MAP2K1

MAP2K1
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
	1S9J, 2P55, 3DV3, 3DY7, 3E8N, 3EQB, 3EQC, 3EQD, 3EQF, 3EQG, 3EQH, 3EQI, 3MBL, 3ORN, 3OS3, 3PP1, 3SLS, 3V01, 3V04, 3VVH, 3W8Q, 3WIG, 3ZLS, 3ZLW, 3ZLX, 3ZLY, 3ZM4, 4AN2, 4AN3, 4AN9, 4ANB, 4ARK, 4LMN, 4MNE, 4U7Z, 4U80, 4U81, 5BX0
識別子
記号	MAP2K1, CFC3, MAPKK1, MEK1, MKK1, PRKMK1, mitogen-activated protein kinase kinase 1, MEL
外部ID	OMIM: 176872 MGI: 1346866 HomoloGene: 2063 GeneCards: MAP2K1
遺伝子の位置 (ヒト)
染色体	15番染色体 (ヒト)
終点	66,491,656 bp
遺伝子の位置 (マウス)
染色体	9番染色体 (マウス)
終点	64,160,913 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 N-terminus binding; • キナーゼ活性; • protein C-terminus binding; • ATP binding; • トランスフェラーゼ活性; • protein serine/threonine kinase activator activity; • 血漿タンパク結合; • protein serine/threonine/tyrosine kinase activity; • protein tyrosine kinase activity; • ヌクレオチド結合; • MAP kinase kinase activity; • protein kinase activity; • protein serine/threonine kinase activity; • scaffold protein binding;
細胞の構成要素	• 膜; • 焦点接着; • 微小管形成中心; • ミトコンドリア; • 細胞骨格; • 細胞核; • 小胞体; • late endosome; • ゴルジ体; • early endosome; • 細胞質; • 細胞質基質; • 細胞膜;
生物学的プロセス	• regulation of protein phosphorylation; • positive regulation of axonogenesis; • positive regulation of protein serine/threonine kinase activity; • 細胞老化; • face development; • cerebellar cortex formation; • negative regulation of cell population proliferation; • 胸腺発生; • cell motility; • 遺伝子発現の負の調節; • 心臓発生; • positive regulation of cell differentiation; • regulation of stress-activated MAPK cascade; • リン酸化; • epithelial cell proliferation involved in lung morphogenesis; • 走化性; • 甲状腺発生; • neuron differentiation; • trachea formation; • regulation of axon regeneration; • lung morphogenesis; • regulation of early endosome to late endosome transport; • labyrinthine layer development; • placenta blood vessel development; • keratinocyte differentiation; • MAPK cascade; • positive regulation of gene expression; • Bergmann glial cell differentiation; • peptidyl-tyrosine phosphorylation; • regulation of Golgi inheritance; • シグナル伝達; • positive regulation of production of miRNAs involved in gene silencing by miRNA; • positive regulation of ERK1 and ERK2 cascade; • positive regulation of transcription, DNA-templated; • regulation of mitotic cell cycle; • regulation of apoptotic process; • タンパク質リン酸化; • peptidyl-threonine phosphorylation; • ERK1 and ERK2 cascade; • stress-activated protein kinase signaling cascade; • activation of protein kinase activity;
	出典:Amigo / QuickGO
オルソログ
	5604
	26395
	ENSG00000169032
	ENSMUSG00000004936
	Q02750
	P31938
	NM_002755
	NM_008927
	NP_002746
	NP_032953
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

MAP2K1（mitogen-activated protein kinase kinase 1）またはMEK1は、ヒトではMAP2K1遺伝子にコードされるタンパク質である^[5]^[6]。

機能

MAP2K1遺伝子にコードされるMAP2K1タンパク質は二重特異性プロテインキナーゼ（英語版）ファミリーの一員であり、MAPキナーゼキナーゼとして作用する。細胞外シグナル調節キナーゼ（ERK）としても知られるMAPキナーゼは複数の生化学シグナルの統合点として機能する。このプロテインキナーゼはMAPキナーゼの上流に位置し、細胞内外の広範囲のシグナルによる活性化に伴ってMAPキナーゼの酵素活性を刺激する。このキナーゼはMAPキナーゼシグナル伝達経路（英語版）の必須の構成要素として、増殖、分化、転写調節、発生など多くの細胞過程に関与する^[7]。MAP2K1はヒトの全てのがんの1.05%で変化が生じている^[8]。

減数分裂

二倍体生物の自然集団のゲノムは、挿入や欠失などの多型に富んでいる。減数分裂時にこうした多型領域内で形成された二本鎖切断は、相同染色体間の交換（乗換え）ではなく姉妹染色分体交換（英語版）によって修復される必要がある。出芽酵母の減数分裂時の組換えに関する分子レベルでの研究では、相同染色体間で対応配列を欠く領域に形成された二本鎖切断によって開始された組換えイベントは、姉妹染色分体交換によって効率的に修復されることが示されている^[9]。

MAP2K1はMEK1としても知られる（MAPキナーゼキナーゼを参照）。MEK1は減数分裂期染色体軸結合キナーゼであり、姉妹染色分体交換を完全に遮断するわけではないが、低下させると考えられている。MEK1の喪失によって姉妹染色分体間での二本鎖切断修復が可能となり、姉妹染色分体間のホリデイジャンクション中間体が増加する。MEK1の正常な活性は姉妹染色分体間での組換えを低下させるものの、こうした組換えは出芽酵母の減数分裂時に頻繁に生じ（ただし有糸分裂時よりは低頻度である）、全ての組換えイベントの最大1/3が姉妹染色分体間での組換えである^[9]。

相互作用

MAP2K1は、c-Raf^[10]、PEBP1（英語版）^[10]、MAP2K1IP1（英語版）^[11]^[12]、GRB10（英語版）^[13]、MAPK3（英語版）^[12]^[14]^[15]^[16]^[17]、MAPK8IP3（英語版）^[18]^[19]、MAPK1^[10]^[11]^[20]^[21]^[22]^[23]、MAP3K1（英語版）^[24]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: ENSG00000169032 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000004936 - Ensembl, May 2017
^ Human PubMed Reference:
^ Mouse PubMed Reference:
^ “Chromosomal localization of four MAPK signaling cascade genes: MEK1, MEK3, MEK4 and MEKK5”. Cytogenet Cell Genet 78 (3–4): 301–3. (Mar 1998). doi:10.1159/000134677. PMID 9465908.
^ “Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2”. J Biol Chem 268 (15): 11435–9. (Jun 1993). doi:10.1016/S0021-9258(18)82142-1. PMID 8388392.
^ “Entrez Gene: MAP2K1 mitogen-activated protein kinase kinase 1”. 2022年11月19日閲覧。
^ “MAP2K1 - My Cancer Genome”. 2022年11月19日閲覧。
^ ^a ^b “Frequent and efficient use of the sister chromatid for DNA double-strand break repair during budding yeast meiosis”. PLOS Biol. 8 (10): e1000520. (2010). doi:10.1371/journal.pbio.1000520. PMC 2957403. PMID 20976044.
^ ^a ^b ^c Yeung, K; Janosch P; McFerran B; Rose D W; Mischak H; Sedivy J M; Kolch W (May 2000). “Mechanism of Suppression of the Raf/MEK/Extracellular Signal-Regulated Kinase Pathway by the Raf Kinase Inhibitor Protein”. Mol. Cell. Biol. (UNITED STATES) 20 (9): 3079–85. doi:10.1128/MCB.20.9.3079-3085.2000. PMC 85596. PMID 10757792.
^ ^a ^b Wunderlich, W; Fialka I; Teis D; Alpi A; Pfeifer A; Parton R G; Lottspeich F; Huber L A (Feb 2001). “A Novel 14-Kilodalton Protein Interacts with the Mitogen-Activated Protein Kinase Scaffold Mp1 on a Late Endosomal/Lysosomal Compartment”. J. Cell Biol. (United States) 152 (4): 765–76. doi:10.1083/jcb.152.4.765. PMC 2195784. PMID 11266467.
^ ^a ^b Schaeffer, H J; Catling A D; Eblen S T; Collier L S; Krauss A; Weber M J (Sep 1998). “MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade”. Science (UNITED STATES) 281 (5383): 1668–71. Bibcode: 1998Sci...281.1668S. doi:10.1126/science.281.5383.1668. PMID 9733512.
^ Nantel, A; Mohammad-Ali K; Sherk J; Posner B I; Thomas D Y (Apr 1998). “Interaction of the Grb10 adapter protein with the Raf1 and MEK1 kinases”. J. Biol. Chem. (UNITED STATES) 273 (17): 10475–84. doi:10.1074/jbc.273.17.10475. PMID 9553107.
^ Marti, A; Luo Z; Cunningham C; Ohta Y; Hartwig J; Stossel T P; Kyriakis J M; Avruch J (Jan 1997). “Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells”. J. Biol. Chem. (UNITED STATES) 272 (5): 2620–8. doi:10.1074/jbc.272.5.2620. PMID 9006895.
^ Butch, E R; Guan K L (Feb 1996). “Characterization of ERK1 activation site mutants and the effect on recognition by MEK1 and MEK2”. J. Biol. Chem. (UNITED STATES) 271 (8): 4230–5. doi:10.1074/jbc.271.8.4230. PMID 8626767.
^ Yung, Y; Yao Z; Hanoch T; Seger R (May 2000). “ERK1b, a 46-kDa ERK isoform that is differentially regulated by MEK”. J. Biol. Chem. (UNITED STATES) 275 (21): 15799–808. doi:10.1074/jbc.M910060199. PMID 10748187.
^ Zheng, C F; Guan K L (Nov 1993). “Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases”. J. Biol. Chem. (UNITED STATES) 268 (32): 23933–9. doi:10.1016/S0021-9258(20)80474-8. PMID 8226933.
^ Kuboki, Y; Ito M; Takamatsu N; Yamamoto K I; Shiba T; Yoshioka K (Dec 2000). “A scaffold protein in the c-Jun NH2-terminal kinase signaling pathways suppresses the extracellular signal-regulated kinase signaling pathways”. J. Biol. Chem. (UNITED STATES) 275 (51): 39815–8. doi:10.1074/jbc.C000403200. PMID 11044439.
^ Ito, M; Yoshioka K; Akechi M; Yamashita S; Takamatsu N; Sugiyama K; Hibi M; Nakabeppu Y et al. (Nov 1999). “JSAP1, a Novel Jun N-Terminal Protein Kinase (JNK)-Binding Protein That Functions as a Scaffold Factor in the JNK Signaling Pathway”. Mol. Cell. Biol. (UNITED STATES) 19 (11): 7539–48. doi:10.1128/mcb.19.11.7539. PMC 84763. PMID 10523642.
^ Sanz-Moreno, Victoria; Casar Berta; Crespo Piero (May 2003). “p38α Isoform Mxi2 Binds to Extracellular Signal-Regulated Kinase 1 and 2 Mitogen-Activated Protein Kinase and Regulates Its Nuclear Activity by Sustaining Its Phosphorylation Levels”. Mol. Cell. Biol. (United States) 23 (9): 3079–90. doi:10.1128/MCB.23.9.3079-3090.2003. PMC 153192. PMID 12697810.
^ Robinson, Fred L; Whitehurst Angelique W; Raman Malavika; Cobb Melanie H (Apr 2002). “Identification of novel point mutations in ERK2 that selectively disrupt binding to MEK1”. J. Biol. Chem. (United States) 277 (17): 14844–52. doi:10.1074/jbc.M107776200. PMID 11823456.
^ Xu Be, Be; Stippec S; Robinson F L; Cobb M H (Jul 2001). “Hydrophobic as well as charged residues in both MEK1 and ERK2 are important for their proper docking”. J. Biol. Chem. (United States) 276 (28): 26509–15. doi:10.1074/jbc.M102769200. PMID 11352917.
^ Chen, Z; Cobb M H (May 2001). “Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2”. J. Biol. Chem. (United States) 276 (19): 16070–5. doi:10.1074/jbc.M100681200. PMID 11279118.
^ Karandikar, M; Xu S; Cobb M H (Dec 2000). “MEKK1 binds raf-1 and the ERK2 cascade components”. J. Biol. Chem. (UNITED STATES) 275 (51): 40120–7. doi:10.1074/jbc.M005926200. PMID 10969079.

外部リンク

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000169032 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000004936 - Ensembl, May 2017

[3] Human PubMed Reference:

[4] Mouse PubMed Reference:

[pmid9465908-5] “Chromosomal localization of four MAPK signaling cascade genes: MEK1, MEK3, MEK4 and MEKK5”. Cytogenet Cell Genet 78 (3–4): 301–3. (Mar 1998). doi:10.1159/000134677. PMID 9465908.

[pmid8388392-6] “Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2”. J Biol Chem 268 (15): 11435–9. (Jun 1993). doi:10.1016/S0021-9258(18)82142-1. PMID 8388392.

[:0-7] “Entrez Gene: MAP2K1 mitogen-activated protein kinase kinase 1”. 2022年11月19日閲覧。

[:1-8] “MAP2K1 - My Cancer Genome”. 2022年11月19日閲覧。

[Goldfarb-9] “Frequent and efficient use of the sister chromatid for DNA double-strand break repair during budding yeast meiosis”. PLOS Biol. 8 (10): e1000520. (2010). doi:10.1371/journal.pbio.1000520. PMC 2957403. PMID 20976044.

[pmid10757792-10] Yeung, K; Janosch P; McFerran B; Rose D W; Mischak H; Sedivy J M; Kolch W (May 2000). “Mechanism of Suppression of the Raf/MEK/Extracellular Signal-Regulated Kinase Pathway by the Raf Kinase Inhibitor Protein”. Mol. Cell. Biol. (UNITED STATES) 20 (9): 3079–85. doi:10.1128/MCB.20.9.3079-3085.2000. PMC 85596. PMID 10757792.

[pmid11266467-11] Wunderlich, W; Fialka I; Teis D; Alpi A; Pfeifer A; Parton R G; Lottspeich F; Huber L A (Feb 2001). “A Novel 14-Kilodalton Protein Interacts with the Mitogen-Activated Protein Kinase Scaffold Mp1 on a Late Endosomal/Lysosomal Compartment”. J. Cell Biol. (United States) 152 (4): 765–76. doi:10.1083/jcb.152.4.765. PMC 2195784. PMID 11266467.

[pmid9733512-12] Schaeffer, H J; Catling A D; Eblen S T; Collier L S; Krauss A; Weber M J (Sep 1998). “MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade”. Science (UNITED STATES) 281 (5383): 1668–71. Bibcode: 1998Sci...281.1668S. doi:10.1126/science.281.5383.1668. PMID 9733512.

[pmid9553107-13] Nantel, A; Mohammad-Ali K; Sherk J; Posner B I; Thomas D Y (Apr 1998). “Interaction of the Grb10 adapter protein with the Raf1 and MEK1 kinases”. J. Biol. Chem. (UNITED STATES) 273 (17): 10475–84. doi:10.1074/jbc.273.17.10475. PMID 9553107.

[pmid9006895-14] Marti, A; Luo Z; Cunningham C; Ohta Y; Hartwig J; Stossel T P; Kyriakis J M; Avruch J (Jan 1997). “Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells”. J. Biol. Chem. (UNITED STATES) 272 (5): 2620–8. doi:10.1074/jbc.272.5.2620. PMID 9006895.

[pmid8626767-15] Butch, E R; Guan K L (Feb 1996). “Characterization of ERK1 activation site mutants and the effect on recognition by MEK1 and MEK2”. J. Biol. Chem. (UNITED STATES) 271 (8): 4230–5. doi:10.1074/jbc.271.8.4230. PMID 8626767.

[pmid10748187-16] Yung, Y; Yao Z; Hanoch T; Seger R (May 2000). “ERK1b, a 46-kDa ERK isoform that is differentially regulated by MEK”. J. Biol. Chem. (UNITED STATES) 275 (21): 15799–808. doi:10.1074/jbc.M910060199. PMID 10748187.

[pmid8226933-17] Zheng, C F; Guan K L (Nov 1993). “Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases”. J. Biol. Chem. (UNITED STATES) 268 (32): 23933–9. doi:10.1016/S0021-9258(20)80474-8. PMID 8226933.

[pmid11044439-18] Kuboki, Y; Ito M; Takamatsu N; Yamamoto K I; Shiba T; Yoshioka K (Dec 2000). “A scaffold protein in the c-Jun NH2-terminal kinase signaling pathways suppresses the extracellular signal-regulated kinase signaling pathways”. J. Biol. Chem. (UNITED STATES) 275 (51): 39815–8. doi:10.1074/jbc.C000403200. PMID 11044439.

[pmid10523642-19] Ito, M; Yoshioka K; Akechi M; Yamashita S; Takamatsu N; Sugiyama K; Hibi M; Nakabeppu Y et al. (Nov 1999). “JSAP1, a Novel Jun N-Terminal Protein Kinase (JNK)-Binding Protein That Functions as a Scaffold Factor in the JNK Signaling Pathway”. Mol. Cell. Biol. (UNITED STATES) 19 (11): 7539–48. doi:10.1128/mcb.19.11.7539. PMC 84763. PMID 10523642.

[pmid12697810-20] Sanz-Moreno, Victoria; Casar Berta; Crespo Piero (May 2003). “p38α Isoform Mxi2 Binds to Extracellular Signal-Regulated Kinase 1 and 2 Mitogen-Activated Protein Kinase and Regulates Its Nuclear Activity by Sustaining Its Phosphorylation Levels”. Mol. Cell. Biol. (United States) 23 (9): 3079–90. doi:10.1128/MCB.23.9.3079-3090.2003. PMC 153192. PMID 12697810.

[pmid11823456-21] Robinson, Fred L; Whitehurst Angelique W; Raman Malavika; Cobb Melanie H (Apr 2002). “Identification of novel point mutations in ERK2 that selectively disrupt binding to MEK1”. J. Biol. Chem. (United States) 277 (17): 14844–52. doi:10.1074/jbc.M107776200. PMID 11823456.

[pmid11352917-22] Xu Be, Be; Stippec S; Robinson F L; Cobb M H (Jul 2001). “Hydrophobic as well as charged residues in both MEK1 and ERK2 are important for their proper docking”. J. Biol. Chem. (United States) 276 (28): 26509–15. doi:10.1074/jbc.M102769200. PMID 11352917.

[pmid11279118-23] Chen, Z; Cobb M H (May 2001). “Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2”. J. Biol. Chem. (United States) 276 (19): 16070–5. doi:10.1074/jbc.M100681200. PMID 11279118.

[pmid10969079-24] Karandikar, M; Xu S; Cobb M H (Dec 2000). “MEKK1 binds raf-1 and the ERK2 cascade components”. J. Biol. Chem. (UNITED STATES) 275 (51): 40120–7. doi:10.1074/jbc.M005926200. PMID 10969079.

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機能

減数分裂

相互作用

出典

関連文献

外部リンク