LOCUS       NM_198586               2238 bp    mRNA    linear   PRI 07-FEB-2025
DEFINITION  Homo sapiens NHL repeat containing E3 ubiquitin protein ligase 1
            (NHLRC1), mRNA.
ACCESSION   NM_198586
VERSION     NM_198586.3
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 2238)
  AUTHORS   Faltus,C., Lahnsteiner,A., Barrdahl,M., Assenov,Y., Husing,A.,
            Bogatyrova,O., Laplana,M., Johnson,T., Muley,T., Meister,M.,
            Warth,A., Thomas,M., Plass,C., Kaaks,R. and Risch,A.
  TITLE     Identification of NHLRC1 as a Novel AKT Activator from a Lung
            Cancer Epigenome-Wide Association Study (EWAS)
  JOURNAL   Int J Mol Sci 23 (18), 10699 (2022)
   PUBMED   36142605
  REMARK    GeneRIF: Identification of NHLRC1 as a Novel AKT Activator from a
            Lung Cancer Epigenome-Wide Association Study (EWAS).
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 2238)
  AUTHORS   Tang,X., Li,X., Chen,Y. and Wu,D.
  TITLE     Compound heterozygosity for novel variations of the NHLRC1 Gene in
            a family with Lafora disease
  JOURNAL   Clin Neurol Neurosurg 218, 107255 (2022)
   PUBMED   35569391
  REMARK    GeneRIF: Compound heterozygosity for novel variations of the NHLRC1
            Gene in a family with Lafora disease.
REFERENCE   3  (bases 1 to 2238)
  AUTHORS   Haryanyan,G., Ozdemir,O., Tutkavul,K., Dervent,A., Ayta,S.,
            Ozkara,C., Salman,B., Yucesan,E., Kesim,Y., Susgun,S., Ozbek,U.,
            Baykan,B., Ugur Iseri,S.A. and Bebek,N.
  TITLE     The rare rs769301934 variant in NHLRC1 is a common cause of Lafora
            disease in Turkey
  JOURNAL   J Hum Genet 66 (12), 1145-1151 (2021)
   PUBMED   34117373
  REMARK    GeneRIF: The rare rs769301934 variant in NHLRC1 is a common cause
            of Lafora disease in Turkey.
REFERENCE   4  (bases 1 to 2238)
  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   5  (bases 1 to 2238)
  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   6  (bases 1 to 2238)
  AUTHORS   Gentry,M.S., Worby,C.A. and Dixon,J.E.
  TITLE     Insights into Lafora disease: malin is an E3 ubiquitin ligase that
            ubiquitinates and promotes the degradation of laforin
  JOURNAL   Proc Natl Acad Sci U S A 102 (24), 8501-8506 (2005)
   PUBMED   15930137
  REMARK    GeneRIF: Malin is an E3 ubiquitin ligase that ubiquitinates and
            promotes the degradation of laforin.
REFERENCE   7  (bases 1 to 2238)
  AUTHORS   Gomez-Abad,C., Gomez-Garre,P., Gutierrez-Delicado,E., Saygi,S.,
            Michelucci,R., Tassinari,C.A., Rodriguez de Cordoba,S. and
            Serratosa,J.M.
  TITLE     Lafora disease due to EPM2B mutations: a clinical and genetic study
  JOURNAL   Neurology 64 (6), 982-986 (2005)
   PUBMED   15781812
  REMARK    GeneRIF: Genetic allelic heterogeneity is present in Lafora disease
            associated with mutations in EPM2B. Patients with mutations in
            EPM2A and EPM2B express similar clinical manifestation.
REFERENCE   8  (bases 1 to 2238)
  AUTHORS   Mungall,A.J., Palmer,S.A., Sims,S.K., Edwards,C.A., Ashurst,J.L.,
            Wilming,L., Jones,M.C., Horton,R., Hunt,S.E., Scott,C.E.,
            Gilbert,J.G., Clamp,M.E., Bethel,G., Milne,S., Ainscough,R.,
            Almeida,J.P., Ambrose,K.D., Andrews,T.D., Ashwell,R.I.,
            Babbage,A.K., Bagguley,C.L., Bailey,J., Banerjee,R., Barker,D.J.,
            Barlow,K.F., Bates,K., Beare,D.M., Beasley,H., Beasley,O.,
            Bird,C.P., Blakey,S., Bray-Allen,S., Brook,J., Brown,A.J.,
            Brown,J.Y., Burford,D.C., Burrill,W., Burton,J., Carder,C.,
            Carter,N.P., Chapman,J.C., Clark,S.Y., Clark,G., Clee,C.M.,
            Clegg,S., Cobley,V., Collier,R.E., Collins,J.E., Colman,L.K.,
            Corby,N.R., Coville,G.J., Culley,K.M., Dhami,P., Davies,J.,
            Dunn,M., Earthrowl,M.E., Ellington,A.E., Evans,K.A., Faulkner,L.,
            Francis,M.D., Frankish,A., Frankland,J., French,L., Garner,P.,
            Garnett,J., Ghori,M.J., Gilby,L.M., Gillson,C.J., Glithero,R.J.,
            Grafham,D.V., Grant,M., Gribble,S., Griffiths,C., Griffiths,M.,
            Hall,R., Halls,K.S., Hammond,S., Harley,J.L., Hart,E.A.,
            Heath,P.D., Heathcott,R., Holmes,S.J., Howden,P.J., Howe,K.L.,
            Howell,G.R., Huckle,E., Humphray,S.J., Humphries,M.D., Hunt,A.R.,
            Johnson,C.M., Joy,A.A., Kay,M., Keenan,S.J., Kimberley,A.M.,
            King,A., Laird,G.K., Langford,C., Lawlor,S., Leongamornlert,D.A.,
            Leversha,M., Lloyd,C.R., Lloyd,D.M., Loveland,J.E., Lovell,J.,
            Martin,S., Mashreghi-Mohammadi,M., Maslen,G.L., Matthews,L.,
            McCann,O.T., McLaren,S.J., McLay,K., McMurray,A., Moore,M.J.,
            Mullikin,J.C., Niblett,D., Nickerson,T., Novik,K.L., Oliver,K.,
            Overton-Larty,E.K., Parker,A., Patel,R., Pearce,A.V., Peck,A.I.,
            Phillimore,B., Phillips,S., Plumb,R.W., Porter,K.M., Ramsey,Y.,
            Ranby,S.A., Rice,C.M., Ross,M.T., Searle,S.M., Sehra,H.K.,
            Sheridan,E., Skuce,C.D., Smith,S., Smith,M., Spraggon,L.,
            Squares,S.L., Steward,C.A., Sycamore,N., Tamlyn-Hall,G., Tester,J.,
            Theaker,A.J., Thomas,D.W., Thorpe,A., Tracey,A., Tromans,A.,
            Tubby,B., Wall,M., Wallis,J.M., West,A.P., White,S.S.,
            Whitehead,S.L., Whittaker,H., Wild,A., Willey,D.J., Wilmer,T.E.,
            Wood,J.M., Wray,P.W., Wyatt,J.C., Young,L., Younger,R.M.,
            Bentley,D.R., Coulson,A., Durbin,R., Hubbard,T., Sulston,J.E.,
            Dunham,I., Rogers,J. and Beck,S.
  TITLE     The DNA sequence and analysis of human chromosome 6
  JOURNAL   Nature 425 (6960), 805-811 (2003)
   PUBMED   14574404
REFERENCE   9  (bases 1 to 2238)
  AUTHORS   Chan,E.M., Young,E.J., Ianzano,L., Munteanu,I., Zhao,X.,
            Christopoulos,C.C., Avanzini,G., Elia,M., Ackerley,C.A.,
            Jovic,N.J., Bohlega,S., Andermann,E., Rouleau,G.A.,
            Delgado-Escueta,A.V., Minassian,B.A. and Scherer,S.W.
  TITLE     Mutations in NHLRC1 cause progressive myoclonus epilepsy
  JOURNAL   Nat Genet 35 (2), 125-127 (2003)
   PUBMED   12958597
  REMARK    GeneRIF: Laforin and malin colocalize to the ER, suggesting they
            operate in a related pathway protecting against polyglucosan
            accumulation and epilepsy
REFERENCE   10 (bases 1 to 2238)
  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 AL589723.7 and BK001510.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 17, 2019 this sequence version replaced NM_198586.2.
            
            Summary: The protein encoded by this gene is a single subunit E3
            ubiquitin ligase. Laforin is polyubiquitinated by the encoded
            protein. Defects in this intronless gene lead to an accumulation of
            laforin and onset of Lafora disease, also known as progressive
            myoclonic epilepsy type 2 (EPM2).[provided by RefSeq, Mar 2010].
            
            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 is intronless :: BK001510.1, SRR1803615.16296.1
                                        [ECO:0000345]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000340650.6/ ENSP00000345464.3
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-57                AL589723.7         85176-85232         c
            58-2191             BK001510.1         1-2134
            2192-2238           AL589723.7         82995-83041         c
FEATURES             Location/Qualifiers
     source          1..2238
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6p22.3"
     gene            1..2238
                     /gene="NHLRC1"
                     /gene_synonym="bA204B7.2; EPM2A; EPM2B; MALIN; MELF2"
                     /note="NHL repeat containing E3 ubiquitin protein ligase
                     1"
                     /db_xref="GeneID:378884"
                     /db_xref="HGNC:HGNC:21576"
                     /db_xref="MIM:608072"
     exon            1..2238
                     /gene="NHLRC1"
                     /gene_synonym="bA204B7.2; EPM2A; EPM2B; MALIN; MELF2"
                     /inference="alignment:Splign:2.1.0"
     CDS             72..1259
                     /gene="NHLRC1"
                     /gene_synonym="bA204B7.2; EPM2A; EPM2B; MALIN; MELF2"
                     /EC_number="2.3.2.27"
                     /note="NHL repeat-containing protein 1; NHL repeat
                     containing 1; RING-type E3 ubiquitin transferase NHLRC1"
                     /codon_start=1
                     /product="E3 ubiquitin-protein ligase NHLRC1"
                     /protein_id="NP_940988.2"
                     /db_xref="CCDS:CCDS4542.1"
                     /db_xref="GeneID:378884"
                     /db_xref="HGNC:HGNC:21576"
                     /db_xref="MIM:608072"
                     /translation="MAAEASESGPALHELMREAEISLLECKVCFEKFGHRQQRRPRNL
                     SCGHVVCLACVAALAHPRTLALECPFCRRACRGCDTSDCLPVLHLIELLGSALRQSPA
                     AHRAAPSAPGALTCHHTFGGWGTLVNPTGLALCPKTGRVVVVHDGRRRVKIFDSGGGC
                     AHQFGEKGDAAQDIRYPVDVTITNDCHVVVTDAGDRSIKVFDFFGQIKLVIGGQFSLP
                     WGVETTPQNGIVVTDAEAGSLHLLDVDFAEGVLRRTERLQAHLCNPRGVAVSWLTGAI
                     AVLEHPLALGTGVCSTRVKVFSSSMQLVGQVDTFGLSLYFPSKITASAVTFDHQGNVI
                     VADTSGPAILCLGKPEEFPVPKPMVTHGLSHPVALTFTKENSLLVLDTASHSIKVYKV
                     DWG"
     regulatory      1362..1367
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NHLRC1"
                     /gene_synonym="bA204B7.2; EPM2A; EPM2B; MALIN; MELF2"
                     /note="hexamer: ATTAAA"
     polyA_site      1388
                     /gene="NHLRC1"
                     /gene_synonym="bA204B7.2; EPM2A; EPM2B; MALIN; MELF2"
                     /note="major polyA site"
     regulatory      2173..2178
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NHLRC1"
                     /gene_synonym="bA204B7.2; EPM2A; EPM2B; MALIN; MELF2"
                     /note="hexamer: ATTAAA"
     regulatory      2181..2186
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NHLRC1"
                     /gene_synonym="bA204B7.2; EPM2A; EPM2B; MALIN; MELF2"
                     /note="hexamer: AGTAAA"
     polyA_site      2192
                     /gene="NHLRC1"
                     /gene_synonym="bA204B7.2; EPM2A; EPM2B; MALIN; MELF2"
                     /note="major polyA site"
     polyA_site      2204
                     /gene="NHLRC1"
                     /gene_synonym="bA204B7.2; EPM2A; EPM2B; MALIN; MELF2"
ORIGIN      
        1 gactgtgacc gtgaccgaga gcgtcgctgg ggcacggcca ggcggcgcgg cgggagtgca
       61 caggacgcgc catggcggcc gaagcctcgg agagcgggcc agcgctgcat gagctcatgc
      121 gcgaggcgga gatcagcctg ctcgagtgca aggtgtgctt tgagaagttt ggccaccggc
      181 agcagcggcg cccgcgcaac ctgtcctgcg gccacgtggt ctgcctggcc tgcgtggccg
      241 ccctggcgca cccgcgcact ctggccctcg agtgcccatt ctgcaggcga gcttgccggg
      301 gctgcgacac cagcgactgc ctgccggtgc tgcacctcat agagctcctg ggctcagcgc
      361 ttcgccagtc cccggccgcc catcgcgccg cccccagcgc ccccggagcc ctcacctgcc
      421 accacacctt cggcggctgg gggaccctgg tcaaccccac cggactggcg ctttgtccca
      481 agacggggcg tgtcgtggtg gtgcacgacg gcaggaggcg tgtcaagatt tttgactcag
      541 ggggaggatg cgcgcatcag tttggagaga agggggacgc tgcccaagac attaggtacc
      601 ctgtggatgt caccatcacc aacgactgcc atgtggttgt cactgacgcc ggcgatcgct
      661 ccatcaaagt gtttgatttt tttggccaga tcaagcttgt cattggaggc caattctcct
      721 taccttgggg tgtggagacc acccctcaga atgggattgt ggtaactgat gcggaggcag
      781 ggtccctgca cctcctggac gtcgacttcg cggaaggggt ccttcggaga actgaaaggt
      841 tgcaagctca tctgtgcaat ccccgagggg tggcagtgtc ttggctcacc ggggccattg
      901 cggtcctgga gcaccccctg gccctgggga ctggggtttg cagcaccagg gtgaaagtgt
      961 ttagctcaag tatgcagctt gtcggccaag tggatacctt tgggctgagc ctctactttc
     1021 cctccaaaat aactgcctcc gctgtgacct ttgatcacca gggaaatgtg attgttgcag
     1081 atacatctgg tccagctatc ctttgcttag gaaaacctga ggagtttcca gtaccgaagc
     1141 ccatggtcac tcatggtctt tcgcatcctg tggctcttac cttcaccaag gagaattctc
     1201 ttcttgtgct ggacacagca tctcattcta taaaagtcta taaagttgac tgggggtgat
     1261 gggctggggt gggtccctgg aatcagaagc actagtgctg ccattaatga attgtttaac
     1321 cctggataag tcacttaaac tcatctatcc aggcagggat aattaaaacc atctggcaga
     1381 cttacaaagc ttgggacagt tattggagat taatctacca tttattgaat gcatactctg
     1441 tgcaaggaaa tttgcaaata ttagcttatt taatctgtac tatccagtga ggtaatttct
     1501 tcccccccaa gatagagtca agctctgtca cccaggctgg agtgcagaag catgatcaca
     1561 gctcactaca gtttcaacgt cccccgctca ggtggtcctt ccacctcagc ctcccaagta
     1621 gctgggacca caagtgtgca ttaccacact cagctaattt ttgtattttg gcagagatgg
     1681 ggtttcacca tgttgcccag gctggtctca aactcctgag ttcaagcaat ccaccttcct
     1741 cggcctccca aagtactagg agtacaggca tagccacttg ctcagccata atttttatta
     1801 ttaatctcat tgtacaagtg agaaaactga gacccagaga gcttaagtga cttcctcgag
     1861 gtcatagtta cttactgcct tagtcccaat ttgaattcaa ttctgattcc aaataagttg
     1921 cgcttaaata agacaacaga tgtgggaaaa atatgtgaat gtgtagtgtt gctatgtgta
     1981 ctgtctttac aagtagctaa ttattttagc acaaagatgt gcaaagaaag gagactttat
     2041 ggagagttca ggagaaaaag gattttgtgg tggccatcac tttcattcaa tttgcgactg
     2101 ctctgatggc acattagatg aagttactgt tgatcctgag ttacgtgaat aagaaaaaca
     2161 attgaactgc ttattaaaaa agtaaacatg tcttttaacg cctatatctt ctccactata
     2221 caaactcaga aaatacca
//
