Liver X receptor alpha

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Nuclear receptor subfamily 1, group H, member 3
Image:PBB Protein NR1H3 image.jpg
PDB rendering based on 1uhl.
Available structures:
For the file format that describes the 3D structures of molecules found in the Protein Data Bank, see Protein Data Bank (file format).

The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. These data, typically obtained by X-ray crystallography or NMR spectroscopy, are submitted by biologists and biochemists from around the world, are released into the public domain, and can be accessed for free.

Contents

History

Founded in 1971 by Drs. Edgar Meyer and Walter Hamilton Brookhaven National Laboratory, management of the Protein Data Bank was transferred in 1998 to members of the Research Collaboratory for Structural Bioinformatics (RCSB).

The Worldwide Protein Data Bank (wwPDB) consists of organizations that act as deposition, data processing and distribution centers for PDB data. The founding members are RCSB PDB (USA), MSD-EBI (Europe) and PDBj (Japan). The BMRB (USA) group joined the wwPDB in 2006. The mission of the wwPDB is to maintain a single Protein Data Bank Archive of macromolecular structural data that is freely and publicly available to the global community.

The PDB is a key resource in structural biology and is critical to more recent work in structural genomics.

Countless derived databases and projects have been developed to integrate and classify the PDB in terms of protein structure, protein function and protein evolution.

Growth

When the PDB was originally founded it contained just 7 protein structures. Since then it has undergone an approximate exponential growth in the number of structures, which does not show any sign of falling off.

The growth rate of the PDB has been the subject of fairly extensive analysis.

Contents

As of 26 September, 2006, the database contained 39,051 released atomic coordinate entries (or "structures"), 35,767 of that proteins, the rest being nucleic acids, nucleic acid-protein complexes, and a few other molecules. About 5,000 new structures are released each year. Data are stored in the mmCIF format specifically developed for the purpose.

Note that the database stores information about the exact location of all atoms in a large biomolecule (although, usually without the hydrogen atoms, as their positions are more of a statistical estimate); if one is only interested in sequence data, i.e. the list of amino acids making up a particular protein or the list of nucleotides making up a particular nucleic acid, the much larger databases from Swiss-Prot and the International Nucleotide Sequence Database Collaboration should be used.

Statistics

As of 11 September, 2007, the "PDB Holdings List" at RCSB reported the following statistics:

Proteins Nucleic Acids Protein/NA complexes Other Total
X-ray diffraction 36223 983 1684 24 38914
NMR 5665 781 134 7 6587
Electron microscopy 105 10 38 0 153
Other 80 4 4 2 90
Total 42073 1778 1860 33 45744

Note that theoretical models are no longer accepted in the PDB.

22461 structures in the PDB have a structure factor file. 3138 structures in the PDB have an NMR restraint file.

The current breakdown of holdings is updated weekly.

File format

Through the years the PDB file format has undergone many, many changes and revisions. Its original format was dictated by the width of computer punch cards.

This legacy format has caused many problems with the format, and consequently there are 'clean-up' projects;

The MMDB uses ASN.1 (and an XML conversion of this format). The wwPDB members RCSB PDB, MSD-EBI, and PDBj are working together to make the data uniform across the archive. Some believe this to be desirable; others argue that, without a universal repository of information (i.e., a common dictionary), it is not possible to draw comparisons.

Each structure published in PDB receives a four-character alphanumeric identifier, its PDB ID. This should not be used as an identifier for biomolecules, since often several structures for the same molecule (in different environments or conformations) are contained in PDB with different PDB IDs.

If a biologist submits structure data for a protein or nucleic acid, wwPDB staff reviews and annotates the entry. The data are then automatically checked for plausibility. The source code for this validation software has been released for free. The main data base accepts only experimentally derived structures, and not theoretically predicted ones (see protein structure prediction).

Various funding agencies and scientific journals now require scientists to submit their structure data to PDB.

Viewing the data

The structural data can be used to visualize the biomolecules with appropriate software, such as VMD, RasMol, PyMOL, Jmol, MDL Chime, QuteMol, web browser VRML plugin or any web-based software designed to visualize and analyse the protein structures such as STING. A recent desktop software addition is Sirius. The RCSB PDB website also contains resources for education, structural genomics, and related software.

References

Printed

  • H.M. Berman, K. Henrick, H. Nakamura (2003): Announcing the worldwide Protein Data Bank. Nature Structural Biology 10 (12), p. 980 PMID 14634627.
  • H.M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H. Weissig, I.N. Shindyalov, P.E. Bourne: The Protein Data Bank. Nucleic Acids Research, 28 pp. 235-242 (2000). PMID 10592235
  • Bernstein FC, Koetzle TF, Williams GJ, Meyer Jr EF, Brice MD, Rodgers JR, Kennard O, Shimanouchi T, Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol 1977;112:535-542. PMID 875032.
  • E.F. Meyer “The First Years of the Protein Data Bank“, Protein Science 6:1591-1597 (1997)
  • Sussman, JL, Lin, D, Jiang, J, Manning, NO, Prilusky, J, Ritter, O & Abola, EE. Protein data bank (PDB): a database of 3D structural information of biological macromolecules. Acta Cryst 1998; D54:1078-1084. PMID 10089483.

Online

Other external links

Links to enzyme database data

  • [1] The best mapping is provided by Kim Henrick's group at EBI as part of the MSD SIFTS initiative.
  • [2] PDB provide a mapping on their beta site, but it is at the whole PDB level not chain level.
  • [3] Search at BRENDA enzyme database portal.
  • [4] PDBSProtEC:

Molecular graphic visualisation tools

The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. These data, typically obtained by X-ray crystallography or NMR spectroscopy, are submitted by biologists and biochemists from around the world, are released into the public domain, and can be accessed for free.

History

Founded in 1971 by Drs. Edgar Meyer and Walter Hamilton Brookhaven National Laboratory, management of the Protein Data Bank was transferred in 1998 to members of the Research Collaboratory for Structural Bioinformatics (RCSB).

The Worldwide Protein Data Bank (wwPDB) consists of organizations that act as deposition, data processing and distribution centers for PDB data. The founding members are RCSB PDB (USA), MSD-EBI (Europe) and PDBj (Japan). The BMRB (USA) group joined the wwPDB in 2006. The mission of the wwPDB is to maintain a single Protein Data Bank Archive of macromolecular structural data that is freely and publicly available to the global community.

The PDB is a key resource in structural biology and is critical to more recent work in structural genomics.

Countless derived databases and projects have been developed to integrate and classify the PDB in terms of protein structure, protein function and protein evolution.

Growth

When the PDB was originally founded it contained just 7 protein structures. Since then it has undergone an approximate exponential growth in the number of structures, which does not show any sign of falling off.

The growth rate of the PDB has been the subject of fairly extensive analysis.

Contents

As of 26 September, 2006, the database contained 39,051 released atomic coordinate entries (or "structures"), 35,767 of that proteins, the rest being nucleic acids, nucleic acid-protein complexes, and a few other molecules. About 5,000 new structures are released each year. Data are stored in the mmCIF format specifically developed for the purpose.

Note that the database stores information about the exact location of all atoms in a large biomolecule (although, usually without the hydrogen atoms, as their positions are more of a statistical estimate); if one is only interested in sequence data, i.e. the list of amino acids making up a particular protein or the list of nucleotides making up a particular nucleic acid, the much larger databases from Swiss-Prot and the International Nucleotide Sequence Database Collaboration should be used.

Statistics

As of 11 September, 2007, the "PDB Holdings List" at RCSB reported the following statistics:

Proteins Nucleic Acids Protein/NA complexes Other Total
X-ray diffraction 36223 983 1684 24 38914
NMR 5665 781 134 7 6587
Electron microscopy 105 10 38 0 153
Other 80 4 4 2 90
Total 42073 1778 1860 33 45744

Note that theoretical models are no longer accepted in the PDB.

22461 structures in the PDB have a structure factor file. 3138 structures in the PDB have an NMR restraint file.

The current breakdown of holdings is updated weekly.

File format

Through the years the PDB file format has undergone many, many changes and revisions. Its original format was dictated by the width of computer punch cards.

This legacy format has caused many problems with the format, and consequently there are 'clean-up' projects;

The MMDB uses ASN.1 (and an XML conversion of this format). The wwPDB members RCSB PDB, MSD-EBI, and PDBj are working together to make the data uniform across the archive. Some believe this to be desirable; others argue that, without a universal repository of information (i.e., a common dictionary), it is not possible to draw comparisons.

Each structure published in PDB receives a four-character alphanumeric identifier, its PDB ID. This should not be used as an identifier for biomolecules, since often several structures for the same molecule (in different environments or conformations) are contained in PDB with different PDB IDs.

If a biologist submits structure data for a protein or nucleic acid, wwPDB staff reviews and annotates the entry. The data are then automatically checked for plausibility. The source code for this validation software has been released for free. The main data base accepts only experimentally derived structures, and not theoretically predicted ones (see protein structure prediction).

Various funding agencies and scientific journals now require scientists to submit their structure data to PDB.

Viewing the data

The structural data can be used to visualize the biomolecules with appropriate software, such as VMD, RasMol, PyMOL, Jmol, MDL Chime, QuteMol, web browser VRML plugin or any web-based software designed to visualize and analyse the protein structures such as STING. A recent desktop software addition is Sirius. The RCSB PDB website also contains resources for education, structural genomics, and related software.

References

Printed

  • H.M. Berman, K. Henrick, H. Nakamura (2003): Announcing the worldwide Protein Data Bank. Nature Structural Biology 10 (12), p. 980 PMID 14634627.
  • H.M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H. Weissig, I.N. Shindyalov, P.E. Bourne: The Protein Data Bank. Nucleic Acids Research, 28 pp. 235-242 (2000). PMID 10592235
  • Bernstein FC, Koetzle TF, Williams GJ, Meyer Jr EF, Brice MD, Rodgers JR, Kennard O, Shimanouchi T, Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol 1977;112:535-542. PMID 875032.
  • E.F. Meyer “The First Years of the Protein Data Bank“, Protein Science 6:1591-1597 (1997)
  • Sussman, JL, Lin, D, Jiang, J, Manning, NO, Prilusky, J, Ritter, O & Abola, EE. Protein data bank (PDB): a database of 3D structural information of biological macromolecules. Acta Cryst 1998; D54:1078-1084. PMID 10089483.

Online

Other external links

Links to enzyme database data

  • [5] The best mapping is provided by Kim Henrick's group at EBI as part of the MSD SIFTS initiative.
  • [6] PDB provide a mapping on their beta site, but it is at the whole PDB level not chain level.
  • [7] Search at BRENDA enzyme database portal.
  • [8] PDBSProtEC:

Molecular graphic visualisation tools

Identifiers
Symbol(s) NR1H3; LXR-a; LXRA; RLD-1
External IDs OMIM: 602423 MGI: 1352462 Homologene: 21165
RNA expression pattern

Image:PBB GE NR1H3 203920 at tn.png

More reference expression data

Orthologs
Human Mouse
Entrez 10062 22259
Ensembl ENSG00000025434 ENSMUSG00000002108
Uniprot Q13133 Q91X41
Refseq NM_005693 (mRNA)
NP_005684 (protein) 		NM_013839 (mRNA)
NP_038867 (protein)
Location Chr 11: 47.23 - 47.25 Mb Chr 2: 90.98 - 91 Mb
Pubmed search [9] [10]

Liver X receptor alpha (LXR-alpha) is a nuclear receptor protein encoded by the NR1H3 gene (nuclear receptor subfamily 1, group H, member 3).[1][1]


References

Further reading

  • Willy PJ, Umesono K, Ong ES, et al. (1995). "LXR, a nuclear receptor that defines a distinct retinoid response pathway.". Genes Dev. 9 (9): 1033-45. PMID 7744246.
  • Miyata KS, McCaw SE, Patel HV, et al. (1996). "The orphan nuclear hormone receptor LXR alpha interacts with the peroxisome proliferator-activated receptor and inhibits peroxisome proliferator signaling.". J. Biol. Chem. 271 (16): 9189-92. PMID 8621574.
  • Lehmann JM, Kliewer SA, Moore LB, et al. (1997). "Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway.". J. Biol. Chem. 272 (6): 3137-40. PMID 9013544.
  • Auboeuf D, Rieusset J, Fajas L, et al. (1997). "Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: no alteration in adipose tissue of obese and NIDDM patients.". Diabetes 46 (8): 1319-27. PMID 9231657.
  • Peet DJ, Turley SD, Ma W, et al. (1998). "Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha.". Cell 93 (5): 693-704. PMID 9630215.
  • Miyata KS, McCaw SE, Meertens LM, et al. (1999). "Receptor-interacting protein 140 interacts with and inhibits transactivation by, peroxisome proliferator-activated receptor alpha and liver-X-receptor alpha.". Mol. Cell. Endocrinol. 146 (1-2): 69-76. PMID 10022764.
  • Venkateswaran A, Laffitte BA, Joseph SB, et al. (2000). "Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha.". Proc. Natl. Acad. Sci. U.S.A. 97 (22): 12097-102. doi:10.1073/pnas.200367697. PMID 11035776.
  • Chinetti G, Lestavel S, Bocher V, et al. (2001). "PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway.". Nat. Med. 7 (1): 53-8. doi:10.1038/83348. PMID 11135616.
  • Laffitte BA, Repa JJ, Joseph SB, et al. (2001). "LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes.". Proc. Natl. Acad. Sci. U.S.A. 98 (2): 507-12. doi:10.1073/pnas.021488798. PMID 11149950.
  • Li Y, Bolten C, Bhat BG, et al. (2002). "Induction of human liver X receptor alpha gene expression via an autoregulatory loop mechanism.". Mol. Endocrinol. 16 (3): 506-14. PMID 11875109.
  • Mak PA, Laffitte BA, Desrumaux C, et al. (2002). "Regulated expression of the apolipoprotein E/C-I/C-IV/C-II gene cluster in murine and human macrophages. A critical role for nuclear liver X receptors alpha and beta.". J. Biol. Chem. 277 (35): 31900-8. doi:10.1074/jbc.M202993200. PMID 12032151.
  • Brendel C, Gelman L, Auwerx J (2003). "Multiprotein bridging factor-1 (MBF-1) is a cofactor for nuclear receptors that regulate lipid metabolism.". Mol. Endocrinol. 16 (6): 1367-77. PMID 12040021.
  • Steffensen KR, Schuster GU, Parini P, et al. (2002). "Different regulation of the LXRalpha promoter activity by isoforms of CCAAT/enhancer-binding proteins.". Biochem. Biophys. Res. Commun. 293 (5): 1333-40. doi:10.1016/S0006-291X(02)00390-X. PMID 12054659.
  • Gbaguidi GF, Agellon LB (2002). "The atypical interaction of peroxisome proliferator-activated receptor alpha with liver X receptor alpha antagonizes the stimulatory effect of their respective ligands on the murine cholesterol 7alpha-hydroxylase gene promoter.". Biochim. Biophys. Acta 1583 (2): 229-36. PMID 12117567.
  • Pawar A, Xu J, Jerks E, et al. (2002). "Fatty acid regulation of liver X receptors (LXR) and peroxisome proliferator-activated receptor alpha (PPARalpha ) in HEK293 cells.". J. Biol. Chem. 277 (42): 39243-50. doi:10.1074/jbc.M206170200. PMID 12161442.
  • Brendel C, Schoonjans K, Botrugno OA, et al. (2003). "The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity.". Mol. Endocrinol. 16 (9): 2065-76. PMID 12198243.
  • Oberkofler H, Schraml E, Krempler F, Patsch W (2003). "Potentiation of liver X receptor transcriptional activity by peroxisome-proliferator-activated receptor gamma co-activator 1 alpha.". Biochem. J. 371 (Pt 1): 89-96. doi:10.1042/BJ20021665. PMID 12470296.
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899-903. doi:10.1073/pnas.242603899. PMID 12477932.
  • Wang M, Thomas J, Burris TP, et al. (2004). "Molecular determinants of LXRalpha agonism.". J. Mol. Graph. Model. 22 (2): 173-81. doi:10.1016/S1093-3263(03)00159-1. PMID 12932788.
  • Fukuchi J, Song C, Ko AL, Liao S (2004). "Transcriptional regulation of farnesyl pyrophosphate synthase by liver X receptors.". Steroids 68 (7-8): 685-91. PMID 12957674.
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v • d • e
Transcription factors and intracellular receptors
(1) Basic domains
(1.1) Basic leucine zipper (bZIP) Activating transcription factor (1, 2, 3, 4, 5, 6) • AP-1 (c-Fos, FOSB, FOSL1, FOSL2, c-Jun, JUNB, JUND) • BACH (1, 2) • C/EBP (α, β, γ, δ, ε, ζ) • CREB (1, 3) • GABPA • MAF (B, F, G, K) • NRL • NRF1 • XBP1
(1.2) Basic helix-loop-helix (bHLH) ATOH1 • AhR • AHRR • ARNT • ASCL1 • BMAL (ARNTL, ARNTL2) • CLOCK • HIF (1A, 3A) • Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) • NEUROD1 • Twist • USF1
(1.3) bHLH-ZIP Myc • MITF • SREBP (1, 2)
(1.6) Basic helix-span-helix (bHSH) AP-2
(2) Zinc finger
DNA-binding domains
(2.1) Nuclear receptor (Cys4) subfamily 1 (Thyroid hormone (α, β), CAR, FXR, LXR (α, β), PPAR (α, β/δ, γ), PXR, RAR (α, β, γ), ROR (α, β, γ), Rev-ErbA (α, β), VDR) • subfamily 2 (COUP-TF (I, II), Ear-2, HNF4 (α, γ), PNR, RXR (α, β, γ), Testicular receptor (2, 4), TLX) • subfamily 3 (Steroid hormone (Estrogen (α, β), Estrogen related (α, β, γ), Androgen, Glucocorticoid, Mineralocorticoid, Progesterone)) • subfamily 4 NUR (NGFIB, NOR1, NURR1) • subfamily 5 (LRH-1, SF1) • subfamily 6 (GCNF) • subfamily 0 (DAX1, SHP)
(2.2) Other Cys4 GATA (1, 2, 3, 4, 5, 6)
(2.3) Cys2His2 General transcription factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH: 1, 2) • GLI-Krüppel family (1, 2, 3, YY1) • KLF (2, 4, 5, 6, 10, 11, 12, 13) • Sp1 • zinc finger (3, 35, 43, 146, 148, 165, 217, 268, 281, 350) • Zbtb7 (7A) • ZBT (16, 17, 33)
(2.4) Cys6 HIVEP1
(3) Helix-turn-helix
domains
(3.1) Homeo domain ARX • Homeobox (A1, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C6, C8, C9, C13, D1, D3, D4, D9, D10, D11, D12, D13) • NANOG • NKX (2-1, 2-5, 3-1) • POU domain (PIT-1, BRN-3: 1, 2, Octamer transcription factor: 1, 2, 3/4, 6, 7)
(3.2) Paired box PAX (1, 2, 3, 4, 5, 6, 7, 8, 9)
(3.3) Fork head / winged helix E2F (1, 2, 3, 4, 5) • FOX proteins (C1, C2, E1, G1, H1, L2, M1, N3, O3, O4, P1, P2, P3)
(3.4) Heat Shock Factors HSF1
(3.5) Tryptophan clusters ELF (4, 5) • Interferon regulatory factors (1, 2, 3, 4, 5, 6, 7, 8) • MYB
(3.6) TEA domain transcriptional enhancer factor 1, 2
(4) β-Scaffold factors with
minor groove contacts
(4.1) Rel homology region NF-κB (NFKB1, NFKB2, REL, RELA, RELB) • NFAT (5, C1, C2, C3, C4)
(4.2) STAT STAT (1, 2, 3, 4, 5, 6)
(4.3) p53 p53
(4.4) MADS box Mef2 (A, B, C, D) • SRF
(4.7) High mobility group HNF (1A, 1B) • LEF1 • SOX (3, 4, 6, 9, 10, 13, 18) • SRY • SSRP1
(4.10) Cold-shock domain CSDA
(0) Other
transcription factors
(0.2) HMGI(Y) HMGA (1, 2)
(0.3) Pocket domain Rb • RBL1 • RBL2
(0.6) Miscellaneous ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • Rho/Sigma • R-SMAD

Acknowledgement and Attribution Regarding Sources of Content

Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .

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