMGIGRSFEEAFQKALRMVDENCVGFDHTVKPVS
                     DMELETPTDKRIFVVAAALWAGYSVDRLYELTRIDRWFLHRMKRIIAHAQLLEQHRGQ
                     PLPPDLLQQAKCLGFSDKQIALAVLSTELAVRKLRQELGICPAVKQIDTVAAEWPAQT
                     NYLYLTYWGTTHDLTFRTPHVLVLGSGVYRIGSSVEFDWCAVGCIQQLRKMGYKTIMV
                     NYNPETVSTDYDMCDRLYFDEISFEVVMDIYELENPEGVILSMGGQLPNNMAMALHRQ
                     QCRVLGTSPEAIDSAENRFKFSRLLDTIGISQPQWRELSDLESARQFCQTVGYPCVVR
                     PSYVLSGAAMNVAYTDGDLERFLSSAAAVSKEHPVVISKFIQEAKEIDVDAVASDGVV
                     AAIAISEHVENAGVHSGDATLVTPPQDITAKTLERIKAIVHAVGQELQVTGPFNLQLI
                     AKDDQLKVIECNVRVSRSFPFVSKTLGVDLVALATRVIMGEEVEPVGLMTGSGVVGVK
                     VPQFSFSRLAGADVVLGVEMTSTGEVAGFGESRCEAYLKAMLSTGFKIPKKNILLTIG
                     SYKNKSELLPTVRLLESLGYSLYASLGTADFYTEHGVKVTAVDWHFEEAVDGECPPQR
                     SILEQLAEKNFELVINLSMRGAGGRRLSSFVTKGYRTRRLAADFSVPLIIDIKCTKLF
                     VEALGQIGPAPPLKVHVDCMTSQKLVRLPGLIDVHVHLREPGGTHKEDFASGTAAALA
                     GGITMVCAMPNTRPPIIDAPALALAQKLAEAGARCDFALFLGASSENAGTLGTVAGSA
                     AGLKLYLNETFSELRLDSVVQWMEHFETWPSHLPIVAHAEQQTVAAVLMVAQLTQRSV
                     HICHVARKEEILLIKAAKARGLPVTCEVAPHHLFLSHDDLERLGPGKGEVRPELGSRQ
                     DVEALWENMAVIDCFASDHAPHTLEEKCGSRPPPGFPGLETMLPLLLTAVSEGRLSLD
                     DLLQRLHHNPRRIFHLPPQEDTYVEVDLEHEWTIPSHMPFSKAHWTPFEGQKVKGTVR
                     RVVLRGEVAYIDGQVLVPPGYGQDVRKWPQGAVPQLPPSAPATSEMTTTPERPRRGIP
                     GLPDGRFHLPPRIHRASDPGLPAEEPKEKSSRKVAEPELMGTPDGTCYPPPPVPRQAS
                     PQNLGTPGLLHPQTSPLLHSLVGQHILSVQQFTKDQMSHLFNVAHTLRMMVQKERSLD
                     ILKGKVMASMFYEVSTRTSSSFAAAMARLGGAVLSFSEATSSVQKGESLADSVQTMSC
                     YADVVVLRHPQPGAVELAAKHCRRPVINAGDGVGEHPTQALLDIFTIREELGTVNGMT
                     ITMVGDLKHGRTVHSLACLLTQYRVSLRYVAPPSLRMPPTVRAFVASRGTKQEEFESI
                     EEALPDTDVLYMTRIQKERFGSTQEYEACFGQFILTPHIMTRAKKKMVVMHPMPRVNE
                     ISVEVDSDPRAAYFRQAENGMYIRMALLATVLGRF"
     exon            266..405
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            406..535
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            536..678
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            679..820
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            821..992
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            993..1178
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            1179..1291
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            1292..1437
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            1438..1569
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            1570..1803
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            1804..2025
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            2026..2214
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            2215..2339
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            2340..2470
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            2471..2583
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            2584..2828
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            2829..3075
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            3076..3174
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            3175..3399
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            3400..3582
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            3583..3801
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            3802..3969
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            3970..4152
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            4153..4257
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            4258..4497
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            4498..4579
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            4580..4746
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            4747..4911
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            4912..5043
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            5044..5245
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            5246..5436
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            5437..5577
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            5578..5679
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            5680..5776
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            5777..5821
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            5822..5991
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            5992..6066
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            6067..6279
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            6280..6405
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            6406..6561
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            6562..6663
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            6664..6758
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     exon            6759..7286
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      7105..7110
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /note="hexamer: AATAAA"
     polyA_site      7129
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
                     /note="major polyA site"
     polyA_site      7286
                     /gene="CAD"
                     /gene_synonym="CDG1Z; DEE50; EIEE50; GATD4"
ORIGIN      
        1 agtctctgct gctgccgcca agcgcgcccg aggctcctac gctgccgcgc ccggcttctc
       61 tccagcgccc cgcgccgtta gccacgtgga ccgactccgg cgcgccgtcc tcacgtggtt
      121 ccagtggagt ttgcagtcct tcccgcttct ccgtactcgc ccccgcctct gagctccctt
      181 cccatggcgg ccctagtgtt ggaggacggg tcggtcctgc ggggccagcc ctttggggcc
      241 gccgtgtcga ctgccgggga agtggtgttt caaaccggca tggtcggcta ccccgaggcc
      301 ctcactgatc cctcctacaa ggcacagatc ttagtgctca cctatcctct gatcggcaac
      361 tatggcatcc ccccagatga aatggatgag ttcggtctct gcaagtggtt tgaatcctcg
      421 ggcatccacg tagcagcact ggtagtggga gagtgctgtc ctactcccag ccactggagt
      481 gccacccgca ccctgcatga gtggctgcag cagcatggca tccctggctt gcaaggagta
      541 gacactcggg agctgaccaa gaagttgcgg gaacaggggt ctctgctggg gaagctggtc
      601 cagaatggaa cagaaccttc atccctgcca ttcttggacc ccaatgcccg ccccctggta
      661 ccagaggtct ccattaagac tccacgggta ttcaatacag ggggtgcccc tcggatcctt
      721 gctttggact gtggcctcaa gtataatcag atccgatgcc tctgccagcg tggggctgag
      781 gtcactgtgg taccctggga ccatgcacta gacagccaag agtatgaggg tctcttctta
      841 agtaatgggc ctggtgaccc tgcctcctat cccagtgtcg tatccacact gagccgtgtt
      901 ttatctgagc ctaatccccg acctgtcttt gggatctgcc tgggacacca gctattggcc
      961 ttagccattg gggccaagac ttacaagatg agatatggga accgaggcca taaccagccc
     1021 tgcttgttgg tgggctctgg gcgctgcttt ctgacatccc agaaccatgg gtttgctgtg
     1081 gagacagact cactgccagc agactgggct cctctcttca ccaacgccaa tgatggttcc
     1141 aatgaaggca ttgtgcacaa cagcttgcct ttcttcagtg tccagtttca cccagagcac
     1201 caagctggcc cttcagatat ggaactgctt ttcgatatct ttctggaaac tgtgaaagag
     1261 gccacagctg ggaaccctgg gggccagaca gttagagagc ggctgactga gcgcctctgt
     1321 ccccctggga ttcccactcc cggctctgga cttccaccac cacgaaaggt tctgatcctg
     1381 ggctcagggg gcctctccat tggccaagct ggagaatttg actactcggg ctctcaggca
     1441 attaaggccc tgaaggagga aaacatccag acgttgctga tcaaccccaa tattgccaca
     1501 gtgcagacct cccaggggct ggccgacaag gtctattttc ttcccataac acctcattat
     1561 gtaacccagg tgatacgtaa tgaacgcccc gatggtgtgt tactgacttt tgggggccag
     1621 actgctctga actgtggtgt ggagctgacc aaggccgggg tgctggctcg gtatggggtc
     1681 cgggtcctgg gcacaccagt ggagaccatt gagctgaccg aggatcgacg ggcctttgct
     1741 gccagaatgg cagagatcgg agagcatgtg gccccgagcg aggcagcaaa ttctcttgaa
     1801 caggcccagg cagccgctga acggctgggg taccctgtgc tagtgcgtgc agcctttgcc
     1861 ctgggtggcc tgggctctgg ctttgcctct aacagggagg agctctctgc tctcgtggcc
     1921 ccagcttttg cccataccag ccaagtgcta gtagacaagt ctctgaaggg atggaaggag
     1981 attgagtacg aggtggtgag agacgcctat ggcaactgtg tcacggtgtg taacatggag
     2041 aacttggacc cactgggcat ccacactggt gagtccatag tggtggcccc tagccagaca
     2101 ctgaatgaca gggagtatca gctcctgagg cagacagcta tcaaggtgac ccagcacctg
     2161 ggaattgttg gggagtgcaa tgtgcagtat gccttgaacc ctgagtctga gcagtattac
     2221 atcattgaag tgaatgccag gctctctcgc agctctgccc tggccagtaa ggccacaggt
     2281 tatccactgg cttatgtggc agccaagcta gcattgggca tccctttgcc tgagctcagg
     2341 aactctgtga cagggggtac agcagccttt gaacccagcg tggattattg tgtggtgaag
     2401 attcctcgat gggaccttag caagttcctg cgagtcagca caaagattgg gagctgcatg
     2461 aagagcgttg gtgaagtcat gggcattggg cgttcatttg aggaggcctt ccagaaggcc
     2521 ctgcgcatgg tggatgagaa ctgtgtgggc tttgatcaca cagtgaaacc agtcagcgat
     2581 atggagttgg agactccaac agataagcgg atttttgtgg tggcagctgc tttgtgggct
     2641 ggttattcag tggaccgcct gtatgagctc acacgcatcg accgctggtt cctgcaccga
     2701 atgaagcgta tcatcgcaca tgcccagctg ctagaacaac accgtggaca gcctttgccg
     2761 ccagacctgc tgcaacaggc caagtgtctt ggcttctcag acaaacagat tgcccttgca
     2821 gttctgagca cagagctggc tgttcgcaag ctgcgtcagg aactggggat ctgtccagca
     2881 gtgaaacaga ttgacacagt tgcagctgag tggccagccc agacaaatta cctataccta
     2941 acgtattggg gcaccaccca tgacctcacc tttcgaacac ctcatgtcct agtccttggc
     3001 tctggcgtct accgtattgg ctctagcgtt gaatttgact ggtgtgctgt aggctgcatc
     3061 cagcagctcc gaaagatggg atataagacc atcatggtga actataaccc agagacagtc
     3121 agcaccgact atgacatgtg tgatcgactc tactttgatg agatctcttt tgaggtggtg
     3181 atggacatct atgagctcga gaaccctgaa ggtgtgatcc tatccatggg tggacagctg
     3241 cccaacaaca tggccatggc gttgcatcgg cagcagtgcc gggtgctggg cacctcccct
     3301 gaagccattg actcggctga gaaccgtttc aagttttccc ggctccttga caccattggt
     3361 atcagccagc ctcagtggag ggagctcagt gacctcgagt ctgctcgcca attctgccag
     3421 accgtggggt acccctgtgt ggtgcgcccc tcctatgtgc tgagcggtgc tgctatgaat
     3481 gtggcctaca cggatggaga cctggagcgc ttcctgagca gcgcagcagc cgtctccaaa
     3541 gagcatcccg tggtcatctc caagttcatc caggaggcta aggagattga cgtggatgcc
     3601 gtggcctctg atggtgtggt ggcagccatc gccatctctg agcatgtgga gaatgcaggt
     3661 gtgcattcag gtgatgcgac gctggtgacc cccccacaag atatcactgc caaaaccctg
     3721 gagcggatca aagccattgt gcatgctgtg ggccaggagc tacaggtcac aggacccttc
     3781 aatctgcagc tcattgccaa ggatgaccag ctgaaagtta ttgaatgcaa cgtacgtgtc
     3841 tctcgctcct tccccttcgt ttccaagaca ctgggtgtgg acctagtagc cttggccacg
     3901 cgggtcatca tgggggaaga agtggaacct gtggggctaa tgactggttc tggagtcgtg
     3961 ggagtaaagg tgcctcagtt ctccttctcc cgcttggcgg gtgctgacgt ggtgttgggt
     4021 gtggaaatga ccagtactgg ggaggtggcc ggctttgggg agagccgctg tgaggcatac
     4081 ctcaaggcca tgctaagcac tggctttaag atccccaaga agaatatcct gctgaccatt
     4141 ggcagctata agaacaaaag cgagctgctc ccaactgtgc ggctactgga gagcctgggc
     4201 tacagcctct atgccagtct cggcacagct gacttctaca ctgagcatgg cgtcaaggta
     4261 acagctgtgg actggcactt tgaggaggct gtggatggtg agtgcccacc acagcggagc
     4321 atcctggagc agctagctga gaaaaacttt gagctggtga ttaacctgtc aatgcgtgga
     4381 gctgggggcc ggcgtctctc ttcctttgtc accaagggct accgcacccg acgcttggcc
     4441 gctgacttct ccgtgcccct aatcatcgat atcaagtgca ccaaactctt tgtggaggcc
     4501 ctaggccaga tcgggccagc ccctcctttg aaggtgcatg ttgactgtat gacctcccaa
     4561 aagcttgtgc gactgccggg attgattgat gtccatgtgc acctgcggga accaggtggg
     4621 acacataagg aggactttgc ttcaggcaca gccgctgccc tggctggggg tatcaccatg
     4681 gtgtgtgcca tgcctaatac ccggcccccc atcattgacg cccctgctct ggccctggcc
     4741 cagaagctgg cagaggctgg cgcccggtgc gactttgcgc tattccttgg ggcctcgtct
     4801 gaaaatgcag gaaccttggg caccgtggcc gggtctgcag ccgggctgaa gctttacctc
     4861 aatgagacct tctctgagct gcggctggac agcgtggtcc agtggatgga gcatttcgag
     4921 acatggccct cccacctccc cattgtggct cacgcagagc agcaaaccgt ggctgctgtc
     4981 ctcatggtgg ctcagctcac tcagcgctca gtgcacatat gtcacgtggc acggaaggag
     5041 gagatcctgc taattaaagc tgcaaaggca cggggcttgc cagtgacctg cgaggtggct
     5101 ccccaccacc tgttcctaag ccatgatgac ctggagcgcc tggggcctgg gaagggggag
     5161 gtccggcctg agcttggctc ccgccaggat gtggaagccc tgtgggagaa catggctgtc
     5221 atcgactgct ttgcctcaga ccatgctccc cataccttgg aggagaagtg tgggtccagg
     5281 cccccacctg ggttcccagg gttagagacc atgctgccac tactcctgac ggctgtaagc
     5341 gagggccggc tcagcctgga cgacctgctg cagcgattgc accacaatcc tcggcgcatc
     5401 tttcacctgc ccccgcagga ggacacctat gtggaggtgg atctggagca tgagtggaca
     5461 attcccagcc acatgccctt ctccaaggcc cactggacac cttttgaagg gcagaaagtg
     5521 aagggcaccg tccgccgtgt ggtcctgcga ggggaggttg cctatatcga tgggcaggtt
     5581 ctggtacccc cgggctatgg acaggatgta cggaagtggc cacagggggc tgttcctcag
     5641 ctcccaccct cagcccctgc cactagtgag atgaccacga cacctgaaag accccgccgt
     5701 ggcatcccag ggcttcctga tggccgcttc catctgccgc cccgaatcca tcgagcctcc
     5761 gacccaggtt tgccagctga ggagccaaag gagaagtcct ctcggaaggt agccgagcca
     5821 gagctgatgg gaacccctga tggcacctgc taccctccac caccagtacc gagacaggca
     5881 tctccccaga acctggggac ccctggcttg ctgcaccccc agacctcacc cctgctgcac
     5941 tcattagtgg gccaacatat cctgtccgtc cagcagttca ccaaggatca gatgtctcac
     6001 ctgttcaatg tggcacacac actgcgtatg atggtgcaga aggagcggag cctcgacatc
     6061 ctgaagggga aggtcatggc ctccatgttc tatgaagtga gcacacggac cagcagctcc
     6121 tttgcagcag ccatggcccg gctgggaggt gctgtgctca gcttctcgga agccacatcg
     6181 tccgtccaga agggcgaatc cctggctgac tccgtgcaga ccatgagctg ctatgccgac
     6241 gtcgtcgtgc tccggcaccc ccagcctgga gcagtggagc tggccgccaa gcactgccgg
     6301 aggccagtga tcaatgctgg ggatggggtc ggagagcacc ccacccaggc cctgctggac
     6361 atcttcacca tccgtgagga gctgggaact gtcaatggca tgacgatcac gatggtgggt
     6421 gacctgaagc acggacgcac agtacattcc ctggcctgcc tgctcaccca gtatcgtgtc
     6481 agcctgcgct acgtggcacc tcccagcctg cgcatgccac ccactgtgcg ggccttcgtg
     6541 gcctcccgcg gcaccaagca ggaggaattc gagagcattg aggaggcgct gcctgacact
     6601 gatgtgctct acatgactcg aatccagaag gaacgatttg gctctaccca ggagtacgaa
     6661 gcttgctttg gtcagttcat cctcactccc cacatcatga cccgggccaa gaagaagatg
     6721 gtggtgatgc acccgatgcc ccgtgtcaac gagataagcg tggaagtgga ctcggatccc
     6781 cgcgcagcct acttccgcca ggctgagaac ggcatgtaca tccgcatggc tctgttagcc
     6841 accgtgctgg gccgtttcta gggcctggct tcctcagcct cttctcttta ggcccagctg
     6901 ctgggcaagg aattccagtg cctcctacgg gggcagcaca cttagatatt cctggacatc
     6961 cagatagctc acatgtgctg accacacttc aggctctgga ctggagctct ctggcatggg
     7021 ggtggggcct cagatgctgg ggcccagtct gccccatctt cattcctgca ccttaaacct
     7081 gtacagtcat ttttctactg acttaataaa cagccgagct gtcccttgat gctgagtgta
     7141 gtagaacaga gctttctttt agaaaattga gcagattccc aaattataag agcagcctca
     7201 ccaggcaggg ctctggctag ggctgcgtgc ccacactcgg cattttcaca ctcgtgactc
     7261 tttgggactc ggcaggagcg tgttaa
//
