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Protein

Cold-inducible RNA-binding protein

Gene

CIRBP

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

Functioni

Cold-inducible mRNA binding protein that plays a protective role in the genotoxic stress response by stabilizing transcripts of genes involved in cell survival. Acts as a translational activator. Seems to play an essential role in cold-induced suppression of cell proliferation. Binds specifically to the 3'-untranslated regions (3'-UTRs) of stress-responsive transcripts RPA2 and TXN. Acts as a translational repressor (By similarity). Promotes assembly of stress granules (SGs), when overexpressed.By similarity2 Publications

GO - Molecular functioni

  • mRNA 3'-UTR binding Source: UniProtKB
  • nucleotide binding Source: InterPro
  • poly(A) RNA binding Source: UniProtKB
  • small ribosomal subunit rRNA binding Source: UniProtKB
  • translation repressor activity Source: UniProtKB

GO - Biological processi

  • mRNA stabilization Source: UniProtKB
  • positive regulation of translation Source: UniProtKB
  • response to cold Source: ProtInc
  • response to UV Source: UniProtKB
  • stress granule assembly Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Stress response

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000099622-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Cold-inducible RNA-binding protein
Alternative name(s):
A18 hnRNP
Glycine-rich RNA-binding protein CIRP
Gene namesi
Name:CIRBP
Synonyms:A18HNRNP, CIRP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:1982. CIRBP.

Subcellular locationi

  • Nucleusnucleoplasm 1 Publication
  • Cytoplasm 1 Publication

  • Note: Translocates from the nucleus to the cytoplasm after exposure to UV radiation. Translocates from the nucleus to the cytoplasm into stress granules upon various cytoplasmic stresses, such as osmotic and heat shocks. Its recruitment into stress granules occurs in the absence of TIAR proteins (By similarity).By similarity

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytoplasmic stress granule Source: UniProtKB
  • nucleolus Source: HPA
  • nucleoplasm Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi1153.
OpenTargetsiENSG00000099622.
PharmGKBiPA26519.

Polymorphism and mutation databases

BioMutaiCIRBP.
DMDMi5921786.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000815031 – 172Cold-inducible RNA-binding proteinAdd BLAST172

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei130PhosphoserineCombined sources1
Modified residuei138PhosphoserineCombined sources1
Modified residuei146PhosphoserineCombined sources1
Modified residuei156PhosphoserineCombined sources1
Modified residuei159PhosphoserineCombined sources1
Modified residuei163PhosphoserineCombined sources1

Post-translational modificationi

Methylated on arginine residues. Methylation of the RGG motifs is a prerequisite for recruitment into SGs (By similarity).By similarity
Phosphorylated by CK2, GSK3A and GSK3B. Phosphorylation by GSK3B increases RNA-binding activity to the TXN 3'-UTR transcript upon exposure to UV radiation.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ14011.
PaxDbiQ14011.
PeptideAtlasiQ14011.
PRIDEiQ14011.

2D gel databases

REPRODUCTION-2DPAGEIPI00180954.

PTM databases

iPTMnetiQ14011.
PhosphoSitePlusiQ14011.

Expressioni

Tissue specificityi

Ubiquitous.

Inductioni

By cold stress in response to DNA damage induced by UV irradiation or UV mimetic agents. Up-regulated by hypoxia.1 Publication

Gene expression databases

BgeeiENSG00000099622.
CleanExiHS_CIRBP.
ExpressionAtlasiQ14011. baseline and differential.
GenevisibleiQ14011. HS.

Organism-specific databases

HPAiHPA067579.

Interactioni

Subunit structurei

Interacts with EIF4G1. Associates with ribosomes.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
HNRNPKP619785EBI-538850,EBI-304185
HNRPKQ6IBN13EBI-538850,EBI-3440248
KHDRBS2Q5VWX13EBI-538850,EBI-742808
LNX1Q8TBB13EBI-538850,EBI-739832
RBMXP381594EBI-538850,EBI-743526
RBMY1A1P0DJD33EBI-538850,EBI-8638511
RBMY1JQ154153EBI-538850,EBI-8642021
SNRPAP090123EBI-538850,EBI-607085

Protein-protein interaction databases

BioGridi107573. 79 interactors.
IntActiQ14011. 34 interactors.
MINTiMINT-5004534.
STRINGi9606.ENSP00000322887.

Structurei

Secondary structure

1172
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi6 – 12Combined sources7
Helixi19 – 29Combined sources11
Beta strandi34 – 37Combined sources4
Beta strandi41 – 43Combined sources3
Beta strandi48 – 53Combined sources6
Helixi57 – 67Combined sources11
Beta strandi78 – 83Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X5SNMR-A1-89[»]
ProteinModelPortaliQ14011.
SMRiQ14011.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ14011.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini6 – 84RRMPROSITE-ProRule annotationAdd BLAST79

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi92 – 158Gly-richAdd BLAST67

Domaini

Both the RRM domain and the arginine, glycine (RGG) rich domain are necessary for binding to the TXN 3'-untranslated region. Both the RRM domain and the arginine, glycine (RGG) rich domain (RGG repeats) are necessary for optimal recruitment into SGs upon cellular stress. The C-terminal domain containing RGG repeats is necessary for translational repression (By similarity).By similarity

Sequence similaritiesi

Contains 1 RRM (RNA recognition motif) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0118. Eukaryota.
COG0724. LUCA.
GeneTreeiENSGT00710000106295.
HOGENOMiHOG000276232.
HOVERGENiHBG107480.
InParanoidiQ14011.
KOiK13195.
PhylomeDBiQ14011.

Family and domain databases

Gene3Di3.30.70.330. 1 hit.
InterProiIPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
IPR003954. RRM_dom_euk.
[Graphical view]
PfamiPF00076. RRM_1. 1 hit.
[Graphical view]
SMARTiSM00360. RRM. 1 hit.
SM00361. RRM_1. 1 hit.
[Graphical view]
SUPFAMiSSF54928. SSF54928. 1 hit.
PROSITEiPS50102. RRM. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q14011-1) [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
MASDEGKLFV GGLSFDTNEQ SLEQVFSKYG QISEVVVVKD RETQRSRGFG
60 70 80 90 100
FVTFENIDDA KDAMMAMNGK SVDGRQIRVD QAGKSSDNRS RGYRGGSAGG
110 120 130 140 150
RGFFRGGRGR GRGFSRGGGD RGYGGNRFES RSGGYGGSRD YYSSRSQSGG
160 170
YSDRSSGGSY RDSYDSYATH NE
Length:172
Mass (Da):18,648
Last modified:November 1, 1996 - v1
Checksum:i003FABF28F5405D0
GO
Isoform 2 (identifier: Q14011-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     83-116: Missing.
     167-167: Y → YGKSHSEGAT...PLHCACFLSS

Note: No experimental confirmation available.
Show »
Length:263
Mass (Da):28,359
Checksum:i448CFD5BB4EB08C5
GO
Isoform 3 (identifier: Q14011-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-69: MASDEGKLFV...AKDAMMAMNG → MSSRWSRSSQSTDRSL
     167-167: Y → YGKSHSEGAT...PLHCACFLSS

Note: No experimental confirmation available.
Show »
Length:244
Mass (Da):26,130
Checksum:iDAFAD25578042649
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0568951 – 69MASDE…MAMNG → MSSRWSRSSQSTDRSL in isoform 3. 1 PublicationAdd BLAST69
Alternative sequenceiVSP_05640283 – 116Missing in isoform 2. 1 PublicationAdd BLAST34
Alternative sequenceiVSP_056403167Y → YGKSHSEGATLLWPAVGARF TLVPSPSTLGWTLRPCHCAC PEEAHLSSQSHFYRRTQKPN ETDQKGKGERGPAGQSARCM CGRRPASLGCGGWLLPGRRP RPGLASGVKLPLVASVPLHC ACFLSS in isoform 2 and isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D78134 mRNA. Translation: BAA11212.1.
AF021336 mRNA. Translation: AAC51787.1.
AK094781 mRNA. Translation: BAG52929.1.
AK304470 mRNA. Translation: BAG65284.1.
AC004221 Genomic DNA. No translation available.
AC004258 Genomic DNA. Translation: AAC04895.1.
BC000403 mRNA. Translation: AAH00403.1.
BC000901 mRNA. Translation: AAH00901.1.
CCDSiCCDS12059.1. [Q14011-1]
RefSeqiNP_001271.1. NM_001280.2. [Q14011-1]
NP_001287744.1. NM_001300815.1.
NP_001287758.1. NM_001300829.1.
XP_006722700.1. XM_006722637.1. [Q14011-1]
UniGeneiHs.618145.
Hs.634522.

Genome annotation databases

EnsembliENST00000320936; ENSP00000322887; ENSG00000099622. [Q14011-1]
ENST00000413636; ENSP00000412831; ENSG00000099622. [Q14011-2]
ENST00000585630; ENSP00000466110; ENSG00000099622. [Q14011-1]
ENST00000586472; ENSP00000465779; ENSG00000099622. [Q14011-1]
ENST00000588030; ENSP00000468788; ENSG00000099622. [Q14011-1]
ENST00000588090; ENSP00000466207; ENSG00000099622. [Q14011-1]
GeneIDi1153.
KEGGihsa:1153.
UCSCiuc010xgl.2. human. [Q14011-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D78134 mRNA. Translation: BAA11212.1.
AF021336 mRNA. Translation: AAC51787.1.
AK094781 mRNA. Translation: BAG52929.1.
AK304470 mRNA. Translation: BAG65284.1.
AC004221 Genomic DNA. No translation available.
AC004258 Genomic DNA. Translation: AAC04895.1.
BC000403 mRNA. Translation: AAH00403.1.
BC000901 mRNA. Translation: AAH00901.1.
CCDSiCCDS12059.1. [Q14011-1]
RefSeqiNP_001271.1. NM_001280.2. [Q14011-1]
NP_001287744.1. NM_001300815.1.
NP_001287758.1. NM_001300829.1.
XP_006722700.1. XM_006722637.1. [Q14011-1]
UniGeneiHs.618145.
Hs.634522.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X5SNMR-A1-89[»]
ProteinModelPortaliQ14011.
SMRiQ14011.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107573. 79 interactors.
IntActiQ14011. 34 interactors.
MINTiMINT-5004534.
STRINGi9606.ENSP00000322887.

PTM databases

iPTMnetiQ14011.
PhosphoSitePlusiQ14011.

Polymorphism and mutation databases

BioMutaiCIRBP.
DMDMi5921786.

2D gel databases

REPRODUCTION-2DPAGEIPI00180954.

Proteomic databases

EPDiQ14011.
PaxDbiQ14011.
PeptideAtlasiQ14011.
PRIDEiQ14011.

Protocols and materials databases

DNASUi1153.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000320936; ENSP00000322887; ENSG00000099622. [Q14011-1]
ENST00000413636; ENSP00000412831; ENSG00000099622. [Q14011-2]
ENST00000585630; ENSP00000466110; ENSG00000099622. [Q14011-1]
ENST00000586472; ENSP00000465779; ENSG00000099622. [Q14011-1]
ENST00000588030; ENSP00000468788; ENSG00000099622. [Q14011-1]
ENST00000588090; ENSP00000466207; ENSG00000099622. [Q14011-1]
GeneIDi1153.
KEGGihsa:1153.
UCSCiuc010xgl.2. human. [Q14011-1]

Organism-specific databases

CTDi1153.
DisGeNETi1153.
GeneCardsiCIRBP.
HGNCiHGNC:1982. CIRBP.
HPAiHPA067579.
MIMi602649. gene.
neXtProtiNX_Q14011.
OpenTargetsiENSG00000099622.
PharmGKBiPA26519.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0118. Eukaryota.
COG0724. LUCA.
GeneTreeiENSGT00710000106295.
HOGENOMiHOG000276232.
HOVERGENiHBG107480.
InParanoidiQ14011.
KOiK13195.
PhylomeDBiQ14011.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000099622-MONOMER.

Miscellaneous databases

ChiTaRSiCIRBP. human.
EvolutionaryTraceiQ14011.
GeneWikiiCIRBP.
GenomeRNAii1153.
PROiQ14011.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000099622.
CleanExiHS_CIRBP.
ExpressionAtlasiQ14011. baseline and differential.
GenevisibleiQ14011. HS.

Family and domain databases

Gene3Di3.30.70.330. 1 hit.
InterProiIPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
IPR003954. RRM_dom_euk.
[Graphical view]
PfamiPF00076. RRM_1. 1 hit.
[Graphical view]
SMARTiSM00360. RRM. 1 hit.
SM00361. RRM_1. 1 hit.
[Graphical view]
SUPFAMiSSF54928. SSF54928. 1 hit.
PROSITEiPS50102. RRM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCIRBP_HUMAN
AccessioniPrimary (citable) accession number: Q14011
Secondary accession number(s): B3KT17, B4E2X2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1996
Last modified: November 2, 2016
This is version 162 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: 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.