ID1

ID1
識別子
記号	ID1, ID, bHLHb24, inhibitor of DNA binding 1, HLH protein
外部ID	OMIM: 600349 MGI: 96396 HomoloGene: 1631 GeneCards: ID1
遺伝子の位置 (ヒト)
染色体	20番染色体 (ヒト)
終点	31,606,515 bp
遺伝子の位置 (マウス)
染色体	2番染色体 (マウス)
終点	152,579,330 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	• protein homodimerization activity; • protein dimerization activity; • DNA-binding transcription factor activity; • protein self-association; • protein C-terminus binding; • 血漿タンパク結合; • DNA-binding transcription factor activity, RNA polymerase II-specific; • 転写因子結合; • protein N-terminus binding; • proteasome binding;
細胞の構成要素	• 細胞質; • 中心体; • ゴルジ体; • 核質; • 細胞核;
生物学的プロセス	• cell-abiotic substrate adhesion; • cellular response to transforming growth factor beta stimulus; • cellular response to nerve growth factor stimulus; • cellular response to peptide; • regulation of transcription, DNA-templated; • regulation of MAPK cascade; • blood vessel morphogenesis; • lung morphogenesis; • 有機環状化合物への反応; • blood vessel endothelial cell migration; • positive regulation of epithelial cell proliferation; • 周期的プロセス; • cellular response to dopamine; • response to antibiotic; • negative regulation of DNA binding; • endothelial cell morphogenesis; • collagen metabolic process; • negative regulation of apoptotic process; • negative regulation of endothelial cell differentiation; • negative regulation of transcription by RNA polymerase II; • regulation of angiogenesis; • negative regulation of protein binding; • BMP signaling pathway; • negative regulation of DNA-binding transcription factor activity; • transcription, DNA-templated; • negative regulation of osteoblast differentiation; • 遺伝子発現の負の調節; • cellular response to epidermal growth factor stimulus; • 多細胞個体の発生; • 心臓発生; • 脳発生; • positive regulation of gene expression; • regulation of vasculature development; • negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding; • negative regulation of dendrite morphogenesis; • 概日リズム; • protein destabilization; • 血管新生; • neuron differentiation; • negative regulation of protein homodimerization activity; • positive regulation of actin filament bundle assembly; • negative regulation of transcription by transcription factor localization; • lung vasculature development; • negative regulation of transcription, DNA-templated; • transforming growth factor beta receptor signaling pathway; • negative regulation of neuron differentiation; • regulation of cell cycle; • negative regulation of cold-induced thermogenesis;
	出典:Amigo / QuickGO
オルソログ
	3397
	15901
	ENSG00000125968
	ENSMUSG00000042745
	P41134
	P20067,Q6GTZ3
	NM_181353; NM_002165
	NM_010495; NM_001355113; NM_001369018
	NP_002156; NP_851998
	NP_034625; NP_001342042; NP_001355947
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

ID1（inhibitor of DNA binding 1）は、ヒトではID1遺伝子によってコードされているタンパク質である^[5]^[6]。

機能

ID1タンパク質はヘリックスループヘリックス（HLH）タンパク質であり、塩基性ヘリックスループヘリックス（bHLH）ファミリーの転写因子とヘテロ二量体を形成することができる^[5]。ID1はDNA結合活性を持たないため、相互作用するbHLHタンパク質のDNA結合と転写活性化作用を阻害する^[5]。このタンパク質は、細胞成長、老化、そして分化に関与している可能性がある^[7]^[8]^[9]。

相互作用

ID1はMyoD（英語版）と弱く相互作用することが示されているが^[5]^[10]^[11]^[12]^[13]^[14]^[15]、E2A（英語版）遺伝子にコードされ普遍的に発現しているEタンパク質と極めて強固に結合する^[16]。Eタンパク質はMyoDやNeuroD（英語版）といった組織限定型bHLHタンパク質とヘテロ二量体を形成して活性型転写因子複合体を形成する。そのため、IDタンパク質はEタンパク質を隔離することで、複数の細胞系統において同一の生化学的機構によって組織限定型の遺伝子発現を阻害する。ID1の他の相互作用パートナーとしてはCASK（英語版）が知られている^[17]。

臨床的意義

ID1は、腫瘍の成長や血管新生に重要な血管内皮前駆細胞（英語版）を標識するために利用される^[18]^[19]。また、ID1を標的化して阻害することによって腫瘍の成長が低下する^[20]^[21]。ID1は特定種の神経膠腫や乳がんにおいてカンナビジオールによって標的化されることが示されている^[22]^[23]。

出典

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000125968 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000042745 - Ensembl, May 2017
^ Human PubMed Reference:
^ Mouse PubMed Reference:
^ ^a ^b ^c ^d “The protein Id: a negative regulator of helix-loop-helix DNA binding proteins”. Cell 61 (1): 49–59. (April 1990). doi:10.1016/0092-8674(90)90214-Y. PMID 2156629.
^ “Id-related genes encoding helix-loop-helix proteins are required for G1 progression and are repressed in senescent human fibroblasts”. The Journal of Biological Chemistry 269 (3): 2139–45. (January 1994). doi:10.1016/S0021-9258(17)42146-6. PMID 8294468.
^ “Id proteins in development, cell cycle and cancer”. Trends in Cell Biology 13 (8): 410–8. (August 2003). doi:10.1016/S0962-8924(03)00147-8. PMID 12888293.
^ “Id family of helix-loop-helix proteins in cancer”. Nature Reviews. Cancer 5 (8): 603–14. (August 2005). doi:10.1038/nrc1673. PMID 16034366.
^ Cunningham, Thomas J.; Yu, Michael S.; McKeithan, Wesley L.; Spiering, Sean; Carrette, Florent; Huang, Chun-Teng; Bushway, Paul J.; Tierney, Matthew et al. (2017-07-01). “Id genes are essential for early heart formation”. Genes & Development 31 (13): 1325–1338. doi:10.1101/gad.300400.117. ISSN 1549-5477. PMC 5580654. PMID 28794185.
^ “The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis”. Nature 428 (6980): 328–32. (March 2004). Bibcode: 2004Natur.428..328G. doi:10.1038/nature02329. PMID 15029197.
^ “Differential interactions of Id proteins with basic-helix-loop-helix transcription factors”. The Journal of Biological Chemistry 272 (32): 19785–93. (August 1997). doi:10.1074/jbc.272.32.19785. PMID 9242638.
^ “Detection and modulation in vivo of helix-loop-helix protein-protein interactions”. The Journal of Biological Chemistry 268 (1): 5–8. (January 1993). doi:10.1016/S0021-9258(18)54105-3. PMID 8380166.
^ “Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc”. Oncogene 16 (9): 1149–59. (March 1998). doi:10.1038/sj.onc.1201634. PMID 9528857.
^ “The LIM-only protein DRAL/FHL2 interacts with and is a corepressor for the promyelocytic leukemia zinc finger protein”. The Journal of Biological Chemistry 277 (40): 37045–53. (October 2002). doi:10.1074/jbc.M203336200. PMID 12145280.
^ “Id-1 induces proteasome-dependent degradation of the HBX protein”. Journal of Molecular Biology 382 (1): 34–43. (September 2008). doi:10.1016/j.jmb.2007.06.020. PMID 18674781.
^ “Overexpression of Id protein inhibits the muscle differentiation program: in vivo association of Id with E2A proteins”. Genes & Development 6 (8): 1466–79. (August 1992). doi:10.1101/gad.6.8.1466. PMID 1644289.
^ “CASK inhibits ECV304 cell growth and interacts with Id1”. Biochemical and Biophysical Research Communications 328 (2): 517–21. (March 2005). doi:10.1016/j.bbrc.2005.01.014. PMID 15694377.
^ “Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts”. Nature 401 (6754): 670–7. (October 1999). Bibcode: 1999Natur.401..670L. doi:10.1038/44334. PMID 10537105.
^ “Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth”. Nature Medicine 7 (11): 1194–201. (November 2001). doi:10.1038/nm1101-1194. PMID 11689883.
^ “Peptide-conjugated antisense oligonucleotides for targeted inhibition of a transcriptional regulator in vivo”. Nature Biotechnology 26 (1): 91–100. (January 2008). doi:10.1038/nbt1366. PMID 18176556.
^ “Using the transcription factor inhibitor of DNA binding 1 to selectively target endothelial progenitor cells offers novel strategies to inhibit tumor angiogenesis and growth”. Cancer Research 70 (18): 7273–82. (September 2010). doi:10.1158/0008-5472.CAN-10-1142. PMC 3058751. PMID 20807818.
^ “Therapeutic reversal of prenatal pontine ID1 signaling in DIPG”. Neuro Oncol 23 (supplement 1): i48. (June 2021). doi:10.1093/neuonc/noab090.193. PMC 8168201.
^ “Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells”. Molecular Cancer Therapeutics 6 (11): 2921–7. (November 2007). doi:10.1158/1535-7163.MCT-07-0371. PMID 18025276.

外部リンク

ID1 protein, human - 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）
Overview of all the structural information available in the PDB for UniProt: P20067 (Mouse DNA-binding protein inhibitor ID-1) at the PDBe-KB.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000125968 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000042745 - Ensembl, May 2017

[3] Human PubMed Reference:

[4] Mouse PubMed Reference:

[HalId-5] “The protein Id: a negative regulator of helix-loop-helix DNA binding proteins”. Cell 61 (1): 49–59. (April 1990). doi:10.1016/0092-8674(90)90214-Y. PMID 2156629.

[pmid8294468-6] “Id-related genes encoding helix-loop-helix proteins are required for G1 progression and are repressed in senescent human fibroblasts”. The Journal of Biological Chemistry 269 (3): 2139–45. (January 1994). doi:10.1016/S0021-9258(17)42146-6. PMID 8294468.

[:0-7] “Id proteins in development, cell cycle and cancer”. Trends in Cell Biology 13 (8): 410–8. (August 2003). doi:10.1016/S0962-8924(03)00147-8. PMID 12888293.

[:1-8] “Id family of helix-loop-helix proteins in cancer”. Nature Reviews. Cancer 5 (8): 603–14. (August 2005). doi:10.1038/nrc1673. PMID 16034366.

[9] Cunningham, Thomas J.; Yu, Michael S.; McKeithan, Wesley L.; Spiering, Sean; Carrette, Florent; Huang, Chun-Teng; Bushway, Paul J.; Tierney, Matthew et al. (2017-07-01). “Id genes are essential for early heart formation”. Genes & Development 31 (13): 1325–1338. doi:10.1101/gad.300400.117. ISSN 1549-5477. PMC 5580654. PMID 28794185.

[pmid15029197-10] “The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis”. Nature 428 (6980): 328–32. (March 2004). Bibcode: 2004Natur.428..328G. doi:10.1038/nature02329. PMID 15029197.

[pmid9242638-11] “Differential interactions of Id proteins with basic-helix-loop-helix transcription factors”. The Journal of Biological Chemistry 272 (32): 19785–93. (August 1997). doi:10.1074/jbc.272.32.19785. PMID 9242638.

[pmid8380166-12] “Detection and modulation in vivo of helix-loop-helix protein-protein interactions”. The Journal of Biological Chemistry 268 (1): 5–8. (January 1993). doi:10.1016/S0021-9258(18)54105-3. PMID 8380166.

[pmid9528857-13] “Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc”. Oncogene 16 (9): 1149–59. (March 1998). doi:10.1038/sj.onc.1201634. PMID 9528857.

[pmid12145280-14] “The LIM-only protein DRAL/FHL2 interacts with and is a corepressor for the promyelocytic leukemia zinc finger protein”. The Journal of Biological Chemistry 277 (40): 37045–53. (October 2002). doi:10.1074/jbc.M203336200. PMID 12145280.

[pmid18674781-15] “Id-1 induces proteasome-dependent degradation of the HBX protein”. Journal of Molecular Biology 382 (1): 34–43. (September 2008). doi:10.1016/j.jmb.2007.06.020. PMID 18674781.

[pmid1644289-16] “Overexpression of Id protein inhibits the muscle differentiation program: in vivo association of Id with E2A proteins”. Genes & Development 6 (8): 1466–79. (August 1992). doi:10.1101/gad.6.8.1466. PMID 1644289.

[pmid15694377-17] “CASK inhibits ECV304 cell growth and interacts with Id1”. Biochemical and Biophysical Research Communications 328 (2): 517–21. (March 2005). doi:10.1016/j.bbrc.2005.01.014. PMID 15694377.

[pmid10537105-18] “Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts”. Nature 401 (6754): 670–7. (October 1999). Bibcode: 1999Natur.401..670L. doi:10.1038/44334. PMID 10537105.

[pmid11689883-19] “Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth”. Nature Medicine 7 (11): 1194–201. (November 2001). doi:10.1038/nm1101-1194. PMID 11689883.

[pmid18176556-20] “Peptide-conjugated antisense oligonucleotides for targeted inhibition of a transcriptional regulator in vivo”. Nature Biotechnology 26 (1): 91–100. (January 2008). doi:10.1038/nbt1366. PMID 18176556.

[pmid20807818-21] “Using the transcription factor inhibitor of DNA binding 1 to selectively target endothelial progenitor cells offers novel strategies to inhibit tumor angiogenesis and growth”. Cancer Research 70 (18): 7273–82. (September 2010). doi:10.1158/0008-5472.CAN-10-1142. PMC 3058751. PMID 20807818.

[PMC8168201-22] “Therapeutic reversal of prenatal pontine ID1 signaling in DIPG”. Neuro Oncol 23 (supplement 1): i48. (June 2021). doi:10.1093/neuonc/noab090.193. PMC 8168201.

[PMID18025276-23] “Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells”. Molecular Cancer Therapeutics 6 (11): 2921–7. (November 2007). doi:10.1158/1535-7163.MCT-07-0371. PMID 18025276.

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ID1

目次

機能

相互作用

臨床的意義

出典

関連文献

関連項目

外部リンク