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O00625

- PIR_HUMAN

UniProt

O00625 - PIR_HUMAN

Protein

Pirin

Gene

PIR

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 1 (01 Jul 1997)
      Previous versions | rss
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    Functioni

    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).4 Publications

    Catalytic activityi

    Quercetin + O2 = 2-(3,4-dihydroxybenzoyloxy)-4,6-dihydroxybenzoate + CO + H+.1 Publication

    Cofactori

    Binds 1 iron ion per subunit.2 Publications

    Enzyme regulationi

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

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi56 – 561Iron
    Metal bindingi58 – 581Iron
    Metal bindingi101 – 1011Iron
    Metal bindingi103 – 1031Iron

    GO - Molecular functioni

    1. metal ion binding Source: UniProtKB
    2. protein binding Source: UniProtKB
    3. quercetin 2,3-dioxygenase activity Source: UniProtKB
    4. transcription cofactor activity Source: UniProtKB

    GO - Biological processi

    1. monocyte differentiation Source: MGI
    2. regulation of transcription, DNA-templated Source: UniProtKB-KW
    3. transcription from RNA polymerase II promoter Source: ProtInc

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    Iron, Metal-binding

    Enzyme and pathway databases

    UniPathwayiUPA00724.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Pirin (EC:1.13.11.24)
    Alternative name(s):
    Probable quercetin 2,3-dioxygenase PIR
    Short name:
    Probable quercetinase
    Gene namesi
    Name:PIR
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome X

    Organism-specific databases

    HGNCiHGNC:30048. PIR.

    Subcellular locationi

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

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134870022.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 290290PirinPRO_0000214051Add
    BLAST

    Proteomic databases

    MaxQBiO00625.
    PaxDbiO00625.
    PeptideAtlasiO00625.
    PRIDEiO00625.

    2D gel databases

    UCD-2DPAGEO00625.

    PTM databases

    PhosphoSiteiO00625.

    Expressioni

    Tissue specificityi

    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.2 Publications

    Inductioni

    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.2 Publications

    Gene expression databases

    BgeeiO00625.
    CleanExiHS_PIR.
    GenevestigatoriO00625.

    Organism-specific databases

    HPAiHPA000697.

    Interactioni

    Subunit structurei

    May interact with NF1/CTF1. Interacts with BCL3. Identified in a complex comprised of PIR, BLC3, NFKB1 and target DNA.4 Publications

    Protein-protein interaction databases

    BioGridi114114. 13 interactions.
    IntActiO00625. 1 interaction.
    MINTiMINT-1189585.
    STRINGi9606.ENSP00000369785.

    Structurei

    Secondary structure

    1
    290
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi7 – 126
    Beta strandi14 – 185
    Beta strandi22 – 265
    Helixi31 – 333
    Beta strandi39 – 479
    Beta strandi52 – 6716
    Beta strandi69 – 713
    Beta strandi73 – 775
    Beta strandi82 – 854
    Beta strandi90 – 945
    Beta strandi99 – 1057
    Beta strandi107 – 1093
    Beta strandi111 – 1199
    Helixi122 – 1243
    Beta strandi130 – 1345
    Helixi136 – 1383
    Beta strandi147 – 15610
    Beta strandi169 – 1768
    Beta strandi181 – 1855
    Beta strandi191 – 1999
    Beta strandi201 – 2044
    Beta strandi210 – 2123
    Beta strandi216 – 2205
    Beta strandi224 – 2296
    Beta strandi232 – 2343
    Beta strandi236 – 2438
    Beta strandi251 – 2533
    Beta strandi256 – 2605
    Helixi261 – 27212
    Helixi279 – 2813
    Turni287 – 2893

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliO00625.
    SMRiO00625. Positions 3-290.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO00625.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the pirin family.Curated

    Phylogenomic databases

    eggNOGiCOG1741.
    HOGENOMiHOG000248360.
    HOVERGENiHBG019151.
    InParanoidiO00625.
    KOiK06911.
    OMAiQWMTAAR.
    OrthoDBiEOG7JMGFH.
    PhylomeDBiO00625.
    TreeFamiTF300002.

    Family and domain databases

    Gene3Di2.60.120.10. 1 hit.
    InterProiIPR012093. Pirin.
    IPR008778. Pirin_C_dom.
    IPR003829. Pirin_N_dom.
    IPR014710. RmlC-like_jellyroll.
    IPR011051. RmlC_Cupin.
    [Graphical view]
    PANTHERiPTHR13903. PTHR13903. 1 hit.
    PfamiPF02678. Pirin. 1 hit.
    PF05726. Pirin_C. 1 hit.
    [Graphical view]
    PIRSFiPIRSF006232. Pirin. 1 hit.
    SUPFAMiSSF51182. SSF51182. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    O00625-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGSSKKVTLS VLSREQSEGV GARVRRSIGR PELKNLDPFL LFDEFKGGRP    50
    GGFPDHPHRG FETVSYLLEG GSMAHEDFCG HTGKMNPGDL QWMTAGRGIL 100
    HAEMPCSEEP AHGLQLWVNL RSSEKMVEPQ YQELKSEEIP KPSKDGVTVA 150
    VISGEALGIK SKVYTRTPTL YLDFKLDPGA KHSQPIPKGW TSFIYTISGD 200
    VYIGPDDAQQ KIEPHHTAVL GEGDSVQVEN KDPKRSHFVL IAGEPLREPV 250
    IQHGPFVMNT NEEISQAILD FRNAKNGFER AKTWKSKIGN 290
    Length:290
    Mass (Da):32,113
    Last modified:July 1, 1997 - v1
    Checksum:iD06AC100F356496D
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti24 – 241V → D in CAG46621. 1 PublicationCurated
    Sequence conflicti162 – 1621K → R in CAG46621. 1 PublicationCurated

    Polymorphismi

    Genetic variations in PIR might have a sex-specific influence on bone mineral density differences in some populations, as reported by PubMed:19766747. 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.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti228 – 2281V → A.
    Corresponds to variant rs34104000 [ dbSNP | Ensembl ].
    VAR_050543

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS14167.1.
    RefSeqiNP_001018119.1. NM_001018109.2.
    NP_003653.1. NM_003662.3.
    UniGeneiHs.495728.
    Hs.732521.

    Genome annotation databases

    EnsembliENST00000380420; ENSP00000369785; ENSG00000087842.
    ENST00000380421; ENSP00000369786; ENSG00000087842.
    GeneIDi8544.
    KEGGihsa:8544.
    UCSCiuc004cwu.3. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS14167.1.
    RefSeqi NP_001018119.1. NM_001018109.2.
    NP_003653.1. NM_003662.3.
    UniGenei Hs.495728.
    Hs.732521.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1J1L X-ray 2.10 A 1-290 [» ]
    3ACL X-ray 2.35 A 2-290 [» ]
    4ERO X-ray 2.65 A 1-290 [» ]
    4EWA X-ray 2.47 A 1-290 [» ]
    4EWD X-ray 2.15 A 1-290 [» ]
    4EWE X-ray 1.56 A 1-290 [» ]
    4GUL X-ray 1.80 A 3-290 [» ]
    4HLT X-ray 1.70 A 3-290 [» ]
    ProteinModelPortali O00625.
    SMRi O00625. Positions 3-290.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114114. 13 interactions.
    IntActi O00625. 1 interaction.
    MINTi MINT-1189585.
    STRINGi 9606.ENSP00000369785.

    Chemistry

    ChEMBLi CHEMBL2010627.

    PTM databases

    PhosphoSitei O00625.

    2D gel databases

    UCD-2DPAGE O00625.

    Proteomic databases

    MaxQBi O00625.
    PaxDbi O00625.
    PeptideAtlasi O00625.
    PRIDEi O00625.

    Protocols and materials databases

    DNASUi 8544.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000380420 ; ENSP00000369785 ; ENSG00000087842 .
    ENST00000380421 ; ENSP00000369786 ; ENSG00000087842 .
    GeneIDi 8544.
    KEGGi hsa:8544.
    UCSCi uc004cwu.3. human.

    Organism-specific databases

    CTDi 8544.
    GeneCardsi GC0XM015402.
    HGNCi HGNC:30048. PIR.
    HPAi HPA000697.
    MIMi 603329. gene.
    neXtProti NX_O00625.
    PharmGKBi PA134870022.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1741.
    HOGENOMi HOG000248360.
    HOVERGENi HBG019151.
    InParanoidi O00625.
    KOi K06911.
    OMAi QWMTAAR.
    OrthoDBi EOG7JMGFH.
    PhylomeDBi O00625.
    TreeFami TF300002.

    Enzyme and pathway databases

    UniPathwayi UPA00724 .

    Miscellaneous databases

    EvolutionaryTracei O00625.
    GeneWikii PIR_(gene).
    GenomeRNAii 8544.
    NextBioi 32006.
    PROi O00625.
    SOURCEi Search...

    Gene expression databases

    Bgeei O00625.
    CleanExi HS_PIR.
    Genevestigatori O00625.

    Family and domain databases

    Gene3Di 2.60.120.10. 1 hit.
    InterProi IPR012093. Pirin.
    IPR008778. Pirin_C_dom.
    IPR003829. Pirin_N_dom.
    IPR014710. RmlC-like_jellyroll.
    IPR011051. RmlC_Cupin.
    [Graphical view ]
    PANTHERi PTHR13903. PTHR13903. 1 hit.
    Pfami PF02678. Pirin. 1 hit.
    PF05726. Pirin_C. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF006232. Pirin. 1 hit.
    SUPFAMi SSF51182. SSF51182. 1 hit.
    ProtoNeti Search...

    Publicationsi

    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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    12. 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. Cited for: X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS), FUNCTION.

    Entry informationi

    Entry nameiPIR_HUMAN
    AccessioniPrimary (citable) accession number: O00625
    Secondary accession number(s): Q5U0G0, Q6FHD2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 2001
    Last sequence update: July 1, 1997
    Last modified: October 1, 2014
    This is version 124 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 X
      Human chromosome X: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3