NHLC1_RAT
ID NHLC1_RAT Reviewed; 396 AA.
AC Q6IMG5;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 113.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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).
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:0000250}.
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 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum {ECO:0000250}. Nucleus
CC {ECO:0000250}. Note=Localizes at the endoplasmic reticulum and, to a
CC lesser extent, in the nucleus. {ECO:0000250}.
CC -!- DOMAIN: The RING domain is essential for ubiquitin E3 ligase activity.
CC {ECO:0000250}.
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DR EMBL; BK001524; DAA01959.1; -; mRNA.
DR RefSeq; NP_954706.1; NM_199236.1.
DR AlphaFoldDB; Q6IMG5; -.
DR SMR; Q6IMG5; -.
DR STRING; 10116.ENSRNOP00000030625; -.
DR PaxDb; Q6IMG5; -.
DR Ensembl; ENSRNOT00000031656; ENSRNOP00000030625; ENSRNOG00000026286.
DR GeneID; 364682; -.
DR KEGG; rno:364682; -.
DR CTD; 378884; -.
DR RGD; 735081; Nhlrc1.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00730000111361; -.
DR HOGENOM; CLU_696320_0_0_1; -.
DR InParanoid; Q6IMG5; -.
DR OMA; RKLECPF; -.
DR OrthoDB; 711255at2759; -.
DR PhylomeDB; Q6IMG5; -.
DR TreeFam; TF331018; -.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q6IMG5; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000026286; Expressed in skeletal muscle tissue and 18 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISO:RGD.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; ISO:RGD.
DR GO; GO:0044260; P:cellular macromolecule metabolic process; ISO:RGD.
DR GO; GO:0005978; P:glycogen biosynthetic process; ISO:RGD.
DR GO; GO:0005977; P:glycogen metabolic process; ISO:RGD.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISO:RGD.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0045859; P:regulation of protein kinase activity; ISO:RGD.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; ISO:RGD.
DR GO; GO:0001932; P:regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0031396; P:regulation of protein ubiquitination; ISO:RGD.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISO:RGD.
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 2: Evidence at transcript level;
KW Autophagy; Endoplasmic reticulum; Metal-binding; Nucleus;
KW Reference proteome; Repeat; Transferase; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..396
FT /note="E3 ubiquitin-protein ligase NHLRC1"
FT /id="PRO_0000055982"
FT REPEAT 110..154
FT /note="NHL 1"
FT REPEAT 158..201
FT /note="NHL 2"
FT REPEAT 202..242
FT /note="NHL 3"
FT REPEAT 245..298
FT /note="NHL 4"
FT REPEAT 299..347
FT /note="NHL 5"
FT REPEAT 348..391
FT /note="NHL 6"
FT ZN_FING 23..69
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
SQ SEQUENCE 396 AA; 42089 MW; A62522DC97976099 CRC64;
MGEEAAGVRP ELVREAEVSL LECKVCFERF GHRQQRRPRN LPCGHVVCLA CVAALAHPRT
LALECPFCRR ACRACDTSDC LPVLHLLELL GSTLHASPAA LSAASCAPGA LTCYHAFGGW
GTLVNPTGLA LCPKTGRVVV VHDGKRRVKI FDSGGGGAHQ FGEKGDAAHD VKYPLDVAVT
NDCHVVVTDA GDCSLKVFDF FGQIKLVVGK QFSLPWGVEI TPHNGVLVTD AEAGTLHLLE
ADFPEGVLRR IERLQAHLCN PRGVAVSWLT GAIAVLEHPC ALGTSSGNNT RVKVFNSSMQ
LIGQVDSFGL NLLFPSKITA SAVTFDHQGN VIVADTSGPA IVCLGKPEEF PALKPMVTHG
LSRPVALVFT KENSLLVLDS ASHSIKVFKV MEGNGG
