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Protein

E3 ubiquitin-protein ligase MYLIP

Gene

MYLIP

Organism
Homo sapiens (Human)
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.6 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.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
  • metal ion binding Source: UniProtKB-KW
  • ubiquitin protein ligase activity Source: MGI
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway
LigandIron, 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: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
Synonyms:BZF1, IDOL
ORF Names:BM-023, PP5242
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000007944.14
HGNCiHGNC:21155 MYLIP
MIMi610082 gene
neXtProtiNX_Q8WY64

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
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
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
PeptideAtlasiQ8WY64
PRIDEiQ8WY64
ProteomicsDBi75131
75132 [Q8WY64-2]

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

Show more details

GO - Molecular functioni

  • cytoskeletal protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi118882, 26 interactors
IntActiQ8WY64, 25 interactors
MINTiQ8WY64
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.

Zinc finger

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

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IG7I Eukaryota
ENOG410XRZN LUCA
GeneTreeiENSGT00920000148976
HOGENOMiHOG000007353
HOVERGENiHBG052549
InParanoidiQ8WY64
KOiK10637
OMAiLNIICEM
OrthoDBiEOG091G0A4V
PhylomeDBiQ8WY64
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: 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 → S4 PublicationsCorresponds to variant dbSNP:rs9370867Ensembl.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 No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiMYLIP_HUMAN
AccessioniPrimary (citable) accession number: Q8WY64
Secondary accession number(s): Q5TIA4
, Q9BU73, Q9NRL9, Q9UHE7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 9, 2004
Last sequence update: December 20, 2005
Last modified: June 20, 2018
This is version 155 of the entry and version 2 of the sequence. See 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

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