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Database: UniProt
Entry: NHLC1_HUMAN
LinkDB: NHLC1_HUMAN
Original site: NHLC1_HUMAN 
ID   NHLC1_HUMAN             Reviewed;         395 AA.
AC   Q6VVB1; Q3SYB1; Q5VUK7; Q6IMH1;
DT   19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2004, sequence version 2.
DT   11-DEC-2019, entry version 147.
DE   RecName: Full=E3 ubiquitin-protein ligase NHLRC1;
DE            EC=2.3.2.27;
DE   AltName: Full=Malin;
DE   AltName: Full=NHL repeat-containing protein 1;
DE   AltName: Full=RING-type E3 ubiquitin transferase NHLRC1 {ECO:0000305};
GN   Name=NHLRC1; Synonyms=EPM2B;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP   VARIANTS EPM2 SER-26; SER-33; ALA-69; PRO-87; ASN-146 AND PRO-302, AND
RP   VARIANT LEU-111.
RX   PubMed=12958597; DOI=10.1038/ng1238;
RA   Chan E.M., Young E.J., Ianzano L., Munteanu I., Zhao X.,
RA   Christopoulos C.C., Avanzini G., Elia M., Ackerley C.A., Jovic N.J.,
RA   Bohlega S., Andermann E., Rouleau G.A., Delgado-Escueta A.V.,
RA   Minassian B.A., Scherer S.W.;
RT   "Mutations in NHLRC1 cause progressive myoclonus epilepsy.";
RL   Nat. Genet. 35:125-127(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-111.
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   FUNCTION, INTERACTION WITH EPM2A, DOMAIN RING, CHARACTERIZATION OF VARIANT
RP   EPM2 PRO-302, AND MUTAGENESIS OF GLU-280.
RX   PubMed=15930137; DOI=10.1073/pnas.0503285102;
RA   Gentry M.S., Worby C.A., Dixon J.E.;
RT   "Insights into Lafora disease: malin is an E3 ubiquitin ligase that
RT   ubiquitinates and promotes the degradation of laforin.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:8501-8506(2005).
RN   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH AGL.
RX   PubMed=17908927; DOI=10.1101/gad.1553207;
RA   Cheng A., Zhang M., Gentry M.S., Worby C.A., Dixon J.E., Saltiel A.R.;
RT   "A role for AGL ubiquitination in the glycogen storage disorders of Lafora
RT   and Cori's disease.";
RL   Genes Dev. 21:2399-2409(2007).
RN   [6]
RP   FUNCTION.
RX   PubMed=18070875; DOI=10.1074/jbc.m708712200;
RA   Worby C.A., Gentry M.S., Dixon J.E.;
RT   "Malin decreases glycogen accumulation by promoting the degradation of
RT   protein targeting to glycogen (PTG).";
RL   J. Biol. Chem. 283:4069-4076(2008).
RN   [7]
RP   FUNCTION, AND COMPLEX FORMATION WITH EPM2A AND HSP70.
RX   PubMed=19036738; DOI=10.1093/hmg/ddn398;
RA   Garyali P., Siwach P., Singh P.K., Puri R., Mittal S., Sengupta S.,
RA   Parihar R., Ganesh S.;
RT   "The malin-laforin complex suppresses the cellular toxicity of misfolded
RT   proteins by promoting their degradation through the ubiquitin-proteasome
RT   system.";
RL   Hum. Mol. Genet. 18:688-700(2009).
RN   [8]
RP   INTERACTION WITH PRDM8.
RX   PubMed=22961547; DOI=10.1093/brain/aws205;
RA   Turnbull J., Girard J.M., Lohi H., Chan E.M., Wang P., Tiberia E., Omer S.,
RA   Ahmed M., Bennett C., Chakrabarty A., Tyagi A., Liu Y., Pencea N., Zhao X.,
RA   Scherer S.W., Ackerley C.A., Minassian B.A.;
RT   "Early-onset Lafora body disease.";
RL   Brain 135:2684-2698(2012).
RN   [9]
RP   FUNCTION.
RX   PubMed=23624058; DOI=10.1016/j.biocel.2013.04.019;
RA   Rubio-Villena C., Garcia-Gimeno M.A., Sanz P.;
RT   "Glycogenic activity of R6, a protein phosphatase 1 regulatory subunit, is
RT   modulated by the laforin-malin complex.";
RL   Int. J. Biochem. Cell Biol. 45:1479-1488(2013).
RN   [10]
RP   VARIANTS EPM2 MET-153; ARG-160; ARG-219; ASN-245 AND LYS-253, AND VARIANT
RP   LEU-111.
RX   PubMed=16021330; DOI=10.1007/s10038-005-0263-7;
RA   Singh S., Suzuki T., Uchiyama A., Kumada S., Moriyama N., Hirose S.,
RA   Takahashi Y., Sugie H., Mizoguchi K., Inoue Y., Kimura K., Sawaishi Y.,
RA   Yamakawa K., Ganesh S.;
RT   "Mutations in the NHLRC1 gene are the common cause for Lafora disease in
RT   the Japanese population.";
RL   J. Hum. Genet. 50:347-352(2005).
RN   [11]
RP   VARIANTS EPM2 GLN-67; TYR-68; ASN-198; ALA-233; HIS-264; 294-VAL-LYS-295
RP   DEL AND ALA-308.
RX   PubMed=15781812; DOI=10.1212/01.wnl.0000154519.10805.f7;
RA   Gomez-Abad C., Gomez-Garre P., Gutierrez-Delicado E., Saygi S.,
RA   Michelucci R., Tassinari C.A., Rodriguez de Cordoba S., Serratosa J.M.;
RT   "Lafora disease due to EPM2B mutations: a clinical and genetic study.";
RL   Neurology 64:982-986(2005).
RN   [12]
RP   VARIANTS EPM2 ARG-22; PRO-126 AND PRO-279, AND CHARACTERIZATION OF VARIANTS
RP   EPM2 ARG-22; PRO-126 AND PRO-279.
RX   PubMed=18311786; DOI=10.1002/humu.20737;
RA   Singh S., Satishchandra P., Shankar S.K., Ganesh S.;
RT   "Lafora disease in the Indian population: EPM2A and NHLRC1 gene mutations
RT   and their impact on subcellular localization of laforin and malin.";
RL   Hum. Mutat. 29:E1-12(2008).
RN   [13]
RP   VARIANTS EPM2 TYR-46; ALA-69; ASN-146 AND PRO-261, CHARACTERIZATION OF
RP   VARIANTS EPM2 TYR-46; ALA-69; ASN-146 AND PRO-261, FUNCTION, SUBCELLULAR
RP   LOCATION, AND INTERACTION WITH EPM2A.
RX   PubMed=21505799; DOI=10.1007/s00109-011-0758-y;
RA   Couarch P., Vernia S., Gourfinkel-An I., Lesca G., Gataullina S.,
RA   Fedirko E., Trouillard O., Depienne C., Dulac O., Steschenko D.,
RA   Leguern E., Sanz P., Baulac S.;
RT   "Lafora progressive myoclonus epilepsy: NHLRC1 mutations affect glycogen
RT   metabolism.";
RL   J. Mol. Med. 89:915-925(2011).
CC   -!- FUNCTION: E3 ubiquitin-protein ligase. Together with the phosphatase
CC       EPM2A/laforin, appears to be involved in the clearance of toxic
CC       polyglucosan and protein aggregates via multiple pathways. In complex
CC       with EPM2A/laforin and HSP70, suppresses the cellular toxicity of
CC       misfolded proteins by promoting their degradation through the
CC       ubiquitin-proteasome system (UPS). Ubiquitinates the glycogen-targeting
CC       protein phosphatase subunits PPP1R3C/PTG and PPP1R3D in a laforin-
CC       dependent manner and targets them for proteasome-dependent degradation,
CC       thus decreasing glycogen accumulation. Polyubiquitinates EPM2A/laforin
CC       and ubiquitinates AGL and targets them for proteasome-dependent
CC       degradation. Also promotes proteasome-independent protein degradation
CC       through the macroautophagy pathway. {ECO:0000269|PubMed:15930137,
CC       ECO:0000269|PubMed:17908927, ECO:0000269|PubMed:18070875,
CC       ECO:0000269|PubMed:19036738, ECO:0000269|PubMed:21505799,
CC       ECO:0000269|PubMed:23624058}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC         [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC         cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC         EC=2.3.2.27;
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Interacts with AGL. Interacts (via the NHL repeats) with
CC       EPM2A/laforin. Forms a complex with EPM2A/laforin and HSP70. Interacts
CC       with PRDM8 (PubMed:22961547). {ECO:0000269|PubMed:15930137,
CC       ECO:0000269|PubMed:17908927, ECO:0000269|PubMed:21505799,
CC       ECO:0000269|PubMed:22961547}.
CC   -!- INTERACTION:
CC       O95278:EPM2A; NbExp=7; IntAct=EBI-6426628, EBI-2506661;
CC       Q9WUA5:Epm2a (xeno); NbExp=12; IntAct=EBI-6426628, EBI-1040928;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum. Nucleus. Note=Localizes at
CC       the endoplasmic reticulum and, to a lesser extent, in the nucleus.
CC   -!- TISSUE SPECIFICITY: Expressed in brain, cerebellum, spinal cord,
CC       medulla, heart, liver, skeletal muscle and pancreas.
CC       {ECO:0000269|PubMed:12958597}.
CC   -!- DOMAIN: The RING domain is essential for ubiquitin E3 ligase activity.
CC       {ECO:0000269|PubMed:15930137}.
CC   -!- DISEASE: Epilepsy, progressive myoclonic 2 (EPM2) [MIM:254780]: An
CC       autosomal recessive and severe form of adolescent-onset progressive
CC       epilepsy. Typically, as seizures increase in frequency, cognitive
CC       function declines towards dementia, and affected individuals die
CC       usually within 10 years after onset. EPM2 occurs worldwide, but it is
CC       particularly common in the mediterranean countries of southern Europe
CC       and northern Africa, in southern India and in the Middle East. At the
CC       cellular level, it is characterized by accumulation of starch-like
CC       polyglucosans called Lafora bodies (LBs) that are most abundant in
CC       organs with the highest glucose metabolism: brain, heart, liver and
CC       skeletal muscle. Among other conditions involving polyglucosans, EPM2
CC       is unique in that the inclusions are in neuronal dendrites but not
CC       axons and the forming polyglucosan fibrils are associated with the
CC       endoplasmic reticulum. {ECO:0000269|PubMed:12958597,
CC       ECO:0000269|PubMed:15781812, ECO:0000269|PubMed:15930137,
CC       ECO:0000269|PubMed:16021330, ECO:0000269|PubMed:18311786,
CC       ECO:0000269|PubMed:21505799}. Note=The disease is caused by mutations
CC       affecting the gene represented in this entry.
CC   -!- WEB RESOURCE: Name=The Lafora progressive myoclonus epilepsy mutation
CC       and polymorphism database;
CC       URL="http://projects.tcag.ca/lafora/";
DR   EMBL; AY324850; AAQ19671.1; -; mRNA.
DR   EMBL; AL589723; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC103888; AAI03889.1; -; mRNA.
DR   EMBL; BC103889; AAI03890.1; -; mRNA.
DR   EMBL; BC103890; AAI03891.1; -; mRNA.
DR   EMBL; BK001510; DAA01954.1; -; mRNA.
DR   CCDS; CCDS4542.1; -.
DR   RefSeq; NP_940988.2; NM_198586.2.
DR   SMR; Q6VVB1; -.
DR   BioGrid; 132073; 16.
DR   IntAct; Q6VVB1; 13.
DR   MINT; Q6VVB1; -.
DR   STRING; 9606.ENSP00000345464; -.
DR   iPTMnet; Q6VVB1; -.
DR   PhosphoSitePlus; Q6VVB1; -.
DR   BioMuta; NHLRC1; -.
DR   DMDM; 50400890; -.
DR   MassIVE; Q6VVB1; -.
DR   PaxDb; Q6VVB1; -.
DR   PeptideAtlas; Q6VVB1; -.
DR   PRIDE; Q6VVB1; -.
DR   ProteomicsDB; 67732; -.
DR   ABCD; Q6VVB1; -.
DR   Ensembl; ENST00000340650; ENSP00000345464; ENSG00000187566.
DR   GeneID; 378884; -.
DR   KEGG; hsa:378884; -.
DR   UCSC; uc003ncl.2; human.
DR   CTD; 378884; -.
DR   DisGeNET; 378884; -.
DR   EuPathDB; HostDB:ENSG00000187566.4; -.
DR   GeneCards; NHLRC1; -.
DR   GeneReviews; NHLRC1; -.
DR   HGNC; HGNC:21576; NHLRC1.
DR   HPA; HPA066030; -.
DR   MalaCards; NHLRC1; -.
DR   MIM; 254780; phenotype.
DR   MIM; 608072; gene.
DR   neXtProt; NX_Q6VVB1; -.
DR   OpenTargets; ENSG00000187566; -.
DR   Orphanet; 501; Lafora disease.
DR   PharmGKB; PA134916338; -.
DR   eggNOG; ENOG410ITF2; Eukaryota.
DR   eggNOG; ENOG410ZMHC; LUCA.
DR   GeneTree; ENSGT00730000111361; -.
DR   HOGENOM; HOG000113780; -.
DR   InParanoid; Q6VVB1; -.
DR   KO; K10602; -.
DR   OMA; WGTLINP; -.
DR   OrthoDB; 711255at2759; -.
DR   PhylomeDB; Q6VVB1; -.
DR   TreeFam; TF331018; -.
DR   Reactome; R-HSA-3322077; Glycogen synthesis.
DR   Reactome; R-HSA-3785653; Myoclonic epilepsy of Lafora.
DR   UniPathway; UPA00143; -.
DR   GeneWiki; NHLRC1; -.
DR   GenomeRNAi; 378884; -.
DR   Pharos; Q6VVB1; Tbio.
DR   PRO; PR:Q6VVB1; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; Q6VVB1; protein.
DR   Bgee; ENSG00000187566; Expressed in 89 organ(s), highest expression level in liver.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR   GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR   GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR   GO; GO:0005978; P:glycogen biosynthetic process; TAS:Reactome.
DR   GO; GO:0031398; P:positive regulation of protein ubiquitination; IEA:Ensembl.
DR   GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR   GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR   GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
DR   GO; GO:0045859; P:regulation of protein kinase activity; IEA:Ensembl.
DR   GO; GO:1903076; P:regulation of protein localization to plasma membrane; IEA:Ensembl.
DR   GO; GO:0034976; P:response to endoplasmic reticulum stress; IEA:Ensembl.
DR   Gene3D; 2.120.10.30; -; 2.
DR   Gene3D; 3.30.40.10; -; 1.
DR   InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR   InterPro; IPR013017; NHL_repeat_subgr.
DR   InterPro; IPR001841; Znf_RING.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   InterPro; IPR017907; Znf_RING_CS.
DR   Pfam; PF14634; zf-RING_5; 1.
DR   SMART; SM00184; RING; 1.
DR   PROSITE; PS51125; NHL; 6.
DR   PROSITE; PS00518; ZF_RING_1; 1.
DR   PROSITE; PS50089; ZF_RING_2; 1.
PE   1: Evidence at protein level;
KW   Autophagy; Disease mutation; Endoplasmic reticulum; Epilepsy;
KW   Metal-binding; Nucleus; Polymorphism; Reference proteome; Repeat;
KW   Transferase; Ubl conjugation pathway; Zinc; Zinc-finger.
FT   CHAIN           1..395
FT                   /note="E3 ubiquitin-protein ligase NHLRC1"
FT                   /id="PRO_0000055980"
FT   REPEAT          113..157
FT                   /note="NHL 1"
FT   REPEAT          161..204
FT                   /note="NHL 2"
FT   REPEAT          205..245
FT                   /note="NHL 3"
FT   REPEAT          248..300
FT                   /note="NHL 4"
FT   REPEAT          301..349
FT                   /note="NHL 5"
FT   REPEAT          350..393
FT                   /note="NHL 6"
FT   ZN_FING         26..72
FT                   /note="RING-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT   VARIANT         22
FT                   /note="S -> R (in EPM2; does not significantly alters the
FT                   subcellular location as compared to the wild-type)"
FT                   /evidence="ECO:0000269|PubMed:18311786"
FT                   /id="VAR_046387"
FT   VARIANT         26
FT                   /note="C -> S (in EPM2; dbSNP:rs28940575)"
FT                   /evidence="ECO:0000269|PubMed:12958597"
FT                   /id="VAR_019482"
FT   VARIANT         33
FT                   /note="F -> S (in EPM2; dbSNP:rs757759398)"
FT                   /evidence="ECO:0000269|PubMed:12958597"
FT                   /id="VAR_019483"
FT   VARIANT         46
FT                   /note="C -> Y (in EPM2; compound heterozygote with A-69;
FT                   loss of interaction with EPM2A; increased levels of PPP1R3C
FT                   and glycogen; dbSNP:rs1193718748)"
FT                   /evidence="ECO:0000269|PubMed:21505799"
FT                   /id="VAR_070793"
FT   VARIANT         67
FT                   /note="E -> Q (in EPM2; dbSNP:rs779507031)"
FT                   /evidence="ECO:0000269|PubMed:15781812"
FT                   /id="VAR_046388"
FT   VARIANT         68
FT                   /note="C -> Y (in EPM2)"
FT                   /evidence="ECO:0000269|PubMed:15781812"
FT                   /id="VAR_046389"
FT   VARIANT         69
FT                   /note="P -> A (in EPM2; compound heterozygote with Y-46;
FT                   severely reduced interaction with EPM2A; increased levels
FT                   of PPP1R3C and glycogen; dbSNP:rs28940576)"
FT                   /evidence="ECO:0000269|PubMed:12958597,
FT                   ECO:0000269|PubMed:21505799"
FT                   /id="VAR_019484"
FT   VARIANT         87
FT                   /note="L -> P (in EPM2)"
FT                   /evidence="ECO:0000269|PubMed:12958597"
FT                   /id="VAR_019485"
FT   VARIANT         111
FT                   /note="P -> L (common polymorphism; dbSNP:rs10949483)"
FT                   /evidence="ECO:0000269|PubMed:12958597,
FT                   ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16021330"
FT                   /id="VAR_019486"
FT   VARIANT         126
FT                   /note="L -> P (in EPM2; the mutant protein targeted
FT                   exclusively nucleus as compared to predominantly
FT                   cytoplasmic and partially nuclear localization of the wild-
FT                   type protein; dbSNP:rs950907157)"
FT                   /evidence="ECO:0000269|PubMed:18311786"
FT                   /id="VAR_046390"
FT   VARIANT         146
FT                   /note="D -> N (in EPM2; compound heterozygote with P-261;
FT                   severely reduced interaction with EPM2A; increased levels
FT                   of PPP1R3C and glycogen; dbSNP:rs769301934)"
FT                   /evidence="ECO:0000269|PubMed:12958597,
FT                   ECO:0000269|PubMed:21505799"
FT                   /id="VAR_019487"
FT   VARIANT         153
FT                   /note="I -> M (in EPM2)"
FT                   /evidence="ECO:0000269|PubMed:16021330"
FT                   /id="VAR_046391"
FT   VARIANT         160
FT                   /note="C -> R (in EPM2; dbSNP:rs200595273)"
FT                   /evidence="ECO:0000269|PubMed:16021330"
FT                   /id="VAR_046392"
FT   VARIANT         198
FT                   /note="I -> N (in EPM2; dbSNP:rs121917876)"
FT                   /evidence="ECO:0000269|PubMed:15781812"
FT                   /id="VAR_046393"
FT   VARIANT         219
FT                   /note="W -> R (in EPM2)"
FT                   /evidence="ECO:0000269|PubMed:16021330"
FT                   /id="VAR_046394"
FT   VARIANT         233
FT                   /note="D -> A (in EPM2)"
FT                   /evidence="ECO:0000269|PubMed:15781812"
FT                   /id="VAR_046395"
FT   VARIANT         245
FT                   /note="D -> N (in EPM2)"
FT                   /evidence="ECO:0000269|PubMed:16021330"
FT                   /id="VAR_046396"
FT   VARIANT         253
FT                   /note="R -> K (in EPM2)"
FT                   /evidence="ECO:0000269|PubMed:16021330"
FT                   /id="VAR_046397"
FT   VARIANT         261
FT                   /note="L -> P (in EPM2; compound heterozygote with N-146;
FT                   loss of interaction with EPM2A; increased levels of PPP1R3C
FT                   and glycogen; dbSNP:rs879745047)"
FT                   /evidence="ECO:0000269|PubMed:21505799"
FT                   /id="VAR_070794"
FT   VARIANT         264
FT                   /note="P -> H (in EPM2)"
FT                   /evidence="ECO:0000269|PubMed:15781812"
FT                   /id="VAR_046398"
FT   VARIANT         279
FT                   /note="L -> P (in EPM2; significantly alters the
FT                   distribution of the protein; a great majority of cells
FT                   expressing the mutant form formed perinuclear inclusion
FT                   when compared with the wild-type form)"
FT                   /evidence="ECO:0000269|PubMed:18311786"
FT                   /id="VAR_046399"
FT   VARIANT         294..295
FT                   /note="Missing (in EPM2)"
FT                   /evidence="ECO:0000269|PubMed:15781812"
FT                   /id="VAR_046400"
FT   VARIANT         302
FT                   /note="Q -> P (in EPM2; loss of interaction with EPM2A;
FT                   dbSNP:rs757858146)"
FT                   /evidence="ECO:0000269|PubMed:12958597,
FT                   ECO:0000269|PubMed:15930137"
FT                   /id="VAR_019488"
FT   VARIANT         308
FT                   /note="D -> A (in EPM2; dbSNP:rs137852859)"
FT                   /evidence="ECO:0000269|PubMed:15781812"
FT                   /id="VAR_046401"
FT   MUTAGEN         280
FT                   /note="E->K: Loss of interaction with EP2MA."
FT                   /evidence="ECO:0000269|PubMed:15930137"
SQ   SEQUENCE   395 AA;  42293 MW;  3E8339D00165FBED CRC64;
     MAAEASESGP ALHELMREAE ISLLECKVCF EKFGHRQQRR PRNLSCGHVV CLACVAALAH
     PRTLALECPF CRRACRGCDT SDCLPVLHLI ELLGSALRQS PAAHRAAPSA PGALTCHHTF
     GGWGTLVNPT GLALCPKTGR VVVVHDGRRR VKIFDSGGGC AHQFGEKGDA AQDIRYPVDV
     TITNDCHVVV TDAGDRSIKV FDFFGQIKLV IGGQFSLPWG VETTPQNGIV VTDAEAGSLH
     LLDVDFAEGV LRRTERLQAH LCNPRGVAVS WLTGAIAVLE HPLALGTGVC STRVKVFSSS
     MQLVGQVDTF GLSLYFPSKI TASAVTFDHQ GNVIVADTSG PAILCLGKPE EFPVPKPMVT
     HGLSHPVALT FTKENSLLVL DTASHSIKVY KVDWG
//
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