ERBB4

ERBB4
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
	2AHX, 2L2T, 2LCX, 2R4B, 3BBT, 3BBW, 3BCE, 3U2P, 3U7U, 3U9U
識別子
記号	ERBB4, ALS19, HER4, p180erbB4, erb-b2 receptor tyrosine kinase 4
外部ID	OMIM: 600543 MGI: 104771 HomoloGene: 21084 GeneCards: ERBB4
遺伝子の位置 (ヒト)
染色体	2番染色体 (ヒト)
終点	212,538,841 bp
遺伝子の位置 (マウス)
染色体	1番染色体 (マウス)
終点	69,147,218 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	• トランスフェラーゼ活性; • ヌクレオチド結合; • protein kinase activity; • protein homodimerization activity; • epidermal growth factor receptor binding; • キナーゼ活性; • 血漿タンパク結合; • transmembrane receptor protein tyrosine kinase activity; • ATP binding; • protein tyrosine kinase activity; • phosphatidylinositol-4,5-bisphosphate 3-kinase activity; • 受容体型チロシンキナーゼ; • 膜貫通シグナル伝達受容体活性;
細胞の構成要素	• integral component of membrane; • 細胞質基質; • 膜; • receptor complex; • 細胞膜; • 核質; • 細胞外領域; • ミトコンドリアマトリックス; • basolateral plasma membrane; • ミトコンドリア; • 細胞核; • postsynaptic membrane; • glutamatergic synapse; • GABA-ergic synapse; • integral component of presynaptic membrane; • integral component of postsynaptic density membrane; • 細胞質; • integral component of plasma membrane; • basal plasma membrane;
生物学的プロセス	• mitochondrial fragmentation involved in apoptotic process; • negative regulation of neuron migration; • cell fate commitment; • positive regulation of protein phosphorylation; • regulation of cell migration; • regulation of transcription, DNA-templated; • olfactory bulb interneuron differentiation; • embryonic pattern specification; • リン酸化; • transmembrane receptor protein tyrosine kinase signaling pathway; • central nervous system morphogenesis; • mammary gland alveolus development; • transcription, DNA-templated; • 神経系発生; • mammary gland epithelial cell differentiation; • MAPK cascade; • positive regulation of phosphatidylinositol 3-kinase activity; • positive regulation of transcription, DNA-templated; • 多細胞個体の発生; • 心臓発生; • タンパク質リン酸化; • positive regulation of cardiac muscle cell proliferation; • neural crest cell migration; • positive regulation of ERK1 and ERK2 cascade; • positive regulation of protein localization to cell surface; • 自己リン酸化; • cardiac muscle tissue regeneration; • positive regulation of phosphatidylinositol 3-kinase signaling; • peptidyl-tyrosine phosphorylation; • 授乳; • 細胞増殖; • 遊走; • シグナル伝達; • negative regulation of cell population proliferation; • アポトーシス; • ERBB2 signaling pathway; • phosphatidylinositol phosphate biosynthetic process; • peptidyl-tyrosine autophosphorylation; • positive regulation of cell population proliferation; • positive regulation of apoptotic process; • regulation of cell motility; • negative regulation of apoptotic process; • cellular response to epidermal growth factor stimulus; • positive regulation of tyrosine phosphorylation of STAT protein; • positive regulation of protein kinase B signaling; • positive regulation of receptor signaling pathway via JAK-STAT; • シナプス形成; • negative regulation of signal transduction; • 細胞分化;
	出典:Amigo / QuickGO
オルソログ
	2066
	13869
	ENSG00000178568
	ENSMUSG00000062209
	Q15303,H3BLT0
	Q61527
	NM_001042599; NM_005235
	NM_010154
	NP_001036064; NP_005226
	NP_034284
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

ERBB4（erb-b2 receptor tyrosine kinase 4）またはHER4（human epidermal growth factor receptor 4）は、ヒトではERBB4遺伝子によってコードされている酵素である^[5]^[6]。

機能

ERBB4はErbBファミリーに属する受容体型チロシンキナーゼである。ERBB4はI型の1回膜貫通タンパク質であり、複数のフーリン様システインリッチドメイン、チロシンキナーゼドメイン、PI3キナーゼ結合部位、PDZドメイン結合モチーフを有する。このタンパク質はニューレグリン2（英語版）、3、4（英語版）、HB-EGF、ベータセルリン（英語版）を結合し、活性化される。リガンド結合は、有糸分裂の促進や分化など、さまざまな細胞応答を誘導する。複数のタンパク質分解イベントによって、細胞質側断片や細胞外断片が放出される場合がある^[7]。

臨床的意義

ERBB4遺伝子の変異はがんと関連している^[7]。また、統合失調症と関連したSNPやハプロタイプが知られている^[8]。家族性筋萎縮性側索硬化症のtype 19は、ERBB4遺伝子のSNPと関連している^[9]。

相互作用

ERBB4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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000178568 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000062209 - Ensembl, May 2017
^ Human PubMed Reference:
^ Mouse PubMed Reference:
^ Zimonjic DB, Alimandi M, Miki T, Popescu NC, Kraus MH (Mar 1995). “Localization of the human HER4/erbB-4 gene to chromosome 2”. Oncogene 10 (6): 1235–7. PMID 7700649.
^ Sardi SP, Murtie J, Koirala S, Patten BA, Corfas G (Oct 2006). “Presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis in the developing brain”. Cell 127 (1): 185–97. doi:10.1016/j.cell.2006.07.037. PMID 17018285.
^ ^a ^b “Entrez Gene: ERBB4 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian)”. 2025年6月8日閲覧。
^ Silberberg G, Darvasi A, Pinkas-Kramarski R, Navon R (Mar 2006). “The involvement of ErbB4 with schizophrenia: association and expression studies”. American Journal of Medical Genetics Part B 141B (2): 142–8. doi:10.1002/ajmg.b.30275. PMID 16402353.
^ Takahashi Y, Fukuda Y, Yoshimura J, Toyoda A, Kurppa K, Moritoyo H, Belzil VV, Dion PA, Higasa K, Doi K, Ishiura H, Mitsui J, Date H, Ahsan B, Matsukawa T, Ichikawa Y, Moritoyo T, Ikoma M, Hashimoto T, Kimura F, Murayama S, Onodera O, Nishizawa M, Yoshida M, Atsuta N, Sobue G, Fifita JA, Williams KL, Blair IP, Nicholson GA, Gonzalez-Perez P, Brown RH, Nomoto M, Elenius K, Rouleau GA, Fujiyama A, Morishita S, Goto J, Tsuji S (Nov 2013). “ERBB4 mutations that disrupt the neuregulin-ErbB4 pathway cause amyotrophic lateral sclerosis type 19”. American Journal of Human Genetics 93 (5): 900–5. doi:10.1016/j.ajhg.2013.09.008. PMC 3824132. PMID 24119685.
^ Garcia RA, Vasudevan K, Buonanno A (Mar 2000). “The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses”. Proceedings of the National Academy of Sciences of the United States of America 97 (7): 3596–601. doi:10.1073/pnas.070042497. PMC 16285. PMID 10725395.
^ Huang YZ, Won S, Ali DW, Wang Q, Tanowitz M, Du QS, Pelkey KA, Yang DJ, Xiong WC, Salter MW, Mei L (May 2000). “Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses”. Neuron 26 (2): 443–55. doi:10.1016/S0896-6273(00)81176-9. PMID 10839362.
^ Williams CC, Allison JG, Vidal GA, Burow ME, Beckman BS, Marrero L, Jones FE (Nov 2004). “The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone”. The Journal of Cell Biology 167 (3): 469–78. doi:10.1083/jcb.200403155. PMC 2172499. PMID 15534001.
^ Schulze WX, Deng L, Mann M (2005). “Phosphotyrosine interactome of the ErbB-receptor kinase family”. Molecular Systems Biology 1 (1): 2005.0008. doi:10.1038/msb4100012. PMC 1681463. PMID 16729043.
^ Omerovic J, Puggioni EM, Napoletano S, Visco V, Fraioli R, Frati L, Gulino A, Alimandi M (Apr 2004). “Ligand-regulated association of ErbB-4 to the transcriptional co-activator YAP65 controls transcription at the nuclear level”. Experimental Cell Research 294 (2): 469–79. doi:10.1016/j.yexcr.2003.12.002. PMID 15023535.

外部リンク

Overview of all the structural information available in the PDB for UniProt: Q15303 (Receptor tyrosine-protein kinase erbB-4) at the PDBe-KB.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000178568 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000062209 - Ensembl, May 2017

[3] Human PubMed Reference:

[4] Mouse PubMed Reference:

[pmid7700649-5] Zimonjic DB, Alimandi M, Miki T, Popescu NC, Kraus MH (Mar 1995). “Localization of the human HER4/erbB-4 gene to chromosome 2”. Oncogene 10 (6): 1235–7. PMID 7700649.

[pmid17018285-6] Sardi SP, Murtie J, Koirala S, Patten BA, Corfas G (Oct 2006). “Presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis in the developing brain”. Cell 127 (1): 185–97. doi:10.1016/j.cell.2006.07.037. PMID 17018285.

[entrez-7] “Entrez Gene: ERBB4 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian)”. 2025年6月8日閲覧。

[pmid16402353-8] Silberberg G, Darvasi A, Pinkas-Kramarski R, Navon R (Mar 2006). “The involvement of ErbB4 with schizophrenia: association and expression studies”. American Journal of Medical Genetics Part B 141B (2): 142–8. doi:10.1002/ajmg.b.30275. PMID 16402353.

[pmid24119685-9] Takahashi Y, Fukuda Y, Yoshimura J, Toyoda A, Kurppa K, Moritoyo H, Belzil VV, Dion PA, Higasa K, Doi K, Ishiura H, Mitsui J, Date H, Ahsan B, Matsukawa T, Ichikawa Y, Moritoyo T, Ikoma M, Hashimoto T, Kimura F, Murayama S, Onodera O, Nishizawa M, Yoshida M, Atsuta N, Sobue G, Fifita JA, Williams KL, Blair IP, Nicholson GA, Gonzalez-Perez P, Brown RH, Nomoto M, Elenius K, Rouleau GA, Fujiyama A, Morishita S, Goto J, Tsuji S (Nov 2013). “ERBB4 mutations that disrupt the neuregulin-ErbB4 pathway cause amyotrophic lateral sclerosis type 19”. American Journal of Human Genetics 93 (5): 900–5. doi:10.1016/j.ajhg.2013.09.008. PMC 3824132. PMID 24119685.

[pmid10725395-10] Garcia RA, Vasudevan K, Buonanno A (Mar 2000). “The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses”. Proceedings of the National Academy of Sciences of the United States of America 97 (7): 3596–601. doi:10.1073/pnas.070042497. PMC 16285. PMID 10725395.

[pmid10839362-11] Huang YZ, Won S, Ali DW, Wang Q, Tanowitz M, Du QS, Pelkey KA, Yang DJ, Xiong WC, Salter MW, Mei L (May 2000). “Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses”. Neuron 26 (2): 443–55. doi:10.1016/S0896-6273(00)81176-9. PMID 10839362.

[pmid15534001-12] Williams CC, Allison JG, Vidal GA, Burow ME, Beckman BS, Marrero L, Jones FE (Nov 2004). “The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone”. The Journal of Cell Biology 167 (3): 469–78. doi:10.1083/jcb.200403155. PMC 2172499. PMID 15534001.

[pmid16729043-13] Schulze WX, Deng L, Mann M (2005). “Phosphotyrosine interactome of the ErbB-receptor kinase family”. Molecular Systems Biology 1 (1): 2005.0008. doi:10.1038/msb4100012. PMC 1681463. PMID 16729043.

[pmid15023535-14] Omerovic J, Puggioni EM, Napoletano S, Visco V, Fraioli R, Frati L, Gulino A, Alimandi M (Apr 2004). “Ligand-regulated association of ErbB-4 to the transcriptional co-activator YAP65 controls transcription at the nuclear level”. Experimental Cell Research 294 (2): 469–79. doi:10.1016/j.yexcr.2003.12.002. PMID 15023535.

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機能

臨床的意義

相互作用

出典

関連文献

外部リンク