SHP (タンパク質)とは？わかりやすく解説

NR0B2
PDBに登録されている構造
PDB	オルソログ検索: RCSB PDBe PDBj
PDBのIDコード一覧
	1YUC, 2Q3Y, 2Z4J, 4DOR, 4ONI
識別子
記号	NR0B2, SHP, SHP1, nuclear receptor subfamily 0 group B member 2
外部ID	OMIM: 604630 MGI: 1346344 HomoloGene: 8030 GeneCards: NR0B2
遺伝子の位置 (ヒト)
染色体	1番染色体 (ヒト)
終点	26,913,975 bp
遺伝子の位置 (マウス)
染色体	4番染色体 (マウス)
終点	133,283,847 bp
RNA発現パターン
	さらなる参照発現データ
遺伝子オントロジー
分子機能	• DNA結合; • protein homodimerization activity; • protein domain specific binding; • steroid hormone receptor activity; • 血漿タンパク結合; • transcription corepressor activity; • DNA-binding transcription factor activity, RNA polymerase II-specific; • protein-containing complex binding; • 転写因子結合; • retinoic acid receptor binding; • peroxisome proliferator activated receptor binding; • retinoid X receptor binding; • 甲状腺ホルモン結合;
細胞の構成要素	• 核質; • 細胞核; • 細胞質; • 高分子複合体;
生物学的プロセス	• Notchシグナリング; • regulation of transcription, DNA-templated; • cholesterol metabolic process; • negative regulation of transcription by RNA polymerase II; • response to glucose; • negative regulation of DNA-binding transcription factor activity; • 遺伝子発現の負の調節; • transcription, DNA-templated; • positive regulation of gene expression; • animal organ regeneration; • transcription initiation from RNA polymerase II promoter; • negative regulation of transcription, DNA-templated; • positive regulation of insulin secretion; • steroid hormone mediated signaling pathway; • 概日リズム; • circadian regulation of gene expression; • 周期的プロセス;
	出典:Amigo / QuickGO
オルソログ
	8431
	23957
	ENSG00000131910
	ENSMUSG00000037583
	Q15466
	Q62227
	NM_021969
	NM_011850
	NP_068804
	NP_035980
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

SHP（small heterodimer partner）もしくはNR0B2（nuclear receptor subfamily 0 group B member 2）は、ヒトではNR0B2遺伝子によってコードされているタンパク質である^[5]。SHPは核内受容体ファミリーに属するが^[6]、DNA結合ドメインを欠いているという点で例外的存在である。そのため厳密には転写因子でも核内受容体でもないが、核内受容体ファミリーの他のメンバーと比較的高い配列相同性を有するためこのファミリーに分類されている。

機能

SHPの主要な機能は、他の核内受容体と結合して非生産的なヘテロ二量体を形成することで、その受容体の機能を抑制することのようである^[7]。SHPは代謝と概日時計とを連結している因子としても同定されている^[8]。SHPはレチノイド受容体（英語版）や甲状腺ホルモン受容体と相互作用し、リガンド依存的な転写活性化を阻害することが示されている。さらに、エストロゲン受容体とも相互作用し、機能の阻害をもたらす。SHPは、コアクチベーターとの競合、転写リプレッサーとしての機能、という2つの異なる段階でホルモン受容体を介した活性化を抑制していることが示唆されている^[5]。

構造とリガンド

SHPのリガンド結合ドメイン（LBD）は、EID1（英語版）由来ペプチドとの共結晶の構造が得られている。SHPの全体構造は他の核内受容体のLBDのアポ型（リガンドを結合していない状態）の構造と類似している。EID1は核内受容体がコアクチベーターとの相互作用に利用するAF-2部位ではなく、他のLBDのヘリックス1を模倣する形でSHPに結合する。一部の合成レチノイドリガンドはSHPのLBDに結合し、LXXLLモチーフを有するコリプレッサーとのAF-2部位を介した相互作用を促進する^[9]。

相互作用

中規模・大規模スケールの酵母ツーハイブリッド法実験や核内受容体に関する文献のテキストマイニングにより、SHPが核内受容体の二量体化ネットワークに重要な役割を果たしており、他の核内受容体と比較して高度に連結されたハブとなっていることが明らかにされている^[10]。

SHPは次に挙げる因子と相互作用することが示されている。

出典

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000131910 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000037583 - Ensembl, May 2017
^ Human PubMed Reference:
^ Mouse PubMed Reference:
^ ^a ^b “Entrez Gene: NR0B2 nuclear receptor subfamily 0, group B, member 2”. 2025年12月31日閲覧。
^ Lee HK, Lee YK, Park SH, Kim YS, Park SH, Lee JW, Kwon HB, Soh J, Moore DD, Choi HS (June 1998). “Structure and expression of the orphan nuclear receptor SHP gene”. The Journal of Biological Chemistry 273 (23): 14398–402. doi:10.1074/jbc.273.23.14398. PMID 9603951.
^ Båvner A, Sanyal S, Gustafsson JA, Treuter E (December 2005). “Transcriptional corepression by SHP: molecular mechanisms and physiological consequences”. Trends in Endocrinology and Metabolism 16 (10): 478–88. doi:10.1016/j.tem.2005.10.005. PMID 16275121.
^ Wu N, Kim KH, Zhou Y, Lee JM, Kettner NM, Mamrosh JL, Choi S, Fu L, Moore DD (September 2016). “Small Heterodimer Partner (NR0B2) Coordinates Nutrient Signaling and the Circadian Clock in Mice”. Molecular Endocrinology 30 (9): 988–95. doi:10.1210/me.2015-1295. PMC 5004116. PMID 27427832.
^ Zhi, Xiaoyong; Zhou, X. Edward; He, Yuanzheng; Zechner, Christoph; Suino-Powell, Kelly M.; Kliewer, Steven A.; Melcher, Karsten; Mangelsdorf, David J. et al. (2014-01-14). “Structural insights into gene repression by the orphan nuclear receptor SHP”. Proceedings of the National Academy of Sciences of the United States of America 111 (2): 839–844. doi:10.1073/pnas.1322827111. ISSN 1091-6490. PMC 3896210. PMID 24379397.
^ Amoutzias GD, Pichler EE, Mian N, De Graaf D, Imsiridou A, Robinson-Rechavi M, Bornberg-Bauer E, Robertson DL, Oliver SG (July 2007). “A protein interaction atlas for the nuclear receptors: properties and quality of a hub-based dimerisation network”. BMC Systems Biology 1: 34. doi:10.1186/1752-0509-1-34. PMC 1971058. PMID 17672894.
^ Gobinet J, Auzou G, Nicolas JC, Sultan C, Jalaguier S (December 2001). “Characterization of the interaction between androgen receptor and a new transcriptional inhibitor, SHP”. Biochemistry 40 (50): 15369–77. doi:10.1021/bi011384o. PMID 11735420.
^ Klinge CM, Jernigan SC, Risinger KE (March 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. doi:10.1210/endo.143.3.8676. PMID 11861507.
^ ^a ^b Lee YK, Dell H, Dowhan DH, Hadzopoulou-Cladaras M, Moore DD (January 2000). “The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression”. Molecular and Cellular Biology 20 (1): 187–95. doi:10.1128/MCB.20.1.187-195.2000. PMC 85074. PMID 10594021.
^ ^a ^b ^c Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J (September 2002). “The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity”. Molecular Endocrinology 16 (9): 2065–76. doi:10.1210/me.2001-0194. PMID 12198243.
^ Lee YK, Moore DD (January 2002). “Dual mechanisms for repression of the monomeric orphan receptor liver receptor homologous protein-1 by the orphan small heterodimer partner”. The Journal of Biological Chemistry 277 (4): 2463–7. doi:10.1074/jbc.M105161200. PMID 11668176.
^ Nishizawa H, Yamagata K, Shimomura I, Takahashi M, Kuriyama H, Kishida K, Hotta K, Nagaretani H, Maeda N, Matsuda M, Kihara S, Nakamura T, Nishigori H, Tomura H, Moore DD, Takeda J, Funahashi T, Matsuzawa Y (January 2002). “Small heterodimer partner, an orphan nuclear receptor, augments peroxisome proliferator-activated receptor gamma transactivation”. The Journal of Biological Chemistry 277 (2): 1586–92. doi:10.1074/jbc.M104301200. PMID 11696534.
^ Seol W, Choi HS, Moore DD (May 1996). “An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors”. Science 272 (5266): 1336–9. Bibcode: 1996Sci...272.1336S. doi:10.1126/science.272.5266.1336. PMID 8650544.
^ Seol W, Hanstein B, Brown M, Moore DD (October 1998). “Inhibition of estrogen receptor action by the orphan receptor SHP (short heterodimer partner)”. Molecular Endocrinology 12 (10): 1551–7. doi:10.1210/me.12.10.1551. PMID 9773978.
^ Zhi X, Zhou XE, He Y, Zechner C, Suino-Powell KM, Kliewer SA, Melcher K, Mangelsdorf DJ, Xu HE (January 2014). “Structural insights into gene repression by the orphan nuclear receptor SHP”. Proceedings of the National Academy of Sciences of the United States of America 111 (2): 839–44. Bibcode: 2014PNAS..111..839Z. doi:10.1073/pnas.1322827111. PMC 3896210. PMID 24379397.

外部リンク

small heterodimer partner protein - MeSH・アメリカ国立医学図書館・生命科学用語シソーラス（英語）

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000131910 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000037583 - Ensembl, May 2017

[3] Human PubMed Reference:

[4] Mouse PubMed Reference:

[entrez-5] “Entrez Gene: NR0B2 nuclear receptor subfamily 0, group B, member 2”. 2025年12月31日閲覧。

[pmid9603951-6] Lee HK, Lee YK, Park SH, Kim YS, Park SH, Lee JW, Kwon HB, Soh J, Moore DD, Choi HS (June 1998). “Structure and expression of the orphan nuclear receptor SHP gene”. The Journal of Biological Chemistry 273 (23): 14398–402. doi:10.1074/jbc.273.23.14398. PMID 9603951.

[pmid16275121-7] Båvner A, Sanyal S, Gustafsson JA, Treuter E (December 2005). “Transcriptional corepression by SHP: molecular mechanisms and physiological consequences”. Trends in Endocrinology and Metabolism 16 (10): 478–88. doi:10.1016/j.tem.2005.10.005. PMID 16275121.

[:0-8] Wu N, Kim KH, Zhou Y, Lee JM, Kettner NM, Mamrosh JL, Choi S, Fu L, Moore DD (September 2016). “Small Heterodimer Partner (NR0B2) Coordinates Nutrient Signaling and the Circadian Clock in Mice”. Molecular Endocrinology 30 (9): 988–95. doi:10.1210/me.2015-1295. PMC 5004116. PMID 27427832.

[9] Zhi, Xiaoyong; Zhou, X. Edward; He, Yuanzheng; Zechner, Christoph; Suino-Powell, Kelly M.; Kliewer, Steven A.; Melcher, Karsten; Mangelsdorf, David J. et al. (2014-01-14). “Structural insights into gene repression by the orphan nuclear receptor SHP”. Proceedings of the National Academy of Sciences of the United States of America 111 (2): 839–844. doi:10.1073/pnas.1322827111. ISSN 1091-6490. PMC 3896210. PMID 24379397.

[:1-10] Amoutzias GD, Pichler EE, Mian N, De Graaf D, Imsiridou A, Robinson-Rechavi M, Bornberg-Bauer E, Robertson DL, Oliver SG (July 2007). “A protein interaction atlas for the nuclear receptors: properties and quality of a hub-based dimerisation network”. BMC Systems Biology 1: 34. doi:10.1186/1752-0509-1-34. PMC 1971058. PMID 17672894.

[pmid11735420-11] Gobinet J, Auzou G, Nicolas JC, Sultan C, Jalaguier S (December 2001). “Characterization of the interaction between androgen receptor and a new transcriptional inhibitor, SHP”. Biochemistry 40 (50): 15369–77. doi:10.1021/bi011384o. PMID 11735420.

[pmid11861507-12] Klinge CM, Jernigan SC, Risinger KE (March 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. doi:10.1210/endo.143.3.8676. PMID 11861507.

[pmid10594021-13] Lee YK, Dell H, Dowhan DH, Hadzopoulou-Cladaras M, Moore DD (January 2000). “The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression”. Molecular and Cellular Biology 20 (1): 187–95. doi:10.1128/MCB.20.1.187-195.2000. PMC 85074. PMID 10594021.

[pmid12198243-14] Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J (September 2002). “The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity”. Molecular Endocrinology 16 (9): 2065–76. doi:10.1210/me.2001-0194. PMID 12198243.

[pmid11668176-15] Lee YK, Moore DD (January 2002). “Dual mechanisms for repression of the monomeric orphan receptor liver receptor homologous protein-1 by the orphan small heterodimer partner”. The Journal of Biological Chemistry 277 (4): 2463–7. doi:10.1074/jbc.M105161200. PMID 11668176.

[pmid11696534-16] Nishizawa H, Yamagata K, Shimomura I, Takahashi M, Kuriyama H, Kishida K, Hotta K, Nagaretani H, Maeda N, Matsuda M, Kihara S, Nakamura T, Nishigori H, Tomura H, Moore DD, Takeda J, Funahashi T, Matsuzawa Y (January 2002). “Small heterodimer partner, an orphan nuclear receptor, augments peroxisome proliferator-activated receptor gamma transactivation”. The Journal of Biological Chemistry 277 (2): 1586–92. doi:10.1074/jbc.M104301200. PMID 11696534.

[pmid8650544-17] Seol W, Choi HS, Moore DD (May 1996). “An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors”. Science 272 (5266): 1336–9. Bibcode: 1996Sci...272.1336S. doi:10.1126/science.272.5266.1336. PMID 8650544.

[pmid9773978-18] Seol W, Hanstein B, Brown M, Moore DD (October 1998). “Inhibition of estrogen receptor action by the orphan receptor SHP (short heterodimer partner)”. Molecular Endocrinology 12 (10): 1551–7. doi:10.1210/me.12.10.1551. PMID 9773978.

[pmid24379397-19] Zhi X, Zhou XE, He Y, Zechner C, Suino-Powell KM, Kliewer SA, Melcher K, Mangelsdorf DJ, Xu HE (January 2014). “Structural insights into gene repression by the orphan nuclear receptor SHP”. Proceedings of the National Academy of Sciences of the United States of America 111 (2): 839–44. Bibcode: 2014PNAS..111..839Z. doi:10.1073/pnas.1322827111. PMC 3896210. PMID 24379397.

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SHP (タンパク質)とは？わかりやすく解説