Swiss-Prot entry
ID PXR_HUMAN STANDARD; PRT; 434 AA.
AC O75469; Q96AC7; Q9UJ22; Q9UJ23; Q9UJ24; Q9UJ25; Q9UJ26; Q9UJ27;
DT 15-JUL-1999 (Rel. 38, Created)
DT 15-JUL-1999 (Rel. 38, Last sequence update)
DT 01-MAY-2005 (Rel. 47, Last annotation update)
DE Orphan nuclear receptor PXR (Pregnane X receptor) (Orphan nuclear
DE receptor PAR1) (Steroid and xenobiotic receptor) (SXR).
GN Name=NR1I2; Synonyms=PXR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1A).
RC TISSUE=Liver;
RX MEDLINE=98395173; PubMed=9727070 [NCBI, ExPASy, EBI, Israel, Japan];
RA Lehmann J.M., McKee D.D., Watson M.A., Willson T.M., Moore J.T.,
RA Kliewer S.A.;
RT "The human orphan nuclear receptor PXR is activated by compounds that
RT regulate CYP3A4 gene expression and cause drug interactions.";
RL J. Clin. Invest. 102:1016-1023(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1A).
RC TISSUE=Liver;
RX MEDLINE=98445350; PubMed=9770465 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1073/pnas.95.21.12208;
RA Bertilsson G., Heidrich J., Svensson K., Asman M., Jendeberg L.,
RA Sydow-Backman M., Ohlsson R., Postlind H., Blomquist P.,
RA Berkenstam A.;
RT "Identification of a human nuclear receptor defines a new signaling
RT pathway for CYP3A induction.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:12208-12213(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1A), AND VARIANTS SER-27; ARG-36 AND
RP GLN-122.
RX MEDLINE=21525146; PubMed=11668216 [NCBI, ExPASy, EBI, Israel, Japan];
RA Zhang J., Kuehl P., Green E.D., Touchman J.W., Watkins P.B., Daly A.,
RA Hall S.D., Maurel P., Relling M., Brimer C., Yasuda K., Wrighton S.A.,
RA Hancock M., Kim R.B., Strom S., Thummel K., Russell C.G.,
RA Hudson J.R. Jr., Schuetz E.G., Boguski M.S.;
RT "The human pregnane X receptor: genomic structure and identification
RT and functional characterization of natural allelic variants.";
RL Pharmacogenetics 11:555-572(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE (ISOFORMS 1A; 1B; 1C; 2A; 2B AND 2C).
RC TISSUE=Liver;
RA Heard D.J., Holloway J., Hansen C., Tommerup N., Aagaard L.,
RA Vissing H.;
RT "Identification of a novel protein isoform of the human nuclear
RT hormone receptor PXR/SXR and localization to chromosome 3q12.1
RT -13.3.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1A).
RX MEDLINE=99003072; PubMed=9784494 [NCBI, ExPASy, EBI, Israel, Japan];
RA Blumberg B., Sabbagh W. Jr., Juguilon H., Bolado J. Jr.,
RA van Meter C.M., Ong E.S., Evans R.M.;
RT "SXR, a novel steroid and xenobiotic-sensing nuclear receptor.";
RL Genes Dev. 12:3195-3205(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1B).
RC TISSUE=Liver;
RX MEDLINE=22388257; PubMed=12477932 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1073/pnas.242603899;
RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G.,
RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D.,
RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K.,
RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F.,
RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L.,
RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E.,
RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C.,
RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J.,
RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H.,
RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W.,
RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A.,
RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A.,
RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C.,
RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M.,
RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E.,
RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.;
RT "Generation and initial analysis of more than 15,000 full-length human
RT and mouse cDNA sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
RN [7]
RP NUCLEAR LOCALIZATION SIGNAL.
RX MEDLINE=22495207; PubMed=12606758 [NCBI, ExPASy, EBI, Israel, Japan];
RA Kawana K., Ikuta T., Kobayashi Y., Gotoh O., Takeda K., Kawajiri K.;
RT "Molecular mechanism of nuclear translocation of an orphan nuclear
RT receptor, SXR.";
RL Mol. Pharmacol. 63:524-531(2003).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) OF 130-434.
RX MEDLINE=21317412; PubMed=11408620 [NCBI, ExPASy, EBI, Israel, Japan]; DOI=10.1126/science.1060762;
RA Watkins R.E., Wisely G.B., Moore L.B., Collins J.L., Lambert M.H.,
RA Williams S.P., Willson T.M., Kliewer S.A., Redinbo M.R.;
RT "The human nuclear xenobiotic receptor PXR: structural determinants of
RT directed promiscuity.";
RL Science 292:2329-2333(2001).
RN [9]
RP VARIANTS CYS-98; GLN-148; TRP-381 AND VAL-403.
RX PubMed=15618712 [NCBI, ExPASy, EBI, Israel, Japan];
RA Koyano S., Kurose K., Ozawa S., Saeki M., Nakajima Y., Hasegawa R.,
RA Komamura K., Ueno K., Kamakura S., Nakajima T., Saito H., Kimura H.,
RA Goto Y.-I., Saitoh O., Katoh M., Ohnuma T., Kawai M., Sugai K.,
RA Ohtsuki T., Suzuki C., Minami N., Saito Y., Sawada J.-I.;
RT "Eleven novel single nucleotide polymorphisms in the NR1I2 (PXR) gene,
RT four of which induce non-synonymous amino acid alterations.";
RL Drug Metab. Pharmacokinet. 17:561-565(2002).
CC -!- FUNCTION: Orphan receptor; its natural ligand is probably
CC pregnane. Binds to a response element in the CYP3A4 gene promoter.
CC Activates its expression in response to a wide variety of
CC endobiotics and xenobiotics.
CC -!- SUBUNIT: Forms a heterodimer with RXR.
CC -!- SUBCELLULAR LOCATION: Nuclear (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1A; Synonyms=1, PRR1-A;
CC IsoId=O75469-1; Sequence=Displayed;
CC Name=1B; Synonyms=PRR1-B;
CC IsoId=O75469-2; Sequence=VSP_003668;
CC Name=1C; Synonyms=PRR1-C;
CC IsoId=O75469-3; Sequence=VSP_003667;
CC Name=2A; Synonyms=2, PRR2-A;
CC IsoId=O75469-4; Sequence=VSP_003669;
CC Name=2B; Synonyms=PRR2-B;
CC IsoId=O75469-5; Sequence=VSP_003668, VSP_003669;
CC Name=2C; Synonyms=PRR2-C;
CC IsoId=O75469-6; Sequence=VSP_003667, VSP_003669;
CC -!- TISSUE SPECIFICITY: Expressed in liver, colon and small intestine.
CC -!- INDUCTION: Activated by naturally occurring steroids such as
CC pregnenolone and progesterone.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily.
CC -!- SIMILARITY: Contains 1 nuclear receptor DNA-binding domain.
CC --------------------------------------------------------------------------
CC This Swiss-Prot entry is copyright. It is produced through a collaboration
CC between the Swiss Institute of Bioinformatics and the EMBL outstation -
CC the European Bioinformatics Institute. There are no restrictions on its
CC use as long as its content is in no way modified and this statement is not
CC removed.
CC --------------------------------------------------------------------------
DR EMBL; AF061056; AAD05436.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AF084645; AAC64558.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AF364606; AAK38720.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AF364606; AAK38721.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AJ009936; CAB55489.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AJ009936; CAB55490.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AJ009936; CAB55491.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AJ009937; CAB55492.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AJ009937; CAB55493.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AJ009937; CAB55494.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; AY091855; AAM26736.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR EMBL; BC017304; AAH17304.1; -. [EMBL / GenBank / DDBJ] [CoDingSequence]
DR PDB; 1ILG; X-ray; A=119-434. [ExPASy / RCSB]
DR PDB; 1ILH; X-ray; A=119-434. [ExPASy / RCSB]
DR PDB; 1M13; X-ray; A=119-434. [ExPASy / RCSB]
DR PDB; 1NRL; X-ray; A/B=119-434. [ExPASy / RCSB]
DR TRANSFAC; T04610; -.
DR TRANSFAC; T04617; -.
DR Ensembl; ENSG00000144852; Homo_sapiens
DR Genew; HGNC:7968; NR1I2.
DR CleanEx; HGNC:7968; NR1I2.
DR H-InvDB; HIX0003588; -.
DR MIM; 603065; -. [NCBI / EBI]
DR GeneCards; NR1I2.
DR GeneLynx; NR1I2.
DR GenAtlas; NR1I2.
DR SOURCE; NR1I2.
DR GO; GO:0004879; F:ligand-dependent nuclear receptor activity; TAS.
DR GO; GO:0003713; F:transcription coactivator activity; TAS.
DR GO; GO:0007165; P:signal transduction; TAS.
DR GO; GO:0008202; P:steroid metabolism; TAS.
DR GO; GO:0006805; P:xenobiotic metabolism; TAS.
DR InterPro; IPR000536; Hrmon_recept_lig.
DR InterPro; IPR001723; Stdhrmn_receptor.
DR InterPro; IPR008946; Str_ncl_receptor.
DR InterPro; IPR000324; VitD_receptor.
DR InterPro; IPR001628; Znf_C4steroid.
DR InterPro; Graphical view of domain structure.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR Pfam; Graphical view of domain structure.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR PRINTS; PR00350; VITAMINDR.
DR ProDom; PD000035; Znf_C4steroid; 1.
DR ProDom [Domain structure / List of seq. sharing at least 1 domain ]
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
DR CMR; O75469.
DR HOVERGEN [Family / Alignment / Tree]
DR BLOCKS; O75469.
DR ProtoNet; O75469.
DR ProtoMap; O75469.
DR PRESAGE; O75469.
DR DIP; O75469.
DR ModBase; O75469.
DR SWISS-2DPAGE; GET REGION ON 2D PAGE.
KW 3D-structure; Alternative splicing; DNA-binding; Nuclear protein;
KW Polymorphism; Receptor; Transcription; Transcription regulation;
KW Zinc-finger.
FT DNA_BIND 22 90 Nuclear receptor-type.
FT DNA_BIND 38 107 Nuclear receptor-type.
FT ZN_FING 41 61 C4-type.
FT DOMAIN 66 92 Bipartite nuclear localization signal.
FT ZN_FING 77 102 C4-type.
FT DOMAIN 108 204 Hinge.
FT DOMAIN 205 434 Ligand-binding.
FT VARSPLIC 1 1 M -> MDPRGEVGAKNLPPNSPRGPEANL (in isoform
FT 1C and isoform 2C).
FT /FTId=VSP_003667.
FT VARSPLIC 1 55 Missing (in isoform 1B and isoform 2B).
FT /FTId=VSP_003668.
FT VARSPLIC 174 210 Missing (in isoform 2A, isoform 2B and
FT isoform 2C).
FT /FTId=VSP_003669.
FT VARIANT 27 27 P -> S (in allele PXR*2; dbSNP:12721613).
FT /FTId=VAR_012228.
FT VARIANT 36 36 G -> R (in allele PXR*3; dbSNP:12721607).
FT /FTId=VAR_012229.
FT VARIANT 98 98 R -> C.
FT /FTId=VAR_018340.
FT VARIANT 122 122 R -> Q (in allele PXR*4; rare
FT polymorphism).
FT /FTId=VAR_012230.
FT VARIANT 148 148 R -> Q.
FT /FTId=VAR_018341.
FT VARIANT 381 381 R -> W.
FT /FTId=VAR_018342.
FT VARIANT 403 403 I -> V.
FT /FTId=VAR_018343.
FT CONFLICT 12 12 A -> T (in Ref. 4).
FT CONFLICT 109 109 K -> N (in Ref. 4).
FT HELIX 145 161
FT TURN 164 165
FT TURN 167 168
FT HELIX 199 203
FT HELIX 204 208
FT STRAND 211 216
FT TURN 218 219
FT STRAND 222 225
FT HELIX 234 237
FT TURN 238 239
FT HELIX 240 260
FT HELIX 262 265
FT TURN 266 266
FT HELIX 269 290
FT TURN 291 291
FT STRAND 292 293
FT TURN 294 297
FT STRAND 298 301
FT TURN 302 303
FT STRAND 304 308
FT TURN 312 313
FT HELIX 314 318
FT TURN 319 320
FT HELIX 322 332
FT TURN 333 333
FT HELIX 337 348
FT TURN 349 349
FT TURN 351 352
FT TURN 354 355
FT HELIX 359 380
FT HELIX 384 386
FT TURN 387 388
FT HELIX 389 417
FT HELIX 423 429
FT TURN 430 430
SQ SEQUENCE 434 AA; 49762 MW; 1DF6A2AE3109C4DA CRC64;
MEVRPKESWN HADFVHCEDT ESVPGKPSVN ADEEVGGPQI CRVCGDKATG YHFNVMTCEG
CKGFFRRAMK RNARLRCPFR KGACEITRKT RRQCQACRLR KCLESGMKKE MIMSDEAVEE
RRALIKRKKS ERTGTQPLGV QGLTEEQRMM IRELMDAQMK TFDTTFSHFK NFRLPGVLSS
GCELPESLQA PSREEAAKWS QVRKDLCSLK VSLQLRGEDG SVWNYKPPAD SGGKEIFSLL
PHMADMSTYM FKGIISFAKV ISYFRDLPIE DQISLLKGAA FELCQLRFNT VFNAETGTWE
CGRLSYCLED TAGGFQQLLL EPMLKFHYML KKLQLHEEEY VLMQAISLFS PDRPGVLQHR
VVDQLQEQFA ITLKSYIECN RPQPAHRFLF LKIMAMLTEL RSINAQHTQR LLRIQDIHPF
ATPLMQELFG ITGS
//