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Protein

RWD domain-containing protein 3

Gene

RWDD3

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

Functioni

Enhancer of SUMO conjugation. Via its interaction with UBE2I/UBC9, increases SUMO conjugation to proteins by promoting the binding of E1 and E2 enzymes, thioester linkage between SUMO and UBE2I/UBC9 and transfer of SUMO to specific target proteins which include HIF1A, PIAS, NFKBIA, NR3C1 and TOP1. Isoform 1 and isoform 2 positively regulate the NF-kappa-B signaling pathway by enhancing the sumoylation of NF-kappa-B inhibitor alpha (NFKBIA), promoting its stabilization which consequently leads to an increased inhibition of NF-kappa-B transcriptional activity. Isoform 1 and isoform 2 negatively regulate the hypoxia-inducible factor-1 alpha (HIF1A) signaling pathway by increasing the sumoylation of HIF1A, promoting its stabilization, transcriptional activity and the expression of its target gene VEGFA during hypoxia. Isoform 2 promotes the sumoylation and transcriptional activity of the glucocorticoid receptor NR3C1 and enhances the interaction of SUMO1 and NR3C1 with UBE2I/UBC9. Has no effect on ubiquitination.4 Publications

GO - Biological processi

  • negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of hypoxia-inducible factor-1alpha signaling pathway Source: UniProtKB
  • positive regulation of protein sumoylation Source: UniProtKB
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000122481-MONOMER.
ReactomeiR-HSA-3065678. SUMO is transferred from E1 to E2 (UBE2I, UBC9).
SIGNORiQ9Y3V2.

Names & Taxonomyi

Protein namesi
Recommended name:
RWD domain-containing protein 3
Alternative name(s):
RWD domain-containing sumoylation enhancer
Short name:
RSUME1 Publication
Gene namesi
Name:RWDD3
Synonyms:RSUME
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:21393. RWDD3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi61 – 62YP → AA: Abolishes enhancement of NFKBIA and NR3C1 sumoylation. No effect on NR3C1 transcriptional activity. 2 Publications2

Organism-specific databases

DisGeNETi25950.
OpenTargetsiENSG00000122481.
PharmGKBiPA134974302.

Polymorphism and mutation databases

BioMutaiRWDD3.
DMDMi296453018.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000975451 – 267RWD domain-containing protein 3Add BLAST267

Proteomic databases

EPDiQ9Y3V2.
PaxDbiQ9Y3V2.
PeptideAtlasiQ9Y3V2.
PRIDEiQ9Y3V2.

PTM databases

iPTMnetiQ9Y3V2.
PhosphoSitePlusiQ9Y3V2.

Expressioni

Tissue specificityi

Isoform 1 and isoform 2 are expressed in glioma tumors (at protein level). Expressed in a wide number of tissues with highest expression in cerebellum, pituitary, heart, kidney, liver, stomach, pancreas, prostate and spleen. Low levels in thalamus, spinal cord, esophagus, thymus, lung and peripheral blood leukocytes. A higher level expression seen in pituitary tumors as compared to the pituitary gland.3 Publications

Inductioni

Induced by hypoxia and heat shock.3 Publications

Gene expression databases

BgeeiENSG00000122481.
CleanExiHS_RWDD3.
GenevisibleiQ9Y3V2. HS.

Organism-specific databases

HPAiHPA046146.

Interactioni

Subunit structurei

Isoform 1 and isoform 2 interact with UBE2I/UBC9 (PubMed:17956732, PubMed:23469069, PubMed:25918163). Isoform 1 shows a greater interaction with NFKBIA and HIF1A as compared to isoform 2 (PubMed:17956732, PubMed:23469069). Isoform 2 interacts with NCOA2 and NR3C1 (PubMed:23508108).4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
SUMO1P631652EBI-1549885,EBI-80140
UBE2IP632795EBI-1549885,EBI-80168

Protein-protein interaction databases

BioGridi117445. 6 interactors.
IntActiQ9Y3V2. 4 interactors.
MINTiMINT-4712049.
STRINGi9606.ENSP00000359221.

Structurei

Secondary structure

1267
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 15Combined sources13
Beta strandi18 – 26Combined sources9
Turni29 – 31Combined sources3
Beta strandi33 – 37Combined sources5
Turni43 – 46Combined sources4
Beta strandi52 – 57Combined sources6
Turni59 – 63Combined sources5
Beta strandi73 – 75Combined sources3
Helixi78 – 87Combined sources10
Helixi89 – 93Combined sources5
Turni94 – 96Combined sources3
Helixi100 – 106Combined sources7
Beta strandi107 – 109Combined sources3
Helixi111 – 115Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EBKNMR-A1-121[»]
4Y1LX-ray2.70C2-113[»]
ProteinModelPortaliQ9Y3V2.
SMRiQ9Y3V2.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y3V2.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini7 – 114RWDPROSITE-ProRule annotationAdd BLAST108

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni13 – 15Interaction with UBE2I/UBC91 Publication3
Regioni100 – 102Interaction with UBE2I/UBC91 Publication3

Domaini

The RWD domain is required for the sumoylation enhancement activity.By similarity

Sequence similaritiesi

Contains 1 RWD domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IGD3. Eukaryota.
ENOG4111KZ9. LUCA.
GeneTreeiENSGT00390000000954.
HOVERGENiHBG057524.
InParanoidiQ9Y3V2.
OMAiQLTRAQC.
OrthoDBiEOG091G0OZC.
PhylomeDBiQ9Y3V2.
TreeFamiTF324344.

Family and domain databases

Gene3Di3.10.110.10. 1 hit.
InterProiIPR006575. RWD-domain.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]
PfamiPF05773. RWD. 1 hit.
[Graphical view]
SMARTiSM00591. RWD. 1 hit.
[Graphical view]
SUPFAMiSSF54495. SSF54495. 1 hit.
PROSITEiPS50908. RWD. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9Y3V2-1) [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
MAEPVQEELS VLAAIFCRPH EWEVLSRSET DGTVFRIHTK AEGFMDVDIP
60 70 80 90 100
LELVFHLPVN YPSCLPGISI NSEQLTRAQC VTVKENLLEQ AESLLSEPMV
110 120 130 140 150
HELVLWIQQN LRHILSQPET GSGSEKCTFS TSTTMDDGLW ITLLHLDHMR
160 170 180 190 200
AKTKYVKIVE KWASDLRLTG RLMFMGKIIL ILLQGDRNNL KEYLILQKTS
210 220 230 240 250
KVDVDSSGKK CKEKMISVLF ETKVQTEHKR FLAFEVKEYS ALDELQKEFE
260
TAGLKKLFSE FVLALVK
Length:267
Mass (Da):30,543
Last modified:May 18, 2010 - v4
Checksum:i00F6892F29A57CA7
GO
Isoform 2 (identifier: Q9Y3V2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     192-195: EYLI → VPKS
     196-267: Missing.

Show »
Length:195
Mass (Da):22,154
Checksum:iD46523537F9E2BD9
GO
Isoform 3 (identifier: Q9Y3V2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: MAEPVQEELSVLAAIFCRPHEWEVLSRS → MFLSCGSLHQRGP
     177-267: KIILILLQGD...FSEFVLALVK → VLDSSENLQSRCGLKWKEMQREND

Show »
Length:185
Mass (Da):21,062
Checksum:iC048C80A699BC846
GO
Isoform 4 (identifier: Q9Y3V2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     177-267: KIILILLQGD...FSEFVLALVK → VLDSSENLQSRCGLKWKEMQREND

Show »
Length:200
Mass (Da):22,857
Checksum:i944D99E6BA3AE41C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti79Q → R in CAG38524 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03442047V → A.4 PublicationsCorresponds to variant rs259358dbSNPEnsembl.1
Natural variantiVAR_02434686N → K.4 PublicationsCorresponds to variant rs2296308dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0354111 – 28MAEPV…VLSRS → MFLSCGSLHQRGP in isoform 3. 1 PublicationAdd BLAST28
Alternative sequenceiVSP_035412177 – 267KIILI…LALVK → VLDSSENLQSRCGLKWKEMQ REND in isoform 3 and isoform 4. 1 PublicationAdd BLAST91
Alternative sequenceiVSP_034176192 – 195EYLI → VPKS in isoform 2. 4 Publications4
Alternative sequenceiVSP_034177196 – 267Missing in isoform 2. 4 PublicationsAdd BLAST72

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL050062 mRNA. Translation: CAB43254.2.
AK292665 mRNA. Translation: BAF85354.1.
AK292699 mRNA. Translation: BAF85388.1.
CR533493 mRNA. Translation: CAG38524.1.
AC092802 Genomic DNA. No translation available.
BC010936 mRNA. No translation available.
BC125142 mRNA. Translation: AAI25143.1.
CCDSiCCDS41357.1. [Q9Y3V2-1]
CCDS44177.1. [Q9Y3V2-2]
RefSeqiNP_001121614.1. NM_001128142.1.
NP_001265176.1. NM_001278247.1.
NP_001265177.1. NM_001278248.1.
UniGeneiHs.483512.
Hs.709591.

Genome annotation databases

EnsembliENST00000263893; ENSP00000263893; ENSG00000122481. [Q9Y3V2-2]
ENST00000370202; ENSP00000359221; ENSG00000122481. [Q9Y3V2-1]
GeneIDi25950.
KEGGihsa:25950.
UCSCiuc001drf.5. human. [Q9Y3V2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL050062 mRNA. Translation: CAB43254.2.
AK292665 mRNA. Translation: BAF85354.1.
AK292699 mRNA. Translation: BAF85388.1.
CR533493 mRNA. Translation: CAG38524.1.
AC092802 Genomic DNA. No translation available.
BC010936 mRNA. No translation available.
BC125142 mRNA. Translation: AAI25143.1.
CCDSiCCDS41357.1. [Q9Y3V2-1]
CCDS44177.1. [Q9Y3V2-2]
RefSeqiNP_001121614.1. NM_001128142.1.
NP_001265176.1. NM_001278247.1.
NP_001265177.1. NM_001278248.1.
UniGeneiHs.483512.
Hs.709591.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EBKNMR-A1-121[»]
4Y1LX-ray2.70C2-113[»]
ProteinModelPortaliQ9Y3V2.
SMRiQ9Y3V2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117445. 6 interactors.
IntActiQ9Y3V2. 4 interactors.
MINTiMINT-4712049.
STRINGi9606.ENSP00000359221.

PTM databases

iPTMnetiQ9Y3V2.
PhosphoSitePlusiQ9Y3V2.

Polymorphism and mutation databases

BioMutaiRWDD3.
DMDMi296453018.

Proteomic databases

EPDiQ9Y3V2.
PaxDbiQ9Y3V2.
PeptideAtlasiQ9Y3V2.
PRIDEiQ9Y3V2.

Protocols and materials databases

DNASUi25950.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263893; ENSP00000263893; ENSG00000122481. [Q9Y3V2-2]
ENST00000370202; ENSP00000359221; ENSG00000122481. [Q9Y3V2-1]
GeneIDi25950.
KEGGihsa:25950.
UCSCiuc001drf.5. human. [Q9Y3V2-1]

Organism-specific databases

CTDi25950.
DisGeNETi25950.
GeneCardsiRWDD3.
HGNCiHGNC:21393. RWDD3.
HPAiHPA046146.
MIMi615875. gene.
neXtProtiNX_Q9Y3V2.
OpenTargetsiENSG00000122481.
PharmGKBiPA134974302.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGD3. Eukaryota.
ENOG4111KZ9. LUCA.
GeneTreeiENSGT00390000000954.
HOVERGENiHBG057524.
InParanoidiQ9Y3V2.
OMAiQLTRAQC.
OrthoDBiEOG091G0OZC.
PhylomeDBiQ9Y3V2.
TreeFamiTF324344.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000122481-MONOMER.
ReactomeiR-HSA-3065678. SUMO is transferred from E1 to E2 (UBE2I, UBC9).
SIGNORiQ9Y3V2.

Miscellaneous databases

EvolutionaryTraceiQ9Y3V2.
GeneWikiiRWDD3.
GenomeRNAii25950.
PROiQ9Y3V2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000122481.
CleanExiHS_RWDD3.
GenevisibleiQ9Y3V2. HS.

Family and domain databases

Gene3Di3.10.110.10. 1 hit.
InterProiIPR006575. RWD-domain.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]
PfamiPF05773. RWD. 1 hit.
[Graphical view]
SMARTiSM00591. RWD. 1 hit.
[Graphical view]
SUPFAMiSSF54495. SSF54495. 1 hit.
PROSITEiPS50908. RWD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRWDD3_HUMAN
AccessioniPrimary (citable) accession number: Q9Y3V2
Secondary accession number(s): A6NP44
, A8K9F0, C9J9L7, C9JI45, Q08AJ7, Q6FID3, Q9BX35
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: May 18, 2010
Last modified: November 30, 2016
This is version 125 of the entry and version 4 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.