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Protein

E3 ubiquitin-protein ligase MGRN1

Gene

MGRN1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase. Mediates monoubiquitination at multiple sites of TSG101 in the presence of UBE2D1, but not of UBE2G1, nor UBE2H. 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.3 Publications

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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri278 – 31740RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • endosome to lysosome transport Source: UniProtKB
  • negative regulation of cAMP-mediated signaling Source: UniProtKB
  • negative regulation of G-protein coupled receptor protein signaling pathway Source: UniProtKB
  • protein monoubiquitination Source: UniProtKB
  • protein polyubiquitination Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi6.3.2.19. 2681.
ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase MGRN1 (EC:6.3.2.-)
Alternative name(s):
Mahogunin RING finger protein 1
RING finger protein 156
Gene namesi
Name:MGRN1
Synonyms:KIAA0544, RNF156
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:20254. MGRN1.

Subcellular locationi

Isoform 1 :
  • Cytoplasmcytosol
  • Nucleus

  • Note: Translocation from the cytosol to the nucleus is seen only in the presence of MC1R and MC4R, but not TBXA2R. Excluded from nucleoli.
Isoform 2 :
  • Cytoplasmcytosol
  • Nucleus

  • Note: Translocation from the cytosol to the nucleus is seen only in the presence of MC1R and MC4R, but not TBXA2R. Excluded from nucleoli.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB-SubCell
  • early endosome Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • membrane Source: UniProtKB
  • nucleus Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endosome, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi406 – 4094PSAP → ASAA: Loss of TSG101-binding and drastic reduction of TSG101-ubiquitination. 1 Publication

Organism-specific databases

PharmGKBiPA134941221.

Polymorphism and mutation databases

BioMutaiMGRN1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved
Chaini2 – 552551E3 ubiquitin-protein ligase MGRN1PRO_0000246687Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine1 Publication
Modified residuei411 – 4111PhosphotyrosineBy similarity
Modified residuei471 – 4711PhosphoserineBy similarity
Modified residuei524 – 5241PhosphoserineCombined sources

Post-translational modificationi

Autoubiquitinated in vitro.By similarity

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO60291.
PaxDbiO60291.
PeptideAtlasiO60291.
PRIDEiO60291.

PTM databases

iPTMnetiO60291.
PhosphoSiteiO60291.

Expressioni

Gene expression databases

BgeeiENSG00000102858.
CleanExiHS_MGRN1.
ExpressionAtlasiO60291. baseline and differential.
GenevisibleiO60291. HS.

Organism-specific databases

HPAiHPA007653.

Interactioni

Subunit structurei

Interacts with MC1R and MC4R, but not with TBXA2R. Interacts with TSG101. Interacts with mislocalized cytosolically exposed PRNP; this interaction alters MGRN1 subcellular location and causes lysosomal enlargement (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
TSG101Q998164EBI-2129851,EBI-346882

Protein-protein interaction databases

BioGridi116890. 45 interactions.
IntActiO60291. 19 interactions.
STRINGi9606.ENSP00000262370.

Structurei

3D structure databases

ProteinModelPortaliO60291.
SMRiO60291. Positions 269-317.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi406 – 4094Required for TSG101-binding

Domaini

The RING finger is required for ubiquitin ligase activity.By similarity

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri278 – 31740RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4265. Eukaryota.
ENOG410XRAE. LUCA.
GeneTreeiENSGT00390000009925.
HOGENOMiHOG000231196.
HOVERGENiHBG061762.
InParanoidiO60291.
KOiK10604.
PhylomeDBiO60291.
TreeFamiTF314969.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O60291-1) [UniParc]FASTAAdd to basket
Also known as: (+)S

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
KDDADSPTED GDKPRVLYSL EFTFDADARV AITIYCQASE EFLNGRAVYS
160 170 180 190 200
PKSPSLQSET VHYKRGVSQQ FSLPSFKIDF SEWKDDELNF DLDRGVFPVV
210 220 230 240 250
IQAVVDEGDV VEVTGHAHVL LAAFEKHMDG SFSVKPLKQK QIVDRVSYLL
260 270 280 290 300
QEIYGIENKN NQETKPSDDE NSDNSNECVV CLSDLRDTLI LPCRHLCLCT
310 320 330 340 350
SCADTLRYQA NNCPICRLPF RALLQIRAVR KKPGALSPVS FSPVLAQSLE
360 370 380 390 400
HDEHSCPFKK SKPHPASLAS KKPKRETNSD SVPPGYEPIS LLEALNGLRA
410 420 430 440 450
VSPAIPSAPL YEEITYSGIS DGLSQASCPL AAIDHILDSS RQKGRPQSKA
460 470 480 490 500
PDSTLRSPSS PIHEEDEEKL SEDVDAPPPL GGAELALRES SSPESFITEE
510 520 530 540 550
VDESSSPQQG TRAASIENVL QDSSPEHCGR GPPADIYLPA LGPDSCSVGI

DE
Length:552
Mass (Da):60,753
Last modified:July 25, 2006 - v2
Checksum:i1F923D25FB49DB4D
GO
Isoform 2 (identifier: O60291-2) [UniParc]FASTAAdd to basket
Also known as: (+)L

The sequence of this isoform differs from the canonical sequence as follows:
     540-552: ALGPDSCSVGIDE → GRPTSMETAHGLATTSPTWPPLGGPSPDPSAAELTPL

Show »
Length:576
Mass (Da):63,190
Checksum:i220A9470E51853B9
GO
Isoform 3 (identifier: O60291-3) [UniParc]FASTAAdd to basket
Also known as: (-)L

The sequence of this isoform differs from the canonical sequence as follows:
     356-377: Missing.
     540-552: ALGPDSCSVGIDE → GRPTSMETAHGLATTSPTWPPLGGPSPDPSAAELTPL

Show »
Length:554
Mass (Da):60,742
Checksum:iA7D83CB4E643D35E
GO
Isoform 4 (identifier: O60291-4) [UniParc]FASTAAdd to basket
Also known as: (-)S

The sequence of this isoform differs from the canonical sequence as follows:
     356-377: Missing.

Show »
Length:530
Mass (Da):58,305
Checksum:iECFFB3444A87127A
GO

Sequence cautioni

The sequence BAA25470 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti248 – 2481Y → H in ABO69623 (PubMed:19737927).Curated
Sequence conflicti248 – 2481Y → H in ABO69624 (PubMed:19737927).Curated
Sequence conflicti537 – 5371Y → H in ABO69623 (PubMed:19737927).Curated
Sequence conflicti537 – 5371Y → H in ABO69624 (PubMed:19737927).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei356 – 37722Missing in isoform 3 and isoform 4. 1 PublicationVSP_036462Add
BLAST
Alternative sequencei540 – 55213ALGPD…VGIDE → GRPTSMETAHGLATTSPTWP PLGGPSPDPSAAELTPL in isoform 2 and isoform 3. 2 PublicationsVSP_019853Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EF471397 mRNA. Translation: ABO69623.2.
EF471398 mRNA. Translation: ABO69624.2.
AB011116 mRNA. Translation: BAA25470.1. Different initiation.
AC023830 Genomic DNA. No translation available.
BC050389 mRNA. Translation: AAH50389.1.
CCDSiCCDS42115.1. [O60291-2]
CCDS45401.2. [O60291-4]
CCDS45402.1. [O60291-1]
CCDS59256.1. [O60291-3]
RefSeqiNP_001135761.2. NM_001142289.2. [O60291-3]
NP_001135762.1. NM_001142290.2. [O60291-1]
NP_001135763.2. NM_001142291.2. [O60291-4]
NP_056061.1. NM_015246.3. [O60291-2]
XP_005255277.1. XM_005255220.3. [O60291-1]
XP_005255278.1. XM_005255221.3. [O60291-4]
UniGeneiHs.526494.

Genome annotation databases

EnsembliENST00000262370; ENSP00000262370; ENSG00000102858. [O60291-2]
ENST00000399577; ENSP00000382487; ENSG00000102858. [O60291-1]
ENST00000415496; ENSP00000393311; ENSG00000102858. [O60291-4]
ENST00000586183; ENSP00000465860; ENSG00000102858. [O60291-4]
ENST00000588994; ENSP00000468819; ENSG00000102858. [O60291-3]
GeneIDi23295.
KEGGihsa:23295.
UCSCiuc002cwz.4. human. [O60291-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EF471397 mRNA. Translation: ABO69623.2.
EF471398 mRNA. Translation: ABO69624.2.
AB011116 mRNA. Translation: BAA25470.1. Different initiation.
AC023830 Genomic DNA. No translation available.
BC050389 mRNA. Translation: AAH50389.1.
CCDSiCCDS42115.1. [O60291-2]
CCDS45401.2. [O60291-4]
CCDS45402.1. [O60291-1]
CCDS59256.1. [O60291-3]
RefSeqiNP_001135761.2. NM_001142289.2. [O60291-3]
NP_001135762.1. NM_001142290.2. [O60291-1]
NP_001135763.2. NM_001142291.2. [O60291-4]
NP_056061.1. NM_015246.3. [O60291-2]
XP_005255277.1. XM_005255220.3. [O60291-1]
XP_005255278.1. XM_005255221.3. [O60291-4]
UniGeneiHs.526494.

3D structure databases

ProteinModelPortaliO60291.
SMRiO60291. Positions 269-317.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116890. 45 interactions.
IntActiO60291. 19 interactions.
STRINGi9606.ENSP00000262370.

PTM databases

iPTMnetiO60291.
PhosphoSiteiO60291.

Polymorphism and mutation databases

BioMutaiMGRN1.

Proteomic databases

MaxQBiO60291.
PaxDbiO60291.
PeptideAtlasiO60291.
PRIDEiO60291.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262370; ENSP00000262370; ENSG00000102858. [O60291-2]
ENST00000399577; ENSP00000382487; ENSG00000102858. [O60291-1]
ENST00000415496; ENSP00000393311; ENSG00000102858. [O60291-4]
ENST00000586183; ENSP00000465860; ENSG00000102858. [O60291-4]
ENST00000588994; ENSP00000468819; ENSG00000102858. [O60291-3]
GeneIDi23295.
KEGGihsa:23295.
UCSCiuc002cwz.4. human. [O60291-1]

Organism-specific databases

CTDi23295.
GeneCardsiMGRN1.
H-InvDBHIX0012786.
HGNCiHGNC:20254. MGRN1.
HPAiHPA007653.
MIMi607559. gene.
neXtProtiNX_O60291.
PharmGKBiPA134941221.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4265. Eukaryota.
ENOG410XRAE. LUCA.
GeneTreeiENSGT00390000009925.
HOGENOMiHOG000231196.
HOVERGENiHBG061762.
InParanoidiO60291.
KOiK10604.
PhylomeDBiO60291.
TreeFamiTF314969.

Enzyme and pathway databases

UniPathwayiUPA00143.
BRENDAi6.3.2.19. 2681.
ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

ChiTaRSiMGRN1. human.
GenomeRNAii23295.
PROiO60291.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000102858.
CleanExiHS_MGRN1.
ExpressionAtlasiO60291. baseline and differential.
GenevisibleiO60291. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMGRN1_HUMAN
AccessioniPrimary (citable) accession number: O60291
Secondary accession number(s): A4URL3, A4URL4, Q86W76
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: July 25, 2006
Last modified: September 7, 2016
This is version 126 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. 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.