LOCUS       NM_001144967            8633 bp    mRNA    linear   PRI 29-OCT-2024
DEFINITION  Homo sapiens NEDD4 like E3 ubiquitin protein ligase (NEDD4L),
            transcript variant j, mRNA.
ACCESSION   NM_001144967
VERSION     NM_001144967.3
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 8633)
  AUTHORS   Chen,G., Pei,Y., Ye,Q., Xie,Z., Gyawali,L. and Liang,X.
  TITLE     NEDD4L-mediated RASGRP2 suppresses high-glucose and oxLDL-induced
            vascular endothelial cell dysfunctions by activating Rap1 and R-Ras
  JOURNAL   Biochim Biophys Acta Mol Cell Res 1871 (8), 119844 (2024)
   PUBMED   39260747
  REMARK    GeneRIF: NEDD4L-mediated RASGRP2 suppresses high-glucose and
            oxLDL-induced vascular endothelial cell dysfunctions by activating
            Rap1 and R-Ras.
REFERENCE   2  (bases 1 to 8633)
  AUTHORS   Wang,R., Wang,R., Zhou,S., Liu,T., Dang,J., Chen,Q., Chen,J. and
            Wang,Z.
  TITLE     Ubiquitination of angiotensin-converting enzyme 2 contributes to
            the development of pulmonary arterial hypertension mediated by
            neural precursor cell-expressed developmentally down-regulated gene
            4-Like
  JOURNAL   Respir Res 25 (1), 326 (2024)
   PUBMED   39210401
  REMARK    GeneRIF: Ubiquitination of angiotensin-converting enzyme 2
            contributes to the development of pulmonary arterial hypertension
            mediated by neural precursor cell-expressed developmentally
            down-regulated gene 4-Like.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 8633)
  AUTHORS   Shi,Y., Fang,N., Wu,Y., Xu,H., Ning,A., Zhang,W., Liu,Y., Tao,X.,
            Chen,Q., Tian,T., Zhang,L., Chu,M. and Cui,J.
  TITLE     NEDD4L mediates ITGB4 ubiquitination and degradation to suppress
            esophageal carcinoma progression
  JOURNAL   Cell Commun Signal 22 (1), 302 (2024)
   PUBMED   38831335
  REMARK    GeneRIF: NEDD4L mediates ITGB4 ubiquitination and degradation to
            suppress esophageal carcinoma progression.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 8633)
  AUTHORS   Yang,B. and Kumar,S.
  TITLE     Nedd4 and Nedd4-2: closely related ubiquitin-protein ligases with
            distinct physiological functions
  JOURNAL   Cell Death Differ 17 (1), 68-77 (2010)
   PUBMED   19557014
  REMARK    Review article
REFERENCE   5  (bases 1 to 8633)
  AUTHORS   Russo,C.J., Melista,E., Cui,J., DeStefano,A.L., Bakris,G.L.,
            Manolis,A.J., Gavras,H. and Baldwin,C.T.
  TITLE     Association of NEDD4L ubiquitin ligase with essential hypertension
  JOURNAL   Hypertension 46 (3), 488-491 (2005)
   PUBMED   16103266
  REMARK    GeneRIF: Significant association between several SNPs and
            hypertension in US whites, Greek whites, and African-Americans.
            Genetic variation in NEDD4L may play role in development or
            progression of some forms of hypertension.
            GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   6  (bases 1 to 8633)
  AUTHORS   Qi,H., Grenier,J., Fournier,A. and Labrie,C.
  TITLE     Androgens differentially regulate the expression of NEDD4L
            transcripts in LNCaP human prostate cancer cells
  JOURNAL   Mol Cell Endocrinol 210 (1-2), 51-62 (2003)
   PUBMED   14615060
  REMARK    GeneRIF: Results describe the isolation of three new NEDD4L
            transcripts designated NEDD4Lf, NEDD4Lg and NEDD4Lh, which encode
            different forms of the NEDD4L protein.
REFERENCE   7  (bases 1 to 8633)
  AUTHORS   Itani,O.A., Campbell,J.R., Herrero,J., Snyder,P.M. and Thomas,C.P.
  TITLE     Alternate promoters and variable splicing lead to hNedd4-2 isoforms
            with a C2 domain and varying number of WW domains
  JOURNAL   Am J Physiol Renal Physiol 285 (5), F916-F929 (2003)
   PUBMED   12876068
  REMARK    GeneRIF: Alternate transcripts of Nedd4-2 may interact with ENaC
            differently. hNedd4-2 has role in regulation of ENaC. Protein
            domains are important for Nedd4-2 function.
            GeneRIF: Identification of multiple splice forms and 5' variants of
            Nedd4l.  5' variants inhibit ENaC-mediated Na+ transport when
            reconstituted in FRT epithelia.  Other splice forms encode Nedd4L
            isoforms with 2 to 4 WW domains having varying affinity for ENaC.
REFERENCE   8  (bases 1 to 8633)
  AUTHORS   Chen,H., Ross,C.A., Wang,N., Huo,Y., MacKinnon,D.F., Potash,J.B.,
            Simpson,S.G., McMahon,F.J., DePaulo,J.R. Jr. and McInnis,M.G.
  TITLE     NEDD4L on human chromosome 18q21 has multiple forms of transcripts
            and is a homologue of the mouse Nedd4-2 gene
  JOURNAL   Eur J Hum Genet 9 (12), 922-930 (2001)
   PUBMED   11840194
  REMARK    GeneRIF: Candidate gene for autosomal dominant orthostatic
            hypotensive disorder.
REFERENCE   9  (bases 1 to 8633)
  AUTHORS   Winberg,G., Matskova,L., Chen,F., Plant,P., Rotin,D., Gish,G.,
            Ingham,R., Ernberg,I. and Pawson,T.
  TITLE     Latent membrane protein 2A of Epstein-Barr virus binds WW domain E3
            protein-ubiquitin ligases that ubiquitinate B-cell tyrosine kinases
  JOURNAL   Mol Cell Biol 20 (22), 8526-8535 (2000)
   PUBMED   11046148
REFERENCE   10 (bases 1 to 8633)
  AUTHORS   Nuber,U., Schwarz,S., Kaiser,P., Schneider,R. and Scheffner,M.
  TITLE     Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7
            (E2-F1) and characterization of their interaction with E6-AP and
            RSP5
  JOURNAL   J Biol Chem 271 (5), 2795-2800 (1996)
   PUBMED   8576257
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC107896.7, AY312514.1,
            AC090236.4 and BQ215431.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 24, 2018 this sequence version replaced NM_001144967.2.
            
            Summary: This gene encodes a member of the Nedd4 family of HECT
            domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases
            transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein
            substrates, thus targeting specific proteins for lysosomal
            degradation. The encoded protein mediates the ubiquitination of
            multiple target substrates and plays a critical role in epithelial
            sodium transport by regulating the cell surface expression of the
            epithelial sodium channel, ENaC. Single nucleotide polymorphisms in
            this gene may be associated with essential hypertension.
            Alternatively spliced transcript variants encoding multiple
            isoforms have been observed for this gene. [provided by RefSeq, Mar
            2012].
            
            Transcript Variant: This variant (j) represents the longest
            transcript and encodes the longest 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##
            RNAseq introns :: single sample supports all introns SAMEA1965299,
                              SAMEA1968540 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000400345.8/ ENSP00000383199.2
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-435               AC107896.7         20741-21175
            436-996             AY312514.1         1-561
            997-997             AC090236.4         87648-87648         c
            998-2912            AY312514.1         563-2477
            2913-3311           BQ215431.1         325-723
            3312-8633           AC090236.4         11153-16474         c
FEATURES             Location/Qualifiers
     source          1..8633
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="18"
                     /map="18q21.31"
     gene            1..8633
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /note="NEDD4 like E3 ubiquitin protein ligase"
                     /db_xref="GeneID:23327"
                     /db_xref="HGNC:HGNC:7728"
                     /db_xref="MIM:606384"
     exon            1..483
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     CDS             436..3363
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /EC_number="2.3.2.26"
                     /EC_number="2.3.2.36"
                     /note="isoform 1 is encoded by transcript variant j;
                     ubiquitin-protein ligase Rsp5; HECT-type E3 ubiquitin
                     transferase NED4L; neural precursor cell expressed,
                     developmentally down-regulated 4-like, E3 ubiquitin
                     protein ligase"
                     /codon_start=1
                     /product="E3 ubiquitin-protein ligase NEDD4-like isoform
                     1"
                     /protein_id="NP_001138439.1"
                     /db_xref="CCDS:CCDS45872.1"
                     /db_xref="GeneID:23327"
                     /db_xref="HGNC:HGNC:7728"
                     /db_xref="MIM:606384"
                     /translation="MATGLGEPVYGLSEDEGESRILRVKVVSGIDLAKKDIFGASDPY
                     VKLSLYVADENRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLTRD
                     DFLGQVDVPLSHLPTEDPTMERPYTFKDFLLRPRSHKSRVKGFLRLKMAYMPKNGGQD
                     EENSDQRDDMEHGWEVVDSNDSASQHQEELPPPPLPPGWEEKVDNLGRTYYVNHNNRT
                     TQWHRPSLMDVSSESDNNIRQINQEAAHRRFRSRRHISEDLEPEPSEGGDVPEPWETI
                     SEEVNIAGDSLGLALPPPPASPGSRTSPQELSEELSRRLQITPDSNGEQFSSLIQREP
                     SSRLRSCSVTDAVAEQGHLPPPSAPAGRARSSTVTGGEEPTPSVAYVHTTPGLPSGWE
                     ERKDAKGRTYYVNHNNRTTTWTRPIMQLAEDGASGSATNSNNHLIEPQIRRPRSLSSP
                     TVTLSAPLEGAKDSPVRRAVKDTLSNPQSPQPSPYNSPKPQHKVTQSFLPPGWEMRIA
                     PNGRPFFIDHNTKTTTWEDPRLKFPVHMRSKTSLNPNDLGPLPPGWEERIHLDGRTFY
                     IDHNSKITQWEDPRLQNPAITGPAVPYSREFKQKYDYFRKKLKKPADIPNRFEMKLHR
                     NNIFEESYRRIMSVKRPDVLKARLWIEFESEKGLDYGGVAREWFFLLSKEMFNPYYGL
                     FEYSATDNYTLQINPNSGLCNEDHLSYFTFIGRVAGLAVFHGKLLDGFFIRPFYKMML
                     GKQITLNDMESVDSEYYNSLKWILENDPTELDLMFCIDEENFGQTYQVDLKPNGSEIM
                     VTNENKREYIDLVIQWRFVNRVQKQMNAFLEGFTELLPIDLIKIFDENELELLMCGLG
                     DVDVNDWRQHSIYKNGYCPNHPVIQWFWKAVLLMDAEKRIRLLQFVTGTSRVPMNGFA
                     ELYGSNGPQLFTIEQWGSPEKLPRAHTCFNRLDLPPYETFEDLREKLLMAVENAQGFE
                     GVD"
     exon            484..557
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            558..639
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            640..678
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            679..732
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            733..783
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            784..845
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            846..948
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            949..1115
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            1116..1248
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            1249..1425
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            1426..1500
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            1501..1560
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            1561..1692
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            1693..1812
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            1813..2010
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            2011..2088
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            2089..2143
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            2144..2202
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            2203..2268
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            2269..2498
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            2499..2620
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            2621..2691
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            2692..2787
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            2788..2861
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            2862..2922
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            2923..2982
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            2983..3090
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            3091..3187
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            3188..3260
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     exon            3261..8633
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3773..3778
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /note="hexamer: ATTAAA"
     polyA_site      3800
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /note="major polyA site"
     regulatory      4468..4473
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /note="hexamer: ATTAAA"
     polyA_site      4499
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
     regulatory      4728..4733
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /note="hexamer: ATTAAA"
     polyA_site      4751
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
     regulatory      8601..8606
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
                     /note="hexamer: AATAAA"
     polyA_site      8633
                     /gene="NEDD4L"
                     /gene_synonym="hNEDD4-2; NEDD4-2; NEDD4.2; PVNH7; RSP5"
ORIGIN      
        1 gagagcgggg gcccggacgg cgctagcgag gaggcgggcg agccgggtcc ccgggagcgc
       61 agaggaggct cggagggggg cggagagcgg cggggcggga gggaggcgcg ggtcgcgggg
      121 agggaaagcc cggccgggtc tgcgccgccg ccgcgcgcag tgagaggcgc cggggctgcc
      181 gcccggtgct cggcgcgctc tcgggagccg cccgcccgct ggtcccgcag ccttccggga
      241 ggaagcggtg ccggcagcgt ccagggcgcg ctctcgggca ccctcacctg ccggcgcccg
      301 gccgcttacc cggcagggcg tgcgcagggt agggtgcggg accgggggga cctggaggca
      361 gaggggagaa ccggccgtcc gcgccgcagc acagccgctg ggagcgcctc agaccccgcg
      421 cggggcgccg gctccatggc gaccgggctc ggggagccgg tctatggact ttccgaagac
      481 gagggagagt cccgtattct cagagtaaaa gttgtttctg gaattgatct cgccaaaaag
      541 gacatctttg gagccagtga tccgtatgtg aaactttcat tgtacgtagc ggatgagaat
      601 agagaacttg ctttggtcca gacaaaaaca attaaaaaga cactgaaccc aaaatggaat
      661 gaagaatttt atttcagggt aaacccatct aatcacagac tcctatttga agtatttgac
      721 gaaaatagac tgacacgaga cgacttcctg ggccaggtgg acgtgcccct tagtcacctt
      781 ccgacagaag atccaaccat ggagcgaccc tatacattta aggactttct cctcagacca
      841 agaagtcata agtctcgagt taagggattt ttgcgattga aaatggccta tatgccaaaa
      901 aatggaggtc aagatgaaga aaacagtgac cagagggatg acatggagca tggatgggaa
      961 gttgttgact caaatgactc ggcttctcag caccaagagg aacttcctcc tcctcctctg
     1021 cctcccgggt gggaagaaaa agtggacaat ttaggccgaa cttactatgt caaccacaac
     1081 aaccggacca ctcagtggca cagaccaagc ctgatggacg tgtcctcgga gtcggacaat
     1141 aacatcagac agatcaacca ggaggcagca caccggcgct tccgctcccg caggcacatc
     1201 agcgaagact tggagcccga gccctcggag ggcggggatg tccccgagcc ttgggagacc
     1261 atttcagagg aagtgaatat cgctggagac tctctcggtc tggctctgcc cccaccaccg
     1321 gcctccccag gatctcggac cagccctcag gagctgtcag aggaactaag cagaaggctt
     1381 cagatcactc cagactccaa tggggaacag ttcagctctt tgattcaaag agaaccctcc
     1441 tcaaggttga ggtcatgcag tgtcaccgac gcagttgcag aacagggcca tctaccaccg
     1501 cccagtgccc cagctgggag agcgcgttca tcaactgtca cgggtggtga ggaaccaacg
     1561 ccatcagtgg cctatgtaca taccacgccg ggtctgcctt caggctggga agaaagaaaa
     1621 gatgctaagg ggcgcacata ctatgtcaat cataacaatc gaaccacaac ttggactcga
     1681 cctatcatgc agcttgcaga agatggtgcg tccggatcag ccacaaacag taacaaccat
     1741 ctaatcgagc ctcagatccg ccggcctcgt agcctcagct cgccaacagt aactttatct
     1801 gccccgctgg agggtgccaa ggactcaccc gtacgtcggg ctgtgaaaga caccctttcc
     1861 aacccacagt ccccacagcc atcaccttac aactccccca aaccacaaca caaagtcaca
     1921 cagagcttct tgccacccgg ctgggaaatg aggatagcgc caaacggccg gcccttcttc
     1981 attgatcata acacaaagac tacaacctgg gaagatccac gtttgaaatt tccagtacat
     2041 atgcggtcaa agacatcttt aaaccccaat gaccttggcc cccttcctcc tggctgggaa
     2101 gaaagaattc acttggatgg ccgaacgttt tatattgatc ataatagcaa aattactcag
     2161 tgggaagacc caagactgca gaacccagct attactggtc cggctgtccc ttactccaga
     2221 gaatttaagc agaaatatga ctacttcagg aagaaattaa agaaacctgc tgatatcccc
     2281 aataggtttg aaatgaaact tcacagaaat aacatatttg aagagtccta tcggagaatt
     2341 atgtccgtga aaagaccaga tgtcctaaaa gctagactgt ggattgagtt tgaatcagag
     2401 aaaggtcttg actatggggg tgtggccaga gaatggttct tcttactgtc caaagagatg
     2461 ttcaacccct actacggcct ctttgagtac tctgccacgg acaactacac ccttcagatc
     2521 aaccctaatt caggcctctg taatgaggat catttgtcct acttcacttt tattggaaga
     2581 gttgctggtc tggccgtatt tcatgggaag ctcttagatg gtttcttcat tagaccattt
     2641 tacaagatga tgttgggaaa gcagataacc ctgaatgaca tggaatctgt ggatagtgaa
     2701 tattacaact ctttgaaatg gatcctggag aatgacccta ctgagctgga cctcatgttc
     2761 tgcatagacg aagaaaactt tggacagaca tatcaagtgg atttgaagcc caatgggtca
     2821 gaaataatgg tcacaaatga aaacaaaagg gaatatatcg acttagtcat ccagtggaga
     2881 tttgtgaaca gggtccagaa gcagatgaac gccttcttgg agggattcac agaactactt
     2941 cctattgatt tgattaaaat ttttgatgaa aatgagctgg agttgctcat gtgcggcctc
     3001 ggtgatgtgg atgtgaatga ctggagacag cattctattt acaagaacgg ctactgccca
     3061 aaccaccccg tcattcagtg gttctggaag gctgtgctac tcatggacgc cgaaaagcgt
     3121 atccggttac tgcagtttgt cacagggaca tcgcgagtac ctatgaatgg atttgccgaa
     3181 ctttatggtt ccaatggtcc tcagctgttt acaatagagc aatggggcag tcctgagaaa
     3241 ctgcccagag ctcacacatg ctttaatcgc cttgacttac ctccatatga aacctttgaa
     3301 gatttacgag agaaacttct catggccgtg gaaaatgctc aaggatttga aggggtggat
     3361 taagcaccct gtgcctcggg ggtggttgtt cttcaagcaa gttctgcttg cacttttgca
     3421 tttgcctaac agacttttgc agaggcgatg gcagagagca gctgcaggca tggtccctgg
     3481 agccgagcct tcaccacgca ctcgtccaag ttcggatgcg ggaacctggt cccagcttga
     3541 gttcctgcct ttcccaccac aaattatcaa ctggttgatg tgtacactaa ttacatttca
     3601 ggaggactta atgctattta tgttgtgcct ctgcaggcaa agcccttaat aaatatttta
     3661 catcctttct aatgacaatg aatggaatta atcactcaac aggtatagta ttacgactca
     3721 tgtttacttt ttaaaatgat ttagaccgat tttcagattt tatttcgtta tgattaaaga
     3781 tgtctcatgt acttggaaaa gtgagcattt tttttttttt tgtatttcac tttcatacca
     3841 ggcttaatgt caatgacatt tttatttttg aagtactctg acacctccac cctctacttt
     3901 attagaattg gaaggcaaat ttttgtccaa aaacctacag acaagtactt tgagagaatt
     3961 tccaatataa tattagacat aatgataatt ttttccatac tcagaatgaa aaactggata
     4021 ttacgttttt gttttggggt ttttttgtac aaatttagct aatagctaca ggctgagaga
     4081 attgtaacat agcatgacaa attttgtgtt gacttgaaag gaatcacacc attattcctt
     4141 agaagtaatt acatgtgttc taacacattt gagacagggt tggactccca tttctcatcc
     4201 gagaaattac ttaacccttc ctggcgctgt acagtcatct tttattctat ttcctctttg
     4261 ctgtttgtag tagagacatt ttgaatgaaa cttggcactg cttgattcaa aactgtggaa
     4321 accagatctg tttagtctcc tgtttgtatg cgtttgctaa tggtagctaa ataaccagtt
     4381 tttgttgtaa atgcaccaat tctgaaggca ctttatgtac tacatggagg tcatatctgg
     4441 ttttgttttt atttttttat catgaacatt aaatgtgatg atgatttctt ttccctgcac
     4501 acatctttcc ggtgcaatat ctatcaattg tgaatctggc tgctggtgta taaaaacctg
     4561 gatgtaaagc tgagcctaca gacctgtcct caccaactgt tttgtgattt ctactcaact
     4621 acaaagattt atttaatgta ctcttaatct aactgagttt tgttaccaat gacctgttgc
     4681 atgcttcaat accgtgtact gcctgagttg tgcctcttgt gtgctagatt aaaagtgaga
     4741 cagagacttg acttgatcct ctgagctcaa gctattgagc tggtagtggc agaggactga
     4801 gggtacctgc acagtttgat tcttttccac gtgtaagtct ccattgcaga attgtcgtgc
     4861 tttgagaaaa cacctgaggc agtgtgggag ttgaacgacc ctgctgtcct ttttaacctg
     4921 tgttgtccta gaccctgtcg gggcagtcag gggacactag agatttgatc tcatgcgagt
     4981 catcaatagg acaaaaaagt tgtggtttgg ggaggtctgt ttgttacata aaaaggacct
     5041 ttcggtgtaa gaaattgccg tttttaccct gccctggctg gcatgtgaga agccatggaa
     5101 ggttgtggtt gtaaatgagt tgtctaaagg ggtgcagagg cctgaggttt ctaaaagaag
     5161 gtagatttct acagagctga gtgttggttc ctttttctta ttggttgaaa attacctggt
     5221 agtgatcaga aaacttagat gctatgtaac taaaaaaaaa aaaaaaaaaa aaaaaaaaaa
     5281 aaaaaaaatt cccgctcatg agttttgact attggtgaga tgttttccgc tacagttaac
     5341 atgacaaatg tctcagtggc aaaaatcccc tttttgtaag cccccatagt ctagaggcag
     5401 ttttcttttt aagaatcatg ccagagcctg agtcgagcag tatgctttct tggtttttga
     5461 gagtaattgt gtaattgtag agggagaaat ccaattctaa cctaagaact gggattcttc
     5521 tgtcatcttg taaaccgtat attgaaaaaa acagaatgtc actaaatgca tattaagtca
     5581 agtattggaa agtataaaag aaaaatcatt ctgacaattt ctaagccaga agcaaacaag
     5641 aattactgaa atctacccca tgaatacttg gaaggcagta attgtgagtg acacctcagt
     5701 tcatcaaccc cttaataata tcagcttaat tttaatgaca actaaatatg ctgaagtgag
     5761 gatttagtat tttttaaaaa agcaaaacaa ggttcagtag tcctcagcaa ttctccaagt
     5821 ttctctcttt gcctaaaatg gtcatagatc ttgatttctc tgaatcgtga tgaccacacc
     5881 cagtcatctt cacagcataa ttgcaggtgg cagtaaagag agtgtgctgg gtaaggagca
     5941 gttgctgggt cattccttgg gccccgacct gcccggggag tagccctggg ggagagaggg
     6001 cagtgttgcc tatcccagag gtcccagcag tcacactgct ctgcaggccg ggctctcttt
     6061 atagccagag aaatcacctt aatgcagtct ctttagttgt ctgctgaagc tgtagttatt
     6121 atgggccact tacatgaggc tgagaagtac gtgccggagc tcacacactg cctgttgcgg
     6181 ttctcttaac atcagttatc acagctgcct gtgggtcccg ggtatttcca ttcctgcccc
     6241 ttgttggccc gaggaaggat gtggaaagag cacctggtgg gatgaaggtc caacagcctg
     6301 tgcctctcca ctgctggccc tggagccggc agcagtgagg cattcattgt ctgtgttgcg
     6361 gtgtattccc agcttcagtg ctcttttcct ttttgcctga aatgtttatg cttctctgca
     6421 gccagtcctc taacaaatct caagaacaaa ggtaagacac ttggtttttg tttccaggac
     6481 ccttcagaag gtgacatcag atattcccta aattcagaca atgagggata cagagcgact
     6541 tggcatgtat tatttctccc atgtaaggac aaagggacag attattattg ttatttctga
     6601 gacagagtct tgctctgtag ctcaggctgg agtgcagtgg ctcaatctca gctcaccaca
     6661 acctctgcct cctggcttca agcgattctt ctgcctcagc ctccccgaat agttgggatt
     6721 acaggcaccc accaccacgc ctggctaatt tttgtatttt tagtagagat ggtttcacca
     6781 tgctggccag gctggtcttg aactcctgac ctcaggtgat cctcccgcct cagccttcca
     6841 aagtgctggg attacaagca tgagccaccg cacccggcct cacagtgaca gattctgaga
     6901 aacagcatgc aaaacatttg aaccattttc tacatctccc attgttgcat agagagtgtg
     6961 caccgctgct atcttgccag atccacactg gtcctcccga aagccaggtt catacacagc
     7021 aactttttaa ttattctaac agttacccat taacagtcga ctcctgtatt tctgagagtc
     7081 ttgtactcac ctctgaaatt taaaaacgta taaagagagc ctgggttaat cagttctgca
     7141 gcccctacgt gacactgtgc tagttctcct tcttctgtct cctccttacc ctggccctgc
     7201 acccctgtac ttaagaggga gaggtgggag gtgctgtctg gtatcatttg ctgcctcgcc
     7261 agtagagggt gccgctgtgc agggtaactg cccgcctgct cccttcctga cctcccctga
     7321 ccccgaagat cactacctct gtcattcagg cattggggta catcctgata agtcgtgtca
     7381 gaactgccaa tttcaggact gagatgtgtt tttaaaaaac aaatccttat aaactccact
     7441 ttgtacttta gattttaaaa ctggggaaaa atgtgatatt ctttggacca cttttttaat
     7501 ttatataagc cttaatgaac agtgtctata catttgcata cacacacccc caccccagag
     7561 tgttctcagt atgtcagaga aagtgccaca gcattaggac gggagcttgg agaacgtttt
     7621 ctagaaaagg gttagcttcc tgttggcatg aaattttcca agcaaacctc attaaacatc
     7681 tgttgtttgt taaagatgtt ccactgaaag caacgcatgt ttcaaaggca cgtctttccg
     7741 ttcgttggtt ttctgtgtgt aaggagtagc attgctgttg gcgcctaacc tcgcgtgcac
     7801 tgcattctca accccgtacc agtgcatcat cagaagcctt cctcgtgacc ataactctgt
     7861 gtctgcagat atgtgttccc gtgtaagcca gttttcccct tttactcaga ctgatttcac
     7921 ctagattgtc acggtttcct tcatgttaac tttgcgtgac tttgttcttc ctttactact
     7981 ctgtatgtaa tatatataca tatatacgta catatgctgt ccaaatatat ttgtatatat
     8041 ttgtatagca tttttacacc tttattgagt aatctggttt cgaaaggagg tgagagttta
     8101 gtcccttctg cagttttctc caagctgtgt cctgtgaatt tcaacccttg gagcctaaga
     8161 aaaccctagg aagatgatgt taatttgctg tcatttccta attcaggatc tatcatcaaa
     8221 tgaaacatga aaaaaacagt gacttttaag gtgaaaagag tttcaagcat tccaaataaa
     8281 ttatcaatgt ttcataactt tttattataa acccacctcc taataggaag ccaagtacta
     8341 tttgatacag tggtaaaaac caaactacct tgaatttttt taaggcaact tatgaataat
     8401 gctcattttc acagtcagaa tagctttaaa atatggttga atttgataca cacaggaagt
     8461 tttcttgaag aacaatcctt tcgcttttct tttttcttga gagatctaaa gagaaactgt
     8521 agattgtttt cctgacagca aaagactaat gtgacaaaat gaagtcattg taaagaagcg
     8581 atgcaacttg tcaaatattt aataaagaat tatggaagct ggaacatttt cta
//
