O00625 (PIR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pirin
EC=1.13.11.24

Alternative name(s):
Probable quercetin 2,3-dioxygenase PIR
Short name=Probable quercetinase

Gene names

Name:

PIR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	290 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Possible transcriptional coregulator. May contribute to the regulation of cellular processes via its interaction with BCL3. May be required for efficient terminal myeloid maturation of hematopoietic cells. May play a role in the regulation of cell migration. May promote apoptosis when overexpressed. Has quercetin 2,3-dioxygenase activity (in vitro). Ref.1 Ref.7 Ref.10 Ref.13
Catalytic activity	Quercetin + O2 = 2-(3,4-dihydroxybenzoyloxy)-4,6-dihydroxybenzoate + CO + H+. Ref.6
Cofactor	Binds 1 iron ion per subunit. Ref.12 Ref.13
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.13
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.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Ligand	Iron Metal-binding
Molecular function	Dioxygenase Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	monocyte differentiation Inferred from mutant phenotype Ref.10. Source: MGI transcription from RNA polymerase II promoter Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytoplasm Inferred from direct assay Ref.8. Source: UniProtKB nucleus Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	metal ion binding Inferred from direct assay Ref.13. Source: UniProtKB quercetin 2,3-dioxygenase activity Inferred from direct assay Ref.6. Source: UniProtKB transcription cofactor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 290

290

Pirin

PRO_0000214051

Sites

Metal binding

56

1

Iron

Metal binding

58

1

Iron

Metal binding

101

1

Iron

Metal binding

103

1

Iron

Natural variations

Natural variant

228

1

V → A.
Corresponds to variant rs34104000 [ dbSNP | Ensembl ].

VAR_050543

Experimental info

Sequence conflict

24

1

V → D in CAG46621. Ref.2

Sequence conflict

162

1

K → R in CAG46621. Ref.2

Secondary structure

1

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290

Helix Strand Turn

Details...

Beta strand

7 – 12

6

Beta strand

15 – 18

4

Beta strand

22 – 26

5

Helix

31 – 33

3

Beta strand

39 – 47

9

Beta strand

52 – 67

16

Beta strand

69 – 71

3

Beta strand

73 – 77

5

Beta strand

82 – 85

4

Beta strand

90 – 94

5

Beta strand

99 – 105

7

Beta strand

107 – 109

3

Beta strand

111 – 119

9

Helix

122 – 124

3

Beta strand

130 – 134

5

Helix

136 – 138

3

Beta strand

147 – 156

10

Beta strand

169 – 176

8

Beta strand

181 – 185

5

Beta strand

191 – 199

9

Beta strand

201 – 204

4

Beta strand

210 – 212

3

Beta strand

216 – 220

5

Beta strand

224 – 229

6

Beta strand

232 – 234

3

Beta strand

236 – 243

8

Beta strand

251 – 253

3

Beta strand

256 – 260

5

Helix

261 – 272

12

Helix

279 – 281

3

Sequences

	Sequence		Length	Mass (Da)
	O00625 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: D06AC100F356496D	FASTA	290	32,113
	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

References

	« Hide 'large scale' referencesShow '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]	"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.
[13]	"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.
+	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.

IPI

IPI00012575.

RefSeq

NP_001018119.1. NM_001018109.2.
NP_003653.1. NM_003662.3.

UniGene

Hs.495728.
Hs.732521.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1J1L	X-ray	2.10	A	1-290	[»]
3ACL	X-ray	2.35	A	2-290	[»]

ProteinModelPortal

O00625.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-1189585.

STRING

9606.ENSP00000369785.

PTM databases

PhosphoSite

O00625.

2D gel databases

UCD-2DPAGE

O00625.

Proteomic databases

PaxDb

O00625.

PeptideAtlas

O00625.

PRIDE

O00625.

Protocols and materials databases

DNASU

8544.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000380420; ENSP00000369785; ENSG00000087842.
ENST00000380421; ENSP00000369786; ENSG00000087842.

GeneID

8544.

KEGG

hsa:8544.

UCSC

uc004cwu.3. human.

Organism-specific databases

CTD

8544.

GeneCards

GC0XM015402.

HGNC

HGNC:30048. PIR.

HPA

HPA000697.

MIM

603329. gene.

neXtProt

NX_O00625.

PharmGKB

PA134870022.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1741.

HOGENOM

HOG000248360.

HOVERGEN

HBG019151.

InParanoid

O00625.

KO

K06911.

OMA

PIVMNTW.

OrthoDB

EOG4MCX12.

PhylomeDB

O00625.

Enzyme and pathway databases

UniPathway

UPA00724.

Gene expression databases

Bgee

O00625.

CleanEx

HS_PIR.

Genevestigator

O00625.

GermOnline

ENSG00000087842. Homo sapiens.

Family and domain databases

Gene3D

2.60.120.10. 1 hit.

InterPro

IPR012093. Pirin.
IPR008778. Pirin_C_dom.
IPR003829. Pirin_N_dom.
IPR014710. RmlC-like_jellyroll.
IPR011051. RmlC_Cupin.
[Graphical view]

PANTHER

PTHR13903. PTHR13903. 1 hit.

Pfam

PF02678. Pirin. 1 hit.
PF05726. Pirin_C. 1 hit.
[Graphical view]

PIRSF

PIRSF006232. Pirin. 1 hit.

SUPFAM

SSF51182. RmlC_like_cupin. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

O00625.

GenomeRNAi

8544.

NextBio

32006.

SOURCE

Search...

Entry information

Entry name

PIR_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 112 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.