PIR_HUMAN
ID PIR_HUMAN Reviewed; 290 AA.
AC O00625; Q5U0G0; Q6FHD2;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Pirin;
DE EC=1.13.11.24 {ECO:0000269|PubMed:15951572};
DE AltName: Full=Probable quercetin 2,3-dioxygenase PIR;
DE Short=Probable quercetinase;
GN Name=PIR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROPOSED FUNCTION, SUBUNIT, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Cervix carcinoma;
RX PubMed=9079676; DOI=10.1074/jbc.272.13.8482;
RA Wendler W.M.F., Kremmer E., Foerster R., Winnacker E.-L.;
RT "Identification of pirin, a novel highly conserved nuclear protein.";
RL J. Biol. Chem. 272:8482-8489(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INTERACTION WITH BCL3, AND IDENTIFICATION IN A COMPLEX WITH BLC3; NFKB1;
RP PIR AND TARGET DNA.
RX PubMed=10362352; DOI=10.1038/sj.onc.1202717;
RA Dechend R., Hirano F., Lehmann K., Heissmeyer V., Ansieau S., Wulczyn F.G.,
RA Scheidereit C., Leutz A.;
RT "The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and
RT nuclear co-regulators.";
RL Oncogene 18:3316-3323(1999).
RN [6]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND FUNCTION.
RX PubMed=15951572; DOI=10.1074/jbc.m501034200;
RA Adams M., Jia Z.;
RT "Structural and biochemical analysis reveal pirins to possess quercetinase
RT activity.";
RL J. Biol. Chem. 280:28675-28682(2005).
RN [7]
RP FUNCTION, AND INDUCTION.
RX PubMed=17288615; DOI=10.1186/1465-9921-8-10;
RA Gelbman B.D., Heguy A., O'Connor T.P., Zabner J., Crystal R.G.;
RT "Upregulation of pirin expression by chronic cigarette smoking is
RT associated with bronchial epithelial cell apoptosis.";
RL Respir. Res. 8:10-10(2007).
RN [8]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=20089166; DOI=10.1186/1471-2121-11-5;
RA Licciulli S., Luise C., Zanardi A., Giorgetti L., Viale G., Lanfrancone L.,
RA Carbone R., Alcalay M.;
RT "Pirin delocalization in melanoma progression identified by high content
RT immuno-detection based approaches.";
RL BMC Cell Biol. 11:5-5(2010).
RN [9]
RP POSSIBLE INFLUENCE OF PIR POLYMORPHISMS ON BONE MINERAL DENSITY.
RX PubMed=19766747; DOI=10.1016/j.bone.2009.09.012;
RA Tang N.L., Liao C.D., Ching J.K., Suen E.W., Chan I.H., Orwoll E., Ho S.C.,
RA Chan F.W., Kwok A.W., Kwok T., Woo J., Leung P.C.;
RT "Sex-specific effect of Pirin gene on bone mineral density in a cohort of
RT 4000 Chinese.";
RL Bone 46:543-550(2010).
RN [10]
RP FUNCTION, AND INDUCTION.
RX PubMed=20010624; DOI=10.1038/leu.2009.247;
RA Licciulli S., Cambiaghi V., Scafetta G., Gruszka A.M., Alcalay M.;
RT "Pirin downregulation is a feature of AML and leads to impairment of
RT terminal myeloid differentiation.";
RL Leukemia 24:429-437(2010).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH IRON IONS, AND
RP COFACTOR.
RX PubMed=14573596; DOI=10.1074/jbc.m310022200;
RA Pang H., Bartlam M., Zeng Q., Miyatake H., Hisano T., Miki K., Wong L.L.,
RA Gao G.F., Rao Z.;
RT "Crystal structure of human pirin: an iron-binding nuclear protein and
RT transcription cofactor.";
RL J. Biol. Chem. 279:1491-1498(2004).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) IN COMPLEX WITH A SYNTHETIC
RP INHIBITOR AND IRON IONS, INTERACTION WITH BCL3, COFACTOR, AND FUNCTION.
RX PubMed=20711196; DOI=10.1038/nchembio.423;
RA Miyazaki I., Simizu S., Okumura H., Takagi S., Osada H.;
RT "A small-molecule inhibitor shows that pirin regulates migration of
RT melanoma cells.";
RL Nat. Chem. Biol. 6:667-673(2010).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS), AND FUNCTION.
RX PubMed=23716661; DOI=10.1073/pnas.1221743110;
RA Liu F., Rehmani I., Esaki S., Fu R., Chen L., de Serrano V., Liu A.;
RT "Pirin is an iron-dependent redox regulator of NF-kappaB.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:9722-9727(2013).
CC -!- FUNCTION: Transcriptional coregulator of NF-kappa-B which facilitates
CC binding of NF-kappa-B proteins to target kappa-B genes in a redox-
CC state-dependent manner. May be required for efficient terminal myeloid
CC maturation of hematopoietic cells. Has quercetin 2,3-dioxygenase
CC activity (in vitro). {ECO:0000269|PubMed:15951572,
CC ECO:0000269|PubMed:17288615, ECO:0000269|PubMed:20010624,
CC ECO:0000269|PubMed:20711196, ECO:0000269|PubMed:23716661}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + quercetin = 2-(3,4-dihydroxybenzoyloxy)-4,6-
CC dihydroxybenzoate + CO; Xref=Rhea:RHEA:15381, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17245, ChEBI:CHEBI:57628, ChEBI:CHEBI:57694;
CC EC=1.13.11.24; Evidence={ECO:0000269|PubMed:15951572};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000269|PubMed:14573596, ECO:0000269|PubMed:20711196};
CC Note=Binds 1 Fe cation per subunit. {ECO:0000269|PubMed:14573596,
CC ECO:0000269|PubMed:20711196};
CC -!- ACTIVITY REGULATION: Inhibited by kojic acid, sodium
CC diethyldithiocarbamate and 1,10-phenanthroline monohydrochloride.
CC {ECO:0000269|PubMed:15951572}.
CC -!- PATHWAY: Flavonoid metabolism; quercetin degradation.
CC {ECO:0000305|PubMed:15951572}.
CC -!- SUBUNIT: May interact with NF1/CTF1. Interacts with BCL3. Identified in
CC a complex comprised of PIR, BLC3, NFKB1 and target DNA.
CC {ECO:0000269|PubMed:10362352, ECO:0000269|PubMed:14573596,
CC ECO:0000269|PubMed:20711196, ECO:0000269|PubMed:9079676}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20089166,
CC ECO:0000269|PubMed:9079676}. Cytoplasm {ECO:0000269|PubMed:20089166}.
CC Note=Predominantly localized in dot-like subnuclear structures.
CC Cytoplasmic localization of PIR seems to positively correlate with
CC melanoma progression. {ECO:0000269|PubMed:20089166,
CC ECO:0000269|PubMed:9079676}.
CC -!- TISSUE SPECIFICITY: Highly expressed in a subset of melanomas. Detected
CC at very low levels in most tissues (at protein level). Expressed in all
CC tissues, with highest level of expression in heart and liver.
CC {ECO:0000269|PubMed:20089166, ECO:0000269|PubMed:9079676}.
CC -!- INDUCTION: Up-regulated in CD34(+) cells upon myelomonocytic
CC differentiation. Down-regulated in many acute myeloid leukemias. Up-
CC regulated in primary bronchial epithelial cells exposed to cigarette
CC smoke extract. {ECO:0000269|PubMed:17288615,
CC ECO:0000269|PubMed:20010624}.
CC -!- POLYMORPHISM: Genetic variations in PIR might have a sex-specific
CC influence on bone mineral density differences in some populations, as
CC reported by PubMed:19766747. In a cohort of 4000 Chinese, a significant
CC statistical association has been identified, in women but not in men,
CC between the intronic SNP rs5935970 and lumbar spine bone mineral
CC density, and between a haplotype composed of three SNPs with bone
CC mineral density at other sites. {ECO:0000305|PubMed:19766747}.
CC -!- SIMILARITY: Belongs to the pirin family. {ECO:0000305}.
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DR EMBL; Y07868; CAA69195.1; -; mRNA.
DR EMBL; Y07867; CAA69194.1; -; mRNA.
DR EMBL; CR541822; CAG46621.1; -; mRNA.
DR EMBL; BT019583; AAV38390.1; -; mRNA.
DR EMBL; BT019584; AAV38391.1; -; mRNA.
DR EMBL; BC002517; AAH02517.1; -; mRNA.
DR CCDS; CCDS14167.1; -.
DR RefSeq; NP_001018119.1; NM_001018109.2.
DR RefSeq; NP_003653.1; NM_003662.3.
DR PDB; 1J1L; X-ray; 2.10 A; A=1-290.
DR PDB; 3ACL; X-ray; 2.35 A; A=2-290.
DR PDB; 4ERO; X-ray; 2.65 A; A=1-290.
DR PDB; 4EWA; X-ray; 2.47 A; A=1-290.
DR PDB; 4EWD; X-ray; 2.15 A; A=1-290.
DR PDB; 4EWE; X-ray; 1.56 A; A=1-290.
DR PDB; 4GUL; X-ray; 1.80 A; A=3-290.
DR PDB; 4HLT; X-ray; 1.70 A; A=3-290.
DR PDB; 5JCT; X-ray; 1.73 A; A=1-290.
DR PDB; 6H1H; X-ray; 1.54 A; A=1-290.
DR PDB; 6H1I; X-ray; 1.69 A; A=1-290.
DR PDB; 6N0J; X-ray; 1.79 A; A=2-290.
DR PDB; 6N0K; X-ray; 1.46 A; A=2-290.
DR PDBsum; 1J1L; -.
DR PDBsum; 3ACL; -.
DR PDBsum; 4ERO; -.
DR PDBsum; 4EWA; -.
DR PDBsum; 4EWD; -.
DR PDBsum; 4EWE; -.
DR PDBsum; 4GUL; -.
DR PDBsum; 4HLT; -.
DR PDBsum; 5JCT; -.
DR PDBsum; 6H1H; -.
DR PDBsum; 6H1I; -.
DR PDBsum; 6N0J; -.
DR PDBsum; 6N0K; -.
DR AlphaFoldDB; O00625; -.
DR SMR; O00625; -.
DR BioGRID; 114114; 61.
DR IntAct; O00625; 6.
DR MINT; O00625; -.
DR STRING; 9606.ENSP00000369786; -.
DR BindingDB; O00625; -.
DR ChEMBL; CHEMBL2010627; -.
DR iPTMnet; O00625; -.
DR PhosphoSitePlus; O00625; -.
DR BioMuta; PIR; -.
DR UCD-2DPAGE; O00625; -.
DR EPD; O00625; -.
DR jPOST; O00625; -.
DR MassIVE; O00625; -.
DR MaxQB; O00625; -.
DR PaxDb; O00625; -.
DR PeptideAtlas; O00625; -.
DR PRIDE; O00625; -.
DR ProteomicsDB; 47999; -.
DR TopDownProteomics; O00625; -.
DR Antibodypedia; 358; 214 antibodies from 31 providers.
DR DNASU; 8544; -.
DR Ensembl; ENST00000380420.10; ENSP00000369785.5; ENSG00000087842.11.
DR Ensembl; ENST00000380421.3; ENSP00000369786.3; ENSG00000087842.11.
DR GeneID; 8544; -.
DR KEGG; hsa:8544; -.
DR MANE-Select; ENST00000380420.10; ENSP00000369785.5; NM_001018109.3; NP_001018119.1.
DR UCSC; uc004cwu.5; human.
DR CTD; 8544; -.
DR DisGeNET; 8544; -.
DR GeneCards; PIR; -.
DR HGNC; HGNC:30048; PIR.
DR HPA; ENSG00000087842; Low tissue specificity.
DR MIM; 300931; gene.
DR neXtProt; NX_O00625; -.
DR OpenTargets; ENSG00000087842; -.
DR PharmGKB; PA134870022; -.
DR VEuPathDB; HostDB:ENSG00000087842; -.
DR eggNOG; ENOG502QQ5A; Eukaryota.
DR GeneTree; ENSGT00390000008044; -.
DR HOGENOM; CLU_045717_0_1_1; -.
DR InParanoid; O00625; -.
DR OMA; TPWHPHR; -.
DR OrthoDB; 1328043at2759; -.
DR PhylomeDB; O00625; -.
DR TreeFam; TF300002; -.
DR PathwayCommons; O00625; -.
DR Reactome; R-HSA-8935690; Digestion.
DR SignaLink; O00625; -.
DR UniPathway; UPA00724; -.
DR BioGRID-ORCS; 8544; 4 hits in 706 CRISPR screens.
DR ChiTaRS; PIR; human.
DR EvolutionaryTrace; O00625; -.
DR GeneWiki; PIR_(gene); -.
DR GenomeRNAi; 8544; -.
DR Pharos; O00625; Tchem.
DR PRO; PR:O00625; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; O00625; protein.
DR Bgee; ENSG00000087842; Expressed in C1 segment of cervical spinal cord and 184 other tissues.
DR ExpressionAtlas; O00625; baseline and differential.
DR Genevisible; O00625; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IDA:UniProtKB.
DR GO; GO:0008127; F:quercetin 2,3-dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0003712; F:transcription coregulator activity; IMP:UniProtKB.
DR GO; GO:0007586; P:digestion; TAS:Reactome.
DR GO; GO:0030224; P:monocyte differentiation; IMP:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; TAS:ProtInc.
DR Gene3D; 2.60.120.10; -; 2.
DR InterPro; IPR012093; Pirin.
DR InterPro; IPR008778; Pirin_C_dom.
DR InterPro; IPR003829; Pirin_N_dom.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR InterPro; IPR011051; RmlC_Cupin_sf.
DR PANTHER; PTHR13903; PTHR13903; 1.
DR Pfam; PF02678; Pirin; 1.
DR Pfam; PF05726; Pirin_C; 1.
DR PIRSF; PIRSF006232; Pirin; 1.
DR SUPFAM; SSF51182; SSF51182; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Dioxygenase; Iron; Metal-binding; Nucleus;
KW Oxidoreductase; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..290
FT /note="Pirin"
FT /id="PRO_0000214051"
FT BINDING 56
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:14573596,
FT ECO:0000269|PubMed:20711196, ECO:0007744|PDB:1J1L,
FT ECO:0007744|PDB:3ACL"
FT BINDING 58
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:14573596,
FT ECO:0000269|PubMed:20711196, ECO:0007744|PDB:1J1L,
FT ECO:0007744|PDB:3ACL"
FT BINDING 101
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:14573596,
FT ECO:0000269|PubMed:20711196, ECO:0007744|PDB:1J1L,
FT ECO:0007744|PDB:3ACL"
FT BINDING 103
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:14573596,
FT ECO:0000269|PubMed:20711196, ECO:0007744|PDB:1J1L,
FT ECO:0007744|PDB:3ACL"
FT VARIANT 228
FT /note="V -> A (in dbSNP:rs34104000)"
FT /id="VAR_050543"
FT CONFLICT 24
FT /note="V -> D (in Ref. 2; CAG46621)"
FT /evidence="ECO:0000305"
FT CONFLICT 162
FT /note="K -> R (in Ref. 2; CAG46621)"
FT /evidence="ECO:0000305"
FT STRAND 7..12
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 15..18
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 22..26
FT /evidence="ECO:0007829|PDB:6N0K"
FT HELIX 31..33
FT /evidence="ECO:0007829|PDB:5JCT"
FT STRAND 39..47
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 52..67
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:6N0J"
FT STRAND 73..77
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 90..94
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 99..105
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 111..119
FT /evidence="ECO:0007829|PDB:6N0K"
FT HELIX 122..124
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 130..134
FT /evidence="ECO:0007829|PDB:6N0K"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 147..156
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 169..176
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 181..185
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 191..199
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 201..204
FT /evidence="ECO:0007829|PDB:6N0K"
FT HELIX 206..208
FT /evidence="ECO:0007829|PDB:6H1I"
FT STRAND 210..212
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 216..220
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 222..229
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 236..243
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 251..253
FT /evidence="ECO:0007829|PDB:6N0K"
FT STRAND 256..260
FT /evidence="ECO:0007829|PDB:6N0K"
FT HELIX 261..273
FT /evidence="ECO:0007829|PDB:6N0K"
FT HELIX 279..281
FT /evidence="ECO:0007829|PDB:6N0K"
FT TURN 287..289
FT /evidence="ECO:0007829|PDB:4EWA"
SQ SEQUENCE 290 AA; 32113 MW; D06AC100F356496D CRC64;
MGSSKKVTLS VLSREQSEGV GARVRRSIGR PELKNLDPFL LFDEFKGGRP GGFPDHPHRG
FETVSYLLEG GSMAHEDFCG HTGKMNPGDL QWMTAGRGIL HAEMPCSEEP AHGLQLWVNL
RSSEKMVEPQ YQELKSEEIP KPSKDGVTVA VISGEALGIK SKVYTRTPTL YLDFKLDPGA
KHSQPIPKGW TSFIYTISGD VYIGPDDAQQ KIEPHHTAVL GEGDSVQVEN KDPKRSHFVL
IAGEPLREPV IQHGPFVMNT NEEISQAILD FRNAKNGFER AKTWKSKIGN
