Q14011 (CIRBP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cold-inducible RNA-binding protein

Alternative name(s):
A18 hnRNP
Glycine-rich RNA-binding protein CIRP

Gene names

Name:	CIRBP
Synonyms:	A18HNRNP, CIRP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	172 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.5 Ref.7
Subunit structure	Interacts with EIF4G1. Associates with ribosomes. Ref.7
Subcellular location	Nucleus › nucleoplasm. Cytoplasm. 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. Ref.5
Tissue specificity	Ubiquitous.
Induction	By cold stress in response to DNA damage induced by UV irradiation or UV mimetic agents. Up-regulated by hypoxia. Ref.6
Domain	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.
Post-translational modification	Methylated on arginine residues. Methylation of the RGG motifs is a prerequisite for recruitment into SGs 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. Ref.7
Sequence similarities	Contains 1 RRM (RNA recognition motif) domain.

Ontologies

Keywords
Biological process	Stress response
Cellular component	Cytoplasm Nucleus
Ligand	RNA-binding
Molecular function	Activator Repressor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	mRNA stabilization Inferred from direct assay Ref.5. Source: UniProtKB positive regulation of translation Inferred from direct assay Ref.5. Source: UniProtKB response to UV Inferred from direct assay Ref.5. Source: UniProtKB response to cold Traceable author statement. Source: ProtInc stress granule assembly Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytoplasmic stress granule Inferred from sequence or structural similarity. Source: UniProtKB nucleoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	SSU rRNA binding Inferred from direct assay Ref.5. Source: UniProtKB mRNA 3'-UTR binding Inferred from direct assay Ref.5Ref.7. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction Ref.7. Source: UniProtKB translation repressor activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 172

172

Cold-inducible RNA-binding protein

PRO_0000081503

Regions

Domain

6 – 84

79

RRM

Compositional bias

92 – 158

67

Gly-rich

Secondary structure

1

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172

Helix Strand Turn

Details...

Beta strand

6 – 12

7

Helix

19 – 29

11

Beta strand

34 – 37

4

Beta strand

41 – 43

3

Beta strand

48 – 53

6

Helix

57 – 67

11

Beta strand

78 – 83

6

Sequences

	Sequence		Length	Mass (Da)
	Q14011 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 003FABF28F5405D0	FASTA	172	18,648
	10 20 30 40 50 60 MASDEGKLFV GGLSFDTNEQ SLEQVFSKYG QISEVVVVKD RETQRSRGFG FVTFENIDDA 70 80 90 100 110 120 KDAMMAMNGK SVDGRQIRVD QAGKSSDNRS RGYRGGSAGG RGFFRGGRGR GRGFSRGGGD 130 140 150 160 170 RGYGGNRFES RSGGYGGSRD YYSSRSQSGG YSDRSSGGSY RDSYDSYATH NE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of human CIRP (cold-inducible RNA-binding protein) cDNA and chromosomal assignment of the gene." Nishiyama H., Higashitsuji H., Yokoi H., Itoh K., Danno S., Matsuda T., Fujita J. Gene 204:115-120(1997) [PubMed: 9434172] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Identification of several human homologs of hamster DNA damage-inducible transcripts. Cloning and characterization of a novel UV-inducible cDNA that codes for a putative RNA-binding protein." Sheikh M.S., Carrier F., Papathanasiou M.A., Hollander M.C., Zhan Q., Yu K., Fornace A.J. Jr. J. Biol. Chem. 272:26720-26726(1997) [PubMed: 9334257] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung and Placenta.
[5]	"The UV-inducible RNA-binding protein A18 (A18 hnRNP) plays a protective role in the genotoxic stress response." Yang C., Carrier F. J. Biol. Chem. 276:47277-47284(2001) [PubMed: 11574538] [Abstract] Cited for: FUNCTION, RNA-BINDING, SUBCELLULAR LOCATION.
[6]	"Oxygen-regulated expression of the RNA-binding proteins RBM3 and CIRP by a HIF-1-independent mechanism." Wellmann S., Buehrer C., Moderegger E., Zelmer A., Kirschner R., Koehne P., Fujita J., Seeger K. J. Cell Sci. 117:1785-1794(2004) [PubMed: 15075239] [Abstract] Cited for: INDUCTION BY HYPOXIA.
[7]	"Post-transcriptional regulation of thioredoxin by the stress inducible heterogenous ribonucleoprotein A18." Yang R., Weber D.J., Carrier F. Nucleic Acids Res. 34:1224-1236(2006) [PubMed: 16513844] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, RNA-BINDING, INTERACTION WITH EIF4G1, ASSOCIATION WITH RIBOSOMES.
[8]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"Solution structure of RRM domain in A18 HNRNP." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 1-90.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D78134 mRNA. Translation: BAA11212.1.
AF021336 mRNA. Translation: AAC51787.1.
AC004258 Genomic DNA. Translation: AAC04895.1.
BC000403 mRNA. Translation: AAH00403.1.
BC000901 mRNA. Translation: AAH00901.1.

IPI

IPI00641579.

RefSeq

NP_001271.1. NM_001280.2.

UniGene

Hs.618145.
Hs.634522.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1X5S	NMR	-	A	1-89	[»]

ProteinModelPortal

Q14011.

SMR

Q14011. Positions 1-90.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q14011. 8 interactions.

MINT

MINT-5004534.

STRING

Q14011.

PTM databases

PhosphoSite

Q14011.

Polymorphism databases

DMDM

5921786.

2D gel databases

REPRODUCTION-2DPAGE

IPI00180954.

Proteomic databases

PRIDE

Q14011.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000320936; ENSP00000322887; ENSG00000099622.

GeneID

1153.

KEGG

hsa:1153.

UCSC

uc002lrr.2. human.

Organism-specific databases

CTD

1153.

GeneCards

GC19P001269.

H-InvDB

HIX0014577.

HGNC

HGNC:1982. CIRBP.

MIM

602649. gene.

neXtProt

NX_Q14011.

PharmGKB

PA26519.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG21015.

HOVERGEN

HBG107480.

InParanoid

Q14011.

OMA

AGKSSEN.

OrthoDB

EOG4HHP40.

PhylomeDB

Q14011.

Gene expression databases

ArrayExpress

Q14011.

Bgee

Q14011.

CleanEx

HS_CIRBP.

Genevestigator

Q14011.

GermOnline

ENSG00000099622. Homo sapiens.

Family and domain databases

InterPro

IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]

Gene3D

G3DSA:3.30.70.330. a_b_plait_nuc_bd. 1 hit.

KO

K13195.

Pfam

PF00076. RRM_1. 1 hit.
[Graphical view]

SMART

SM00360. RRM. 1 hit.
[Graphical view]

PROSITE

PS50102. RRM. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

4788.

SOURCE

Search...

Entry information

Entry name

CIRBP_HUMAN

Accession

Primary (citable) accession number: Q14011

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.