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Protein

E3 ubiquitin-protein ligase MGRN1

Gene

Mgrn1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase. Mediates TSG101 monoubiquitination at multiple sites. Plays a role in the regulation of endosome-to-lysosome trafficking. Impairs MC1R- and MC4R-signaling by competing with GNAS-binding to MCRs and inhibiting agonist-induced cAMP production. Does not inhibit ADRB2-signaling. Does not promote MC1R ubiquitination (By similarity).By similarity2 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.

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.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri277 – 316RING-typePROSITE-ProRule annotationAdd BLAST40

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase MGRN1 (EC:2.3.2.27)
Alternative name(s):
Mahogunin RING finger protein 1
RING-type E3 ubiquitin transferase MGRN1Curated
Gene namesi
Name:Mgrn1
Synonyms:Kiaa0544
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:2447670. Mgrn1.

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, Endosome, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mutant mice have a pleiotropic phenotype that includes the absence of yellow hair pigment, curly hair and whiskers, abnormal craniofacial patterning, reduced embryonic viability due to mispatterning of the left-right body axis and age-dependent spongiform neurodegeneration. Many months before onset of vacuolation, mitochondrial complex IV expression and activity is significantly reduced in mutant brains and oxidative stress is increased. A global reduction of ubiquitinated proteins in the brain is observed. At 1 month of age, null mutant mouse brains have less ubiquitinated TSG101, while adult mutant brains contain more ubiquitinated and insoluble TSG101 than wild type. At 1 month of age, significant increase in EGFR levels in the brains of null mutant mice relative to wild-type mice, suggesting an impaired trafficking to the lysosome for degradation.5 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi278 – 281CVVC → AVVA: Loss of ubiquitin-protein ligase activity. Increase in TSG101-binding. 1 Publication4
Mutagenesisi384 – 387PSAP → ASAA: Loss of TSG101-binding. 1 Publication4

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00002466882 – 532E3 ubiquitin-protein ligase MGRN1Add BLAST531

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Modified residuei389PhosphotyrosineCombined sources1
Modified residuei428PhosphoserineCombined sources1
Modified residuei449PhosphoserineCombined sources1
Modified residuei452PhosphoserineCombined sources1
Modified residuei501PhosphoserineBy similarity1

Post-translational modificationi

Autoubiquitinated in vitro.1 Publication

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9D074.
PeptideAtlasiQ9D074.
PRIDEiQ9D074.

PTM databases

iPTMnetiQ9D074.
PhosphoSitePlusiQ9D074.

Expressioni

Tissue specificityi

Widely expressed, with highest levels in brain, heart, kidney and liver. In the CNS, especially prominent in the Purkinje cells of the cerebellum. In the skin, expressed in the basal layer of the epidermis and hair follicles, primarily in the outer root sheath. Isoforms 1, 3, 4 and 5 are equally expressed in the liver. Isoforms 1, 3 and 4 are most abundant in brain, kidney and heart, respectively.4 Publications

Developmental stagei

In presomite and early somite stage embryos, most strongly expressed in the node and more weakly in the neuroepithelium. In 6- to 12-somite embryos, strongest expression in the node, symmetrically in the floor plate of the neural tube and in the developing heart; weaker expression in paraxial mesoderm, somites, neuroepithelium, as well as in hind- and foregut pockets. By 9.5 dpc, virtually ubiquitous.1 Publication

Gene expression databases

BgeeiENSMUSG00000022517.
CleanExiMM_MGRN1.
GenevisibleiQ9D074. MM.

Interactioni

Subunit structurei

Interacts with MC1R and MC4R (By similarity). Interacts with TSG101. Interacts with mislocalized cytosolically exposed PRNP; this interaction alters MGRN1 subcellular location and causes lysosomal enlargement.By similarity2 Publications

Protein-protein interaction databases

BioGridi201365. 3 interactors.
STRINGi10090.ENSMUSP00000023159.

Structurei

3D structure databases

ProteinModelPortaliQ9D074.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi384 – 387Required for TSG101-binding4

Domaini

The RING finger is required for ubiquitin ligase activity.

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri277 – 316RING-typePROSITE-ProRule annotationAdd BLAST40

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4265. Eukaryota.
ENOG410XRAE. LUCA.
GeneTreeiENSGT00390000009925.
HOGENOMiHOG000231196.
HOVERGENiHBG061762.
InParanoidiQ9D074.
KOiK10604.
OMAiRVPSIEN.
OrthoDBiEOG091G08LF.
PhylomeDBiQ9D074.
TreeFamiTF314969.

Family and domain databases

InterProiView protein in InterPro
IPR001841. Znf_RING.
SMARTiView protein in SMART
SM00184. RING. 1 hit.
PROSITEiView protein in PROSITE
PS50089. ZF_RING_2. 1 hit.

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9D074-1) [UniParc]FASTAAdd to basket
Also known as: I

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
MGSILSRRIA GVEDIDIQAN SAYRYPPKSG NYFASHFFMG GEKFDTPHPE
60 70 80 90 100
GYLFGENMDL NFLGSRPVQF PYVTPAPHEP VKTLRSLVNI RKDSLRLVRY
110 120 130 140 150
KEDADSPTED GEKPRVLYSL EFTFDADARV AITIYCQAVE ELVNGVAVYS
160 170 180 190 200
CKNPSLQSET VHYKRGVSQQ FSLPSFKIDF SEWKDDELNF DLDRGVFPVV
210 220 230 240 250
IQAVVDEGDV VEVTGHAHVL LAAFEKHVDG SFSVKPLKQK QIVDRVSYLL
260 270 280 290 300
QEIYGIENKN NQETKPSDDE NSDNSSECVV CLSDLRDTLI LPCRHLCLCT
310 320 330 340 350
SCADTLRYQA NNCPICRLPF RALLQIRAVR KKPGALSPIS FSPVLAQSVD
360 370 380 390 400
HDEHSSSDSI PPGYEPISLL EALNGLRAVS PAIPSAPLYE EITYSGISDG
410 420 430 440 450
LSQASCPLAG LDRIMESGLQ KGKTQSKSPD STLRSPSFPI HEEDEEKLSE
460 470 480 490 500
DSDAPLPPSG VELVLRESSS PESFGTEEGD EPSLKQGSRV PSIDDVLQDG
510 520 530
SPQHHGCSQP VPPADIYLPA LGPESCSVGI EE
Note: Sufficient for normal development, pigmentation and neuronal integrity.
Length:532
Mass (Da):58,477
Last modified:March 1, 2003 - v2
Checksum:i89C2C1A28F9417EE
GO
Isoform 2 (identifier: Q9D074-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     29-29: S → SA

Show »
Length:533
Mass (Da):58,549
Checksum:i1ACFD952FAC71238
GO
Isoform 3 (identifier: Q9D074-3) [UniParc]FASTAAdd to basket
Also known as: III

The sequence of this isoform differs from the canonical sequence as follows:
     520-532: ALGPESCSVGIEE → GWSTSMETPHSLGTTSSPWPLLSGSSPEPGVAELTPF

Note: Sufficient for normal development, pigmentation and neuronal integrity.
Show »
Length:556
Mass (Da):61,016
Checksum:iE90C158E4A7D50C6
GO
Isoform 4 (identifier: Q9D074-4) [UniParc]FASTAAdd to basket
Also known as: II

The sequence of this isoform differs from the canonical sequence as follows:
     355-355: S → SCPFKKSKSHPASLASKKPKRET

Note: Partial rescue of the phenotype of mutant null mice.
Show »
Length:554
Mass (Da):60,915
Checksum:iC6F0746632E6EBAF
GO
Isoform 5 (identifier: Q9D074-5) [UniParc]FASTAAdd to basket
Also known as: IV

The sequence of this isoform differs from the canonical sequence as follows:
     355-355: S → SCPFKKSKSHPASLASKKPKRET
     520-532: ALGPESCSVGIEE → GWSTSMETPHSLGTTSSPWPLLSGSSPEPGVAELTPF

Note: Unable to rescue the phenotype of mutant null mice. No experimental confirmation available. This sequence has been deduced from the description in PubMed:19422019.
Show »
Length:578
Mass (Da):63,454
Checksum:iFC7F672530E2675A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti15I → F in BAE29360 (PubMed:16141072).Curated1
Sequence conflicti31N → D in BAE29360 (PubMed:16141072).Curated1
Sequence conflicti36H → R in BAE29360 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01985429S → SA in isoform 2. 1 Publication1
Alternative sequenceiVSP_019855355S → SCPFKKSKSHPASLASKKPK RET in isoform 4 and isoform 5. 1 Publication1
Alternative sequenceiVSP_019856520 – 532ALGPE…VGIEE → GWSTSMETPHSLGTTSSPWP LLSGSSPEPGVAELTPF in isoform 3 and isoform 5. 1 PublicationAdd BLAST13

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK011747 mRNA. Translation: BAB27816.2.
AK034100 mRNA. Translation: BAC28587.1.
AK088533 mRNA. Translation: BAC40408.1.
AK150176 mRNA. Translation: BAE29360.1.
AK153407 mRNA. Translation: BAE31967.1.
BC046830 mRNA. Translation: AAH46830.1.
AK129161 mRNA. Translation: BAC97971.1.
CCDSiCCDS49751.1. [Q9D074-1]
CCDS57016.1. [Q9D074-2]
RefSeqiNP_001239366.1. NM_001252437.1. [Q9D074-2]
NP_083933.1. NM_029657.4. [Q9D074-1]
XP_006521895.1. XM_006521832.1. [Q9D074-5]
XP_006521897.1. XM_006521834.1. [Q9D074-3]
XP_017172376.1. XM_017316887.1. [Q9D074-4]
UniGeneiMm.291326.
Mm.391848.

Genome annotation databases

EnsembliENSMUST00000023159; ENSMUSP00000023159; ENSMUSG00000022517. [Q9D074-2]
ENSMUST00000070658; ENSMUSP00000068314; ENSMUSG00000022517. [Q9D074-1]
GeneIDi17237.
KEGGimmu:17237.
UCSCiuc007yap.2. mouse. [Q9D074-1]
uc007yaq.2. mouse. [Q9D074-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiMGRN1_MOUSE
AccessioniPrimary (citable) accession number: Q9D074
Secondary accession number(s): Q3U5V9
, Q3UDA1, Q6ZQ97, Q8BZM9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: March 1, 2003
Last modified: October 25, 2017
This is version 138 of the entry and version 2 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways