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O00625 (PIR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pirin

EC=1.13.11.24
Alternative name(s):
Probable quercetin 2,3-dioxygenase PIR
Short name=Probable quercetinase
Gene names
Name:PIR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length290 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional coregulator of NF-kappa-B which facilitates binding of NF-kappa-B proteins to target kappa-B genes in a redox-state-dependent manner. May be required for efficient terminal myeloid maturation of hematopoietic cells. Has quercetin 2,3-dioxygenase activity (in vitro). Ref.1 Ref.7 Ref.10 Ref.14 Ref.15

Catalytic activity

Quercetin + O2 = 2-(3,4-dihydroxybenzoyloxy)-4,6-dihydroxybenzoate + CO + H+. Ref.6

Cofactor

Binds 1 iron ion per subunit. Ref.13 Ref.14

Enzyme regulation

Inhibited by kojic acid, sodium diethyldithiocarbamate and 1,10-phenanthroline monohydrochloride. Ref.6

Pathway

Flavonoid metabolism; quercetin degradation.

Subunit structure

May interact with NF1/CTF1. Interacts with BCL3. Identified in a complex comprised of PIR, BLC3, NFKB1 and target DNA. Ref.1 Ref.5 Ref.14

Subcellular location

Nucleus. Cytoplasm. Note: Predominantly localized in dot-like subnuclear structures. Cytoplasmic localization of PIR seems to positively correlate with melanoma progression. Ref.1 Ref.8

Tissue specificity

Highly expressed in a subset of melanomas. Detected at very low levels in most tissues (at protein level). Expressed in all tissues, with highest level of expression in heart and liver. Ref.1 Ref.8

Induction

Up-regulated in CD34+ cells upon myelomonocytic differentiation. Down-regulated in many acute myeloid leukemias. Up-regulated in primary bronchial epithelial cells exposed to cigarette smoke extract. Ref.6 Ref.7 Ref.10

Polymorphism

Genetic variations in PIR might have a sex-specific influence on bone mineral density differences in some populations, as reported by Ref.9. In a cohort of 4000 Chinese, a significant statistical association has been identified, in women but not in men, between the intronic SNP rs5935970 and lumbar spine bone mineral density, and between a haplotype composed of three SNPs with bone mineral density at other sites.

Sequence similarities

Belongs to the pirin family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 290290Pirin
PRO_0000214051

Sites

Metal binding561Iron
Metal binding581Iron
Metal binding1011Iron
Metal binding1031Iron

Natural variations

Natural variant2281V → A.
Corresponds to variant rs34104000 [ dbSNP | Ensembl ].
VAR_050543

Experimental info

Sequence conflict241V → D in CAG46621. Ref.2
Sequence conflict1621K → R in CAG46621. Ref.2

Secondary structure

.............................................................. 290
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O00625 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: D06AC100F356496D

FASTA29032,113
        10         20         30         40         50         60 
MGSSKKVTLS VLSREQSEGV GARVRRSIGR PELKNLDPFL LFDEFKGGRP GGFPDHPHRG 

        70         80         90        100        110        120 
FETVSYLLEG GSMAHEDFCG HTGKMNPGDL QWMTAGRGIL HAEMPCSEEP AHGLQLWVNL 

       130        140        150        160        170        180 
RSSEKMVEPQ YQELKSEEIP KPSKDGVTVA VISGEALGIK SKVYTRTPTL YLDFKLDPGA 

       190        200        210        220        230        240 
KHSQPIPKGW TSFIYTISGD VYIGPDDAQQ KIEPHHTAVL GEGDSVQVEN KDPKRSHFVL 

       250        260        270        280        290 
IAGEPLREPV IQHGPFVMNT NEEISQAILD FRNAKNGFER AKTWKSKIGN 

« Hide

References

« Hide 'large scale' references
[1]"Identification of pirin, a novel highly conserved nuclear protein."
Wendler W.M.F., Kremmer E., Foerster R., Winnacker E.-L.
J. Biol. Chem. 272:8482-8489(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROPOSED FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Cervix carcinoma.
[2]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[5]"The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and nuclear co-regulators."
Dechend R., Hirano F., Lehmann K., Heissmeyer V., Ansieau S., Wulczyn F.G., Scheidereit C., Leutz A.
Oncogene 18:3316-3323(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BCL3, IDENTIFICATION IN A COMPLEX WITH BLC3; NFKB1; PIR AND TARGET DNA.
[6]"Structural and biochemical analysis reveal pirins to possess quercetinase activity."
Adams M., Jia Z.
J. Biol. Chem. 280:28675-28682(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION.
[7]"Upregulation of pirin expression by chronic cigarette smoking is associated with bronchial epithelial cell apoptosis."
Gelbman B.D., Heguy A., O'Connor T.P., Zabner J., Crystal R.G.
Respir. Res. 8:10-10(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[8]"Pirin delocalization in melanoma progression identified by high content immuno-detection based approaches."
Licciulli S., Luise C., Zanardi A., Giorgetti L., Viale G., Lanfrancone L., Carbone R., Alcalay M.
BMC Cell Biol. 11:5-5(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]"Sex-specific effect of Pirin gene on bone mineral density in a cohort of 4000 Chinese."
Tang N.L., Liao C.D., Ching J.K., Suen E.W., Chan I.H., Orwoll E., Ho S.C., Chan F.W., Kwok A.W., Kwok T., Woo J., Leung P.C.
Bone 46:543-550(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE INFLUENCE OF PIR POLYMORPHISMS ON BONE MINERAL DENSITY.
[10]"Pirin downregulation is a feature of AML and leads to impairment of terminal myeloid differentiation."
Licciulli S., Cambiaghi V., Scafetta G., Gruszka A.M., Alcalay M.
Leukemia 24:429-437(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[11]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Crystal structure of human pirin: an iron-binding nuclear protein and transcription cofactor."
Pang H., Bartlam M., Zeng Q., Miyatake H., Hisano T., Miki K., Wong L.L., Gao G.F., Rao Z.
J. Biol. Chem. 279:1491-1498(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH IRON IONS, COFACTOR.
[14]"A small-molecule inhibitor shows that pirin regulates migration of melanoma cells."
Miyazaki I., Simizu S., Okumura H., Takagi S., Osada H.
Nat. Chem. Biol. 6:667-673(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) IN COMPLEX WITH A SYNTHETIC INHIBITOR AND IRON IONS, INTERACTION WITH BCL3, COFACTOR, FUNCTION.
[15]"Pirin is an iron-dependent redox regulator of NF-kappaB."
Liu F., Rehmani I., Esaki S., Fu R., Chen L., de Serrano V., Liu A.
Proc. Natl. Acad. Sci. U.S.A. 110:9722-9727(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS), FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y07868 mRNA. Translation: CAA69195.1.
Y07867 mRNA. Translation: CAA69194.1.
CR541822 mRNA. Translation: CAG46621.1.
BT019583 mRNA. Translation: AAV38390.1.
BT019584 mRNA. Translation: AAV38391.1.
BC002517 mRNA. Translation: AAH02517.1.
RefSeqNP_001018119.1. NM_001018109.2.
NP_003653.1. NM_003662.3.
UniGeneHs.495728.
Hs.732521.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1J1LX-ray2.10A1-290[»]
3ACLX-ray2.35A2-290[»]
4EROX-ray2.65A1-290[»]
4EWAX-ray2.47A1-290[»]
4EWDX-ray2.15A1-290[»]
4EWEX-ray1.56A1-290[»]
4GULX-ray1.80A3-290[»]
4HLTX-ray1.70A3-290[»]
ProteinModelPortalO00625.
SMRO00625. Positions 3-290.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114114. 13 interactions.
IntActO00625. 1 interaction.
MINTMINT-1189585.
STRING9606.ENSP00000369785.

Chemistry

ChEMBLCHEMBL2010627.

PTM databases

PhosphoSiteO00625.

2D gel databases

UCD-2DPAGEO00625.

Proteomic databases

PaxDbO00625.
PeptideAtlasO00625.
PRIDEO00625.

Protocols and materials databases

DNASU8544.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000380420; ENSP00000369785; ENSG00000087842.
ENST00000380421; ENSP00000369786; ENSG00000087842.
GeneID8544.
KEGGhsa:8544.
UCSCuc004cwu.3. human.

Organism-specific databases

CTD8544.
GeneCardsGC0XM015402.
HGNCHGNC:30048. PIR.
HPAHPA000697.
MIM603329. gene.
neXtProtNX_O00625.
PharmGKBPA134870022.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1741.
HOGENOMHOG000248360.
HOVERGENHBG019151.
InParanoidO00625.
KOK06911.
OMADPFVHMD.
OrthoDBEOG7JMGFH.
PhylomeDBO00625.
TreeFamTF300002.

Enzyme and pathway databases

UniPathwayUPA00724.

Gene expression databases

BgeeO00625.
CleanExHS_PIR.
GenevestigatorO00625.

Family and domain databases

Gene3D2.60.120.10. 1 hit.
InterProIPR012093. Pirin.
IPR008778. Pirin_C_dom.
IPR003829. Pirin_N_dom.
IPR014710. RmlC-like_jellyroll.
IPR011051. RmlC_Cupin.
[Graphical view]
PANTHERPTHR13903. PTHR13903. 1 hit.
PfamPF02678. Pirin. 1 hit.
PF05726. Pirin_C. 1 hit.
[Graphical view]
PIRSFPIRSF006232. Pirin. 1 hit.
SUPFAMSSF51182. SSF51182. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceO00625.
GeneWikiPIR_(gene).
GenomeRNAi8544.
NextBio32006.
PROO00625.
SOURCESearch...

Entry information

Entry namePIR_HUMAN
AccessionPrimary (citable) accession number: O00625
Secondary accession number(s): Q5U0G0, Q6FHD2
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: July 1, 1997
Last modified: April 16, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM