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 03-AUG-2022, entry version 159.
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/";
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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; 23.
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; 1 sequenced antibody.
DR Antibodypedia; 25182; 280 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 CTD; 378884; -.
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; RKLECPF; -.
DR OrthoDB; 711255at2759; -.
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 UniPathway; UPA00143; -.
DR BioGRID-ORCS; 378884; 10 hits in 1113 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 tissues.
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; -; 1.
DR Gene3D; 3.30.40.10; -; 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 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 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 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; 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
