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 27-MAR-2024, entry version 168. 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 Q6VVB1; O95278: EPM2A; NbExp=7; IntAct=EBI-6426628, EBI-2506661; CC Q6VVB1; 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]: A form CC of progressive myoclonic epilepsy, a clinically and genetically CC heterogeneous group of disorders defined by the combination of action CC and reflex myoclonus, other types of epileptic seizures, and CC progressive neurodegeneration and neurocognitive impairment. EPM2 is 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 variants 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 AlphaFoldDB; Q6VVB1; -. DR SMR; Q6VVB1; -. DR BioGRID; 132073; 25. 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; 9606-ENSP00000345464; -. DR PeptideAtlas; Q6VVB1; -. DR ProteomicsDB; 67732; -. DR ABCD; Q6VVB1; 1 sequenced antibody. DR Antibodypedia; 25182; 301 antibodies from 26 providers. DR DNASU; 378884; -. DR Ensembl; ENST00000340650.6; ENSP00000345464.3; ENSG00000187566.6. DR GeneID; 378884; -. DR KEGG; hsa:378884; -. DR MANE-Select; ENST00000340650.6; ENSP00000345464.3; NM_198586.3; NP_940988.2. DR UCSC; uc003ncl.2; human. DR AGR; HGNC:21576; -. DR DisGeNET; 378884; -. DR GeneCards; NHLRC1; -. DR GeneReviews; NHLRC1; -. DR HGNC; HGNC:21576; NHLRC1. DR HPA; ENSG00000187566; Low tissue specificity. 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 VEuPathDB; HostDB:ENSG00000187566; -. DR eggNOG; KOG2177; Eukaryota. DR GeneTree; ENSGT00730000111361; -. DR HOGENOM; CLU_696320_0_0_1; -. DR InParanoid; Q6VVB1; -. DR OMA; HHAFGGW; -. DR OrthoDB; 3018970at2759; -. DR PhylomeDB; Q6VVB1; -. DR TreeFam; TF331018; -. DR PathwayCommons; Q6VVB1; -. DR Reactome; R-HSA-3322077; Glycogen synthesis. DR Reactome; R-HSA-3785653; Myoclonic epilepsy of Lafora. DR SignaLink; Q6VVB1; -. DR SIGNOR; Q6VVB1; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 378884; 12 hits in 1189 CRISPR screens. 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 prefrontal cortex and 100 other cell types or tissues. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. 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:0030371; F:translation repressor activity; IBA:GO_Central. 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:0017148; P:negative regulation of translation; IBA:GO_Central. 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:1903076; P:regulation of protein localization to plasma membrane; IEA:Ensembl. DR GO; GO:0001932; P:regulation of protein phosphorylation; IEA:Ensembl. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IEA:Ensembl. DR CDD; cd14961; NHL_TRIM32_like; 1. DR CDD; cd16516; RING-HC_malin; 1. DR Gene3D; 2.120.10.30; TolB, C-terminal domain; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like. DR InterPro; IPR001258; NHL_repeat. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR PANTHER; PTHR24104:SF34; E3 UBIQUITIN-PROTEIN LIGASE NHLRC1; 1. DR PANTHER; PTHR24104; E3 UBIQUITIN-PROTEIN LIGASE NHLRC1-RELATED; 1. DR Pfam; PF14634; zf-RING_5; 1. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF101898; NHL repeat; 1. DR SUPFAM; SSF57850; RING/U-box; 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 variant; Endoplasmic reticulum; Epilepsy; Metal-binding; KW Neurodegeneration; Nucleus; Reference proteome; Repeat; Transferase; KW 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; loss of interaction with EPM2A; FT increased levels of PPP1R3C and glycogen; FT 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; severely reduced interaction with FT EPM2A; increased levels of PPP1R3C and glycogen; FT 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 (in 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 FT wild-type protein; dbSNP:rs950907157)" FT /evidence="ECO:0000269|PubMed:18311786" FT /id="VAR_046390" FT VARIANT 146 FT /note="D -> N (in EPM2; severely reduced interaction with FT EPM2A; increased levels of PPP1R3C and glycogen; FT 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; loss of interaction with EPM2A; FT increased levels of PPP1R3C and glycogen; FT 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 //