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A Database of Extreme Multifunctional and Moonlighting Proteins
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About
Protein: Q6ZNA4
UniprotKB AC
UniprotKB ID
Gene name
Full name
Species
Curated set
Q6ZNA4 (Uniprot)
RN111_HUMAN
RNF111
E3 ubiquitin-protein ligase Arkadia
human
No
Protein Function
Uniprot:
E3 ubiquitin-protein ligase (PubMed:26656854). Required for mesoderm patterning during embryonic development (By similarity). Acts as an enhancer of the transcriptional responses of the SMAD2/SMAD3 effectors, which are activated downstream of BMP (PubMed:14657019, PubMed:16601693). Acts by mediating ubiquitinatio
n 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, PubMed:16601693). 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 (PubMed:17591695). Associates with UBE2D2 as an E2 enzyme (PubMed:22411132). Specifically binds polysumoylated chains via SUMO interaction motifs (SIMs) and mediates ubiquitination of sumoylated substrates (PubMed:23751493). Catalyzes 'Lys-63'-linked ubiquitination of sumoylated XPC in response to UV irradiation, promoting nucleotide excision repair (PubMed:23751493). Mediates ubiquitination and degradation of sumoylated PML (By similarity). The regulation of the BMP-SMAD signaling is however independent of sumoylation and is not dependent of SUMO interaction motifs (SIMs) (By similarity).
more..
MoonDB Dissimilar Functions
GO ID 1
Function 1
Module ID 1
GO ID 2
Function 2
Module ID 2
Association Probability
(PrOnto)
Interaction Probability
(PrOnto)
GO:0009056
catabolic process
125
GO:0009059
macromolecule biosynthetic process
192
,
270
6.37e-04
1.88e-40
MoonDB Network Modules
Biological Processes
Module ID
(MoonGO)
GO ID (BP)
GO Name
125
GO:0044248
cellular catabolic process
125
GO:0016567
protein ubiquitination
125
GO:0060255
regulation of macromolecule metabolic process
192
GO:0034645
cellular macromolecule biosynthetic process
192
GO:0006464
cellular protein modification process
192
GO:0010467
gene expression
192
GO:0090304
nucleic acid metabolic process
192
GO:0009893
positive regulation of metabolic process
192
GO:0060255
regulation of macromolecule metabolic process
192
GO:0007165
signal transduction
270
GO:0034645
cellular macromolecule biosynthetic process
270
GO:0010467
gene expression
270
GO:0090304
nucleic acid metabolic process
270
GO:0032446
protein modification by small protein conjugation
270
GO:0060255
regulation of macromolecule metabolic process
270
GO:0007165
signal transduction
Cellular Components
Module ID
(MoonGO)
GO ID (CC)
GO Name
125
GO:0005829
cytosol
125
GO:0005634
nucleus
192
GO:0005829
cytosol
192
GO:0005654
nucleoplasm
270
GO:0005829
cytosol
270
GO:0070013
intracellular organelle lumen
270
GO:0005634
nucleus
Protein GO Annotations
Biological Processes
GO ID (BP)
GO Name
Evidence Code
(GO EC)
GO:0000209
protein polyubiquitination
IBA
GO:0007389
pattern specification process
IEA
GO:0016567
protein ubiquitination
IMP
GO:0030511
positive regulation of transforming growth factor beta receptor signaling pathway
IBA
GO:0030579
ubiquitin-dependent SMAD protein catabolic process
IBA
GO:0031398
positive regulation of protein ubiquitination
IEA
GO:0042787
protein ubiquitination involved in ubiquitin-dependent protein catabolic process
IBA
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
IBA
GO:0045893
positive regulation of transcription, DNA-templated
IMP
GO:0045944
positive regulation of transcription from RNA polymerase II promoter
TAS
GO:0070911
global genome nucleotide-excision repair
TAS
Cellular Components
GO ID (CC)
GO Name
Evidence Code
(GO EC)
GO:0005634
nucleus
IDA
GO:0005654
nucleoplasm
TAS
GO:0005737
cytoplasm
IBA
GO:0005829
cytosol
IDA
GO:0016605
PML body
IEA
GO:0043234
protein complex
IEA
Dissimilar Cellular Components (PrOnto)
No pairs of PrOnto dissimilar CC GO terms found.
All Protein Interactions
Interactor
Also a MoonDB EMF protein
KRA59_HUMAN
No
CSK21_HUMAN
Yes:
P68400 (MoonDB)
HS90B_HUMAN
Yes:
P08238 (MoonDB)
TS101_HUMAN
Yes:
Q99816 (MoonDB)
ACTN3_HUMAN
No
UBA1_HUMAN
No
UBE2N_HUMAN
Yes:
P61088 (MoonDB)
UB2V1_HUMAN
Yes:
Q13404 (MoonDB)
UB2D2_HUMAN
Yes:
P62837 (MoonDB)
CTBP1_HUMAN
No
UB2E3_HUMAN
Yes:
Q969T4 (MoonDB)
LCE4A_HUMAN
No
APC11_HUMAN
No
B2R8Y4_HUMAN
No
CREB1_HUMAN
No
DTX3L_HUMAN
No
EDAD_HUMAN
No
LRSM1_HUMAN
Yes:
Q6UWE0 (MoonDB)
MARH7_HUMAN
No
MVP_HUMAN
No
PHF7_HUMAN
No
PML_HUMAN
No
RO52_HUMAN
No
SMUF2_HUMAN
No
TRAF5_HUMAN
No
TRIM8_HUMAN
Yes:
Q9BZR9 (MoonDB)
UB2D1_HUMAN
Yes:
P51668 (MoonDB)
UB2D3_HUMAN
Yes:
P61077 (MoonDB)
UB2D4_HUMAN
Yes:
Q9Y2X8 (MoonDB)
UB2E1_HUMAN
Yes:
P51965 (MoonDB)
UB2E2_HUMAN
Yes:
Q96LR5 (MoonDB)
UB2G2_HUMAN
No
UB2Q2_HUMAN
No
UBC12_HUMAN
No
UBC9_HUMAN
Yes:
P63279 (MoonDB)
UBE2K_HUMAN
Yes:
P61086 (MoonDB)
UBE2W_HUMAN
Yes:
Q96B02 (MoonDB)
Publications Associated
PMID
Article Title
14657019
Arkadia amplifies TGF-beta superfamily signaling through degradation of Smad7.
14702039
Complete sequencing and characterization of 21,243 full-length human cDNAs.
15489334
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
16572171
Analysis of the DNA sequence and duplication history of human chromosome 15.
16601693
Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia.
17591695
Arkadia activates Smad3/Smad4-dependent transcription by triggering signal-induced SnoN degradation.
17974005
The full-ORF clone resource of the German cDNA consortium.
22411132
NMR-based insights into the conformational and interaction properties of Arkadia RING-H2 E3 Ub ligase.
23086935
PolySUMO-binding proteins identified through a string search.
23751493
RNF111/Arkadia is a SUMO-targeted ubiquitin ligase that facilitates the DNA damage response.
25755297
System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel small ubiquitin-like modified target proteins and acceptor lysines relevant for genome stability.
26656854
Secondary ubiquitin-RING docking enhances Arkadia and Ark2C E3 ligase activity.
28112733
Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.
OMIM Diseases Associated
No results found.
Protein Domains Associated
Domain Name
Domain ID
Source
Znf_RING
IPR001841
InterPro
Znf_RING/FYVE/PHD
IPR013083
InterPro
RNF111_N
IPR029306
InterPro
zf-RING_2
PF13639
Pfam
RNF111_N
PF15303
Pfam
ZF_RING_2
PS50089
PROSITE
RING
SM00184
SMART
T46904
T46904
PIR