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Protein

Roquin-1

Gene

RC3H1

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

Functioni

Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF, TNFRSF4 and in many more mRNAs (PubMed:25026078). Cleaves translationally inactive mRNAs harboring a stem-loop (SL), often located in their 3'-UTRs, during the early phase of inflammation in a helicase UPF1-independent manner (By similarity). Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs (By similarity). In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4 expression, thus preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity (By similarity). In resting or LPS-stimulated macrophages, controls inflammation by suppressing TNF expression (By similarity). Also recognizes CDE in its own mRNA and in that of paralogous RC3H2, possibly leading to feedback loop regulation (By similarity). Recognizes and binds mRNAs containing an hexaloop stem-loop motif, called alternative decay element (ADE) (By similarity). Able to interact with double-stranded RNA (dsRNA) (PubMed:25504471, PubMed:25026078). miRNA-binding protein that regulates microRNA homeostasis. Enhances DICER-mediated processing of pre-MIR146a but reduces mature MIR146a levels through an increase of 3' end uridylation. Both inhibits ICOS mRNA expression and they may act together to exert the suppression (PubMed:25697406). Acts as a ubiquitin E3 ligase. Pairs with E2 enzymes UBE2A, UBE2B, UBE2D2, UBE2F, UBE2G1, UBE2G2 and UBE2L3 and produces polyubiquitin chains (PubMed:26489670). Show the strongest activity when paired with UBE2N:UBE2V1 or UBE2N:UBE2V2 E2 complexes and generate both short and long polyubiquitin chains (PubMed:26489670).By similarity4 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.1 Publication

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.1 Publication
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 bindingi14Zinc 1By similarity1
Metal bindingi17Zinc 1By similarity1
Metal bindingi33Zinc 2By similarity1
Metal bindingi35Zinc 2; via pros nitrogenBy similarity1
Metal bindingi38Zinc 1By similarity1
Metal bindingi50Zinc 2By similarity1
Metal bindingi53Zinc 2By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri14 – 54RING-type; degeneratePROSITE-ProRule annotationAdd BLAST41
Zinc fingeri413 – 441C3H1-typePROSITE-ProRule annotationAdd BLAST29

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionRNA-binding, Transferase
LigandMetal-binding, Zinc

Enzyme and pathway databases

UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Roquin-1Curated (EC:2.3.2.271 Publication)
Short name:
RoquinCurated
Alternative name(s):
RING finger and C3H zinc finger protein 1
RING finger and CCCH-type zinc finger domain-containing protein 1
RING finger protein 198
Gene namesi
Name:RC3H1Imported
Synonyms:KIAA2025, RNF198
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000135870.11
HGNCiHGNC:29434 RC3H1
MIMi609424 gene
neXtProtiNX_Q5TC82

Subcellular locationi

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi135 – 136RK → EE: No effect on CDE RNA-binding but abolishes dsRNA binding; when associated with E-164 or A-322-323-A. 1 Publication2
Mutagenesisi164R → E: No effect on CDE RNA-binding but abolishes dsRNA binding; when associated with 135-E-E-136. 1 Publication1
Mutagenesisi219 – 220RK → AA: Strongly decreases binding to RNA containing CDE stem-loop motifs. Abolishes binding to RNA containing CDE stem-loop motifs and dsRNA; when associated with 259-A-A-260. 1 Publication2
Mutagenesisi239 – 240KT → EA: Abolishes CDE RNA-binding but no effect on dsRNA binding. 1 Publication2
Mutagenesisi247 – 251QLLYR → ALLAE: Abolishes CDE RNA-binding but no effect on dsRNA binding. 1 Publication5
Mutagenesisi259 – 260KR → AA: Strongly decreases binding to RNA containing CDE stem-loop motifs. Abolishes binding to RNA containing CDE stem-loop motifs and dsRNA; when associated with 219-A-A-220. 1 Publication2
Mutagenesisi318 – 319QS → AA: Slightly reduces stem-loop RNA and dsRNA binding. 1 Publication2
Mutagenesisi322 – 323DK → AA: No effect on CDE RNA-binding but abolishes dsRNA binding; when associated with 135-E-E-136. 1 Publication2

Organism-specific databases

DisGeNETi149041
OpenTargetsiENSG00000135870
PharmGKBiPA142671090

Polymorphism and mutation databases

BioMutaiRC3H1
DMDMi73621450

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000559651 – 1133Roquin-1Add BLAST1133

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei462PhosphoserineCombined sources1
Modified residuei531PhosphoserineBy similarity1
Modified residuei535PhosphoserineCombined sources1
Modified residuei863PhosphoserineCombined sources1
Modified residuei1110PhosphoserineBy similarity1

Post-translational modificationi

Proteolytically cleaved after Arg-510 and Arg-579 by MALT1 in activated CD4+ T cells; cleavage at Arg-510 and Arg-579 is critical for promoting RC3H1 degradation in response to T-cell receptor (TCR) stimulation, and hence is necessary for prolonging the stability of a set of mRNAs controlling Th17 cell differentiation.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei510Cleavage; by MALT1By similarity1
Sitei579Cleavage; by MALT1By similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ5TC82
MaxQBiQ5TC82
PaxDbiQ5TC82
PeptideAtlasiQ5TC82
PRIDEiQ5TC82
ProteomicsDBi64943
64944 [Q5TC82-2]

PTM databases

iPTMnetiQ5TC82
PhosphoSitePlusiQ5TC82

Expressioni

Tissue specificityi

Widely expressed. Expressed at higher level in cerebellum, spleen, ovary and liver.1 Publication

Gene expression databases

BgeeiENSG00000135870 Expressed in 206 organ(s), highest expression level in gastrocnemius
CleanExiHS_RC3H1
GenevisibleiQ5TC82 HS

Organism-specific databases

HPAiHPA027428
HPA027434
HPA027448

Interactioni

Subunit structurei

Able to homodimerize (PubMed:25504471, PubMed:25026078, PubMed:25697406). Interacts with DDX6 and EDC4. Interacts with CCR4-NOT deadenylase complex (By similarity). Interacts with RC3H1; the interaction is RNA independent (PubMed:25697406).By similarity3 Publications

Protein-protein interaction databases

BioGridi127186, 174 interactors
IntActiQ5TC82, 6 interactors
MINTiQ5TC82
STRINGi9606.ENSP00000258349

Structurei

Secondary structure

11133
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ5TC82
SMRiQ5TC82
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni89 – 173HEPN-N1 PublicationAdd BLAST85
Regioni174 – 326ROQ2 PublicationsAdd BLAST153
Regioni327 – 396HEPN-C1 PublicationAdd BLAST70

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi533 – 788Pro-richAdd BLAST256

Domaini

The RING-type zinc finger is required for proper localization to stress granules, but not to P-bodies.By similarity
The ROQ region is required for CDE RNA-binding (PubMed:25504471, PubMed:25026078). Has 2 separate RNA-binding sites, one for CDE RNA and the other for dsRNA, both sites are important for mRNA decay (PubMed:25026078). ADE RNA-binding involves an extended binding surface on the ROQ region with a number of additional residues compared with the CDE RNA (By similarity). It may also be involved in localization to stress granules (By similarity).By similarity2 Publications
HEPN (higher eukaryotes and prokaryotes nucleotide-binding) are observed in both N- and C-terminal sides of ROQ domain with 3D structure even if they are poredcted on the basis of sequence.1 Publication

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri14 – 54RING-type; degeneratePROSITE-ProRule annotationAdd BLAST41
Zinc fingeri413 – 441C3H1-typePROSITE-ProRule annotationAdd BLAST29

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG3161 Eukaryota
ENOG410YWQD LUCA
GeneTreeiENSGT00390000004311
HOVERGENiHBG080524
InParanoidiQ5TC82
KOiK15690
OMAiMYPPHYD
OrthoDBiEOG091G02I2
PhylomeDBiQ5TC82
TreeFamiTF317698

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR032671 RC3H1
IPR027370 Znf-RING_LisH
IPR000571 Znf_CCCH
IPR036855 Znf_CCCH_sf
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR13139:SF6 PTHR13139:SF6, 1 hit
PfamiView protein in Pfam
PF00642 zf-CCCH, 1 hit
PF13445 zf-RING_UBOX, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
SM00356 ZnF_C3H1, 1 hit
SUPFAMiSSF90229 SSF90229, 1 hit
PROSITEiView protein in PROSITE
PS50103 ZF_C3H1, 1 hit
PS00518 ZF_RING_1, 1 hit
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: Q5TC82-1) [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
MPVQAPQWTD FLSCPICTQT FDETIRKPIS LGCGHTVCKM CLNKLHRKAC
60 70 80 90 100
PFDQTTINTD IELLPVNSAL LQLVGAQVPE QQPITLCSGV EDTKHYEEAK
110 120 130 140 150
KCVEELALYL KPLSSARGVG LNSTTQSVLS RPMQRKLVTL VHCQLVEEEG
160 170 180 190 200
RIRAMRAARS LGERTVTELI LQHQNPQQLS SNLWAAVRAR GCQFLGPAMQ
210 220 230 240 250
EEALKLVLLA LEDGSALSRK VLVLFVVQRL EPRFPQASKT SIGHVVQLLY
260 270 280 290 300
RASCFKVTKR DEDSSLMQLK EEFRTYEALR REHDSQIVQI AMEAGLRIAP
310 320 330 340 350
DQWSSLLYGD QSHKSHMQSI IDKLQTPASF AQSVQELTIA LQRTGDPANL
360 370 380 390 400
NRLRPHLELL ANIDPSPDAP PPTWEQLENG LVAVRTVVHG LVDYIQNHSK
410 420 430 440 450
KGADQQQPPQ HSKYKTYMCR DMKQRGGCPR GASCTFAHSQ EELEKFRKMN
460 470 480 490 500
KRLVPRRPLS ASLGQLNEVG LPSAAILPDE GAVDLPSRKP PALPNGIVST
510 520 530 540 550
GNTVTQLIPR GTDPSYDSSL KPGKIDHLSS SAPGSPPDLL ESVPKSISAL
560 570 580 590 600
PVNPHSIPPR GPADLPPMPV TKPLQMVPRG SQLYPAQQTD VYYQDPRGAA
610 620 630 640 650
PPFEPAPYQQ GMYYTPPPQC VSRFVRPPPS APEPAPPYLD HYPPYLQERV
660 670 680 690 700
VNSQYGTQPQ QYPPIYPSHY DGRRVYPAPS YTREEIFRES PIPIEIPPAA
710 720 730 740 750
VPSYVPESRE RYQQIESYYP VAPHPTQIRP SYLREPPYSR LPPPPQPHPS
760 770 780 790 800
LDELHRRRKE IMAQLEERKV ISPPPFAPSP TLPPTFHPEE FLDEDLKVAG
810 820 830 840 850
KYKGNDYSQY SPWSCDTIGS YIGTKDAKPK DVVAAGSVEM MNVESKGMRD
860 870 880 890 900
QRLDLQRRAA ETSDDDLIPF GDRPTVSRFG AISRTSKTIY QGAGPMQAMA
910 920 930 940 950
PQGAPTKSIN ISDYSPYGTH GGWGASPYSP HQNIPSQGHF SERERISMSE
960 970 980 990 1000
VASHGKPLPS AEREQLRLEL QQLNHQISQQ TQLRGLEAVS NRLVLQREAN
1010 1020 1030 1040 1050
TLAGQSQPPP PPPPKWPGMI SSEQLSLELH QVEREIGKRT RELSMENQCS
1060 1070 1080 1090 1100
LDMKSKLNTS KQAENGQPEP QNKVPAEDLT LTFSDVPNGS ALTQENISLL
1110 1120 1130
SNKTSSLNLS EDPEGGGDNN DSQRSGVTPS SAP
Length:1,133
Mass (Da):125,736
Last modified:December 21, 2004 - v1
Checksum:iE307838DF80A7099
GO
Isoform 2 (identifier: Q5TC82-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     988-996: Missing.
     1084-1084: S → SS

Note: No experimental confirmation available.
Show »
Length:1,125
Mass (Da):124,842
Checksum:iEFBE5179071DFA94
GO

Sequence cautioni

The sequence BAC04186 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti986L → P in BAC04186 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015015988 – 996Missing in isoform 2. 1 Publication9
Alternative sequenceiVSP_0150161084S → SS in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK093501 mRNA Translation: BAC04186.1 Different initiation.
AK122948 mRNA Translation: BAG53813.1
AL121983 Genomic DNA No translation available.
AL136170 Genomic DNA No translation available.
AB095945 mRNA Translation: BAC23121.1
CCDSiCCDS30940.1 [Q5TC82-1]
CCDS72987.1 [Q5TC82-2]
RefSeqiNP_001287779.1, NM_001300850.1
NP_001287780.1, NM_001300851.1 [Q5TC82-2]
NP_001287781.1, NM_001300852.1
NP_742068.1, NM_172071.3 [Q5TC82-1]
UniGeneiHs.30258

Genome annotation databases

EnsembliENST00000258349; ENSP00000258349; ENSG00000135870 [Q5TC82-1]
ENST00000367694; ENSP00000356667; ENSG00000135870 [Q5TC82-2]
ENST00000367696; ENSP00000356669; ENSG00000135870 [Q5TC82-1]
GeneIDi149041
KEGGihsa:149041
UCSCiuc001gju.5 human [Q5TC82-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK093501 mRNA Translation: BAC04186.1 Different initiation.
AK122948 mRNA Translation: BAG53813.1
AL121983 Genomic DNA No translation available.
AL136170 Genomic DNA No translation available.
AB095945 mRNA Translation: BAC23121.1
CCDSiCCDS30940.1 [Q5TC82-1]
CCDS72987.1 [Q5TC82-2]
RefSeqiNP_001287779.1, NM_001300850.1
NP_001287780.1, NM_001300851.1 [Q5TC82-2]
NP_001287781.1, NM_001300852.1
NP_742068.1, NM_172071.3 [Q5TC82-1]
UniGeneiHs.30258

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3X1OX-ray2.20A/B145-344[»]
4QIKX-ray1.90A/B88-407[»]
4QILX-ray2.90A/B88-407[»]
4ULWX-ray1.91A/B177-328[»]
4YWQX-ray1.70A/B159-328[»]
ProteinModelPortaliQ5TC82
SMRiQ5TC82
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127186, 174 interactors
IntActiQ5TC82, 6 interactors
MINTiQ5TC82
STRINGi9606.ENSP00000258349

PTM databases

iPTMnetiQ5TC82
PhosphoSitePlusiQ5TC82

Polymorphism and mutation databases

BioMutaiRC3H1
DMDMi73621450

Proteomic databases

EPDiQ5TC82
MaxQBiQ5TC82
PaxDbiQ5TC82
PeptideAtlasiQ5TC82
PRIDEiQ5TC82
ProteomicsDBi64943
64944 [Q5TC82-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000258349; ENSP00000258349; ENSG00000135870 [Q5TC82-1]
ENST00000367694; ENSP00000356667; ENSG00000135870 [Q5TC82-2]
ENST00000367696; ENSP00000356669; ENSG00000135870 [Q5TC82-1]
GeneIDi149041
KEGGihsa:149041
UCSCiuc001gju.5 human [Q5TC82-1]

Organism-specific databases

CTDi149041
DisGeNETi149041
EuPathDBiHostDB:ENSG00000135870.11
GeneCardsiRC3H1
HGNCiHGNC:29434 RC3H1
HPAiHPA027428
HPA027434
HPA027448
MIMi609424 gene
neXtProtiNX_Q5TC82
OpenTargetsiENSG00000135870
PharmGKBiPA142671090
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3161 Eukaryota
ENOG410YWQD LUCA
GeneTreeiENSGT00390000004311
HOVERGENiHBG080524
InParanoidiQ5TC82
KOiK15690
OMAiMYPPHYD
OrthoDBiEOG091G02I2
PhylomeDBiQ5TC82
TreeFamiTF317698

Enzyme and pathway databases

UniPathwayi
UPA00143

Miscellaneous databases

ChiTaRSiRC3H1 human
GenomeRNAii149041
PROiPR:Q5TC82
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135870 Expressed in 206 organ(s), highest expression level in gastrocnemius
CleanExiHS_RC3H1
GenevisibleiQ5TC82 HS

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR032671 RC3H1
IPR027370 Znf-RING_LisH
IPR000571 Znf_CCCH
IPR036855 Znf_CCCH_sf
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR13139:SF6 PTHR13139:SF6, 1 hit
PfamiView protein in Pfam
PF00642 zf-CCCH, 1 hit
PF13445 zf-RING_UBOX, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
SM00356 ZnF_C3H1, 1 hit
SUPFAMiSSF90229 SSF90229, 1 hit
PROSITEiView protein in PROSITE
PS50103 ZF_C3H1, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRC3H1_HUMAN
AccessioniPrimary (citable) accession number: Q5TC82
Secondary accession number(s): B3KVK1
, Q5W180, Q5W181, Q8IVE6, Q8N9V1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: December 21, 2004
Last modified: November 7, 2018
This is version 127 of the entry and version 1 of the sequence. See 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. 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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