Small heterodimer partner

From Wikipedia, the free encyclopedia


Nuclear receptor subfamily 0, group B, member 2
Identifiers
Symbol(s) NR0B2; SHP1; SHP
External IDs OMIM: 604630 MGI: 1346344 HomoloGene: 8030
RNA expression pattern

More reference expression data
Orthologs
Human Mouse
Entrez 8431 23957
Ensembl ENSG00000131910 ENSMUSG00000037583
Uniprot Q15466 Q62227
Refseq NM_021969 (mRNA)
NP_068804 (protein)		 NM_011850 (mRNA)
NP_035980 (protein)
Location Chr 1: 27.11 - 27.11 Mb Chr 4: 132.83 - 132.83 Mb
Pubmed search [1] [2]

The small heterodimer partner (SHP) protein is a member of the nuclear receptor family of intracellular transcription factors[1] and is encoded by the NR0B2 (nuclear receptor subfamily 0, group B, member 2) gene.[2] SHP is unusual for a nuclear receptor in that it lacks a DNA binding domain. Therefore technically it is neither a transcription factor nor nuclear receptor but nevertheless it is still classified as such due to relatively high sequence homology with other nuclear receptor family members.


The main function of SHP appears to be repression of other nuclear receptors through association to produce a non-productive heterodimer.[3] The protein has been shown to interact with retinoid and thyroid hormone receptors, inhibiting their ligand-dependent transcriptional activation. In addition, interaction with estrogen receptors has been demonstrated, leading to inhibition of function. Studies suggest that the protein represses nuclear hormone receptor-mediated transactivation via two separate steps: competition with coactivators and the direct effects of its transcriptional repressor function.[2]

[edit] References

  1. ^ Lee HK, Lee YK, Park SH, Kim YS, Park SH, Lee JW, Kwon HB, Soh J, Moore DD, Choi HS (1998). "Structure and expression of the orphan nuclear receptor SHP gene". J. Biol. Chem. 273 (23): 14398–402. doi:10.1074/jbc.273.23.14398. PMID 9603951. 
  2. ^ a b Entrez Gene: NR0B2 nuclear receptor subfamily 0, group B, member 2.
  3. ^ Båvner A, Sanyal S, Gustafsson JA, Treuter E (2005). "Transcriptional corepression by SHP: molecular mechanisms and physiological consequences". Trends Endocrinol. Metab. 16 (10): 478–88. doi:10.1016/j.tem.2005.10.005. PMID 16275121. 

[edit] Further reading

  • Seol W, Choi HS, Moore DD (1996). "An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors.". Science 272 (5266): 1336–9. PMID 8650544. 
  • Lee HK, Lee YK, Park SH, et al. (1998). "Structure and expression of the orphan nuclear receptor SHP gene.". J. Biol. Chem. 273 (23): 14398–402. PMID 9603951. 
  • Seol W, Hanstein B, Brown M, Moore DD (1998). "Inhibition of estrogen receptor action by the orphan receptor SHP (short heterodimer partner).". Mol. Endocrinol. 12 (10): 1551–7. PMID 9773978. 
  • Lee YK, Dell H, Dowhan DH, et al. (2000). "The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression.". Mol. Cell. Biol. 20 (1): 187–95. PMID 10594021. 
  • Johansson L, Båvner A, Thomsen JS, et al. (2000). "The orphan nuclear receptor SHP utilizes conserved LXXLL-related motifs for interactions with ligand-activated estrogen receptors.". Mol. Cell. Biol. 20 (4): 1124–33. PMID 10648597. 
  • Lu TT, Makishima M, Repa JJ, et al. (2000). "Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors.". Mol. Cell 6 (3): 507–15. PMID 11030331. 
  • Nishigori H, Tomura H, Tonooka N, et al. (2001). "Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects.". Proc. Natl. Acad. Sci. U.S.A. 98 (2): 575–80. doi:10.1073/pnas.021544398. PMID 11136233. 
  • Lee YK, Moore DD (2002). "Dual mechanisms for repression of the monomeric orphan receptor liver receptor homologous protein-1 by the orphan small heterodimer partner.". J. Biol. Chem. 277 (4): 2463–7. doi:10.1074/jbc.M105161200. PMID 11668176. 
  • Nishizawa H, Yamagata K, Shimomura I, et al. (2002). "Small heterodimer partner, an orphan nuclear receptor, augments peroxisome proliferator-activated receptor gamma transactivation.". J. Biol. Chem. 277 (2): 1586–92. doi:10.1074/jbc.M104301200. PMID 11696534. 
  • Sanyal S, Kim JY, Kim HJ, et al. (2002). "Differential regulation of the orphan nuclear receptor small heterodimer partner (SHP) gene promoter by orphan nuclear receptor ERR isoforms.". J. Biol. Chem. 277 (3): 1739–48. doi:10.1074/jbc.M106140200. PMID 11705994. 
  • Gobinet J, Auzou G, Nicolas JC, et al. (2002). "Characterization of the interaction between androgen receptor and a new transcriptional inhibitor, SHP.". Biochemistry 40 (50): 15369–77. PMID 11735420. 
  • Klinge CM, Jernigan SC, Risinger KE (2002). "The agonist activity of tamoxifen is inhibited by the short heterodimer partner orphan nuclear receptor in human endometrial cancer cells.". Endocrinology 143 (3): 853–67. PMID 11861507. 
  • Ogata M, Awaji T, Iwasaki N, et al. (2002). "Nuclear translocation of SHP and visualization of interaction with HNF-4alpha in living cells.". Biochem. Biophys. Res. Commun. 292 (1): 8–12. PMID 11890664. 
  • Cao H, Hegele RA (2002). "Identification of polymorphisms in the human SHP1 gene.". J. Hum. Genet. 47 (8): 445–7. doi:10.1007/s100380200062. PMID 12181644. 
  • 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. 
  • Borgius LJ, Steffensen KR, Gustafsson JA, Treuter E (2003). "Glucocorticoid signaling is perturbed by the atypical orphan receptor and corepressor SHP.". J. Biol. Chem. 277 (51): 49761–6. doi:10.1074/jbc.M205641200. PMID 12324453. 
  • 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. 
  • Hung CC, Farooqi IS, Ong K, et al. (2003). "Contribution of variants in the small heterodimer partner gene to birthweight, adiposity, and insulin levels: mutational analysis and association studies in multiple populations.". Diabetes 52 (5): 1288–91. PMID 12716767. 
  • Lai K, Harnish DC, Evans MJ (2003). "Estrogen receptor alpha regulates expression of the orphan receptor small heterodimer partner.". J. Biol. Chem. 278 (38): 36418–29. doi:10.1074/jbc.M303913200. PMID 12842887. 
  • Kovacic A, Speed CJ, Simpson ER, Clyne CD (2004). "Inhibition of aromatase transcription via promoter II by short heterodimer partner in human preadipocytes.". Mol. Endocrinol. 18 (1): 252–9. doi:10.1210/me.2003-0211. PMID 14593077. 

[edit] External links

 This article on a gene on chromosome 1 is a stub. You can help Wikipedia by expanding it.
v • d • e
Transcription factors and intracellular receptors
(1) Basic domains
(1.1) Basic leucine zipper (bZIP)
Activating transcription factor (AATF, 1, 2, 3, 4, 5, 6, 7) • AP-1 (c-Fos, FOSB, FOSL1, FOSL2, c-Jun, JUNB, JUND) • BACH (1, 2) • BATF • BLZF1 • C/EBP (α, β, γ, δ, ε, ζ) • CREB (1, 3, L1) • CREM • DBP • DDIT3 • GABPA • HLF • MAF (B, F, G, K) • NFE (2, L1, L2) • NRL • NRF1 • XBP1
(1.2) Basic helix-loop-helix (bHLH)
ATOH1 • AhR • AHRR • ARNT • ASCL1 • BHLHB2 • BMAL (ARNTL, ARNTL2) • CLOCK • EPAS1 • HAND (1, 2) • HES (5, 6) • HEY (1, 2, L) • HES1 • HIF (1A, 3A) • ID (1, 2, 3, 4) • LYL1 • MXD4 • MYCL1 • MYCN • Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) • Neurogenins • NeuroD (1, 2) • NPAS (1, 2, 3) • OLIG (1, 2) • Scleraxis • TAL1 • Twist • USF1
(1.3) bHLH-ZIP
MAX • MITF • MNT • MLX • MXI1 • Myc • SREBP (1, 2)
(1.6) Basic helix-span-helix (bHSH)
(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) • MTA (1, 2, 3)
(2.3) Cys2His2
ATBF1 • BCL(6, 11A, 11B) • CTCF • E4F1 • EGR (2, 3) • ERV3 • General transcription factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF: 1, 2, TFIIH: 1, 2, 4, 2I, 3A, 3C1, 3C2) • GFI1 • GLI-Krüppel family (1, 2, 3, YY1) • HIC (1, 2) • HIVEP (1, 2, 3) • IKZF (1, 2, 3) • ILF (2, 3) • KLF (2, 4, 5, 6, 9, 10, 11, 12, 13) • MTF1 • MYT1 • OSR1 • Sp1 • zinc finger ((3, 7, 9, 10, 19, 22, 24, 33B, 34, 35, 41, 43, 44, 51, 74, 143, 146, 148, 165, 202, 217, 219, 238, 239, 259, 267, 268, 281, 295, 318, 330, 346, 350, 365, 366, 384, 451, 452, 471, 593, 638, 649, 655) • Zbtb7 (7A) • ZBT (16, 17, 33)
(2.4) Cys6
(2.5) Alternating composition
AIRE • DIDO1 • GRLF1 • ING (1, 2, 4) • JARID (1A, 1B, 1C, 1D, 2) • JMJD1B
(3) Helix-turn-helix
domains
ARX • CDX (1, 2) • CRX • CUTL1 • DLX (3, 4, 5) • EMX2 • EN (1, 2) • FHL (1, 2, 3) • HESX1 • HHEX • HLX • Homeobox (A1, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C5, C6, C8, C9, C10, C11, C13, D1, D3, D4, D8, D9, D10, D11, D12, D13) • HOPX • MEIS (1, 2) • MEOX2 • MNX1 • MSX (1, 2) • NANOG • NKX (2-1, 2-5, 3-1) • PHF (3, 6, 10, 17) • POU domain (PIT-1, BRN-3: 1, 2, Octamer transcription factor: 1, 2, 3/4, 6, 7) • OTX (1, 2) • PDX1
(3.2) Paired box
PAX (1, 2, 3, 4, 5, 6, 7, 8, 9)
E2F (1, 2, 3, 4, 5) • FOX proteins (C1, C2, E1, G1, H1, K2, L2, M1, N3, O1A, , O3A, O4, P1, P2, P3)
HSF (1, 2, 4)
(3.5) Tryptophan clusters
ELF (4, 5) • EGF • ELK (1, 3, 4) • ERF • ERG • ETS (1, 2) • ETV (1, 4, 5, 6) • FLI1 • Interferon regulatory factors (1, 2, 3, 4, 5, 6, 7, 8) • MYB • MYBL2
(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 (C1, C2, C3, C4, 5)
(4.2) STAT
STAT (1, 2, 3, 4, 5, 6)
(4.3) p53
(4.4) MADS box
Mef2 (A, B, C, D) • SRF
HNF (1A, 1B) • LEF1 • SOX (2, 3, 4, 5, 6, 8, 9, 10, 11, 13, 15, 18) • SRY • SSRP1
(4.10) Cold-shock domain
(4.11) Runt
(0) Other
transcription factors
(0.2) HMGI(Y)
HMGA (1, 2) • HBP1
Rb • RBL1 • RBL2
(0.5) AP-2/EREBP-related factors
Apetala 2 • EREBP • B3
(0.6) Miscellaneous
ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • IFI (16, 35) • MLL (2, 3, T1) • MNDA • NFI (A, B, C, X) • NFY (A, B, C) • Rho/Sigma • R-SMAD