Q96RI1 (NR1H4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bile acid receptor

Alternative name(s):
Farnesoid X-activated receptor
Farnesol receptor HRR-1
Nuclear receptor subfamily 1 group H member 4
Retinoid X receptor-interacting protein 14
Short name=RXR-interacting protein 14

Gene names

Name:	NR1H4
Synonyms:	BAR, FXR, HRR1, RIP14

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	486 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus. Ref.8 Ref.9 Ref.10 Ref.12 Ref.14 Ref.16 Ref.18 Ref.19
Subunit structure	Heterodimer of NR1H4 and RXR. After activation by agonist binding, interacts with a coactivator, NCOA1 or NCOA2 By similarity. Interacts with CARM1 and SMARD1. Ref.11 Ref.12 Ref.14 Ref.16 Ref.17 Ref.18 Ref.19
Subcellular location	Nucleus Probable.
Post-translational modification	Methylation may increase transactivation of target genes. Ref.13
Sequence similarities	Belongs to the nuclear hormone receptor family. NR1 subfamily. Contains 1 nuclear receptor DNA-binding domain.
Sequence caution	The sequence BC144183 differs from that shown. Reason: Frameshift at position 156.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Receptor Repressor
PTM	Methylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bile acid metabolic process Traceable author statement Ref.8. Source: ProtInc cellular response to acid Inferred from direct assay PubMed 21757002. Source: BHF-UCL digestive tract development Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity PubMed 21757002. Source: BHF-UCL nitrogen catabolite activation of transcription from RNA polymerase II promoter Inferred by curator PubMed 21757002. Source: BHF-UCL positive regulation of ammonia assimilation cycle Inferred from electronic annotation. Source: Compara positive regulation of glutamate metabolic process Inferred from sequence or structural similarity PubMed 21757002. Source: BHF-UCL regulation of bile acid biosynthetic process Traceable author statement PubMed 21757002. Source: BHF-UCL regulation of carbohydrate metabolic process Inferred from electronic annotation. Source: Compara regulation of cholesterol metabolic process Traceable author statement PubMed 21757002. Source: BHF-UCL regulation of urea metabolic process Inferred from sequence or structural similarity PubMed 21757002. Source: BHF-UCL response to glucose stimulus Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome
Cellular_component	nuclear euchromatin Inferred from direct assay PubMed 21757002. Source: BHF-UCL nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	RNA polymerase II distal enhancer sequence-specific DNA binding Inferred from direct assay PubMed 21757002. Source: BHF-UCL RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 21757002. Source: BHF-UCL RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription Inferred from direct assay PubMed 21757002. Source: BHF-UCL bile acid binding Inferred from sequence or structural similarity PubMed 21757002. Source: BHF-UCL ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Inferred from sequence or structural similarity PubMed 21757002. Source: BHF-UCL ligand-dependent nuclear receptor binding Traceable author statement PubMed 21757002. Source: BHF-UCL peptide binding Inferred from electronic annotation. Source: Compara steroid hormone receptor activity Inferred from electronic annotation. Source: Compara thyroid hormone receptor activity Inferred from electronic annotation. Source: InterPro transcription coactivator activity Traceable author statement Ref.8. Source: ProtInc transcription corepressor activity Traceable author statement Ref.8. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96RI1-3)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q96RI1-4)

The sequence of this isoform differs from the canonical sequence as follows:
     207-210: Missing.

Isoform 3 (identifier: Q96RI1-1)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: MVMQFQGLENPIQISPHCSCTPSGFFMEMMSMKPAK → MGSKMNLIEHSHLPTTDEFSFSENLF

Isoform 4 (identifier: Q96RI1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: MVMQFQGLENPIQISPHCSCTPSGFFMEMMSMKPAK → MGSKMNLIEHSHLPTTDEFSFSENLF
     207-210: Missing.

Isoform 5 (identifier: Q96RI1-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: MVMQFQGLENPIQISPHCSCTPSGFFMEMMSMKPAK → MGSKMNLIEHSHLPTTDEFSFSENLF
     159-209: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 486

486

Bile acid receptor

PRO_0000053538

Regions

DNA binding

134 – 209

76

Nuclear receptor

Zinc finger

137 – 157

21

NR C4-type

Zinc finger

173 – 197

25

NR C4-type

Region

256 – 474

219

Ligand-binding

Region

342 – 350

9

Agonist binding By similarity

Sites

Binding site

375

1

Agonist By similarity

Binding site

383

1

Agonist By similarity

Binding site

461

1

Agonist By similarity

Binding site

483

1

Agonist By similarity

Amino acid modifications

Modified residue

220

1

N6-methyllysine; by SETD7 Ref.13

Natural variations

Alternative sequence

1 – 36

36

MVMQF…MKPAK → MGSKMNLIEHSHLPTTDEFS FSENLF in isoform 3, isoform 4 and isoform 5.

VSP_010135

Alternative sequence

159 – 209

51

Missing in isoform 5.

VSP_044547

Alternative sequence

207 – 210

4

Missing in isoform 2 and isoform 4.

VSP_003665

Experimental info

Sequence conflict

198

1

K → R in AAI44185. Ref.7

Sequence conflict

217

1

C → V in BC144183. Ref.7

Secondary structure

1

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486

Helix Strand Turn

Details...

Helix

261 – 274

14

Helix

281 – 289

9

Helix

297 – 317

21

Helix

322 – 324

3

Helix

327 – 352

26

Helix

356 – 367

12

Turn

368 – 370

3

Turn

373 – 375

3

Helix

376 – 387

12

Turn

388 – 390

3

Helix

393 – 404

12

Beta strand

407 – 411

5

Helix

415 – 436

22

Helix

443 – 455

13

Helix

457 – 470

14

Helix

477 – 483

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 26, 2004. Version 2. Checksum: C23283576A8CF76B	FASTA	486	55,914
	10 20 30 40 50 60 MVMQFQGLEN PIQISPHCSC TPSGFFMEMM SMKPAKGVLT EQVAGPLGQN LEVEPYSQYS 70 80 90 100 110 120 NVQFPQVQPQ ISSSSYYSNL GFYPQQPEEW YSPGIYELRR MPAETLYQGE TEVAEMPVTK 130 140 150 160 170 180 KPRMGASAGR IKGDELCVVC GDRASGYHYN ALTCEGCKGF FRRSITKNAV YKCKNGGNCV 190 200 210 220 230 240 MDMYMRRKCQ ECRLRKCKEM GMLAECMYTG LLTEIQCKSK RLRKNVKQHA DQTVNEDSEG 250 260 270 280 290 300 RDLRQVTSTT KSCREKTELT PDQQTLLHFI MDSYNKQRMP QEITNKILKE EFSAEENFLI 310 320 330 340 350 360 LTEMATNHVQ VLVEFTKKLP GFQTLDHEDQ IALLKGSAVE AMFLRSAEIF NKKLPSGHSD 370 380 390 400 410 420 LLEERIRNSG ISDEYITPMF SFYKSIGELK MTQEEYALLT AIVILSPDRQ YIKDREAVEK 430 440 450 460 470 480 LQEPLLDVLQ KLCKIHQPEN PQHFACLLGR LTELRTFNHH HAEMLMSWRV NDHKFTPLLC EIWDVQ
	Isoform 2 [UniParc]. Checksum: 2B9B563B0999C91D	FASTA	482	55,462
	10 20 30 40 50 60 MVMQFQGLEN PIQISPHCSC TPSGFFMEMM SMKPAKGVLT EQVAGPLGQN LEVEPYSQYS 70 80 90 100 110 120 NVQFPQVQPQ ISSSSYYSNL GFYPQQPEEW YSPGIYELRR MPAETLYQGE TEVAEMPVTK 130 140 150 160 170 180 KPRMGASAGR IKGDELCVVC GDRASGYHYN ALTCEGCKGF FRRSITKNAV YKCKNGGNCV 190 200 210 220 230 240 MDMYMRRKCQ ECRLRKCKEM GMLAECLLTE IQCKSKRLRK NVKQHADQTV NEDSEGRDLR 250 260 270 280 290 300 QVTSTTKSCR EKTELTPDQQ TLLHFIMDSY NKQRMPQEIT NKILKEEFSA EENFLILTEM 310 320 330 340 350 360 ATNHVQVLVE FTKKLPGFQT LDHEDQIALL KGSAVEAMFL RSAEIFNKKL PSGHSDLLEE 370 380 390 400 410 420 RIRNSGISDE YITPMFSFYK SIGELKMTQE EYALLTAIVI LSPDRQYIKD REAVEKLQEP 430 440 450 460 470 480 LLDVLQKLCK IHQPENPQHF ACLLGRLTEL RTFNHHHAEM LMSWRVNDHK FTPLLCEIWD VQ
	Isoform 3 [UniParc]. Checksum: 37FB0351FB447544	FASTA	476	54,862
	10 20 30 40 50 60 MGSKMNLIEH SHLPTTDEFS FSENLFGVLT EQVAGPLGQN LEVEPYSQYS NVQFPQVQPQ 70 80 90 100 110 120 ISSSSYYSNL GFYPQQPEEW YSPGIYELRR MPAETLYQGE TEVAEMPVTK KPRMGASAGR 130 140 150 160 170 180 IKGDELCVVC GDRASGYHYN ALTCEGCKGF FRRSITKNAV YKCKNGGNCV MDMYMRRKCQ 190 200 210 220 230 240 ECRLRKCKEM GMLAECMYTG LLTEIQCKSK RLRKNVKQHA DQTVNEDSEG RDLRQVTSTT 250 260 270 280 290 300 KSCREKTELT PDQQTLLHFI MDSYNKQRMP QEITNKILKE EFSAEENFLI LTEMATNHVQ 310 320 330 340 350 360 VLVEFTKKLP GFQTLDHEDQ IALLKGSAVE AMFLRSAEIF NKKLPSGHSD LLEERIRNSG 370 380 390 400 410 420 ISDEYITPMF SFYKSIGELK MTQEEYALLT AIVILSPDRQ YIKDREAVEK LQEPLLDVLQ 430 440 450 460 470 KLCKIHQPEN PQHFACLLGR LTELRTFNHH HAEMLMSWRV NDHKFTPLLC EIWDVQ
	Isoform 4 [UniParc]. Checksum: 0A53D414B9049C4C	FASTA	472	54,409
	10 20 30 40 50 60 MGSKMNLIEH SHLPTTDEFS FSENLFGVLT EQVAGPLGQN LEVEPYSQYS NVQFPQVQPQ 70 80 90 100 110 120 ISSSSYYSNL GFYPQQPEEW YSPGIYELRR MPAETLYQGE TEVAEMPVTK KPRMGASAGR 130 140 150 160 170 180 IKGDELCVVC GDRASGYHYN ALTCEGCKGF FRRSITKNAV YKCKNGGNCV MDMYMRRKCQ 190 200 210 220 230 240 ECRLRKCKEM GMLAECLLTE IQCKSKRLRK NVKQHADQTV NEDSEGRDLR QVTSTTKSCR 250 260 270 280 290 300 EKTELTPDQQ TLLHFIMDSY NKQRMPQEIT NKILKEEFSA EENFLILTEM ATNHVQVLVE 310 320 330 340 350 360 FTKKLPGFQT LDHEDQIALL KGSAVEAMFL RSAEIFNKKL PSGHSDLLEE RIRNSGISDE 370 380 390 400 410 420 YITPMFSFYK SIGELKMTQE EYALLTAIVI LSPDRQYIKD REAVEKLQEP LLDVLQKLCK 430 440 450 460 470 IHQPENPQHF ACLLGRLTEL RTFNHHHAEM LMSWRVNDHK FTPLLCEIWD VQ
	Isoform 5 [UniParc]. Checksum: F29FB6B5C5FA2257	FASTA	425	48,795
	10 20 30 40 50 60 MGSKMNLIEH SHLPTTDEFS FSENLFGVLT EQVAGPLGQN LEVEPYSQYS NVQFPQVQPQ 70 80 90 100 110 120 ISSSSYYSNL GFYPQQPEEW YSPGIYELRR MPAETLYQGE TEVAEMPVTK KPRMGASAGR 130 140 150 160 170 180 IKGDELCVVC GDRASGYHYN ALTCEGCKGL LTEIQCKSKR LRKNVKQHAD QTVNEDSEGR 190 200 210 220 230 240 DLRQVTSTTK SCREKTELTP DQQTLLHFIM DSYNKQRMPQ EITNKILKEE FSAEENFLIL 250 260 270 280 290 300 TEMATNHVQV LVEFTKKLPG FQTLDHEDQI ALLKGSAVEA MFLRSAEIFN KKLPSGHSDL 310 320 330 340 350 360 LEERIRNSGI SDEYITPMFS FYKSIGELKM TQEEYALLTA IVILSPDRQY IKDREAVEKL 370 380 390 400 410 420 QEPLLDVLQK LCKIHQPENP QHFACLLGRL TELRTFNHHH AEMLMSWRVN DHKFTPLLCE IWDVQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The identification of the cDNA coding for HRR-1, a novel human farnesol receptor." Papetti M., Wood N., Lohmar P.D., Bowman M.R. Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[2]	"Functional analysis of human farnesol receptor (NR1H4) splicing variant." Han J.-I., Bok S.-H., Jeong T.-S. Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
[3]	"Generation of multiple farnesoid-X-receptor isoforms through the use of alternative promoters." Huber R.M., Murphy K., Miao B., Link J.R., Cunningham M.R., Rupar M.J., Gunyuzlu P.L., Haws T.F. Jr., Kassam A., Powell F., Hollis G.F., Young P.R., Mukherjee R., Burn T.C. Gene 290:35-43(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon.
[5]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] (ISOFORMS 3 AND 5).
[8]	"Identification of a nuclear receptor for bile acids." Makishima M., Okamoto A.Y., Repa J.J., Tu H., Learned R.M., Luk A., Hull M.V., Lustig K.D., Mangelsdorf D.J., Shan B. Science 284:1362-1365(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"Bile acids: natural ligands for an orphan nuclear receptor." Parks D.J., Blanchard S.G., Bledsoe R.K., Chandra G., Consler T.G., Kliewer S.A., Stimmel J.B., Willson T.M., Zavacki A.M., Moore D.D., Lehmann J.M. Science 284:1365-1368(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis." Holt J.A., Luo G., Billin A.N., Bisi J., McNeill Y.Y., Kozarsky K.F., Donahee M., Wang D.Y., Mansfield T.A., Kliewer S.A., Goodwin B., Jones S.A. Genes Dev. 17:1581-1591(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"BAF60a mediates critical interactions between nuclear receptors and the BRG1 chromatin-remodeling complex for transactivation." Hsiao P.W., Fryer C.J., Trotter K.W., Wang W., Archer T.K. Mol. Cell. Biol. 23:6210-6220(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SMARD1.
[12]	"Ligand-dependent activation of the farnesoid X-receptor directs arginine methylation of histone H3 by CARM1." Ananthanarayanan M., Li S., Balasubramaniyan N., Suchy F.J., Walsh M.J. J. Biol. Chem. 279:54348-54357(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CARM1.
[13]	"Direct methylation of FXR by Set7/9, a lysine methyltransferase, regulates the expression of FXR target genes." Balasubramaniyan N., Ananthanarayanan M., Suchy F.J. Am. J. Physiol. 302:G937-G947(2012) [PubMed] [Europe PMC] [Abstract] Cited for: METHYLATION AT LYS-220 BY SETD7.
[14]	"A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR." Downes M., Verdecia M.A., Roecker A.J., Hughes R., Hogenesch J.B., Kast-Woelbern H.R., Bowman M.E., Ferrer J.L., Anisfeld A.M., Edwards P.A., Rosenfeld J.M., Alvarez J.G., Noel J.P., Nicolaou K.C., Evans R.M. Mol. Cell 11:1079-1092(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 258-476 IN COMPLEX WITH SYNTHETIC AGONIST FEXARAMINE, FUNCTION, INTERACTION WITH NCOA1.
[15]	"Structural basis for bile acid binding and activation of the nuclear receptor FXR." Mi L.Z., Devarakonda S., Harp J.M., Han Q., Pellicciari R., Willson T.M., Khorasanizadeh S., Rastinejad F. Mol. Cell 11:1093-1100(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 241-469 IN COMPLEXES WITH CHENODEOXYCHOLIC ACID ANALOGS AND NCOA2 COACTIVATOR PEPTIDE.
[16]	"Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064." Akwabi-Ameyaw A., Bass J.Y., Caldwell R.D., Caravella J.A., Chen L., Creech K.L., Deaton D.N., Jones S.A., Kaldor I., Liu Y., Madauss K.P., Marr H.B., McFadyen R.B., Miller A.B., Iii F.N., Parks D.J., Spearing P.K., Todd D., Williams S.P., Wisely G.B. Bioorg. Med. Chem. Lett. 18:4339-4343(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 252-486 IN COMPLEX WITH SYNTHETIC AGONIST, FUNCTION, INTERACTION WITH NCOA1.
[17]	"Identification of a potent synthetic FXR agonist with an unexpected mode of binding and activation." Soisson S.M., Parthasarathy G., Adams A.D., Sahoo S., Sitlani A., Sparrow C., Cui J., Becker J.W. Proc. Natl. Acad. Sci. U.S.A. 105:5337-5342(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 249-486 IN COMPLEX WITH STEROID ANALOG MFA-1 AND NCOA1 PEPTIDE, INTERACTION WITH NCOA1, DOMAIN.
[18]	"Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064." Bass J.Y., Caldwell R.D., Caravella J.A., Chen L., Creech K.L., Deaton D.N., Madauss K.P., Marr H.B., McFadyen R.B., Miller A.B., Parks D.J., Todd D., Williams S.P., Wisely G.B. Bioorg. Med. Chem. Lett. 19:2969-2973(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 260-486 IN COMPLEX WITH SYNTHETIC AGONIST, FUNCTION, INTERACTION WITH NCOA1.
[19]	"FXR agonist activity of conformationally constrained analogs of GW 4064." Akwabi-Ameyaw A., Bass J.Y., Caldwell R.D., Caravella J.A., Chen L., Creech K.L., Deaton D.N., Madauss K.P., Marr H.B., McFadyen R.B., Miller A.B., Navas F. III, Parks D.J., Spearing P.K., Todd D., Williams S.P., Bruce Wisely G. Bioorg. Med. Chem. Lett. 19:4733-4739(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 257-486 IN COMPLEX WITH SYNTHETIC AGONIST, FUNCTION, INTERACTION WITH NCOA1.
[20]	"Discovery of XL335 (WAY-362450), a highly potent, selective, and orally active agonist of the farnesoid X receptor (FXR)." Flatt B., Martin R., Wang T.L., Mahaney P., Murphy B., Gu X.H., Foster P., Li J., Pircher P., Petrowski M., Schulman I., Westin S., Wrobel J., Yan G., Bischoff E., Daige C., Mohan R. J. Med. Chem. 52:904-907(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 258-486 IN COMPLEX WITH SYNTHETIC AGONIST.
[21]	"Improvement of physiochemical properties of the tetrahydroazepinoindole series of farnesoid X receptor (FXR) agonists: beneficial modulation of lipids in primates." Lundquist J.T., Harnish D.C., Kim C.Y., Mehlmann J.F., Unwalla R.J., Phipps K.M., Crawley M.L., Commons T., Green D.M., Xu W., Hum W.T., Eta J.E., Feingold I., Patel V., Evans M.J., Lai K., Borges-Marcucci L., Mahaney P.E., Wrobel J.E. J. Med. Chem. 53:1774-1787(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 248-476 IN COMPLEX WITH SYNTHETIC AGONIST.
+	Additional computationally mapped references.

Web resources

Wikipedia

Farnesoid X receptor entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U68233 mRNA. Translation: AAB08107.1.
AF384555 mRNA. Translation: AAK60271.1.
AF478445 mRNA. Translation: AAM53550.1.
AF478446 mRNA. Translation: AAM53551.1.
AK296612 mRNA. Translation: BAH12398.1.
AC010200 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW97639.1.
BC144183 mRNA. No translation available.
BC144184 mRNA. Translation: AAI44185.1.
BC130573 mRNA. Translation: AAI30574.1.

IPI

IPI00045302.
IPI00168867.
IPI00220798.
IPI00410346.
IPI01022446.

RefSeq

NP_001193906.1. NM_001206977.1.
NP_001193907.1. NM_001206978.1.
NP_001193908.1. NM_001206979.1.
NP_001193921.1. NM_001206992.1.
NP_001193922.1. NM_001206993.1.
NP_005114.1. NM_005123.3.

UniGene

Hs.282735.
Hs.732506.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1OSH	X-ray	1.80	A	258-476	[»]
1OSK	model	-	A	258-486	[»]
3BEJ	X-ray	1.90	A/B	249-486	[»]
3DCT	X-ray	2.50	A	252-486	[»]
3DCU	X-ray	2.95	A	252-486	[»]
3FLI	X-ray	2.00	A	258-486	[»]
3FXV	X-ray	2.26	A	258-486	[»]
3GD2	X-ray	3.20	A	260-486	[»]
3HC5	X-ray	2.60	A	257-486	[»]
3HC6	X-ray	3.20	A	257-486	[»]
3L1B	X-ray	1.90	A	258-486	[»]
3OKH	X-ray	2.50	A	258-486	[»]
3OKI	X-ray	2.00	A/C	258-486	[»]
3OLF	X-ray	1.90	A/C	258-486	[»]
3OMK	X-ray	1.90	A/C	258-486	[»]
3OMM	X-ray	2.10	A/C	258-486	[»]
3OOF	X-ray	2.29	A/C	258-486	[»]
3OOK	X-ray	2.29	A/C	258-486	[»]
3P88	X-ray	2.95	A	258-486	[»]
3P89	X-ray	2.30	A	258-486	[»]
3RUT	X-ray	3.00	A	258-486	[»]
3RUU	X-ray	2.50	A	258-486	[»]
3RVF	X-ray	3.10	A	257-486	[»]

ProteinModelPortal

Q96RI1.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-39370N.

IntAct

Q96RI1. 4 interactions.

STRING

9606.ENSP00000315442.

PTM databases

PhosphoSite

Q96RI1.

Polymorphism databases

DMDM

46577705.

Proteomic databases

PaxDb

Q96RI1.

PRIDE

Q96RI1.

Protocols and materials databases

DNASU

9971.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000188403; ENSP00000188403; ENSG00000012504.
ENST00000392986; ENSP00000376712; ENSG00000012504.
ENST00000548884; ENSP00000448506; ENSG00000012504.
ENST00000549996; ENSP00000448978; ENSG00000012504.
ENST00000551379; ENSP00000447149; ENSG00000012504.

GeneID

9971.

KEGG

hsa:9971.

UCSC

uc001ths.2. human.
uc001tht.2. human.

Organism-specific databases

CTD

9971.

GeneCards

GC12P100850.

HGNC

HGNC:7967. NR1H4.

HPA

HPA047699.

MIM

603826. gene.

neXtProt

NX_Q96RI1.

Orphanet

69665. Intrahepatic cholestasis of pregnancy.

PharmGKB

PA31752.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG302915.

HOVERGEN

HBG108655.

InParanoid

Q96RI1.

KO

K08537.

OMA

FNKKLPA.

OrthoDB

EOG4640C0.

PhylomeDB

Q96RI1.

Enzyme and pathway databases

Pathway_Interaction_DB

rxr_vdr_pathway. RXR and RAR hetrodimerization with other nuclear receptor.

Reactome

REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q96RI1.

Bgee

Q96RI1.

CleanEx

HS_NR1H4.

Genevestigator

Q96RI1.

GermOnline

ENSG00000012504. Homo sapiens.

Family and domain databases

Gene3D

1.10.565.10. 2 hits.
3.30.50.10. 1 hit.

InterPro

IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
IPR001728. ThyrH_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]

Pfam

PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]

PRINTS

PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
PR00546. THYROIDHORMR.

SMART

SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]

SUPFAM

SSF48508. Str_ncl_receptor. 1 hit.

PROSITE

PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q96RI1.

ChEMBL

CHEMBL2047.

EvolutionaryTrace

Q96RI1.

GenomeRNAi

9971.

NextBio

37658.

SOURCE

Search...

Entry information

Entry name

NR1H4_HUMAN

Accession

Primary (citable) accession number: Q96RI1
Secondary accession number(s): A1L4K5 , B7Z412, B7ZM06, F8VYG8, Q8NFP5, Q8NFP6, Q92943

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 27, 2002
Last sequence update:	April 26, 2004
Last modified:	May 1, 2013
This is version 129 of the entry and version 2 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.