Full text data of PIR
PIR
[Confidence: low (only semi-automatic identification from reviews)]
Pirin; 1.13.11.24 (Probable quercetin 2,3-dioxygenase PIR; Probable quercetinase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Pirin; 1.13.11.24 (Probable quercetin 2,3-dioxygenase PIR; Probable quercetinase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O00625
ID PIR_HUMAN Reviewed; 290 AA.
AC O00625; Q5U0G0; Q6FHD2;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1997, sequence version 1.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Pirin;
DE EC=1.13.11.24;
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT 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
RT project: 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;
RP NFKB1; PIR AND TARGET DNA.
RX PubMed=10362352; DOI=10.1038/sj.onc.1202717;
RA Dechend R., Hirano F., Lehmann K., Heissmeyer V., Ansieau S.,
RA Wulczyn F.G., Scheidereit C., Leutz A.;
RT "The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel
RT and nuclear co-regulators.";
RL Oncogene 18:3316-3323(1999).
RN [6]
RP CATALYTIC ACTIVITY, AND ENZYME REGULATION.
RX PubMed=15951572; DOI=10.1074/jbc.M501034200;
RA Adams M., Jia Z.;
RT "Structural and biochemical analysis reveal pirins to possess
RT quercetinase 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.,
RA Lanfrancone L., Carbone R., Alcalay M.;
RT "Pirin delocalization in melanoma progression identified by high
RT content 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.,
RA Ho S.C., 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
RT of 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.,
RA Buerckstuemmer T., 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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal 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.,
RA Wong L.L., 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
RP 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
CC facilitates binding of NF-kappa-B proteins to target kappa-B genes
CC in a redox-state-dependent manner. May be required for efficient
CC terminal myeloid maturation of hematopoietic cells. Has quercetin
CC 2,3-dioxygenase activity (in vitro).
CC -!- CATALYTIC ACTIVITY: Quercetin + O(2) = 2-(3,4-
CC dihydroxybenzoyloxy)-4,6-dihydroxybenzoate + CO + H(+).
CC -!- COFACTOR: Binds 1 iron ion per subunit.
CC -!- ENZYME REGULATION: Inhibited by kojic acid, sodium
CC diethyldithiocarbamate and 1,10-phenanthroline monohydrochloride.
CC -!- PATHWAY: Flavonoid metabolism; quercetin degradation.
CC -!- SUBUNIT: May interact with NF1/CTF1. Interacts with BCL3.
CC Identified in a complex comprised of PIR, BLC3, NFKB1 and target
CC DNA.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Predominantly
CC localized in dot-like subnuclear structures. Cytoplasmic
CC localization of PIR seems to positively correlate with melanoma
CC progression.
CC -!- TISSUE SPECIFICITY: Highly expressed in a subset of melanomas.
CC Detected at very low levels in most tissues (at protein level).
CC Expressed in all tissues, with highest level of expression in
CC heart and liver.
CC -!- INDUCTION: Up-regulated in CD34(+) cells upon myelomonocytic
CC differentiation. Down-regulated in many acute myeloid leukemias.
CC Up-regulated in primary bronchial epithelial cells exposed to
CC cigarette smoke extract.
CC -!- POLYMORPHISM: Genetic variations in PIR might have a sex-specific
CC influence on bone mineral density differences in some populations,
CC as reported by PubMed:19766747. In a cohort of 4000 Chinese, a
CC significant statistical association has been identified, in women
CC but not in men, between the intronic SNP rs5935970 and lumbar
CC spine bone mineral density, and between a haplotype composed of
CC three SNPs with bone mineral density at other sites.
CC -!- SIMILARITY: Belongs to the pirin family.
CC -----------------------------------------------------------------------
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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 RefSeq; NP_001018119.1; NM_001018109.2.
DR RefSeq; NP_003653.1; NM_003662.3.
DR RefSeq; XP_005274667.1; XM_005274610.1.
DR UniGene; Hs.495728; -.
DR UniGene; Hs.732521; -.
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 PDBsum; 1J1L; -.
DR PDBsum; 3ACL; -.
DR PDBsum; 4ERO; -.
DR PDBsum; 4EWA; -.
DR PDBsum; 4EWD; -.
DR PDBsum; 4EWE; -.
DR PDBsum; 4GUL; -.
DR PDBsum; 4HLT; -.
DR ProteinModelPortal; O00625; -.
DR SMR; O00625; 3-290.
DR IntAct; O00625; 1.
DR MINT; MINT-1189585; -.
DR STRING; 9606.ENSP00000369785; -.
DR ChEMBL; CHEMBL2010627; -.
DR PhosphoSite; O00625; -.
DR UCD-2DPAGE; O00625; -.
DR PaxDb; O00625; -.
DR PeptideAtlas; O00625; -.
DR PRIDE; O00625; -.
DR DNASU; 8544; -.
DR Ensembl; ENST00000380420; ENSP00000369785; ENSG00000087842.
DR Ensembl; ENST00000380421; ENSP00000369786; ENSG00000087842.
DR GeneID; 8544; -.
DR KEGG; hsa:8544; -.
DR UCSC; uc004cwu.3; human.
DR CTD; 8544; -.
DR GeneCards; GC0XM015402; -.
DR HGNC; HGNC:30048; PIR.
DR HPA; HPA000697; -.
DR MIM; 603329; gene.
DR neXtProt; NX_O00625; -.
DR PharmGKB; PA134870022; -.
DR eggNOG; COG1741; -.
DR HOGENOM; HOG000248360; -.
DR HOVERGEN; HBG019151; -.
DR InParanoid; O00625; -.
DR KO; K06911; -.
DR OMA; DPFVHMD; -.
DR OrthoDB; EOG7JMGFH; -.
DR PhylomeDB; O00625; -.
DR UniPathway; UPA00724; -.
DR EvolutionaryTrace; O00625; -.
DR GeneWiki; PIR_(gene); -.
DR GenomeRNAi; 8544; -.
DR NextBio; 32006; -.
DR PRO; PR:O00625; -.
DR Bgee; O00625; -.
DR CleanEx; HS_PIR; -.
DR Genevestigator; O00625; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
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 cofactor activity; IMP:UniProtKB.
DR GO; GO:0030224; P:monocyte differentiation; IMP:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc.
DR Gene3D; 2.60.120.10; -; 1.
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.
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; Complete proteome; Cytoplasm; Dioxygenase; Iron;
KW Metal-binding; Nucleus; Oxidoreductase; Polymorphism;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1 290 Pirin.
FT /FTId=PRO_0000214051.
FT METAL 56 56 Iron.
FT METAL 58 58 Iron.
FT METAL 101 101 Iron.
FT METAL 103 103 Iron.
FT VARIANT 228 228 V -> A (in dbSNP:rs34104000).
FT /FTId=VAR_050543.
FT CONFLICT 24 24 V -> D (in Ref. 2; CAG46621).
FT CONFLICT 162 162 K -> R (in Ref. 2; CAG46621).
FT STRAND 7 12
FT STRAND 14 18
FT STRAND 22 26
FT HELIX 31 33
FT STRAND 39 47
FT STRAND 52 67
FT STRAND 69 71
FT STRAND 73 77
FT STRAND 82 85
FT STRAND 90 94
FT STRAND 99 105
FT STRAND 107 109
FT STRAND 111 119
FT HELIX 122 124
FT STRAND 130 134
FT HELIX 136 138
FT STRAND 147 156
FT STRAND 169 176
FT STRAND 181 185
FT STRAND 191 199
FT STRAND 201 204
FT STRAND 210 212
FT STRAND 216 220
FT STRAND 224 229
FT STRAND 232 234
FT STRAND 236 243
FT STRAND 251 253
FT STRAND 256 260
FT HELIX 261 272
FT HELIX 279 281
FT TURN 287 289
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
//
ID PIR_HUMAN Reviewed; 290 AA.
AC O00625; Q5U0G0; Q6FHD2;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1997, sequence version 1.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Pirin;
DE EC=1.13.11.24;
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT 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
RT project: 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;
RP NFKB1; PIR AND TARGET DNA.
RX PubMed=10362352; DOI=10.1038/sj.onc.1202717;
RA Dechend R., Hirano F., Lehmann K., Heissmeyer V., Ansieau S.,
RA Wulczyn F.G., Scheidereit C., Leutz A.;
RT "The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel
RT and nuclear co-regulators.";
RL Oncogene 18:3316-3323(1999).
RN [6]
RP CATALYTIC ACTIVITY, AND ENZYME REGULATION.
RX PubMed=15951572; DOI=10.1074/jbc.M501034200;
RA Adams M., Jia Z.;
RT "Structural and biochemical analysis reveal pirins to possess
RT quercetinase 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.,
RA Lanfrancone L., Carbone R., Alcalay M.;
RT "Pirin delocalization in melanoma progression identified by high
RT content 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.,
RA Ho S.C., 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
RT of 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.,
RA Buerckstuemmer T., 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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal 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.,
RA Wong L.L., 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
RP 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
CC facilitates binding of NF-kappa-B proteins to target kappa-B genes
CC in a redox-state-dependent manner. May be required for efficient
CC terminal myeloid maturation of hematopoietic cells. Has quercetin
CC 2,3-dioxygenase activity (in vitro).
CC -!- CATALYTIC ACTIVITY: Quercetin + O(2) = 2-(3,4-
CC dihydroxybenzoyloxy)-4,6-dihydroxybenzoate + CO + H(+).
CC -!- COFACTOR: Binds 1 iron ion per subunit.
CC -!- ENZYME REGULATION: Inhibited by kojic acid, sodium
CC diethyldithiocarbamate and 1,10-phenanthroline monohydrochloride.
CC -!- PATHWAY: Flavonoid metabolism; quercetin degradation.
CC -!- SUBUNIT: May interact with NF1/CTF1. Interacts with BCL3.
CC Identified in a complex comprised of PIR, BLC3, NFKB1 and target
CC DNA.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Predominantly
CC localized in dot-like subnuclear structures. Cytoplasmic
CC localization of PIR seems to positively correlate with melanoma
CC progression.
CC -!- TISSUE SPECIFICITY: Highly expressed in a subset of melanomas.
CC Detected at very low levels in most tissues (at protein level).
CC Expressed in all tissues, with highest level of expression in
CC heart and liver.
CC -!- INDUCTION: Up-regulated in CD34(+) cells upon myelomonocytic
CC differentiation. Down-regulated in many acute myeloid leukemias.
CC Up-regulated in primary bronchial epithelial cells exposed to
CC cigarette smoke extract.
CC -!- POLYMORPHISM: Genetic variations in PIR might have a sex-specific
CC influence on bone mineral density differences in some populations,
CC as reported by PubMed:19766747. In a cohort of 4000 Chinese, a
CC significant statistical association has been identified, in women
CC but not in men, between the intronic SNP rs5935970 and lumbar
CC spine bone mineral density, and between a haplotype composed of
CC three SNPs with bone mineral density at other sites.
CC -!- SIMILARITY: Belongs to the pirin family.
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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 RefSeq; NP_001018119.1; NM_001018109.2.
DR RefSeq; NP_003653.1; NM_003662.3.
DR RefSeq; XP_005274667.1; XM_005274610.1.
DR UniGene; Hs.495728; -.
DR UniGene; Hs.732521; -.
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 PDBsum; 1J1L; -.
DR PDBsum; 3ACL; -.
DR PDBsum; 4ERO; -.
DR PDBsum; 4EWA; -.
DR PDBsum; 4EWD; -.
DR PDBsum; 4EWE; -.
DR PDBsum; 4GUL; -.
DR PDBsum; 4HLT; -.
DR ProteinModelPortal; O00625; -.
DR SMR; O00625; 3-290.
DR IntAct; O00625; 1.
DR MINT; MINT-1189585; -.
DR STRING; 9606.ENSP00000369785; -.
DR ChEMBL; CHEMBL2010627; -.
DR PhosphoSite; O00625; -.
DR UCD-2DPAGE; O00625; -.
DR PaxDb; O00625; -.
DR PeptideAtlas; O00625; -.
DR PRIDE; O00625; -.
DR DNASU; 8544; -.
DR Ensembl; ENST00000380420; ENSP00000369785; ENSG00000087842.
DR Ensembl; ENST00000380421; ENSP00000369786; ENSG00000087842.
DR GeneID; 8544; -.
DR KEGG; hsa:8544; -.
DR UCSC; uc004cwu.3; human.
DR CTD; 8544; -.
DR GeneCards; GC0XM015402; -.
DR HGNC; HGNC:30048; PIR.
DR HPA; HPA000697; -.
DR MIM; 603329; gene.
DR neXtProt; NX_O00625; -.
DR PharmGKB; PA134870022; -.
DR eggNOG; COG1741; -.
DR HOGENOM; HOG000248360; -.
DR HOVERGEN; HBG019151; -.
DR InParanoid; O00625; -.
DR KO; K06911; -.
DR OMA; DPFVHMD; -.
DR OrthoDB; EOG7JMGFH; -.
DR PhylomeDB; O00625; -.
DR UniPathway; UPA00724; -.
DR EvolutionaryTrace; O00625; -.
DR GeneWiki; PIR_(gene); -.
DR GenomeRNAi; 8544; -.
DR NextBio; 32006; -.
DR PRO; PR:O00625; -.
DR Bgee; O00625; -.
DR CleanEx; HS_PIR; -.
DR Genevestigator; O00625; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
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 cofactor activity; IMP:UniProtKB.
DR GO; GO:0030224; P:monocyte differentiation; IMP:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc.
DR Gene3D; 2.60.120.10; -; 1.
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.
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; Complete proteome; Cytoplasm; Dioxygenase; Iron;
KW Metal-binding; Nucleus; Oxidoreductase; Polymorphism;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1 290 Pirin.
FT /FTId=PRO_0000214051.
FT METAL 56 56 Iron.
FT METAL 58 58 Iron.
FT METAL 101 101 Iron.
FT METAL 103 103 Iron.
FT VARIANT 228 228 V -> A (in dbSNP:rs34104000).
FT /FTId=VAR_050543.
FT CONFLICT 24 24 V -> D (in Ref. 2; CAG46621).
FT CONFLICT 162 162 K -> R (in Ref. 2; CAG46621).
FT STRAND 7 12
FT STRAND 14 18
FT STRAND 22 26
FT HELIX 31 33
FT STRAND 39 47
FT STRAND 52 67
FT STRAND 69 71
FT STRAND 73 77
FT STRAND 82 85
FT STRAND 90 94
FT STRAND 99 105
FT STRAND 107 109
FT STRAND 111 119
FT HELIX 122 124
FT STRAND 130 134
FT HELIX 136 138
FT STRAND 147 156
FT STRAND 169 176
FT STRAND 181 185
FT STRAND 191 199
FT STRAND 201 204
FT STRAND 210 212
FT STRAND 216 220
FT STRAND 224 229
FT STRAND 232 234
FT STRAND 236 243
FT STRAND 251 253
FT STRAND 256 260
FT HELIX 261 272
FT HELIX 279 281
FT TURN 287 289
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
//
MIM
603329
*RECORD*
*FIELD* NO
603329
*FIELD* TI
*603329 PIRIN; PIR
*FIELD* TX
CLONING
NFI/CTF1 (see 164005) is a DNA-binding protein that stimulates
read moreadenovirus replication and RNA polymerase II-mediated transcription.
Using a yeast 2-hybrid screen with NFI/CTF1 as bait, Wendler et al.
(1997) isolated partial cDNAs encoding a protein that they designated
'pirin.' By screening a HeLa cell library with a partial pirin cDNA, the
authors recovered additional cDNAs representing alternatively spliced
transcripts that differed in their 5-prime untranslated regions but
encoded the same 290-amino acid protein. Immunofluorescence studies
indicated that pirin is localized in dot-like structures in the nucleus
of mammalian cells. Antibodies against pirin recognized a single band in
extracts of cells from several mammals, suggesting that pirin is
conserved among mammals. Northern blot analysis revealed that pirin was
expressed as an approximately 1.5-kb mRNA in all tissues tested, with
the highest levels in heart and liver. Additional larger transcripts
were detected at low levels in some tissues.
*FIELD* RF
1. Wendler, W. M. F.; Kremmer, E.; Forster, R.; Winnacker, E.-L.:
Identification of pirin, a novel highly conserved nuclear protein. J.
Biol. Chem. 272: 8482-8489, 1997.
*FIELD* CD
Rebekah S. Rasooly: 12/3/1998
*FIELD* ED
alopez: 01/06/2010
alopez: 12/3/1998
*RECORD*
*FIELD* NO
603329
*FIELD* TI
*603329 PIRIN; PIR
*FIELD* TX
CLONING
NFI/CTF1 (see 164005) is a DNA-binding protein that stimulates
read moreadenovirus replication and RNA polymerase II-mediated transcription.
Using a yeast 2-hybrid screen with NFI/CTF1 as bait, Wendler et al.
(1997) isolated partial cDNAs encoding a protein that they designated
'pirin.' By screening a HeLa cell library with a partial pirin cDNA, the
authors recovered additional cDNAs representing alternatively spliced
transcripts that differed in their 5-prime untranslated regions but
encoded the same 290-amino acid protein. Immunofluorescence studies
indicated that pirin is localized in dot-like structures in the nucleus
of mammalian cells. Antibodies against pirin recognized a single band in
extracts of cells from several mammals, suggesting that pirin is
conserved among mammals. Northern blot analysis revealed that pirin was
expressed as an approximately 1.5-kb mRNA in all tissues tested, with
the highest levels in heart and liver. Additional larger transcripts
were detected at low levels in some tissues.
*FIELD* RF
1. Wendler, W. M. F.; Kremmer, E.; Forster, R.; Winnacker, E.-L.:
Identification of pirin, a novel highly conserved nuclear protein. J.
Biol. Chem. 272: 8482-8489, 1997.
*FIELD* CD
Rebekah S. Rasooly: 12/3/1998
*FIELD* ED
alopez: 01/06/2010
alopez: 12/3/1998