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Protein

E3 ubiquitin-protein ligase MYLIP

Gene

MYLIP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.6 Publications

Enzyme regulationi

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

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 bindingi360Iron1
Metal bindingi363Iron1
Metal bindingi368Iron1

Regions

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

GO - Molecular functioni

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

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-HSA-8866427. VLDLR internalisation and degradation.
R-HSA-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
Synonyms:BZF1, IDOL
ORF Names:BM-023, PP5242
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:21155. MYLIP.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Cell membrane 1 Publication; Peripheral membrane protein 1 Publication

GO - Cellular componenti

  • cytosol Source: Reactome
  • extrinsic component of membrane Source: InterPro
  • intracellular Source: UniProtKB
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi265Y → A: Unable to clear LDLR from the plasma membrane. 1 Publication1
Mutagenesisi269T → R: Unable to clear LDLR from the plasma membrane. 1 Publication1
Mutagenesisi387C → A: Abolishes autoubiquitination. 3 Publications1
Mutagenesisi387C → A: Abolishes ubiquitin ligase activity. 3 Publications1
Mutagenesisi389V → R: Inhibits LDLR degradation. 1 Publication1
Mutagenesisi415L → E: Inhibits LDLR degradation. 1 Publication1

Organism-specific databases

DisGeNETi29116.
MalaCardsiMYLIP.
OpenTargetsiENSG00000007944.
PharmGKBiPA134942677.

Polymorphism and mutation databases

BioMutaiMYLIP.
DMDMi84028296.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000559721 – 445E3 ubiquitin-protein ligase MYLIPAdd BLAST445

Post-translational modificationi

Autoubiquitinated.2 Publications

Keywords - PTMi

Ubl conjugation

Proteomic databases

PaxDbiQ8WY64.
PRIDEiQ8WY64.

PTM databases

iPTMnetiQ8WY64.
PhosphoSitePlusiQ8WY64.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Developmental stagei

Expressed in fetal tissues and higher levels were detected in placenta and fetal lung.1 Publication

Inductioni

Expression is directly activated by NR1H2 and NR1H3. Expression is not dependent of the sterol-response element-binding proteins (SREBPs). Expression is indirectly induced by LDL.1 Publication

Gene expression databases

BgeeiENSG00000007944.
CleanExiHS_MYLIP.
ExpressionAtlasiQ8WY64. baseline and differential.
GenevisibleiQ8WY64. HS.

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 TMEM4.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CNPY2Q9Y2B03EBI-6952711,EBI-1054195
MIPOL1Q8TD103EBI-6952711,EBI-2548751
RASSF5Q8WWW03EBI-6952711,EBI-367390
TSC22D4Q9Y3Q83EBI-6952711,EBI-739485

GO - Molecular functioni

  • cytoskeletal protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi118882. 26 interactors.
IntActiQ8WY64. 13 interactors.
MINTiMINT-268789.
STRINGi9606.ENSP00000349298.

Structurei

Secondary structure

1445
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi374 – 384Combined sources11
Turni388 – 390Combined sources3
Beta strandi391 – 394Combined sources4
Beta strandi397 – 400Combined sources4
Helixi409 – 412Combined sources4
Turni419 – 421Combined sources3
Beta strandi427 – 430Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2YHNX-ray3.00A/B369-445[»]
2YHOX-ray2.10A/C/E/G369-445[»]
ProteinModelPortaliQ8WY64.
SMRiQ8WY64.
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 homodimerization3

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.
The RING-type zinc finger mediates the interaction with UBE2D E2 enzymes.

Sequence similaritiesi

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

Zinc finger

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

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IG7I. Eukaryota.
ENOG410XRZN. LUCA.
GeneTreeiENSGT00860000133686.
HOGENOMiHOG000007353.
HOVERGENiHBG052549.
InParanoidiQ8WY64.
KOiK10637.
OMAiEALLCML.
OrthoDBiEOG091G0A4V.
PhylomeDBiQ8WY64.
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]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q8WY64-1) [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
KEALLAGHLL CSPEQAVELS ALLAQTKFGD YNQNTAKYNY EELCAKELSS
160 170 180 190 200
ATLNSIVAKH KELEGTSQAS AEYQVLQIVS AMENYGIEWH SVRDSEGQKL
210 220 230 240 250
LIGVGPEGIS ICKDDFSPIN RIAYPVVQMA TQSGKNVYLT VTKESGNSIV
260 270 280 290 300
LLFKMISTRA ASGLYRAITE THAFYRCDTV TSAVMMQYSR DLKGHLASLF
310 320 330 340 350
LNENINLGKK YVFDIKRTSK EVYDHARRAL YNAGVVDLVS RNNQSPSHSP
360 370 380 390 400
LKSSESSMNC SSCEGLSCQQ TRVLQEKLRK LKEAMLCMVC CEEEINSTFC
410 420 430 440
PCGHTVCCES CAAQLQSCPV CRSRVEHVQH VYLPTHTSLL NLTVI
Length:445
Mass (Da):49,910
Last modified:December 20, 2005 - v2
Checksum:i342E643B0532B45C
GO
Isoform 2 (identifier: Q8WY64-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-181: Missing.
     316-445: Missing.

Note: No experimental confirmation available.
Show »
Length:134
Mass (Da):14,989
Checksum:i377CBE27A1FAEC6E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti199K → R in AAF18974 (PubMed:10593918).Curated1
Sequence conflicti262 – 263SG → TR in AAF87323 (PubMed:11042152).Curated2
Sequence conflicti309 – 310KK → PRN in AAF87323 (PubMed:11042152).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019805342N → S.4 PublicationsCorresponds to variant rs9370867dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0118281 – 181Missing in isoform 2. 1 PublicationAdd BLAST181
Alternative sequenceiVSP_011829316 – 445Missing in isoform 2. 1 PublicationAdd BLAST130

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF187016 mRNA. Translation: AAF18974.1.
AF006003 mRNA. Translation: AAQ13408.1.
AF006004 Genomic DNA. Translation: AAQ13409.1.
AF212221 mRNA. Translation: AAF87323.1.
AF258586 mRNA. Translation: AAG23789.1.
BT007055 mRNA. Translation: AAP35704.1.
AL021407 Genomic DNA. Translation: CAI19548.1.
CH471087 Genomic DNA. Translation: EAW55366.1.
BC002860 mRNA. Translation: AAH02860.1.
CCDSiCCDS4536.1. [Q8WY64-1]
RefSeqiNP_037394.2. NM_013262.3. [Q8WY64-1]
UniGeneiHs.484738.

Genome annotation databases

EnsembliENST00000356840; ENSP00000349298; ENSG00000007944. [Q8WY64-1]
GeneIDi29116.
KEGGihsa:29116.
UCSCiuc003nbq.4. human. [Q8WY64-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF187016 mRNA. Translation: AAF18974.1.
AF006003 mRNA. Translation: AAQ13408.1.
AF006004 Genomic DNA. Translation: AAQ13409.1.
AF212221 mRNA. Translation: AAF87323.1.
AF258586 mRNA. Translation: AAG23789.1.
BT007055 mRNA. Translation: AAP35704.1.
AL021407 Genomic DNA. Translation: CAI19548.1.
CH471087 Genomic DNA. Translation: EAW55366.1.
BC002860 mRNA. Translation: AAH02860.1.
CCDSiCCDS4536.1. [Q8WY64-1]
RefSeqiNP_037394.2. NM_013262.3. [Q8WY64-1]
UniGeneiHs.484738.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2YHNX-ray3.00A/B369-445[»]
2YHOX-ray2.10A/C/E/G369-445[»]
ProteinModelPortaliQ8WY64.
SMRiQ8WY64.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118882. 26 interactors.
IntActiQ8WY64. 13 interactors.
MINTiMINT-268789.
STRINGi9606.ENSP00000349298.

PTM databases

iPTMnetiQ8WY64.
PhosphoSitePlusiQ8WY64.

Polymorphism and mutation databases

BioMutaiMYLIP.
DMDMi84028296.

Proteomic databases

PaxDbiQ8WY64.
PRIDEiQ8WY64.

Protocols and materials databases

DNASUi29116.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356840; ENSP00000349298; ENSG00000007944. [Q8WY64-1]
GeneIDi29116.
KEGGihsa:29116.
UCSCiuc003nbq.4. human. [Q8WY64-1]

Organism-specific databases

CTDi29116.
DisGeNETi29116.
GeneCardsiMYLIP.
HGNCiHGNC:21155. MYLIP.
MalaCardsiMYLIP.
MIMi610082. gene.
neXtProtiNX_Q8WY64.
OpenTargetsiENSG00000007944.
PharmGKBiPA134942677.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IG7I. Eukaryota.
ENOG410XRZN. LUCA.
GeneTreeiENSGT00860000133686.
HOGENOMiHOG000007353.
HOVERGENiHBG052549.
InParanoidiQ8WY64.
KOiK10637.
OMAiEALLCML.
OrthoDBiEOG091G0A4V.
PhylomeDBiQ8WY64.
TreeFamiTF351936.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiMYLIP. human.
GeneWikiiMYLIP.
GenomeRNAii29116.
PROiQ8WY64.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000007944.
CleanExiHS_MYLIP.
ExpressionAtlasiQ8WY64. baseline and differential.
GenevisibleiQ8WY64. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q8WY64
Secondary accession number(s): Q5TIA4
, Q9BU73, Q9NRL9, Q9UHE7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 9, 2004
Last sequence update: December 20, 2005
Last modified: November 30, 2016
This is version 139 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.