Wikipedia

GRB2

GRB2（growth factor receptor bound protein 2）は、シグナル伝達に関与するアダプタータンパク質である。ヒトでは、GRB2タンパク質はGRB2遺伝子によってコードされている[5][6]。

GRB2
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

1AZE, 1BM2, 1BMB, 1CJ1, 1FHS, 1FYR, 1GCQ, 1GFC, 1GFD, 1GHU, 1GRI, 1IO6, 1JYQ, 1JYR, 1JYU, 1QG1, 1TZE, 1X0N, 1ZFP, 2AOA, 2AOB, 2H5K, 2HUW, 2VVK, 2VWF, 2W0Z, 3C7I, 3IMD, 3IMJ, 3IN7, 3IN8, 3KFJ, 3MXC, 3MXY, 3N7Y, 3N84, 3N8M, 3OV1, 3OVE, 3S8L, 3S8N, 3S8O, 2H46, 3WA4, 4P9V, 4P9Z, 5CDW

識別子
記号GRB2, ASH, EGFRBP-Grb3-3, MST084, MSTP084, NCKAP2, growth factor receptor bound protein 2
外部IDOMIM: 108355 MGI: 95805 HomoloGene: 1576 GeneCards: GRB2
遺伝子の位置 (ヒト)
17番染色体 (ヒト)
染色体17番染色体 (ヒト)[1]
17番染色体 (ヒト)
GRB2遺伝子の位置
GRB2遺伝子の位置
バンドデータ無し開始点75,318,076 bp[1]
終点75,405,709 bp[1]
遺伝子の位置 (マウス)
11番染色体 (マウス)
染色体11番染色体 (マウス)[2]
11番染色体 (マウス)
GRB2遺伝子の位置
GRB2遺伝子の位置
バンドデータ無し開始点115,534,871 bp[2]
終点115,599,423 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• protein domain specific binding
• SH3 domain binding
• プロテインキナーゼ結合
• identical protein binding
• neurotrophin TRKA receptor binding
• protein phosphatase binding
• 血漿タンパク結合
• ephrin receptor binding
• insulin receptor substrate binding
• epidermal growth factor receptor binding
• phosphatidylinositol-4,5-bisphosphate 3-kinase activity
• 1-phosphatidylinositol-3-kinase activity
• phosphoprotein binding
• 酵素結合
• RNA結合
• non-membrane spanning protein tyrosine kinase activity
• phosphotyrosine residue binding
細胞の構成要素• エキソソーム
• 核小体
• 細胞質
• 核質
• COP9シグナロソーム
• ゴルジ体
• 細胞質基質
• 細胞核
• cell-cell junction
• 膜
• Grb2-EGFR complex
• エンドソーム
• vesicle membrane
• 細胞膜
• extrinsic component of cytoplasmic side of plasma membrane
• 高分子複合体
• 細胞内
生物学的プロセス• T cell costimulation
• Fc-gamma receptor signaling pathway involved in phagocytosis
• branching involved in labyrinthine layer morphogenesis
• MAPK cascade
• epidermal growth factor receptor signaling pathway
• fibroblast growth factor receptor signaling pathway
• insulin receptor signaling pathway
• receptor internalization
• 細胞間シグナル伝達
• 軸索誘導
• positive regulation of reactive oxygen species metabolic process
• cellular response to ionizing radiation
• Fc-epsilon receptor signaling pathway
• viral process
• positive regulation of actin filament polymerization
• signal transduction in response to DNA damage
• negative regulation of epidermal growth factor receptor signaling pathway
• leukocyte migration
• regulation of MAPK cascade
• anatomical structure formation involved in morphogenesis
• 老化
• ERBB2 signaling pathway
• phosphatidylinositol phosphate biosynthetic process
• phosphatidylinositol-3-phosphate biosynthetic process
• protein heterooligomerization
• entry of bacterium into host cell
• membrane organization
• 遊走
• 細胞分化
• peptidyl-tyrosine autophosphorylation
• regulation of cell population proliferation
• 自然免疫
• Ras protein signal transduction
• interleukin-15-mediated signaling pathway
• positive regulation of protein kinase B signaling
• 分子機能制御
• サイトカイン媒介シグナル伝達経路
• positive regulation of Ras protein signal transduction
• neurotrophin TRK receptor signaling pathway
出典:Amigo / QuickGO
オルソログ
種ヒトマウス
Entrez

2885

14784

Ensembl

ENSG00000177885

ENSMUSG00000059923

UniProt

P62993,J3KT38

Q60631

RefSeq
(mRNA)

NM_203506
NM_002086

NM_008163
NM_001313936
NM_001313937

RefSeq
(タンパク質)

NP_002077
NP_987102

NP_001300865
NP_001300866
NP_032189

場所
(UCSC)		Chr 17: 75.32 – 75.41 MbChr 17: 115.53 – 115.6 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

GRB2は上皮成長因子受容体などの受容体に結合するタンパク質で、1つのSH2ドメインと2つのSH3ドメインを有する。2つのSH3ドメインは他のタンパク質のプロリンリッチ領域と直接的に相互作用して複合体形成へ差し向け、SH2ドメインはリン酸化されたチロシンを含む配列に結合する。GRB2遺伝子はCaenorhabditis elegansにおいてシグナル伝達経路に関与しているsem-5遺伝子と類似している。GRB2遺伝子には、異なるアイソフォームをコードする2種類の選択的スプライシングバリアントが発見されている[7]。

機能

編集

GRB2は複数の細胞機能に必要不可欠な役割を果たしている。GRB2の機能の阻害によって、さまざまな生物種で発生過程が損なわれ、またさまざまな細胞種で形質転換や増殖が遮断される。GRB2は上皮成長因子受容体と、Rasやその下流のキナーゼであるERK1/2とを関連づける役割が最もよく知られている。一方で、GRB2はHER2の場合には他のキナーゼAKTに対して関連づける。このように、さまざまな受容体型チロシンキナーゼのシグナルがGRB2へ収束する可能性があるものの、これらのシグナルは必ずしも同じ下流キナーゼの活性化を引き起こすためにGRB2を利用しているわけではない[8]。

ドメイン

編集

GRB2はSH2ドメインの両側にSH3ドメインが隣接した構成をしている[9]。

GRB2のSH2ドメインは、受容体やアダプタータンパク質に存在するリン酸化チロシン（pY）含有モチーフに結合する。pY-X-N-X配列（Xは任意のアミノ酸）に対して選択的に結合するが、pY-(L/V)-N-(V/P)配列に対してより高い親和性で結合する[10]。

N末端側のSH3ドメインはプロリンに富むペプチドに結合し、Rasのグアニンヌクレオチド交換因子であるSos（英語版）に結合することができる[11]。

C末端側のSH3ドメインはP-X-X-X-Rモチーフを有するペプチドに結合し、GAB1（英語版）などのタンパク質への特異的結合を可能にしている[12]。

相互作用

編集

GRB2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

編集
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000177885 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000059923 - Ensembl, May 2017
  3. ^ Human PubMed Reference:
  4. ^ Mouse PubMed Reference:
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  6. ^ a b “The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling”. Cell 70 (3): 431–42. (Aug 1992). doi:10.1016/0092-8674(92)90167-B. PMID 1322798. 
  7. ^ “Entrez Gene: GRB2 growth factor receptor-bound protein 2”. 2024年9月29日閲覧。
  8. ^ Tari, A. M.; Lopez-Berestein, G. (2001-10). “GRB2: a pivotal protein in signal transduction”. Seminars in Oncology 28 (5 Suppl 16): 142–147. doi:10.1016/s0093-7754(01)90291-x. ISSN 0093-7754. PMID 11706405. https://pubmed.ncbi.nlm.nih.gov/11706405. 
  9. ^ Yablonski, Deborah (2019). “Bridging the Gap: Modulatory Roles of the Grb2-Family Adaptor, Gads, in Cellular and Allergic Immune Responses”. Frontiers in Immunology 10: 1704. doi:10.3389/fimmu.2019.01704. ISSN 1664-3224. PMC 6669380. PMID 31402911. https://pubmed.ncbi.nlm.nih.gov/31402911. 
  10. ^ Higo, Kunitake; Ikura, Teikichi; Oda, Masayuki; Morii, Hisayuki; Takahashi, Jun; Abe, Ryo; Ito, Nobutoshi (2013). “High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28”. PloS One 8 (9): e74482. doi:10.1371/journal.pone.0074482. ISSN 1932-6203. PMC 3787023. PMID 24098653. https://pubmed.ncbi.nlm.nih.gov/24098653. 
  11. ^ Ogura, Kenji; Okamura, Hideyasu (2013-10-09). “Conformational change of Sos-derived proline-rich peptide upon binding Grb2 N-terminal SH3 domain probed by NMR”. Scientific Reports 3: 2913. doi:10.1038/srep02913. ISSN 2045-2322. PMC 6505672. PMID 24105423. https://pubmed.ncbi.nlm.nih.gov/24105423. 
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