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Protein

E3 ubiquitin-protein ligase MYLIP

Gene

Mylip

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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.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.

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

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-RNO-8866427 VLDLR internalisation and degradation
R-RNO-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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 17

Organism-specific databases

RGDi1305761 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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003971211 – 445E3 ubiquitin-protein ligase MYLIPAdd BLAST445

Post-translational modificationi

Autoubiquitinated.By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

PaxDbiD3ZDI6
PRIDEiD3ZDI6

Expressioni

Tissue specificityi

Expressed in developing and adult brain, hippocampus, cerebellum, cerebral cortex, thalamus and substantia nigra. Predominantly found in neurons.2 Publications

Gene expression databases

BgeeiENSRNOG00000017579
GenevisibleiD3ZDI6 RN

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

STRINGi10116.ENSRNOP00000024021

Structurei

3D structure databases

SMRiD3ZDI6
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.
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
InParanoidiD3ZDI6
KOiK10637
OMAiLNIICEM
OrthoDBiEOG091G0A4V
PhylomeDBiD3ZDI6
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

Sequencei

Sequence statusi: Complete.

D3ZDI6-1 [UniParc]FASTAAdd to basket

« 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
STLNSIVGKH 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 RNDQSPPSSP
360 370 380 390 400
LKSSDSSMSC SSCEGLSCQQ TRVLQEKLRK LKEAMLCMVC CEEEINSTFC
410 420 430 440
PCGHTVCCES CAAQLQSCPV CRSRVEHVQH VYLPTHTSLL NLTVI
Length:445
Mass (Da):49,890
Last modified:April 20, 2010 - v1
Checksum:i6BF6766F610D6000
GO

Sequence databases

RefSeqiNP_001100814.2, NM_001107344.2
UniGeneiRn.1844

Genome annotation databases

EnsembliENSRNOT00000024021; ENSRNOP00000024021; ENSRNOG00000017579
GeneIDi306825
KEGGirno:306825

Similar proteinsi

Entry informationi

Entry nameiMYLIP_RAT
AccessioniPrimary (citable) accession number: D3ZDI6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 10, 2010
Last sequence update: April 20, 2010
Last modified: May 23, 2018
This is version 65 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

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