MAPK1(mitogen-activated protein kinase 1)またはERK2(extracellular signal-regulated kinase 2)は、ヒトではMAPK1遺伝子にコードされる酵素プロテインキナーゼ)である[5]

MAPK1
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

1PME, 1TVO, 1WZY, 2OJG, 2OJI, 2OJJ, 2Y9Q, 3D42, 3D44, 3I5Z, 3I60, 3SA0, 3TEI, 3W55, 4FMQ, 4FUX, 4FUY, 4FV0, 4FV1, 4FV2, 4FV3, 4FV4, 4FV5, 4FV6, 4FV7, 4FV8, 4FV9, 4G6N, 4G6O, 4H3P, 4H3Q, 4IZ5, 4IZ7, 4IZA, 4N0S, 4NIF, 4O6E, 4QTA, 4QTE, 4ZZM, 4ZZN, 4ZZO, 5BUE, 5BUI, 5BUJ, 4QP1, 4QP2, 4QP3, 4QP4, 4QP6, 4QP7, 4QP8, 4QP9, 4QPA, 4XJ0, 5BVD, 5BVE, 5BVF, 5AX3, 4ZXT, 5K4I

識別子
記号MAPK1, ERK, ERK-2, ERK2, ERT1, MAPK2, P42MAPK, PRKM1, PRKM2, p38, p40, p41, p41mapk, p42-MAPK, mitogen-activated protein kinase 1, NS13
外部IDOMIM: 176948 MGI: 1346858 HomoloGene: 37670 GeneCards: MAPK1
遺伝子の位置 (ヒト)
22番染色体 (ヒト)
染色体22番染色体 (ヒト)[1]
22番染色体 (ヒト)
MAPK1遺伝子の位置
MAPK1遺伝子の位置
バンドデータ無し開始点21,759,657 bp[1]
終点21,867,680 bp[1]
遺伝子の位置 (マウス)
16番染色体 (マウス)
染色体16番染色体 (マウス)[2]
16番染色体 (マウス)
MAPK1遺伝子の位置
MAPK1遺伝子の位置
バンドデータ無し開始点16,801,246 bp[2]
終点16,865,317 bp[2]
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 phosphatase binding
ATP binding
protein kinase activity
転写因子結合
トランスフェラーゼ活性
mitogen-activated protein kinase kinase kinase binding
phosphotyrosine residue binding
血漿タンパク結合
プロテインキナーゼ結合
DNA結合
ヌクレオチド結合
RNA polymerase II CTD heptapeptide repeat kinase activity
protein serine/threonine kinase activity
キナーゼ活性
identical protein binding
MAP kinase activity
二本鎖DNA結合
MAP kinase kinase activity
細胞の構成要素 細胞質
細胞質基質
焦点接着
微小管形成中心
ミトコンドリア
カベオラ
dendrite cytoplasm
細胞骨格
細胞核
エキソソーム
細胞体
late endosome
ゴルジ体
紡錘体
神経繊維
early endosome
mitotic spindle
仮足
細胞外領域
核質
azurophil granule lumen
ficolin-1-rich granule lumen
細胞膜
シナプス後肥厚

高分子複合体
生物学的プロセス caveolin-mediated endocytosis
positive regulation of telomere capping
response to exogenous dsRNA
cardiac neural crest cell development involved in heart development
positive regulation of translation
cellular response to DNA damage stimulus
platelet activation
Fc-epsilon receptor signaling pathway
タンパク質リン酸化
face development
cellular response to granulocyte macrophage colony-stimulating factor stimulus
regulation of DNA-binding transcription factor activity
animal organ morphogenesis
細胞周期
ERBB signaling pathway
アポトーシス
B cell receptor signaling pathway
regulation of transcription, DNA-templated
タンパク質安定性の制御
Fc-gamma receptor signaling pathway involved in phagocytosis
胸腺発生
negative regulation of cell differentiation
ERK1 and ERK2 cascade
labyrinthine layer blood vessel development
transcription, DNA-templated
positive regulation of transcription, DNA-templated
心臓発生
viral process
毒性物質への反応
regulation of stress-activated MAPK cascade
化学的シナプス伝達
growth hormone receptor signaling pathway via JAK-STAT
cytosine metabolic process
リン酸化
outer ear morphogenesis
response to estrogen
走化性
リポ多糖への反応
甲状腺発生
response to epidermal growth factor
positive regulation of telomerase activity
侵害受容
peptidyl-threonine phosphorylation
trachea formation
リポ多糖を介したシグナル伝達経路
mammary gland epithelial cell proliferation
intracellular signal transduction
lung morphogenesis
neural crest cell development
positive regulation of cell migration
regulation of early endosome to late endosome transport
ストレスへの反応
positive regulation of telomere maintenance via telomerase
MAPK cascade
軸索誘導
fibroblast growth factor receptor signaling pathway
positive regulation of peptidyl-threonine phosphorylation
peptidyl-serine phosphorylation
positive regulation of cell population proliferation
regulation of cellular response to heat
Bergmann glial cell differentiation
regulation of Golgi inheritance
T cell receptor signaling pathway
regulation of cytoskeleton organization
シグナル伝達
長期増強
regulation of ossification
regulation of phosphatidylinositol 3-kinase signaling
好中球脱顆粒
遺伝子発現調節
有機物への細胞応答
老化
学習と記憶
positive regulation of gene expression
diadenosine tetraphosphate biosynthetic process
regulation of cellular pH
cellular response to amino acid starvation
cellular response to reactive oxygen species
response to nicotine
脱落膜化
stress-activated MAPK cascade
positive regulation of cardiac muscle cell proliferation
cellular response to cadmium ion
cellular response to tumor necrosis factor
cellular response to dopamine
positive regulation of protein import into nucleus
出典:Amigo / QuickGO
オルソログ
ヒトマウス
Entrez
Ensembl
UniProt
RefSeq
(mRNA)

NM_138957
NM_002745

NM_001038663
NM_011949
NM_001357115
NM_028991

RefSeq
(タンパク質)

NP_002736
NP_620407

NP_001033752
NP_036079
NP_001344044

場所
(UCSC)
Chr 22: 21.76 – 21.87 MbChr 22: 16.8 – 16.87 Mb
PubMed検索[3][4]
ウィキデータ
閲覧/編集 ヒト閲覧/編集 マウス

機能

編集

MAPK1はMAPキナーゼファミリーの一員である。ERK(extracellular signal-regulated kinase)としても知られるMAPキナーゼは、複数の生化学的シグナルの統合点として作用しており、細胞増殖、分化転写調節、発生など幅広い細胞過程に関与している。このキナーゼの活性化には、上流のキナーゼによるリン酸化が必要である。活性化に伴って、このキナーゼは刺激された細胞の内へ移行し、そこで核内の標的をリン酸化する。MAPK1遺伝子には、同一のタンパク質をコードするもののUTRが異なる、2種類の選択的スプライシングバリアントが報告されている[6]。MAPK1には複数のリン酸化部位やユビキチン化部位が存在する[7]

モデル生物

編集

MAPK1の機能の研究にはモデル生物が広く利用されている。疾患の動物モデルを作製して関心のある科学者に頒布するハイスループット変異体作製プロジェクトである国際ノックアウトマウスコンソーシアム英語版プログラムの一環として、Mapk1tm1a(EUCOMM)Wtsi[8][9]と呼ばれるコンディショナルノックアウトマウスが作製されている[10][11][12]

オスとメスのマウスに対し、遺伝子欠失の影響を調べるための規格化された表現型スクリーニングが行われている[13][14]。変異体マウスに対して27種類の試験が行われており、3つの重大な異常が観察されている[13]。妊娠中にホモ接合型変異体の胚は観察されず、そのため離乳期まで生存した個体はなかった。その他の試験はヘテロ接合型変異体の成体マウスに対して行われ、オスでは血中アミラーゼ濃度の低下が観察された[13]

B細胞でのMapk1のコンディショナル欠失によって、MAPK1がT細胞依存的な抗体産生に関与していることが示されている[15]Mapk1に優性機能獲得型変異を有するトランスジェニックマウスでは、MAPK1がT細胞の発生に関与していることが示されている[16]。発生中の大脳皮質の神経前駆細胞におけるMapk1のコンディショナル不活性化は、皮質の厚さの減少と神経前駆細胞の増殖の低下をもたらす[17]

相互作用

編集

MAPK1は次に挙げる因子と相互作用することが示されている。

臨床的意義

編集

MAPK1の変異は多くの種類のがんへの関与が示唆されている[56]

出典

編集
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000100030 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000063358 - Ensembl, May 2017
  3. ^ Human PubMed Reference:
  4. ^ Mouse PubMed Reference:
  5. ^ “Extracellular signal-regulated kinases in T cells: characterization of human ERK1 and ERK2 cDNAs”. Biochem. Biophys. Res. Commun. 182 (3): 1416–22. (February 1992). doi:10.1016/0006-291X(92)91891-S. PMID 1540184. 
  6. ^ Entrez Gene: MAPK1 mitogen-activated protein kinase 1”. 2023年7月17日閲覧。
  7. ^ ERK2 (human)”. www.phosphosite.org. 2020年10月31日閲覧。
  8. ^ Mapk1 Mouse Gene Details | mitogen-activated protein kinase 1 | International Mouse Phenotyping Consortium” (英語). www.mousephenotype.org. 2023年7月17日閲覧。
  9. ^ Mapk1 Targeted Allele Detail MGI Mouse (MGI:4432537)”. www.informatics.jax.org. 2023年7月17日閲覧。
  10. ^ “A conditional knockout resource for the genome-wide study of mouse gene function”. Nature 474 (7351): 337–42. (2011). doi:10.1038/nature10163. PMC 3572410. PMID 21677750. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572410/. 
  11. ^ “Mouse library set to be knockout”. Nature 474 (7351): 262–3. (2011). doi:10.1038/474262a. PMID 21677718. 
  12. ^ “A mouse for all reasons”. Cell 128 (1): 9–13. (2007). doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  13. ^ a b c “The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice”. Acta Ophthalmologica 88: 925–7. (2010). doi:10.1111/j.1755-3768.2010.4142.x. 
  14. ^ “The mouse genetics toolkit: revealing function and mechanism”. Genome Biol. 12 (6): 224. (2011). doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218837/. 
  15. ^ “Extracellular signal-regulated protein kinase 2 is required for efficient generation of B cells bearing antigen-specific immunoglobulin G”. Molecular and Cellular Biology 27 (4): 1236–46. (February 2007). doi:10.1128/MCB.01530-06. PMC 1800707. PMID 17145771. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1800707/. 
  16. ^ “The influence of the MAPK pathway on T cell lineage commitment”. Immunity 7 (5): 609–18. (November 1997). doi:10.1016/s1074-7613(00)80382-9. PMID 9390685. 
  17. ^ “Deletion of ERK2 mitogen-activated protein kinase identifies its key roles in cortical neurogenesis and cognitive function”. The Journal of Neuroscience 28 (27): 6983–95. (July 2008). doi:10.1523/JNEUROSCI.0679-08.2008. PMC 4364995. PMID 18596172. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364995/. 
  18. ^ “Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a potential role in regulated shedding”. Mol. Biol. Cell 13 (6): 2031–44. (June 2002). doi:10.1091/mbc.01-11-0561. PMC 117622. PMID 12058067. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC117622/. 
  19. ^ “Mitogen-activated protein kinase ERK1/2 regulates the class II transactivator”. J. Biol. Chem. 283 (14): 9031–9. (April 2008). doi:10.1074/jbc.M706487200. PMC 2431044. PMID 18245089. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2431044/. 
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  21. ^ “Dual-specificity phosphatase 1 ubiquitination in extracellular signal-regulated kinase-mediated control of growth in human hepatocellular carcinoma”. Cancer Res. 68 (11): 4192–200. (June 2008). doi:10.1158/0008-5472.CAN-07-6157. PMID 18519678. 
  22. ^ “Molecular cloning and characterization of a novel dual specificity phosphatase, LMW-DSP2, that lacks the cdc25 homology domain”. J. Biol. Chem. 276 (29): 27575–83. (July 2001). doi:10.1074/jbc.M100408200. PMID 11346645. 
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  28. ^ a b “p38alpha 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. 23 (9): 3079–90. (May 2003). doi:10.1128/mcb.23.9.3079-3090.2003. PMC 153192. PMID 12697810. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC153192/. 
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  30. ^ a b “Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein”. Mol. Cell. Biol. 20 (9): 3079–85. (May 2000). doi:10.1128/mcb.20.9.3079-3085.2000. PMC 85596. PMID 10757792. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC85596/. 
  31. ^ “A novel 14-kilodalton protein interacts with the mitogen-activated protein kinase scaffold mp1 on a late endosomal/lysosomal compartment”. J. Cell Biol. 152 (4): 765–76. (February 2001). doi:10.1083/jcb.152.4.765. PMC 2195784. PMID 11266467. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195784/. 
  32. ^ “Hydrophobic as well as charged residues in both MEK1 and ERK2 are important for their proper docking”. J. Biol. Chem. 276 (28): 26509–15. (July 2001). doi:10.1074/jbc.M102769200. PMID 11352917. 
  33. ^ “Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2”. J. Biol. Chem. 276 (19): 16070–5. (May 2001). doi:10.1074/jbc.M100681200. PMID 11279118. 
  34. ^ “MEKK1 binds raf-1 and the ERK2 cascade components”. J. Biol. Chem. 275 (51): 40120–7. (December 2000). doi:10.1074/jbc.M005926200. PMID 10969079. 
  35. ^ “Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions”. EMBO J. 20 (3): 466–79. (February 2001). doi:10.1093/emboj/20.3.466. PMC 133461. PMID 11157753. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC133461/. 
  36. ^ a b “Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2”. EMBO J. 16 (8): 1909–20. (April 1997). doi:10.1093/emboj/16.8.1909. PMC 1169794. PMID 9155017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1169794/. 
  37. ^ “The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization”. Mol. Cell. Biol. 23 (16): 5692–705. (August 2003). doi:10.1128/mcb.23.16.5692-5705.2003. PMC 166352. PMID 12897141. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC166352/. 
  38. ^ “Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone promotes functional cooperation of Bcl2 and c-Myc through phosphorylation in regulating cell survival and proliferation”. J. Biol. Chem. 279 (38): 40209–19. (September 2004). doi:10.1074/jbc.M404056200. PMID 15210690. 
  39. ^ “MAP kinase binds to the NH2-terminal activation domain of c-Myc”. FEBS Lett. 353 (3): 281–5. (October 1994). doi:10.1016/0014-5793(94)01052-8. PMID 7957875. 
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関連文献

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関連項目

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外部リンク

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