LOCUS       NM_005670               3129 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens EPM2A glucan phosphatase, laforin (EPM2A), transcript
            variant 1, mRNA.
ACCESSION   NM_005670
VERSION     NM_005670.4
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 3129)
  AUTHORS   Lomax,L.B., Verhalen,B. and Minassian,B.A.
  TITLE     EPM2A in-frame deletion slows neurological decline in Lafora
            Disease
  JOURNAL   Seizure 91, 97-98 (2021)
   PUBMED   34147889
  REMARK    GeneRIF: EPM2A in-frame deletion slows neurological decline in
            Lafora Disease.
REFERENCE   2  (bases 1 to 3129)
  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   3  (bases 1 to 3129)
  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   4  (bases 1 to 3129)
  AUTHORS   Sanchez-Martin,P., Lahuerta,M., Viana,R., Knecht,E. and Sanz,P.
  TITLE     Regulation of the autophagic PI3KC3 complex by laforin/malin
            E3-ubiquitin ligase, two proteins involved in Lafora disease
  JOURNAL   Biochim Biophys Acta Mol Cell Res 1867 (2), 118613 (2020)
   PUBMED   31758957
  REMARK    GeneRIF: Laforin/malin complex interacts physically and
            co-localizes intracellularly with core components of the PI3KC3
            complex (Beclin1, Vps34 and Vps15), and that this interaction is
            specific and results in the polyubiquitination of these proteins.
REFERENCE   5  (bases 1 to 3129)
  AUTHORS   Sullivan,M.A., Nitschke,S., Steup,M., Minassian,B.A. and
            Nitschke,F.
  TITLE     Pathogenesis of Lafora Disease: Transition of Soluble Glycogen to
            Insoluble Polyglucosan
  JOURNAL   Int J Mol Sci 18 (8), 1743 (2017)
   PUBMED   28800070
  REMARK    Review article
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 3129)
  AUTHORS   Minassian,B.A., Lee,J.R., Herbrick,J.A., Huizenga,J., Soder,S.,
            Mungall,A.J., Dunham,I., Gardner,R., Fong,C.Y., Carpenter,S.,
            Jardim,L., Satishchandra,P., Andermann,E., Snead,O.C. 3rd,
            Lopes-Cendes,I., Tsui,L.C., Delgado-Escueta,A.V., Rouleau,G.A. and
            Scherer,S.W.
  TITLE     Mutations in a gene encoding a novel protein tyrosine phosphatase
            cause progressive myoclonus epilepsy
  JOURNAL   Nat Genet 20 (2), 171-174 (1998)
   PUBMED   9771710
REFERENCE   7  (bases 1 to 3129)
  AUTHORS   Sainz,J., Minassian,B.A., Serratosa,J.M., Gee,M.N., Sakamoto,L.M.,
            Iranmanesh,R., Bohlega,S., Baumann,R.J., Ryan,S., Sparkes,R.S. and
            Delgado-Escueta,A.V.
  TITLE     Lafora progressive myoclonus epilepsy: narrowing the chromosome
            6q24 locus by recombinations and homozygosities
  JOURNAL   Am J Hum Genet 61 (5), 1205-1209 (1997)
   PUBMED   9345091
REFERENCE   8  (bases 1 to 3129)
  AUTHORS   Maddox,L.O., Descartes,M., Collins,J., Keating,J., Rosenfeld,S.,
            Palmer,C., Carroll,A.J. and Kuzniecky,R.
  TITLE     Identification of a recombination event narrowing the Lafora
            disease gene region
  JOURNAL   J Med Genet 34 (7), 590-591 (1997)
   PUBMED   9222970
REFERENCE   9  (bases 1 to 3129)
  AUTHORS   Labauge,P., Beck,C., Bellet,H., Coquillat,G., Vespignani,H.,
            Dulac,O., Gilgenkrantz,S., Dravet,C., Genton,P., Pellissier,J.F. et
            al.
  TITLE     Lafora disease is not linked to the Unverricht-Lundborg locus
  JOURNAL   Am J Med Genet 60 (1), 80-84 (1995)
   PUBMED   7485240
REFERENCE   10 (bases 1 to 3129)
  AUTHORS   Minassian,B.
  TITLE     Progressive Myoclonus Epilepsy, Lafora Type
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301563
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AF284580.1, AF454494.1 and
            BC005286.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_005670.3.
            
            Summary: This gene encodes a dual-specificity phosphatase and may
            be involved in the regulation of glycogen metabolism. The protein
            acts on complex carbohydrates to prevent glycogen
            hyperphosphorylation, thus avoiding the formation of insoluble
            aggregates. Loss-of-function mutations in this gene have been
            associated with Lafora disease, a rare, adult-onset recessive
            neurodegenerative disease, which results in myoclonus epilepsy and
            usually results in death several years after the onset of symptoms.
            The disease is characterized by the accumulation of insoluble
            particles called Lafora bodies, which are derived from glycogen.
            [provided by RefSeq, Jan 2018].
            
            Transcript Variant: This variant (1) represents the longest
            transcript, and encodes the longest isoform (a). Isoform a has been
            localized to the rough endoplasmic reticulum.
            
            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 :: BC070047.1, AF284580.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1968189
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000367519.9/ ENSP00000356489.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-180               AF284580.1         336-515
            181-323             AF454494.1         87-229
            324-423             AF284580.1         659-758
            424-498             BC005286.1         398-472
            499-1255            AF284580.1         834-1590
            1256-1502           BC005286.1         988-1234
            1503-3129           AF284580.1         1840-3466
FEATURES             Location/Qualifiers
     source          1..3129
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6q24.3"
     gene            1..3129
                     /gene="EPM2A"
                     /gene_synonym="EPM2; MELF; MELF2"
                     /note="EPM2A glucan phosphatase, laforin"
                     /db_xref="GeneID:7957"
                     /db_xref="HGNC:HGNC:3413"
                     /db_xref="MIM:607566"
     exon            1..323
                     /gene="EPM2A"
                     /gene_synonym="EPM2; MELF; MELF2"
                     /inference="alignment:Splign:2.1.0"
     CDS             23..1018
                     /gene="EPM2A"
                     /gene_synonym="EPM2; MELF; MELF2"
                     /EC_number="3.1.3.16"
                     /EC_number="3.1.3.48"
                     /note="isoform a is encoded by transcript variant 1;
                     epilepsy, progressive myoclonus type 2, Lafora disease
                     (laforin); EPM2A, laforin glucan phosphatase; LAFPTPase;
                     lafora PTPase; epilepsy, progressive myoclonus type 2A,
                     Lafora disease (laforin); glycogen phosphatase"
                     /codon_start=1
                     /product="laforin isoform a"
                     /protein_id="NP_005661.1"
                     /db_xref="CCDS:CCDS5206.1"
                     /db_xref="GeneID:7957"
                     /db_xref="HGNC:HGNC:3413"
                     /db_xref="MIM:607566"
                     /translation="MRFRFGVVVPPAVAGARPELLVVGSRPELGRWEPRGAVRLRPAG
                     TAAGDGALALQEPGLWLGEVELAAEEAAQDGAEPGRVDTFWYKFLKREPGGELSWEGN
                     GPHHDRCCTYNENNLVDGVYCLPIGHWIEATGHTNEMKHTTDFYFNIAGHQAMHYSRI
                     LPNIWLGSCPRQVEHVTIKLKHELGITAVMNFQTEWDIVQNSSGCNRYPEPMTPDTMI
                     KLYREEGLAYIWMPTPDMSTEGRVQMLPQAVCLLHALLEKGHIVYVHCNAGVGRSTAA
                     VCGWLQYVMGWNLRKVQYFLMAKRPAVYIDEEALARAQEDFFQKFGKVRSSVCSL"
     exon            324..498
                     /gene="EPM2A"
                     /gene_synonym="EPM2; MELF; MELF2"
                     /inference="alignment:Splign:2.1.0"
     exon            499..740
                     /gene="EPM2A"
                     /gene_synonym="EPM2; MELF; MELF2"
                     /inference="alignment:Splign:2.1.0"
     exon            741..3129
                     /gene="EPM2A"
                     /gene_synonym="EPM2; MELF; MELF2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1622..1627
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EPM2A"
                     /gene_synonym="EPM2; MELF; MELF2"
                     /note="hexamer: ACTAAA"
     polyA_site      1643
                     /gene="EPM2A"
                     /gene_synonym="EPM2; MELF; MELF2"
                     /note="major polyA site"
     regulatory      2878..2883
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EPM2A"
                     /gene_synonym="EPM2; MELF; MELF2"
                     /note="hexamer: ATTAAA"
     polyA_site      2896
                     /gene="EPM2A"
                     /gene_synonym="EPM2; MELF; MELF2"
                     /note="major polyA site"
     regulatory      3110..3115
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EPM2A"
                     /gene_synonym="EPM2; MELF; MELF2"
                     /note="hexamer: AATAAA"
     polyA_site      3129
                     /gene="EPM2A"
                     /gene_synonym="EPM2; MELF; MELF2"
                     /note="major polyA site"
ORIGIN      
        1 attcgcgccg ccgccgcccg ccatgcgctt ccgctttggg gtggtggtgc cacccgccgt
       61 ggccggcgcc cggccggagc tgctggtggt ggggtcgcgg cccgagctgg ggcgttggga
      121 gccgcgcggt gccgtccgcc tgaggccggc cggcaccgcg gcgggcgacg gggccctggc
      181 cctgcaggag ccgggcctgt ggctcgggga ggtggagctg gcggccgagg aggcggcgca
      241 ggacggggcg gagccgggcc gcgtggacac gttctggtac aagttcctga agcgggagcc
      301 gggaggagag ctctcctggg aaggcaatgg acctcatcat gaccgttgct gtacttacaa
      361 tgaaaacaac ttggtggatg gtgtgtattg tctcccaata ggacactgga ttgaggccac
      421 tgggcacacc aatgaaatga agcacacaac agacttctat tttaatattg caggccacca
      481 agccatgcat tattcaagaa ttctaccaaa tatctggctg ggtagctgcc ctcgtcaggt
      541 ggaacatgta accatcaaac tgaagcatga attggggatt acagctgtaa tgaatttcca
      601 gactgaatgg gatattgtac agaattcctc aggctgtaac cgctacccag agcccatgac
      661 tccagacact atgattaaac tatataggga agaaggcttg gcctacatct ggatgccaac
      721 accagatatg agcaccgaag gccgagtaca gatgctgccc caggcggtgt gcctgctgca
      781 tgcgctgctg gagaagggac acatcgtgta cgtgcactgc aacgctgggg tgggccgctc
      841 caccgcggct gtctgcggct ggctccagta tgtgatgggc tggaatctga ggaaggtgca
      901 gtatttcctc atggccaaga ggccggctgt ctacattgac gaagaggcct tggcccgggc
      961 acaagaagat tttttccaga aatttgggaa ggttcgttct tctgtgtgta gcctgtagct
     1021 ggtcagcctg cttctgcccc ctcctgattt ccctaaggag cctgggatga tgttggtcaa
     1081 atgacctaga aacaaggatt ctacctgaac tgaaaggact gtgtgacctc ccccaagcca
     1141 accactttca cctgggatga ctttcgatta tgctttgttt tggggctgta tttttgaaat
     1201 actctacaag aaagctgtgg ctcaacacat gagaagaagc acgaagcagt taggctgtac
     1261 atcagacaga agggtaatgc gtgcagttcc tgctgcctgc aggcagacga ggcctttgct
     1321 ttacagcact gtatgtgttg cacgatggat ccgtgacagc actttcctgt tgcactgaaa
     1381 ctcttggcca tgtagaggaa aagatatgga gttatgtgga tttcatcact agtatgtgtg
     1441 cgtgagctgg tcagttgcca aaggaggaaa taaggttaga agcctgaacc gttacaaaag
     1501 aagagctcac tatggtcaaa aagtgatggc tttcaggact tgttttttat cctgcctcac
     1561 agttgttaaa gtctgttcca aggcatcacc ttccttctct acccaacaac cctgtgtaac
     1621 aactaaagta gaattatctc tcatttgttg ttgtttttcc tcaaaattac caaacaaagc
     1681 aaaaaatacc cttgtttttt atagttgaga tgtcaagaag ttaaattgag gcttaatgag
     1741 cataggtagc ttgtccaagg tctcatgacc agtcaagggc aagctggagt taataatcta
     1801 tatttatttg actcagcact gttttcatca caacttgttt tcccagcatc atgtagtgca
     1861 tttagttttg tctttctcag ggtatagtca atatgcctgc aggagtttct atagcgagac
     1921 atagaatagt attctgatca gttgccaaag aatctaggaa attagttgta ttttgtgcaa
     1981 gctaatttaa aaacatgatg ggctgtttta agaccagagt ggaaattcat gagaggaact
     2041 atactaccaa aagagcccaa atgaccaaat ccatggataa ttgcttcaca gccttggcca
     2101 tcctggctca gctctcaatt tagtataata tgcagttcct gtgcctccag actatgcagc
     2161 tcatcaccct aggttctaca ggaaatacag agatgaacaa ctttgccttc aaaaatgtgc
     2221 tgcctagaaa cagacctgca ttcaaccaac tgtaatgcag gattggacca tgaatgatat
     2281 gctagaatag aagaaagaga agtgtttttt taattgagag cctctatgtg caaggtgata
     2341 tataatcata tccagtttaa tcttcacaat atccaatgaa gaaggtctca ttatctccat
     2401 gataaagatg gggaaactaa ggtcagaagg gttaactcaa ctgtctattg tcacatgatg
     2461 aataaataga tgaagtgaga tacaaagctg ggtttgattc aaagccctta ctttcctaat
     2521 taaactatga tgcgtattta tttttctgca ccttcctttc ttccacaaac acatattgat
     2581 agatgcaaga gactcttatt tagaaggcgt gggggacaag aaggatacaa ggtaagtttc
     2641 agtggagctc agaggacggg gagatagaac tgtggcactt aggggagatg acatttgctt
     2701 tgggcagagg cagctagcca ggacacattt ccactataat tttacaaagt taaatttata
     2761 agctagcatt aagtaaagtg aagtccagct cccttgctaa aaataactag aggtaataat
     2821 tggtattcag gtaactcatt tacagtcata atgtgttgtg aaaatttaat cttaaaaatt
     2881 aaatttttaa actatgtggg tctgtgaatt tctttaatgt ctaagaaatc cagcttcata
     2941 atttccatga tacaaagatc ttttttcagg tggattttta cctttgttcc ttttgctctg
     3001 atagacaaaa tcagtttagg actattaaag aatgttttgg aataaactgt ctttttcctc
     3061 aatgaatggg atgtctaatg tatttcaaaa tcacccaaaa cttttggcaa ataaaagcat
     3121 ttaaaaaga
//
