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Protein

E3 ubiquitin-protein ligase MYLIP

Gene

Mylip

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Activity depends on E2 enzymes of the UBE2D family. Proteasomal degradation of MRLC leads to inhibit neurite outgrowth in presence of NGF by counteracting the stabilization of MRLC by saposin-like protein (CNPY2/MSAP) and reducing CNPY2-stimulated neurite outgrowth. Acts as a sterol-dependent inhibitor of cellular cholesterol uptake by mediating ubiquitination and subsequent degradation of LDLR.2 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.

Enzyme regulationi

Can bind 1 iron ion per dimer. Iron binding seems to decrease LDLR degradation activity.By similarity

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi360IronBy similarity1
Metal bindingi363IronBy similarity1
Metal bindingi368IronBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri387 – 422RING-typePROSITE-ProRule annotationAdd BLAST36

GO - Molecular functioni

  • cytoskeletal protein binding Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • ubiquitin protein ligase activity Source: MGI
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  • cellular response to low-density lipoprotein particle stimulus Source: BHF-UCL
  • cholesterol homeostasis Source: BHF-UCL
  • negative regulation of low-density lipoprotein particle clearance Source: BHF-UCL
  • negative regulation of neuron projection development Source: Ensembl
  • nervous system development Source: MGI
  • positive regulation of protein catabolic process Source: BHF-UCL
  • protein destabilization Source: BHF-UCL
  • protein ubiquitination Source: MGI
  • regulation of low-density lipoprotein particle receptor catabolic process Source: BHF-UCL
  • ubiquitin-dependent protein catabolic process Source: BHF-UCL

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway
LigandIron, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-8866427 VLDLR internalisation and degradation
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase MYLIP (EC:2.3.2.27)
Alternative name(s):
Inducible degrader of the LDL-receptor
Short name:
Idol
Myosin regulatory light chain-interacting protein
Short name:
MIR
RING-type E3 ubiquitin transferase MYLIPCurated
Gene namesi
Name:Mylip
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:2388271 Mylip

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

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi387C → A: Loss of ubiquitin ligase activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000559731 – 445E3 ubiquitin-protein ligase MYLIPAdd BLAST445

Post-translational modificationi

Autoubiquitinated.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

PaxDbiQ8BM54
PRIDEiQ8BM54

PTM databases

PhosphoSitePlusiQ8BM54

Expressioni

Tissue specificityi

Expressed in liver, spleen, intestine and adrenals.1 Publication

Gene expression databases

BgeeiENSMUSG00000038175
CleanExiMM_MYLIP
GenevisibleiQ8BM54 MM

Interactioni

Subunit structurei

Homodimer. Interacts with the E2 ubiquitin-conjugating enzyme, UBE2D1 (via RING-type zinc finger). Interacts with myosin regulatory light chain (MRLC) and TMEM4.By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ8BM54, 1 interactor
MINTiQ8BM54
STRINGi10090.ENSMUSP00000047403

Structurei

3D structure databases

ProteinModelPortaliQ8BM54
SMRiQ8BM54
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 279FERMPROSITE-ProRule annotationAdd BLAST279

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni431 – 433Critical for homodimerizationBy similarity3

Domaini

The RING domain mediates ubiquitination and the neurite outgrowth inhibitory activity.By similarity
The FERM domain binds phospholipids and mediates lipoprotein receptors recognition at the plasma membrane through their cytoplasmic tails.By similarity
The RING-type zinc finger mediates the interaction with UBE2D E2 enzymes.By similarity

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri387 – 422RING-typePROSITE-ProRule annotationAdd BLAST36

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IG7I Eukaryota
ENOG410XRZN LUCA
GeneTreeiENSGT00890000139341
HOGENOMiHOG000007353
HOVERGENiHBG052549
InParanoidiQ8BM54
KOiK10637
OMAiLNIICEM
OrthoDBiEOG091G0A4V
PhylomeDBiQ8BM54
TreeFamiTF351936

Family and domain databases

CDDicd14473 FERM_B-lobe, 1 hit
Gene3Di1.20.80.10, 1 hit
2.30.29.30, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR019749 Band_41_domain
IPR000798 Ez/rad/moesin-like
IPR014352 FERM/acyl-CoA-bd_prot_sf
IPR035963 FERM_2
IPR019748 FERM_central
IPR000299 FERM_domain
IPR018979 FERM_N
IPR018980 FERM_PH-like_C
IPR011993 PH-like_dom_sf
IPR029071 Ubiquitin-like_domsf
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF09380 FERM_C, 1 hit
PF00373 FERM_M, 1 hit
PF09379 FERM_N, 1 hit
PRINTSiPR00935 BAND41
PR00661 ERMFAMILY
SMARTiView protein in SMART
SM00295 B41, 1 hit
SM01196 FERM_C, 1 hit
SUPFAMiSSF47031 SSF47031, 1 hit
SSF54236 SSF54236, 1 hit
PROSITEiView protein in PROSITE
PS50057 FERM_3, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8BM54-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLCYVTRPDA VLMEVEVEAK ANGEDCLNQV CRRLGIIEVD YFGLQFTGSK
60 70 80 90 100
GESLWLNLRN RISQQMDGLA PYRLKLRVKF FVEPHLILQE QTRHIFFLHI
110 120 130 140 150
KESLLAGHLQ CSPEQAVELS ALLAQTKFGD YNQNTAQYSY EDLCEKELSS
160 170 180 190 200
STLNSIVAKH KELEGISQAS AEYQVLQIVS AMENYGIEWH AVRDSEGQKL
210 220 230 240 250
LIGVGPEGIS ICKEDFSPIN RIAYPVVQMA TQSGKNVYLT VTKESGNSIV
260 270 280 290 300
LLFKMISTRA ASGLYRAITE THAFYRCDTV TSAVMMQYSR DLKGHLASLF
310 320 330 340 350
LNENINLGKK YVFDIKRTSK EVYDHARRAL YNAGVVDLVS RSDQSPPSSP
360 370 380 390 400
LKSSDSSMSC SSCEGLSCQQ TRVLQEKLRK LKEAMLCMAC CEEEINSTFC
410 420 430 440
PCGHTVCCES CAAQLQSCPV CRSRVEHVQH VYLPTHTSLL NLTVI
Length:445
Mass (Da):49,849
Last modified:March 1, 2003 - v1
Checksum:i31C73572C95D0711
GO
Isoform 2 (identifier: Q8BM54-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: Missing.

Note: No experimental confirmation available.
Show »
Length:380
Mass (Da):42,446
Checksum:iE505B749FEEBD1CD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti113P → A in AAH10206 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0118301 – 65Missing in isoform 2. 1 PublicationAdd BLAST65

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY434449 mRNA Translation: AAQ98867.1
AK034887 mRNA Translation: BAC28868.1
AK040836 mRNA Translation: BAC30716.1
AK159478 mRNA Translation: BAE35115.1
BC010206 mRNA Translation: AAH10206.1
CCDSiCCDS36648.1 [Q8BM54-1]
RefSeqiNP_722484.2, NM_153789.3 [Q8BM54-1]
UniGeneiMm.212855
Mm.489954

Genome annotation databases

EnsembliENSMUST00000038275; ENSMUSP00000047403; ENSMUSG00000038175 [Q8BM54-1]
ENSMUST00000222178; ENSMUSP00000152597; ENSMUSG00000038175 [Q8BM54-2]
GeneIDi218203
KEGGimmu:218203
UCSCiuc007qgz.1 mouse [Q8BM54-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiMYLIP_MOUSE
AccessioniPrimary (citable) accession number: Q8BM54
Secondary accession number(s): Q3TX01, Q8BLY9, Q91Z47
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 9, 2004
Last sequence update: March 1, 2003
Last modified: April 25, 2018
This is version 140 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health