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Protein

E3 ubiquitin-protein ligase NHLRC1

Gene

Nhlrc1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

Functioni

E3 ubiquitin-protein ligase. Together with the phosphatase EPM2A/laforin, appears to be involved in the clearance of toxic polyglucosan and protein aggregates via multiple pathways. In complex with EPM2A/laforin and HSP70, suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS). Ubiquitinates the glycogen-targeting protein phosphatase subunits PPP1R3C/PTG and PPP1R3D in a laforin-dependent manner and targets them for proteasome-dependent degradation, thus decreasing glycogen accumulation. Polyubiquitinates EPM2A/laforin and ubiquitinates AGL and targets them for proteasome-dependent degradation. Also promotes proteasome-independent protein degradation through the macroautophagy pathway.By similarity

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri23 – 69RING-typePROSITE-ProRule annotationAdd BLAST47

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processAutophagy, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-3322077. Glycogen synthesis.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase NHLRC1 (EC:2.3.2.27)
Alternative name(s):
Malin
NHL repeat-containing protein 1
RING-type E3 ubiquitin transferase NHLRC1Curated
Gene namesi
Name:Nhlrc1
Synonyms:Epm2b
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 17

Organism-specific databases

RGDi735081. Nhlrc1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000559821 – 396E3 ubiquitin-protein ligase NHLRC1Add BLAST396

Proteomic databases

PaxDbiQ6IMG5.
PRIDEiQ6IMG5.

Expressioni

Gene expression databases

BgeeiENSRNOG00000026286.

Interactioni

Subunit structurei

Interacts with AGL. Interacts (via the NHL repeats) with EPM2A/laforin. Forms a complex with EPM2A/laforin and HSP70 (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000030625.

Structurei

3D structure databases

ProteinModelPortaliQ6IMG5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati110 – 154NHL 1Add BLAST45
Repeati158 – 201NHL 2Add BLAST44
Repeati202 – 242NHL 3Add BLAST41
Repeati245 – 298NHL 4Add BLAST54
Repeati299 – 347NHL 5Add BLAST49
Repeati348 – 391NHL 6Add BLAST44

Domaini

The RING domain is essential for ubiquitin E3 ligase activity.By similarity

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri23 – 69RING-typePROSITE-ProRule annotationAdd BLAST47

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ITF2. Eukaryota.
ENOG410ZMHC. LUCA.
GeneTreeiENSGT00730000111361.
HOGENOMiHOG000113780.
HOVERGENiHBG052617.
InParanoidiQ6IMG5.
KOiK10602.
OMAiRFGHRQQ.
OrthoDBiEOG091G08MU.
PhylomeDBiQ6IMG5.
TreeFamiTF331018.

Family and domain databases

Gene3Di2.120.10.30. 1 hit.
2.130.10.10. 1 hit.
3.30.40.10. 1 hit.
InterProiView protein in InterPro
IPR011042. 6-blade_b-propeller_TolB-like.
IPR013017. NHL_repeat_subgr.
IPR015943. WD40/YVTN_repeat-like_dom_sf.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
PfamiView protein in Pfam
PF14634. zf-RING_5. 1 hit.
SMARTiView protein in SMART
SM00184. RING. 1 hit.
PROSITEiView protein in PROSITE
PS51125. NHL. 6 hits.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.

Sequencei

Sequence statusi: Complete.

Q6IMG5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGEEAAGVRP ELVREAEVSL LECKVCFERF GHRQQRRPRN LPCGHVVCLA
60 70 80 90 100
CVAALAHPRT LALECPFCRR ACRACDTSDC LPVLHLLELL GSTLHASPAA
110 120 130 140 150
LSAASCAPGA LTCYHAFGGW GTLVNPTGLA LCPKTGRVVV VHDGKRRVKI
160 170 180 190 200
FDSGGGGAHQ FGEKGDAAHD VKYPLDVAVT NDCHVVVTDA GDCSLKVFDF
210 220 230 240 250
FGQIKLVVGK QFSLPWGVEI TPHNGVLVTD AEAGTLHLLE ADFPEGVLRR
260 270 280 290 300
IERLQAHLCN PRGVAVSWLT GAIAVLEHPC ALGTSSGNNT RVKVFNSSMQ
310 320 330 340 350
LIGQVDSFGL NLLFPSKITA SAVTFDHQGN VIVADTSGPA IVCLGKPEEF
360 370 380 390
PALKPMVTHG LSRPVALVFT KENSLLVLDS ASHSIKVFKV MEGNGG
Length:396
Mass (Da):42,089
Last modified:July 5, 2004 - v1
Checksum:iA62522DC97976099
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BK001524 mRNA. Translation: DAA01959.1.
RefSeqiNP_954706.1. NM_199236.1.
UniGeneiRn.103777.

Genome annotation databases

EnsembliENSRNOT00000031656; ENSRNOP00000030625; ENSRNOG00000026286.
GeneIDi364682.
KEGGirno:364682.

Similar proteinsi

Entry informationi

Entry nameiNHLC1_RAT
AccessioniPrimary (citable) accession number: Q6IMG5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: July 5, 2004
Last modified: November 22, 2017
This is version 96 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways