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Protein

E3 ubiquitin-protein ligase Arkadia

Gene

Rnf111

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

Functioni

E3 ubiquitin-protein ligase required for mesoderm patterning during embryonic development (PubMed:11298452). Acts as an enhancer of the transcriptional responses of the SMAD2/SMAD3 effectors, which are activated downstream of BMP (PubMed:14657019). Acts by mediating ubiquitination and degradation of SMAD inhibitors such as SMAD7, inducing their proteasomal degradation and thereby enhancing the transcriptional activity of TGF-beta and BMP (PubMed:14657019). In addition to enhance transcription of SMAD2/SMAD3 effectors, also regulates their turnover by mediating their ubiquitination and subsequent degradation, coupling their activation with degradation, thereby ensuring that only effectors 'in use' are degraded (By similarity). Activates SMAD3/SMAD4-dependent transcription by triggering signal-induced degradation of SNON isoform of SKIL (By similarity). Associates with UBE2D2 as an E2 enzyme (By similarity). Specifically binds polysumoylated chains via SUMO interaction motifs (SIMs) and mediates ubiquitination of sumoylated substrates (PubMed:23530056). Catalyzes 'Lys-63'-linked ubiquitination of sumoylated XPC in response to UV irradiation, promoting nucleotide excision repair (By similarity). Mediates ubiquitination and degradation of sumoylated PML (PubMed:23530056). The regulation of the BMP-SMAD signaling is however independent of sumoylation and is not dependent of SUMO interaction motifs (SIMs) (PubMed:23530056).By similarity4 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.1 Publication

Enzyme regulationi

Binds free ubiquitin non-covalently via its RING-type zinc finger. Ubiquitin-binding leads to enhance the E3 ubiquitin-protein ligase activity by stabilizing the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and activating ubiquitin transfer.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)DescriptionActionsGraphical viewLength
Metal bindingi937ZincBy similarity1
Metal bindingi940ZincBy similarity1
Metal bindingi960ZincBy similarity1
Metal bindingi963ZincBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri937 – 978RING-type; atypicalPROSITE-ProRule annotationAdd BLAST42

GO - Molecular functioni

  • SUMO polymer binding Source: UniProtKB
  • ubiquitin protein ligase activity Source: BHF-UCL
  • ubiquitin-protein transferase activity Source: Reactome
  • zinc ion binding Source: InterPro

GO - Biological processi

  • DNA repair Source: UniProtKB-KW
  • pattern specification process Source: MGI
  • positive regulation of protein ubiquitination Source: MGI
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of transforming growth factor beta receptor signaling pathway Source: MGI
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
  • protein polyubiquitination Source: BHF-UCL
  • protein ubiquitination Source: MGI
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: GO_Central
  • ubiquitin-dependent SMAD protein catabolic process Source: BHF-UCL

Keywordsi

Molecular functionDevelopmental protein, Transferase
Biological processDNA damage, DNA repair, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-2173796. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
R-MMU-5696395. Formation of Incision Complex in GG-NER.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase Arkadia1 Publication (EC:2.3.2.271 Publication)
Alternative name(s):
RING finger protein 111Imported
RING-type E3 ubiquitin transferase ArkadiaCurated
Gene namesi
Name:Rnf111Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1934919. Rnf111.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: BHF-UCL
  • nucleolus Source: MGI
  • nucleoplasm Source: Reactome
  • nucleus Source: BHF-UCL
  • PML body Source: UniProtKB-SubCell
  • protein complex Source: MGI

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice rarely develop beyond 15 somites, have a reduced head, fail to undergo turning and die at midgestation.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi298 – 301VVVI → AVAA: Abolishes binding to sumoylated proteins and ubiquitination and degradation of PML; when associated with 326-A--A-329 and 382-A--A-385. 1 Publication4
Mutagenesisi324 – 327VEIV → AEAA: Abolishes binding to sumoylated proteins and ubiquitination and degradation of PML; when associated with 300-A--A-303 and 382-A--A-385. 1 Publication4
Mutagenesisi380 – 383VVDL → AADA: Abolishes binding to sumoylated proteins and ubiquitination and degradation of PML; when associated with 300-A--A-303 and 326-A--A-329. 1 Publication4
Mutagenesisi937C → A: No effect on TGF-beta and BMP signaling. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002806911 – 989E3 ubiquitin-protein ligase ArkadiaAdd BLAST989

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki19Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiQ99ML9.
PRIDEiQ99ML9.

PTM databases

PhosphoSitePlusiQ99ML9.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Developmental stagei

Ubiquitously expressed from ES cells to midgestation.1 Publication

Gene expression databases

BgeeiENSMUSG00000032217.
CleanExiMM_RNF111.
GenevisibleiQ99ML9. MM.

Interactioni

Subunit structurei

Monomer (By similarity). Interacts with SMAD6, SMAD7, AXIN1, AXIN2 and SKIL isoform SNON (PubMed:14657019). Interacts with (phosphorylated) SMAD2 and SMAD3 (PubMed:17341133). Part of a complex containing RNF111, AXIN1 and SMAD7 (By similarity). Interacts (via SIM domains) with SUMO1 and SUMO2 (PubMed:23530056).By similarity3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi220311. 11 interactors.
IntActiQ99ML9. 7 interactors.
MINTiMINT-1899537.
STRINGi10090.ENSMUSP00000034739.

Structurei

3D structure databases

ProteinModelPortaliQ99ML9.
SMRiQ99ML9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni240 – 402Interaction with AXIN1By similarityAdd BLAST163
Regioni902 – 904Ubiquitin bindingBy similarity3
Regioni952 – 956Ubiquitin bindingBy similarity5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi298 – 302SUMO interaction motif 1 (SIM)1 Publication5
Motifi323 – 329SUMO interaction motif 2 (SIM)1 Publication7
Motifi380 – 384SUMO interaction motif 3 (SIM)1 Publication5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi218 – 221Poly-Ser4
Compositional biasi250 – 451Ser-richAdd BLAST202
Compositional biasi492 – 521His-richAdd BLAST30
Compositional biasi624 – 776Pro-richAdd BLAST153

Domaini

The SUMO interaction motifs (SIMs) mediates the binding to polysumoylated substrate.1 Publication
The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity and binds directly to free ubiquitin. Non-covalent ubiquitin-binding stabilizes the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and stimulates ubiquitin transfer.By similarity

Sequence similaritiesi

Belongs to the Arkadia family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri937 – 978RING-type; atypicalPROSITE-ProRule annotationAdd BLAST42

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0800. Eukaryota.
ENOG41121N2. LUCA.
GeneTreeiENSGT00730000110863.
HOGENOMiHOG000154152.
HOVERGENiHBG093884.
InParanoidiQ99ML9.
KOiK10635.
OMAiPCRKRFV.
OrthoDBiEOG090B02F4.
PhylomeDBiQ99ML9.
TreeFamiTF331862.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiView protein in InterPro
IPR029306. RNF111_N.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
PfamiView protein in Pfam
PF15303. RNF111_N. 1 hit.
PF13639. zf-RING_2. 1 hit.
SMARTiView protein in SMART
SM00184. RING. 1 hit.
PROSITEiView protein in PROSITE
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: Q99ML9-1) [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
MSQWTPEFNE LYTLKVAMKS GTPDAPTTQE SLKAVLLHPQ PLGATKSFPA
60 70 80 90 100
EVEMINSKVG NEFSHLCDDS QKQEKDMTGN QQEQEKSGVV RKKRKSQQAG
110 120 130 140 150
PSYVQNCVKE NQEILGRRQQ LETPSDEDND SSLSECLSSP SSSLHFGGSD
160 170 180 190 200
TVTSDEDKEV SVRHTQPVLS AKSRSHSARS HKWPRTEADP VPSLLMKRPC
210 220 230 240 250
FHGSALRRVT CRKRLVKSSS SQRTQKQKER MLVQRKKREA LAQRKYALLS
260 270 280 290 300
SSSSSSENDL SSDSSSSSST DGEEDLCASA SENPSNPAAP SGSIDEDVVV
310 320 330 340 350
IEASFTPQVT ANEEINVTST DSEVEIVTVG ESYRSRSTLG HSRSHWSQGS
360 370 380 390 400
SSHTGRPQES RNRSRISTVI QPLRQNAAEV VDLTVDEDEP TIVPTTSARM
410 420 430 440 450
DSQTTSASIN NSNPSTSEQA SDTTSTVASS QPSTVSETEA TLTSNSATGS
460 470 480 490 500
SVGDDVRRTA SSAVPESGPP AMPRLPSCCP QHSPCGGTSQ SHHALAHPHS
510 520 530 540 550
SCFQQHGHHF QHHHHHHHTP HPAVPVSPSF SDPACPVERP QVQAPCGANS
560 570 580 590 600
SSGSSYHDQQ ALPVDLSNSA LRTHGSGGFH GASAFDPCCP VTSSRAAVFG
610 620 630 640 650
HQAAAAPTQP LSIDGYGSSM VAQPQPQPPP QPSLSSCRHY MPPPYASLTR
660 670 680 690 700
PLHHQASACH HSHGNAPPQT QPPPQVDYVI PHPVHAFHSQ ISSHAASHPV
710 720 730 740 750
APPPPTHLGS TAAPIPQHLP PAHQPISHHI PAPAPSAQRL HPHEVMQRME
760 770 780 790 800
VQRRRMMQHP TRAHERPPPH PHRMHPNYGH GHHIHVPQTM SSHPRQAPER
810 820 830 840 850
TAWELGIEAG VTAATYTPGA LHPHLAHYHA PPRLHHLQLG ALPLMVPDMA
860 870 880 890 900
GYPHIRYISS GLDGASFRGP FRGNFEELIH LEERLGNVNR GASQGTIERC
910 920 930 940 950
TYPHKYKKVT TDWFSQRKLH CKQDGEEGTE EDTEEKCTIC LSILEEGEDV
960 970 980
RRLPCMHLFH QVCVDQWLIT NKKCPICRVD IEAQLPSES
Length:989
Mass (Da):107,896
Last modified:June 1, 2001 - v1
Checksum:i212E3C37BC70DCB5
GO
Isoform 2 (identifier: Q99ML9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     909-916: Missing.

Show »
Length:981
Mass (Da):106,931
Checksum:i4BC421580AB2ACEB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti121L → V in BAC29394 (PubMed:16141072).Curated1
Sequence conflicti219S → G in BAC33245 (PubMed:16141072).Curated1
Sequence conflicti256S → N in BAC33245 (PubMed:16141072).Curated1
Sequence conflicti805L → V in AAH54842 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_023842909 – 916Missing in isoform 2. 2 Publications8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF330197 mRNA. Translation: AAK38272.1.
AK048110 mRNA. Translation: BAC33245.1.
AK036351 mRNA. Translation: BAC29394.1.
AK137148 mRNA. Translation: BAE23252.1.
BC054842 mRNA. Translation: AAH54842.1.
BC069835 mRNA. Translation: AAH69835.1.
CCDSiCCDS23321.1. [Q99ML9-1]
RefSeqiNP_291082.1. NM_033604.2. [Q99ML9-1]
XP_006511649.1. XM_006511586.2. [Q99ML9-2]
UniGeneiMm.29783.

Genome annotation databases

EnsembliENSMUST00000034739; ENSMUSP00000034739; ENSMUSG00000032217. [Q99ML9-1]
ENSMUST00000113595; ENSMUSP00000109225; ENSMUSG00000032217. [Q99ML9-1]
ENSMUST00000215848; ENSMUSP00000149445; ENSMUSG00000032217. [Q99ML9-2]
GeneIDi93836.
KEGGimmu:93836.
UCSCiuc009qoa.1. mouse. [Q99ML9-2]
uc009qoe.1. mouse. [Q99ML9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF330197 mRNA. Translation: AAK38272.1.
AK048110 mRNA. Translation: BAC33245.1.
AK036351 mRNA. Translation: BAC29394.1.
AK137148 mRNA. Translation: BAE23252.1.
BC054842 mRNA. Translation: AAH54842.1.
BC069835 mRNA. Translation: AAH69835.1.
CCDSiCCDS23321.1. [Q99ML9-1]
RefSeqiNP_291082.1. NM_033604.2. [Q99ML9-1]
XP_006511649.1. XM_006511586.2. [Q99ML9-2]
UniGeneiMm.29783.

3D structure databases

ProteinModelPortaliQ99ML9.
SMRiQ99ML9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi220311. 11 interactors.
IntActiQ99ML9. 7 interactors.
MINTiMINT-1899537.
STRINGi10090.ENSMUSP00000034739.

PTM databases

PhosphoSitePlusiQ99ML9.

Proteomic databases

PaxDbiQ99ML9.
PRIDEiQ99ML9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034739; ENSMUSP00000034739; ENSMUSG00000032217. [Q99ML9-1]
ENSMUST00000113595; ENSMUSP00000109225; ENSMUSG00000032217. [Q99ML9-1]
ENSMUST00000215848; ENSMUSP00000149445; ENSMUSG00000032217. [Q99ML9-2]
GeneIDi93836.
KEGGimmu:93836.
UCSCiuc009qoa.1. mouse. [Q99ML9-2]
uc009qoe.1. mouse. [Q99ML9-1]

Organism-specific databases

CTDi54778.
MGIiMGI:1934919. Rnf111.

Phylogenomic databases

eggNOGiKOG0800. Eukaryota.
ENOG41121N2. LUCA.
GeneTreeiENSGT00730000110863.
HOGENOMiHOG000154152.
HOVERGENiHBG093884.
InParanoidiQ99ML9.
KOiK10635.
OMAiPCRKRFV.
OrthoDBiEOG090B02F4.
PhylomeDBiQ99ML9.
TreeFamiTF331862.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-MMU-2173796. SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
R-MMU-5696395. Formation of Incision Complex in GG-NER.

Miscellaneous databases

ChiTaRSiRnf111. mouse.
PROiQ99ML9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032217.
CleanExiMM_RNF111.
GenevisibleiQ99ML9. MM.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiView protein in InterPro
IPR029306. RNF111_N.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
PfamiView protein in Pfam
PF15303. RNF111_N. 1 hit.
PF13639. zf-RING_2. 1 hit.
SMARTiView protein in SMART
SM00184. RING. 1 hit.
PROSITEiView protein in PROSITE
PS50089. ZF_RING_2. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiRN111_MOUSE
AccessioniPrimary (citable) accession number: Q99ML9
Secondary accession number(s): Q3UVL7
, Q6NSW2, Q7TMR3, Q8C881, Q8CBC0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: June 1, 2001
Last modified: February 15, 2017
This is version 136 of the entry and version 1 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
  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.