RACGAP1

RACGAP1
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
	2OVJ, 3W6R, 3WPQ, 3WPS, 4B6D, 5C2J, 5C2K
識別子
記号	RACGAP1, CYK4, HsCYK-4, ID-GAP, MgcRacGAP, Rac GTPase activating protein 1, CDAN3B
外部ID	OMIM: 604980 MGI: 1349423 HomoloGene: 8077 GeneCards: RACGAP1
遺伝子の位置 (ヒト)
染色体	12番染色体 (ヒト)
終点	50,033,136 bp
遺伝子の位置 (マウス)
染色体	15番染色体 (マウス)
終点	99,549,537 bp
遺伝子オントロジー
分子機能	• microtubule binding; • alpha-tubulin binding; • 金属イオン結合; • 血漿タンパク結合; • beta-tubulin binding; • gamma-tubulin binding; • プロテインキナーゼ結合; • phosphatidylinositol-3,4,5-trisphosphate binding; • 脂質結合; • GTPase activator activity;
細胞の構成要素	• 細胞質; • 細胞質基質; • centralspindlin complex; • 膜; • extrinsic component of cytoplasmic side of plasma membrane; • 細胞膜; • 紡錘体; • 核質; • 先体; • spindle midzone; • 分裂溝; • mitotic spindle; • 微小管; • エキソソーム; • 細胞骨格; • 細胞核; • cytoplasmic vesicle; • midbody; • Flemming body;
生物学的プロセス	• 細胞分化; • intracellular signal transduction; • antigen processing and presentation of exogenous peptide antigen via MHC class II; • mitotic spindle midzone assembly; • sulfate transport; • mitotic cytokinesis; • イオン輸送; • 細胞分裂; • positive regulation of cytokinesis; • 多細胞個体の発生; • microtubule-based movement; • actomyosin contractile ring assembly; • 精子形成; • neuroblast proliferation; • 細胞周期; • regulation of attachment of spindle microtubules to kinetochore; • regulation of small GTPase mediated signal transduction; • シグナル伝達; • positive regulation of GTPase activity; • retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum; • regulation of embryonic development; • 輸送;
	出典:Amigo / QuickGO
オルソログ
	29127
	26934
	ENSG00000161800
	ENSMUSG00000023015
	Q9H0H5,F8VZ66
	Q9WVM1
NM_001126103; NM_001126104; NM_013277; NM_001319999; NM_001320000;
	NM_001320001; NM_001320002; NM_001320003; NM_001320004; NM_001320005; NM_001320006; NM_001320007
	NM_001253808; NM_001253809; NM_012025
NP_001119575; NP_001119576; NP_001306928; NP_001306929; NP_001306930;
	NP_001306931; NP_001306932; NP_001306933; NP_001306934; NP_001306935; NP_001306936; NP_037409
	NP_001240737; NP_001240738; NP_036155
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

RACGAP1（Rac GTPase activating protein 1）は、ヒトではRACGAP1遺伝子にコードされているタンパク質である^[5]。

機能

Rasスーパーファミリーに属するRhoファミリーのGTPアーゼはさまざまな細胞過程を制御しており、Rho（英語版）、Rac、Cdc42（英語版）の3つのサブタイプが存在する。RACGAP1は活性化型Rho GTPアーゼに対するGTPアーゼ活性化タンパク質（GAP）として機能し、GTPアーゼに結合しているGTPの加水分解を刺激する。この触媒機能によって、Rhoファミリーのシグナルを負に調節し、細胞質分裂、細胞成長、細胞分化の調節に関与している^[6]。RACGAP1の過剰発現は、乳がん^[7]、胃がん^[8]、大腸がん^[9]などヒトの複数のがんで観察されている。乳がんでは、RACGAP1はマイトファジーやミトコンドリア生合成を刺激することでミトコンドリアの品質管理を調節している場合がある^[7]^[10]。In vitroでのCRISPR/Cas9を用いたRACGAP1のノックアウトは、細胞質分裂の欠陥をもたらす^[7]。

相互作用

RACGAP1は、ECT2（英語版）^[7]、RND2（英語版）^[11]、SLC26A8（英語版）^[12]と相互作用することが示されている。

細胞質分裂時には、RACGAP1はKIF23（英語版）と相互作用してセントラルスピンドリン（英語版）複合体を形成することが示されている^[13]。この複合体は中央紡錘体（英語版）の形成に必要不可欠である。RACGAP1はPRC1（英語版）とも相互作用し、有糸分裂後期の進行とともに中央紡錘体を安定化し、維持する^[14]。また後期にはECT2とも相互作用しており、RACGAP1の喪失は細胞質分裂の欠陥をもたらす^[7]。

出典

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000161800 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000023015 - Ensembl, May 2017
^ Human PubMed Reference:
^ Mouse PubMed Reference:
^ “MgcRacGAP, a new human GTPase-activating protein for Rac and Cdc42 similar to Drosophila rotundRacGAP gene product, is expressed in male germ cells”. The Journal of Biological Chemistry 273 (11): 6019–23. (March 1998). doi:10.1074/jbc.273.11.6019. PMID 9497316.
^ “Entrez Gene: RACGAP1 Rac GTPase activating protein 1”. 2024年10月28日閲覧。
^ ^a ^b ^c ^d ^e Ren, Kehan; Zhou, Danmei; Wang, Meili; Li, Ermin; Hou, Chenjian; Su, Ying; Zou, Qiang; Zhou, Ping et al. (2021-03-01). “RACGAP1 modulates ECT2-Dependent mitochondrial quality control to drive breast cancer metastasis” (英語). Experimental Cell Research 400 (1): 112493. doi:10.1016/j.yexcr.2021.112493. ISSN 0014-4827. PMID 33485843.
^ “Clinical significance of RacGAP1 expression at the invasive front of gastric cancer”. Gastric Cancer 18 (1): 84–92. (January 2015). doi:10.1007/s10120-014-0355-1. PMID 24615626.
^ “RacGAP1 expression, increasing tumor malignant potential, as a predictive biomarker for lymph node metastasis and poor prognosis in colorectal cancer”. Carcinogenesis 36 (3): 346–54. (March 2015). doi:10.1093/carcin/bgu327. PMID 25568185.
^ “Long non-coding RNA RACGAP1P promotes breast cancer invasion and metastasis via miR-345-5p/RACGAP1-mediated mitochondrial fission”. Molecular Oncology 15 (2): 543–559. (February 2021). doi:10.1002/1878-0261.12866. ISSN 1574-7891. PMC 7858103. PMID 33252198.
^ “Rho family GTPase Rnd2 interacts and co-localizes with MgcRacGAP in male germ cells”. The Biochemical Journal 372 (Pt 1): 105–112. (May 2003). doi:10.1042/BJ20021652. PMC 1223378. PMID 12590651.
^ “Tat1, a novel sulfate transporter specifically expressed in human male germ cells and potentially linked to rhogtpase signaling”. The Journal of Biological Chemistry 276 (23): 20309–20315. (June 2001). doi:10.1074/jbc.M011740200. PMID 11278976.
^ “Cytokinesis: centralspindlin moonlights as a membrane anchor”. Current Biology 23 (4): R145-7. (February 2013). Bibcode: 2013CBio...23.R145G. doi:10.1016/j.cub.2013.01.006. PMID 23428321.
^ “Direct interaction between centralspindlin and PRC1 reinforces mechanical resilience of the central spindle”. Nature Communications 6: 7290. (June 2015). Bibcode: 2015NatCo...6.7290L. doi:10.1038/ncomms8290. PMC 4557309. PMID 26088160.

関連文献

“Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides”. Gene 138 (1–2): 171–4. (January 1994). doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
“Cloning of a novel mitogen-activated protein kinase kinase kinase, MEKK4, that selectively regulates the c-Jun amino terminal kinase pathway”. The Journal of Biological Chemistry 272 (13): 8288–95. (March 1997). doi:10.1074/jbc.272.13.8288. PMID 9079650.
“Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library”. Gene 200 (1–2): 149–56. (October 1997). doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
“The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily motor KIF3”. The EMBO Journal 17 (1): 149–58. (January 1998). doi:10.1093/emboj/17.1.149. PMC 1170366. PMID 9427749.
“A new rac target POSH is an SH3-containing scaffold protein involved in the JNK and NF-kappaB signalling pathways”. The EMBO Journal 17 (5): 1395–404. (March 1998). doi:10.1093/emboj/17.5.1395. PMC 1170487. PMID 9482736.
“PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia”. The EMBO Journal 17 (22): 6527–40. (November 1998). doi:10.1093/emboj/17.22.6527. PMC 1171000. PMID 9822598.
“A genome-wide survey of RAS transformation targets”. Nature Genetics 24 (2): 144–52. (February 2000). doi:10.1038/72799. PMID 10655059.
“Control of intramolecular interactions between the pleckstrin homology and Dbl homology domains of Vav and Sos1 regulates Rac binding”. The Journal of Biological Chemistry 275 (20): 15074–81. (May 2000). doi:10.1074/jbc.M907269199. PMID 10748082.
“Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro”. DNA Research 7 (2): 143–50. (April 2000). doi:10.1093/dnares/7.2.143. PMID 10819331.
“MgcRacGAP is involved in the control of growth and differentiation of hematopoietic cells”. Blood 96 (6): 2116–24. (September 2000). doi:10.1182/blood.V96.6.2116. PMID 10979956.
“DNA cloning using in vitro site-specific recombination”. Genome Research 10 (11): 1788–95. (November 2000). doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
“MgcRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody”. The Journal of Biological Chemistry 276 (8): 5821–8. (February 2001). doi:10.1074/jbc.M007252200. PMID 11085985.
“Phorbol esters and related analogs regulate the subcellular localization of beta 2-chimaerin, a non-protein kinase C phorbol ester receptor”. The Journal of Biological Chemistry 276 (21): 18303–12. (May 2001). doi:10.1074/jbc.M011368200. PMID 11278894.
“Tat1, a novel sulfate transporter specifically expressed in human male germ cells and potentially linked to rhogtpase signaling”. The Journal of Biological Chemistry 276 (23): 20309–15. (June 2001). doi:10.1074/jbc.M011740200. PMID 11278976.
“Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity”. Developmental Cell 2 (1): 41–54. (January 2002). doi:10.1016/S1534-5807(01)00110-1. PMID 11782313.
“The plexin-B1/Rac interaction inhibits PAK activation and enhances Sema4D ligand binding”. Genes & Development 16 (7): 836–45. (April 2002). doi:10.1101/gad.966402. PMC 186329. PMID 11937491.
“Role of MgcRacGAP/Cyk4 as a regulator of the small GTPase Rho family in cytokinesis and cell differentiation”. Cell Structure and Function 26 (6): 645–51. (December 2001). doi:10.1247/csf.26.645. PMID 11942621.
“Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity”. Journal of Cell Science 115 (Pt 24): 4901–13. (December 2002). doi:10.1242/jcs.00219. PMID 12432077.
“CYK-4: A Rho family gtpase activating protein (GAP) required for central spindle formation and cytokinesis”. The Journal of Cell Biology 149 (7): 1391–404. (June 2000). doi:10.1083/jcb.149.7.1391. PMC 2175131. PMID 10871280.

この項目は、生物学に関連した書きかけの項目です。この項目を加筆・訂正などしてくださる協力者を求めています（プロジェクト:生命科学／Portal:生物学）。

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000161800 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000023015 - Ensembl, May 2017

[3] Human PubMed Reference:

[4] Mouse PubMed Reference:

[pmid9497316-5] “MgcRacGAP, a new human GTPase-activating protein for Rac and Cdc42 similar to Drosophila rotundRacGAP gene product, is expressed in male germ cells”. The Journal of Biological Chemistry 273 (11): 6019–23. (March 1998). doi:10.1074/jbc.273.11.6019. PMID 9497316.

[entrez-6] “Entrez Gene: RACGAP1 Rac GTPase activating protein 1”. 2024年10月28日閲覧。

[:0-7] Ren, Kehan; Zhou, Danmei; Wang, Meili; Li, Ermin; Hou, Chenjian; Su, Ying; Zou, Qiang; Zhou, Ping et al. (2021-03-01). “RACGAP1 modulates ECT2-Dependent mitochondrial quality control to drive breast cancer metastasis” (英語). Experimental Cell Research 400 (1): 112493. doi:10.1016/j.yexcr.2021.112493. ISSN 0014-4827. PMID 33485843.

[:1-8] “Clinical significance of RacGAP1 expression at the invasive front of gastric cancer”. Gastric Cancer 18 (1): 84–92. (January 2015). doi:10.1007/s10120-014-0355-1. PMID 24615626.

[:2-9] “RacGAP1 expression, increasing tumor malignant potential, as a predictive biomarker for lymph node metastasis and poor prognosis in colorectal cancer”. Carcinogenesis 36 (3): 346–54. (March 2015). doi:10.1093/carcin/bgu327. PMID 25568185.

[:3-10] “Long non-coding RNA RACGAP1P promotes breast cancer invasion and metastasis via miR-345-5p/RACGAP1-mediated mitochondrial fission”. Molecular Oncology 15 (2): 543–559. (February 2021). doi:10.1002/1878-0261.12866. ISSN 1574-7891. PMC 7858103. PMID 33252198.

[pmid12590651-11] “Rho family GTPase Rnd2 interacts and co-localizes with MgcRacGAP in male germ cells”. The Biochemical Journal 372 (Pt 1): 105–112. (May 2003). doi:10.1042/BJ20021652. PMC 1223378. PMID 12590651.

[pmid11278976-12] “Tat1, a novel sulfate transporter specifically expressed in human male germ cells and potentially linked to rhogtpase signaling”. The Journal of Biological Chemistry 276 (23): 20309–20315. (June 2001). doi:10.1074/jbc.M011740200. PMID 11278976.

[cytokinesis-13] “Cytokinesis: centralspindlin moonlights as a membrane anchor”. Current Biology 23 (4): R145-7. (February 2013). Bibcode: 2013CBio...23.R145G. doi:10.1016/j.cub.2013.01.006. PMID 23428321.

[:4-14] “Direct interaction between centralspindlin and PRC1 reinforces mechanical resilience of the central spindle”. Nature Communications 6: 7290. (June 2015). Bibcode: 2015NatCo...6.7290L. doi:10.1038/ncomms8290. PMC 4557309. PMID 26088160.

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