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Protein

E3 ubiquitin-protein ligase NHLRC1

Gene

Nhlrc1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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.4 Publications

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 fingeri28 – 74RING-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-MMU-3322077 Glycogen synthesis
UniPathwayi
UPA00143

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:2145264 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

Pathology & Biotechi

Disruption phenotypei

Significant impairment of motor activity, coordination and balance; spontaneous myoclonic seizures; and decreases in episodic memory. 3- and 6-month old mice contain numerous large insoluble aggregates composed mainly of polyglucosans called Lafora bodies (LBs) in skeletal muscle, liver, heart and brain. Glycogen levels are increased 1.6-fold and 1.2-fold respectively in skeletal muscle and liver of 6-month old mice. Glycogen phosphate levels are increased 1.5-fold in skeletal muscle and liver of 6-month old mice. In brain extracts from 1-, 3- and 12-month old mice, total amounts of Epm2b/laforin protein (but not mRNA) are increased. In brain and embryonic fibroblast cells, levels of the autophagy marker Map1lc3b/LC3-II are reduced. In the brain, levels of the autophagy dysfunction marker Sqstm1/p62 are increased.3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000559811 – 401E3 ubiquitin-protein ligase NHLRC1Add BLAST401

Proteomic databases

MaxQBiQ8BR37
PaxDbiQ8BR37
PRIDEiQ8BR37

PTM databases

PhosphoSitePlusiQ8BR37

Expressioni

Gene expression databases

BgeeiENSMUSG00000044231 Expressed in 198 organ(s), highest expression level in quadriceps femoris
CleanExiMM_NHLRC1
ExpressionAtlasiQ8BR37 baseline and differential
GenevisibleiQ8BR37 MM

Interactioni

Subunit structurei

Interacts with AGL. Interacts (via the NHL repeats) with EPM2A/laforin (By similarity). Forms a complex with EPM2A/laforin and HSP70. Interacts with PRDM8 (By similarity).By similarity

Protein-protein interaction databases

BioGridi222784, 2 interactors
STRINGi10090.ENSMUSP00000054990

Structurei

3D structure databases

ProteinModelPortaliQ8BR37
SMRiQ8BR37
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati115 – 159NHL 1Add BLAST45
Repeati163 – 206NHL 2Add BLAST44
Repeati207 – 247NHL 3Add BLAST41
Repeati250 – 303NHL 4Add BLAST54
Repeati304 – 352NHL 5Add BLAST49
Repeati353 – 396NHL 6Add BLAST44

Domaini

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri28 – 74RING-typePROSITE-ProRule annotationAdd BLAST47

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ITF2 Eukaryota
ENOG410ZMHC LUCA
GeneTreeiENSGT00730000111361
HOGENOMiHOG000113780
HOVERGENiHBG052617
InParanoidiQ8BR37
KOiK10602
OMAiHAFGGWG
OrthoDBiEOG091G08MU
PhylomeDBiQ8BR37
TreeFamiTF331018

Family and domain databases

Gene3Di2.120.10.30, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR011042 6-blade_b-propeller_TolB-like
IPR013017 NHL_repeat_subgr
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.

Q8BR37-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGEEATAVAA AGVRPELVRE AEVSLLECKV CFERFGHWQQ RRPRNLPCGH
60 70 80 90 100
VVCLACVAAL AHPRTLGLEC PFCRRACRAC DTSDCLPVLH LLELLGSTLH
110 120 130 140 150
ASPAALSAAP FAPGTLTCYH AFGGWGTLVN PTGLALCPKT GRVVVVHDGK
160 170 180 190 200
RRVKIFDSGG GGAHQFGEKG DAAHDVKYPL DVAVTNDCHV VVTDAGDCSL
210 220 230 240 250
KVFDFFGQIK LVVGKQFSLP WGVEITPHNG VLVTDAEAGT LHLLEADFPE
260 270 280 290 300
GVLRRIERLQ AHLCSPRGLA VSWLTGAIAV LEHPCAFGRT GCNNTRVKVF
310 320 330 340 350
NSTMQLIGQV DSFGLNLLFP SKVTASAVTF DHQGNVIVAD TSGPAIVCLG
360 370 380 390 400
KPEEFPALKP IITHGLSRPV ALAFTKENSL LVLDTASHSI KVFKVMEGNG

G
Length:401
Mass (Da):42,690
Last modified:March 1, 2003 - v1
Checksum:i0A2AF7633B472372
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BK001499 mRNA Translation: DAA01953.1
AK045746 mRNA Translation: BAC32478.1
CCDSiCCDS26487.1
RefSeqiNP_780549.1, NM_175340.4
UniGeneiMm.25593

Genome annotation databases

EnsembliENSMUST00000052747; ENSMUSP00000054990; ENSMUSG00000044231
GeneIDi105193
KEGGimmu:105193
UCSCiuc007qhp.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BK001499 mRNA Translation: DAA01953.1
AK045746 mRNA Translation: BAC32478.1
CCDSiCCDS26487.1
RefSeqiNP_780549.1, NM_175340.4
UniGeneiMm.25593

3D structure databases

ProteinModelPortaliQ8BR37
SMRiQ8BR37
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi222784, 2 interactors
STRINGi10090.ENSMUSP00000054990

PTM databases

PhosphoSitePlusiQ8BR37

Proteomic databases

MaxQBiQ8BR37
PaxDbiQ8BR37
PRIDEiQ8BR37

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000052747; ENSMUSP00000054990; ENSMUSG00000044231
GeneIDi105193
KEGGimmu:105193
UCSCiuc007qhp.2 mouse

Organism-specific databases

CTDi378884
MGIiMGI:2145264 Nhlrc1

Phylogenomic databases

eggNOGiENOG410ITF2 Eukaryota
ENOG410ZMHC LUCA
GeneTreeiENSGT00730000111361
HOGENOMiHOG000113780
HOVERGENiHBG052617
InParanoidiQ8BR37
KOiK10602
OMAiHAFGGWG
OrthoDBiEOG091G08MU
PhylomeDBiQ8BR37
TreeFamiTF331018

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-MMU-3322077 Glycogen synthesis

Miscellaneous databases

PROiPR:Q8BR37
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000044231 Expressed in 198 organ(s), highest expression level in quadriceps femoris
CleanExiMM_NHLRC1
ExpressionAtlasiQ8BR37 baseline and differential
GenevisibleiQ8BR37 MM

Family and domain databases

Gene3Di2.120.10.30, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR011042 6-blade_b-propeller_TolB-like
IPR013017 NHL_repeat_subgr
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
ProtoNetiSearch...

Entry informationi

Entry nameiNHLC1_MOUSE
AccessioniPrimary (citable) accession number: Q8BR37
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: March 1, 2003
Last modified: September 12, 2018
This is version 122 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
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Main funding by: National Institutes of Health

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