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Protein

E3 ubiquitin-protein ligase MYLIP

Gene

Mylip

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-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).By similarity

Enzyme regulationi

Can bind 1 iron ion per dimer. Iron binding seems to decrease LDLR degradation activity (By similarity).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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi360 – 3601IronBy similarity
Metal bindingi363 – 3631IronBy similarity
Metal bindingi368 – 3681IronBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri387 – 42236RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Iron, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-983168. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase MYLIP (EC:6.3.2.-)
Alternative name(s):
Inducible degrader of the LDL-receptor
Short name:
Idol
Myosin regulatory light chain interacting protein
Short name:
MIR
Gene namesi
Name:Mylip
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 17

Organism-specific databases

RGDi1305761. Mylip.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 445445E3 ubiquitin-protein ligase MYLIPPRO_0000397121Add
BLAST

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).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000024021.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 279279FERMPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni431 – 4333Critical for homodimerizationBy similarity

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

Sequence similaritiesi

Contains 1 FERM domain.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri387 – 42236RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IG7I. Eukaryota.
ENOG410XRZN. LUCA.
GeneTreeiENSGT00830000128251.
InParanoidiD3ZDI6.
KOiK10637.
OMAiEALLCML.
OrthoDBiEOG091G0A4V.
PhylomeDBiD3ZDI6.
TreeFamiTF351936.

Family and domain databases

Gene3Di1.20.80.10. 1 hit.
2.30.29.30. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR019749. Band_41_domain.
IPR000798. Ez/rad/moesin-like.
IPR014352. FERM/acyl-CoA-bd_prot_3-hlx.
IPR019748. FERM_central.
IPR000299. FERM_domain.
IPR018979. FERM_N.
IPR018980. FERM_PH-like_C.
IPR011993. PH_dom-like.
IPR029071. Ubiquitin-rel_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF09380. FERM_C. 1 hit.
PF00373. FERM_M. 1 hit.
PF09379. FERM_N. 1 hit.
[Graphical view]
PRINTSiPR00935. BAND41.
PR00661. ERMFAMILY.
SMARTiSM00295. B41. 1 hit.
SM01196. FERM_C. 1 hit.
[Graphical view]
SUPFAMiSSF47031. SSF47031. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF54236. SSF54236. 1 hit.
PROSITEiPS50057. FERM_3. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

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.

Cross-referencesi

Sequence databases

RefSeqiNP_001100814.2. NM_001107344.2.
UniGeneiRn.1844.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000024021.

Proteomic databases

PaxDbiD3ZDI6.
PRIDEiD3ZDI6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000024021; ENSRNOP00000024021; ENSRNOG00000017579.
GeneIDi306825.
KEGGirno:306825.

Organism-specific databases

CTDi29116.
RGDi1305761. Mylip.

Phylogenomic databases

eggNOGiENOG410IG7I. Eukaryota.
ENOG410XRZN. LUCA.
GeneTreeiENSGT00830000128251.
InParanoidiD3ZDI6.
KOiK10637.
OMAiEALLCML.
OrthoDBiEOG091G0A4V.
PhylomeDBiD3ZDI6.
TreeFamiTF351936.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-RNO-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

PROiD3ZDI6.

Gene expression databases

BgeeiENSRNOG00000017579.
GenevisibleiD3ZDI6. RN.

Family and domain databases

Gene3Di1.20.80.10. 1 hit.
2.30.29.30. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR019749. Band_41_domain.
IPR000798. Ez/rad/moesin-like.
IPR014352. FERM/acyl-CoA-bd_prot_3-hlx.
IPR019748. FERM_central.
IPR000299. FERM_domain.
IPR018979. FERM_N.
IPR018980. FERM_PH-like_C.
IPR011993. PH_dom-like.
IPR029071. Ubiquitin-rel_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF09380. FERM_C. 1 hit.
PF00373. FERM_M. 1 hit.
PF09379. FERM_N. 1 hit.
[Graphical view]
PRINTSiPR00935. BAND41.
PR00661. ERMFAMILY.
SMARTiSM00295. B41. 1 hit.
SM01196. FERM_C. 1 hit.
[Graphical view]
SUPFAMiSSF47031. SSF47031. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF54236. SSF54236. 1 hit.
PROSITEiPS50057. FERM_3. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMYLIP_RAT
AccessioniPrimary (citable) accession number: D3ZDI6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 10, 2010
Last sequence update: April 20, 2010
Last modified: September 7, 2016
This is version 48 of the entry and version 1 of the sequence. [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
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.