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Protein

Roquin-1

Gene

Rc3h1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 and in many more mRNAs (PubMed:23663784). 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 (PubMed:26000482). Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs. In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4/Ox40 expression, thus preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity. In resting or LPS-stimulated macrophages, controls inflammation by suppressing TNF expression. Also recognizes CDE in its own mRNA and in that of paralogous RC3H2, possibly leading to feedback loop regulation.8 Publications

Regions

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

GO - Molecular functioni

  • mRNA 3'-UTR binding Source: UniProtKB
  • mRNA binding Source: MGI
  • poly(A) RNA binding Source: MGI
  • RNA stem-loop binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • 3'-UTR-mediated mRNA destabilization Source: UniProtKB
  • B cell homeostasis Source: MGI
  • cellular response to interleukin-1 Source: UniProtKB
  • cytoplasmic mRNA processing body assembly Source: BHF-UCL
  • lymph node development Source: MGI
  • negative regulation of activated T cell proliferation Source: BHF-UCL
  • negative regulation of B cell proliferation Source: BHF-UCL
  • negative regulation of germinal center formation Source: BHF-UCL
  • negative regulation of T-helper cell differentiation Source: MGI
  • nuclear-transcribed mRNA catabolic process Source: BHF-UCL
  • nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source: UniProtKB
  • positive regulation of mRNA catabolic process Source: UniProtKB
  • positive regulation of NIK/NF-kappaB signaling Source: MGI
  • posttranscriptional regulation of gene expression Source: BHF-UCL
  • regulation of gene expression Source: MGI
  • regulation of germinal center formation Source: BHF-UCL
  • regulation of mRNA stability Source: BHF-UCL
  • regulation of T cell receptor signaling pathway Source: BHF-UCL
  • spleen development Source: MGI
  • T cell homeostasis Source: MGI
  • T cell proliferation Source: MGI
  • T follicular helper cell differentiation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Ligandi

Metal-binding, RNA-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Roquin-1
Short name:
Roquin
Alternative name(s):
Protein Sanroque
RING finger and C3H zinc finger protein 1
RING finger and CCCH-type zinc finger domain-containing protein 1
Gene namesi
Name:Rc3h1
Synonyms:Gm551, Kiaa2025
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:2685397. Rc3h1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytoplasmic mRNA processing body Source: UniProtKB
  • cytoplasmic stress granule Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Mutant animals are born at Mendelian ratio, but die within 6 hours after birth. They displayed a curly tail and malformations of the caudal spinal column. Lethality can be rescued by changing the genetic background from C57BL/6 to outbred CD1, which allows about 4% of the animals to survive to adulthood. These animals display enlarged spleens with a trend toward increased numbers of eosinophils and monocytic/macrophage populations, dramatic and selective expansion of CD8+ effector-like T-cells. Splenic follicular organization is normal, and the numbers of CD4+ T-cell subtypes and B-cells are not significantly altered. No spontaneous germinal center formation, autoantibody production, nor autoimmune tissue damage. Ablation of Rc3h1 gene in the T lineage leads to elevated ICOS levels and expansion of effector CD8+ T-cells, but not autoimmunity (PubMed:21844204). Mice lacking both Rc3h1 and Rc3h2 genes in CD4+ T-cells develop lymphadenopathy and splenomegaly with increased spleen weight and cellularity, already at young age (PubMed:23583643). These data suggest that RC3H1 and RC3H2 may have a redundant function in mRNA repression.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi14C → A: No effect on localization to stress granules. 1 Publication1
Mutagenesisi199M → R in sanroque; partial loss of ICOS regulation, no effect on localization to stress granules, no effect on RNA-binding. 2 Publications1
Mutagenesisi419C → R: No effect on RNA-binding. 1 Publication1
Mutagenesisi434C → R: No effect on localization to stress granules, reduces RNA-binding. 1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000559661 – 1130Roquin-1Add BLAST1130

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei462PhosphoserineBy similarity1
Modified residuei531PhosphoserineCombined sources1
Modified residuei535PhosphoserineCombined sources1
Modified residuei861PhosphoserineBy similarity1
Modified residuei1107PhosphoserineCombined sources1
Modified residuei1110PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ4VGL6.
MaxQBiQ4VGL6.
PaxDbiQ4VGL6.
PRIDEiQ4VGL6.

PTM databases

iPTMnetiQ4VGL6.
PhosphoSitePlusiQ4VGL6.

Expressioni

Tissue specificityi

Widely expressed, with highest levels in lymph node and thymus and slightly lesser amounts in brain, lung, and spleen (at protein level). Very weak expression in heart, muscle, and kidney (at protein level). Expressed in CD4+ helper T-cells (at protein level).2 Publications

Gene expression databases

BgeeiENSMUSG00000040423.
CleanExiMM_RC3H1.
ExpressionAtlasiQ4VGL6. baseline and differential.
GenevisibleiQ4VGL6. MM.

Interactioni

Subunit structurei

Interacts with DDX6 and EDC4. Interacts with CCR4-NOT deadenylase complex.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Ago2Q8CJG02EBI-2366263,EBI-528299
Edc4Q3UJB93EBI-2366263,EBI-2553526

Protein-protein interaction databases

BioGridi237867. 5 interactors.
IntActiQ4VGL6. 54 interactors.
MINTiMINT-7711141.
STRINGi10090.ENSMUSP00000124871.

Structurei

Secondary structure

11130
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni15 – 17Combined sources3
Beta strandi23 – 26Combined sources4
Beta strandi28 – 30Combined sources3
Beta strandi36 – 38Combined sources3
Helixi39 – 45Combined sources7
Beta strandi47 – 49Combined sources3
Turni51 – 53Combined sources3
Turni60 – 63Combined sources4
Helixi68 – 71Combined sources4
Turni72 – 74Combined sources3
Helixi90 – 107Combined sources18
Helixi108 – 110Combined sources3
Helixi131 – 141Combined sources11
Helixi148 – 170Combined sources23
Helixi176 – 189Combined sources14
Helixi197 – 211Combined sources15
Beta strandi216 – 218Combined sources3
Helixi219 – 230Combined sources12
Turni231 – 233Combined sources3
Helixi239 – 251Combined sources13
Beta strandi255 – 260Combined sources6
Beta strandi263 – 269Combined sources7
Helixi271 – 273Combined sources3
Helixi276 – 293Combined sources18
Helixi300 – 308Combined sources9
Beta strandi309 – 312Combined sources4
Helixi314 – 324Combined sources11
Helixi329 – 343Combined sources15
Helixi350 – 353Combined sources4
Helixi354 – 361Combined sources8
Helixi374 – 397Combined sources24

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4QI0X-ray1.94A/B147-326[»]
4QI2X-ray3.00A/B/C/D147-326[»]
4TXAX-ray2.75A1-484[»]
5F5FX-ray3.00A/C/E/G171-360[»]
5F5HX-ray2.23A/B147-326[»]
ProteinModelPortaliQ4VGL6.
SMRiQ4VGL6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni181 – 232ROQAdd BLAST52

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi533 – 786Pro-richAdd BLAST254

Domaini

The RING-type zinc finger may be required for proper localization to stress granules, but not to P-bodies.1 Publication
The ROQ region may be required for CDE RNA-binding (PubMed:23663784). It may also be involved in localization to stress granules (PubMed:20412057).3 Publications

Sequence similaritiesi

Contains 1 C3H1-type zinc finger.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

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.
HOGENOMiHOG000232030.
HOVERGENiHBG080524.
InParanoidiQ4VGL6.
KOiK15690.
OMAiICTQTFD.
OrthoDBiEOG091G02I2.
PhylomeDBiQ4VGL6.
TreeFamiTF317698.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
4.10.1000.10. 1 hit.
InterProiIPR032671. RC3H1.
IPR027370. Znf-RING_LisH.
IPR000571. Znf_CCCH.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERiPTHR13139:SF6. PTHR13139:SF6. 1 hit.
PfamiPF00642. zf-CCCH. 1 hit.
PF13445. zf-RING_UBOX. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
SM00356. ZnF_C3H1. 1 hit.
[Graphical view]
SUPFAMiSSF90229. SSF90229. 1 hit.
PROSITEiPS50103. ZF_C3H1. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q4VGL6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPVQAPQWTD FLSCPICTQT FDETIRKPIS LGCGHTVCKM CLNKLHRKAC
60 70 80 90 100
PFDQTTINTD IELLPVNSAL LQLVGAQIPE 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 LPSAPILSDE SAVDLSNRKP PALPNGIASS
510 520 530 540 550
GSTVTQLIPR GTDPSFDSSL KPVKLDHLSS SAPGSPPDLL ESAPKSISAL
560 570 580 590 600
PVNPHPVPPR GPTDLPPMPV TKPIQMVPRG SQLYPAQQAD VYYQDPRGSA
610 620 630 640 650
PAFETAPYQQ GMYYTPPPCV SRFVRPPPSA PEPGPPYLDH YSPYLQDRVI
660 670 680 690 700
NSQYGTQPQQ YPPMYPAHYD GRRVYPAQSY TREEMFRESP IPIDIPSAAV
710 720 730 740 750
PSYVPESRER YQQVEGYYPV APHPAQIRPS YPRDPPYSRL PPPQPHPSLD
760 770 780 790 800
ELHRRRKEIM AQLEERKVIS PPPFAPSPTL PPAFHPEEFL DEDLKVAGKY
810 820 830 840 850
KANDYSQYSP WSCDTIGSYI GTKDAKPKDV VAAGSVEMMN VESKGTREQR
860 870 880 890 900
LDLQRRAVET SDDDLIPFGD RPTVSRFGAI SRTSKTLYQG AGPLQAIAPQ
910 920 930 940 950
GAPTKSINIS DYSAYGAHGG WGDSPYSPHA NIPPQGHFIE REKMSMAEVA
960 970 980 990 1000
SHGKPLLSAE REQLRLELQQ LNHQISQQTQ LRGLEAVSNR LVLQREVNTL
1010 1020 1030 1040 1050
ASQPQPPQLP PKWPGMISSE QLSLELHQVE REIGKRTREL SMENQCSVDM
1060 1070 1080 1090 1100
KSKLGTSKQA ENGQPEPQNK IRTEDLTLTF SDVPNGSALT QENLSLLSNK
1110 1120 1130
TSSLNLSEDS EGGGDNNDSQ RSGVVSNSAP
Length:1,130
Mass (Da):125,378
Last modified:July 5, 2005 - v1
Checksum:i5B750E5D28FC86F2
GO

Sequence cautioni

The sequence BAD32613 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY948287 mRNA. Translation: AAY16368.1.
AK173335 mRNA. Translation: BAD32613.1. Different initiation.
BC138663 mRNA. Translation: AAI38664.1.
CCDSiCCDS15410.1.
RefSeqiNP_001020123.1. NM_001024952.2.
UniGeneiMm.329667.

Genome annotation databases

EnsembliENSMUST00000161609; ENSMUSP00000124871; ENSMUSG00000040423.
GeneIDi381305.
KEGGimmu:381305.
UCSCiuc007del.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY948287 mRNA. Translation: AAY16368.1.
AK173335 mRNA. Translation: BAD32613.1. Different initiation.
BC138663 mRNA. Translation: AAI38664.1.
CCDSiCCDS15410.1.
RefSeqiNP_001020123.1. NM_001024952.2.
UniGeneiMm.329667.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4QI0X-ray1.94A/B147-326[»]
4QI2X-ray3.00A/B/C/D147-326[»]
4TXAX-ray2.75A1-484[»]
5F5FX-ray3.00A/C/E/G171-360[»]
5F5HX-ray2.23A/B147-326[»]
ProteinModelPortaliQ4VGL6.
SMRiQ4VGL6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi237867. 5 interactors.
IntActiQ4VGL6. 54 interactors.
MINTiMINT-7711141.
STRINGi10090.ENSMUSP00000124871.

PTM databases

iPTMnetiQ4VGL6.
PhosphoSitePlusiQ4VGL6.

Proteomic databases

EPDiQ4VGL6.
MaxQBiQ4VGL6.
PaxDbiQ4VGL6.
PRIDEiQ4VGL6.

Protocols and materials databases

DNASUi381305.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000161609; ENSMUSP00000124871; ENSMUSG00000040423.
GeneIDi381305.
KEGGimmu:381305.
UCSCiuc007del.2. mouse.

Organism-specific databases

CTDi149041.
MGIiMGI:2685397. Rc3h1.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG3161. Eukaryota.
ENOG410YWQD. LUCA.
GeneTreeiENSGT00390000004311.
HOGENOMiHOG000232030.
HOVERGENiHBG080524.
InParanoidiQ4VGL6.
KOiK15690.
OMAiICTQTFD.
OrthoDBiEOG091G02I2.
PhylomeDBiQ4VGL6.
TreeFamiTF317698.

Miscellaneous databases

PROiQ4VGL6.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000040423.
CleanExiMM_RC3H1.
ExpressionAtlasiQ4VGL6. baseline and differential.
GenevisibleiQ4VGL6. MM.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
4.10.1000.10. 1 hit.
InterProiIPR032671. RC3H1.
IPR027370. Znf-RING_LisH.
IPR000571. Znf_CCCH.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERiPTHR13139:SF6. PTHR13139:SF6. 1 hit.
PfamiPF00642. zf-CCCH. 1 hit.
PF13445. zf-RING_UBOX. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
SM00356. ZnF_C3H1. 1 hit.
[Graphical view]
SUPFAMiSSF90229. SSF90229. 1 hit.
PROSITEiPS50103. ZF_C3H1. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRC3H1_MOUSE
AccessioniPrimary (citable) accession number: Q4VGL6
Secondary accession number(s): B2RS13, Q69Z31
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: July 5, 2005
Last modified: November 2, 2016
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Treatment of C57BL/6 males with ethylnitrosourea led to the identification of the sanroque mouse strain. The causative mutation in sanroque appears to be RC3H1 Arg-199. Homozygous sanroque mice develop high titers of autoantibodies and display excessive numbers of follicular helper T-cells and germinal centers with pattern of pathology consistent with lupus (PubMed:15917799). Sanroque mice reproducibly develop intestinal inflammation in the small intestine but not the colon. Extensive cytokine dysregulation resulting in both over-expression and under-expression of chemotactic cytokines occurs in the ileum, the region most prone to the development of inflammation in sanroque mice (PubMed:23451046). The lack of compensation of RC3H1 defects by the RC3H2 paralog in sanroque mice may be due to the fact that the mutated protein may retain its scaffolding position within RNA granules, preventing RC3H2 to access mRNAs to be regulated (PubMed:23583642).3 Publications
The RING finger is highly conserved among the paralogs and among species, suggesting it may possess E3 ubiquitin ligase activity. A C. elegans homolog, rle-1, is involved in daf-16 ubiquitin-dependent degradation. Although such an activity has not be observed in mammalian cells so far, it is conceivable that RC3H1 may utilize E3 ubiquitin ligase activity in the promotion of mRNA decay (PubMed:23550652).1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  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.