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Protein

Roquin-1

Gene

RC3H1

Organism
Homo sapiens (Human)
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 (By similarity). 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).By similarity

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: BHF-UCL
  • poly(A) RNA binding Source: UniProtKB
  • RNA stem-loop binding Source: UniProtKB
  • ubiquitin protein ligase activity Source: BHF-UCL
  • zinc ion binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

Metal-binding, RNA-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Roquin-1
Short name:
Roquin
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:RC3H1
Synonyms:KIAA2025, RNF198
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:29434. RC3H1.

Subcellular locationi

  • CytoplasmP-body By similarity
  • Cytoplasmic granule By similarity

  • Note: During stress, such as that induced by arsenite treatment, localizes to cytosolic stress granules (By similarity). Localization to stress granules, but not to P-bodies, depends upon the RING-type zinc finger (By similarity). ICOS repression may correlate with the localization to P-bodies, not to stress granules (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ5TC82.
MaxQBiQ5TC82.
PaxDbiQ5TC82.
PeptideAtlasiQ5TC82.
PRIDEiQ5TC82.

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.
CleanExiHS_RC3H1.
GenevisibleiQ5TC82. HS.

Organism-specific databases

HPAiHPA027428.
HPA027434.
HPA027448.

Interactioni

Subunit structurei

Interacts with DDX6 and EDC4. Interacts with CCR4-NOT deadenylase complex.By similarity

Protein-protein interaction databases

BioGridi127186. 18 interactors.
IntActiQ5TC82. 5 interactors.
MINTiMINT-2809509.
STRINGi9606.ENSP00000258349.

Structurei

Secondary structure

11133
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi92 – 108Combined sources17
Turni112 – 115Combined sources4
Beta strandi119 – 121Combined sources3
Helixi122 – 124Combined sources3
Beta strandi127 – 129Combined sources3
Helixi131 – 142Combined sources12
Helixi148 – 173Combined sources26
Turni176 – 178Combined sources3
Helixi179 – 189Combined sources11
Helixi197 – 211Combined sources15
Beta strandi216 – 218Combined sources3
Helixi219 – 233Combined sources15
Helixi239 – 251Combined sources13
Beta strandi255 – 258Combined sources4
Beta strandi266 – 269Combined sources4
Helixi271 – 273Combined sources3
Helixi276 – 293Combined sources18
Helixi300 – 308Combined sources9
Beta strandi309 – 312Combined sources4
Helixi314 – 325Combined sources12
Helixi329 – 342Combined sources14
Turni343 – 345Combined sources3
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
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...

Family & Domainsi

Region

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

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. It may also be involved in localization to stress granules.By similarity

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.
HOVERGENiHBG080524.
InParanoidiQ5TC82.
KOiK15690.
OMAiICTQTFD.
OrthoDBiEOG091G02I2.
PhylomeDBiQ5TC82.
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]

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.Curated
The sequence CAH70709 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAH70710 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAI19417 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAI19419 differs from that shown. Reason: Erroneous initiation.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, AL136170 Genomic DNA. Translation: CAH70709.1. Different initiation.
AL121983, AL136170 Genomic DNA. Translation: CAH70710.1. Different initiation.
AL136170, AL121983 Genomic DNA. Translation: CAI19417.1. Different initiation.
AL136170, AL121983 Genomic DNA. Translation: CAI19419.1. Different initiation.
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

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, AL136170 Genomic DNA. Translation: CAH70709.1. Different initiation.
AL121983, AL136170 Genomic DNA. Translation: CAH70710.1. Different initiation.
AL136170, AL121983 Genomic DNA. Translation: CAI19417.1. Different initiation.
AL136170, AL121983 Genomic DNA. Translation: CAI19419.1. Different initiation.
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. 18 interactors.
IntActiQ5TC82. 5 interactors.
MINTiMINT-2809509.
STRINGi9606.ENSP00000258349.

PTM databases

iPTMnetiQ5TC82.
PhosphoSitePlusiQ5TC82.

Polymorphism and mutation databases

BioMutaiRC3H1.
DMDMi73621450.

Proteomic databases

EPDiQ5TC82.
MaxQBiQ5TC82.
PaxDbiQ5TC82.
PeptideAtlasiQ5TC82.
PRIDEiQ5TC82.

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.
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.
OMAiICTQTFD.
OrthoDBiEOG091G02I2.
PhylomeDBiQ5TC82.
TreeFamiTF317698.

Miscellaneous databases

ChiTaRSiRC3H1. human.
GenomeRNAii149041.
PROiQ5TC82.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135870.
CleanExiHS_RC3H1.
GenevisibleiQ5TC82. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q5TC82
Secondary accession number(s): B3KVK1
, Q5W180, Q5W181, Q8IVE6, Q8N9V1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: December 21, 2004
Last modified: November 2, 2016
This is version 113 of the entry and version 1 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

Miscellaneous

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. 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.