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Protein

E3 ubiquitin-protein ligase MYLIP

Gene

Mylip

Organism
Mus musculus (Mouse)
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.2 Publications

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

  • cytoskeletal protein binding Source: MGI
  • 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

  • cholesterol homeostasis Source: BHF-UCL
  • negative regulation of low-density lipoprotein particle clearance Source: BHF-UCL
  • nervous system development Source: MGI
  • positive regulation of protein catabolic process Source: BHF-UCL
  • protein destabilization Source: BHF-UCL
  • protein ubiquitination Source: MGI
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: BHF-UCL
  • regulation of low-density lipoprotein particle receptor catabolic process Source: BHF-UCL
  • response to low-density lipoprotein particle Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Iron, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:2388271. Mylip.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi387 – 3871C → A: Loss of ubiquitin ligase activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 445445E3 ubiquitin-protein ligase MYLIPPRO_0000055973Add
BLAST

Post-translational modificationi

Autoubiquitinated.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

PaxDbiQ8BM54.
PRIDEiQ8BM54.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ8BM54.
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).By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ8BM54. 1 interaction.
MINTiMINT-1953687.
STRINGi10090.ENSMUSP00000047403.

Structurei

3D structure databases

ProteinModelPortaliQ8BM54.
SMRiQ8BM54. Positions 3-276, 372-441.
ModBaseiSearch...
MobiDBiSearch...

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.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

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.
HOGENOMiHOG000007353.
HOVERGENiHBG052549.
InParanoidiQ8BM54.
KOiK10637.
OMAiLLCMLCC.
OrthoDBiEOG7060QK.
PhylomeDBiQ8BM54.
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: 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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti113 – 1131P → A in AAH10206 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 6565Missing in isoform 2. 1 PublicationVSP_011830Add
BLAST

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]
GeneIDi218203.
KEGGimmu:218203.
UCSCiuc007qgz.1. mouse. [Q8BM54-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ8BM54.
SMRiQ8BM54. Positions 3-276, 372-441.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ8BM54. 1 interaction.
MINTiMINT-1953687.
STRINGi10090.ENSMUSP00000047403.

Proteomic databases

PaxDbiQ8BM54.
PRIDEiQ8BM54.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi29116.
MGIiMGI:2388271. Mylip.

Phylogenomic databases

eggNOGiENOG410IG7I. Eukaryota.
ENOG410XRZN. LUCA.
GeneTreeiENSGT00830000128251.
HOGENOMiHOG000007353.
HOVERGENiHBG052549.
InParanoidiQ8BM54.
KOiK10637.
OMAiLLCMLCC.
OrthoDBiEOG7060QK.
PhylomeDBiQ8BM54.
TreeFamiTF351936.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiMylip. mouse.
PROiQ8BM54.
SOURCEiSearch...

Gene expression databases

BgeeiQ8BM54.
CleanExiMM_MYLIP.
GenevisibleiQ8BM54. MM.

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...

Publicationsi

« Hide 'large scale' publications
  1. "The zebrafish band 4.1 member Mir is involved in cell movements associated with gastrulation."
    Knowlton M.N., Chan B.M.C., Kelly G.M.
    Dev. Biol. 264:407-429(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J.
    Tissue: Aorta, Embryo and Vein.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: FVB/N.
    Tissue: Mammary tumor.
  4. "LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor."
    Zelcer N., Hong C., Boyadjian R., Tontonoz P.
    Science 325:100-104(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF CYS-387, UBIQUITINATION.
  5. "The E3 ubiquitin ligase IDOL induces the degradation of the low density lipoprotein receptor family members VLDLR and ApoER2."
    Hong C., Duit S., Jalonen P., Out R., Scheer L., Sorrentino V., Boyadjian R., Rodenburg K.W., Foley E., Korhonen L., Lindholm D., Nimpf J., van Berkel T.J., Tontonoz P., Zelcer N.
    J. Biol. Chem. 285:19720-19726(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiMYLIP_MOUSE
AccessioniPrimary (citable) accession number: Q8BM54
Secondary accession number(s): Q3TX01, Q8BLY9, Q91Z47
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 9, 2004
Last sequence update: March 1, 2003
Last modified: June 8, 2016
This is version 122 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. 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.