ACVR1B

ACVR1B
已知的結構
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	3H9R、3MTF、3OOM、3Q4U、4BGG、4C02、4DYM
識別號
别名	ACVR1B；, ACTRIB, ACVRLK4, ALK4, SKR2, activin A receptor type 1B
外部ID	OMIM：601300 MGI：1338944 HomoloGene：20906 GeneCards：ACVR1B
基因位置（人类）
染色体	12號染色體
终止	51,997,078 bp
基因位置（小鼠）
染色体	小鼠15号染色体
终止	101,111,565 bp
基因本體
分子功能	• 轉移酶活性; • 核苷酸結合; • 蛋白激酶活性; • growth factor binding; • activin binding; • 金屬離子結合; • 激酶活性; • transmembrane receptor protein serine/threonine kinase activity; • inhibin binding; • 血浆蛋白结合; • activin-activated receptor activity; • ATP結合; • 泛素蛋白连接酶结合; • 蛋白质丝氨酸/苏氨酸激酶活性; • activin receptor activity, type I; • SMAD binding; • transforming growth factor beta-activated receptor activity; • transforming growth factor beta receptor activity, type I;
細胞組分	• integral component of membrane; • 膜; • receptor complex; • 细胞膜; • integral component of plasma membrane; • activin receptor complex; • cell surface; • 细胞质基质;
生物學過程	• hair follicle development; • regulation of transcription, DNA-templated; • positive regulation of erythrocyte differentiation; • extrinsic apoptotic signaling pathway; • 磷酸化; • positive regulation of pathway-restricted SMAD protein phosphorylation; • in utero embryonic development; • negative regulation of gene expression; • nodal signaling pathway; • positive regulation of trophoblast cell migration; • protein phosphorylation; • central nervous system development; • development of primary female sexual characteristics; • positive regulation of gene expression; • transmembrane receptor protein serine/threonine kinase signaling pathway; • positive regulation of activin receptor signaling pathway; • regulation of signal transduction; • negative regulation of cell growth; • 自體磷酸化; • peptidyl-threonine phosphorylation; • 訊息傳遞; • positive regulation of transcription by RNA polymerase II; • activin receptor signaling pathway; • G1/S transition of mitotic cell cycle; • transforming growth factor beta receptor signaling pathway; • pattern specification process;
	Sources:Amigo / QuickGO
直系同源
	91
	11479
	ENSG00000135503
	ENSMUSG00000000532
	P36896
	Q61271
	NM_004302; NM_020327; NM_020328
	NM_007395
	NP_004293; NP_064732; NP_064733
	NP_031421
	維基數據
檢視/編輯人類	檢視/編輯小鼠

1B型激活素受体（Activin receptor type-1B），缩写为ACVR1B或ALK-4，在人体中是一种由ACVR1B基因编码的蛋白质^[5]^[6]。

ALK-4能够对激活素或激活素样配体（即抑制素）的信号进行转导。激活素首先与ACVR2A（英语：ACVR2A）或ACVR2B（英语：ACVR2B）结合，之后再与ALK-4形成复合物。上述过程能够招募R-SMAD（英语：R-SMAD）、SMAD2（英语：SMAD2）或者SMAD3（英语：SMAD3）分子^[7]。ALK-4也可以转导NODAL（英语：NODAL）、GDF-1、Vg1的信号。但是，和激活素不同，这些分子（与ALK-4的结合）需要Cripto（英语：Cripto）蛋白等共受体^[8]。

功能

激活素是一类二聚体生长分化因子，属于TGF-β蛋白质超家族，一类结构上相关的信号蛋白。激活素信号能够通过一个包含至少两分子1型以及两分子2型受体的受体丝氨酸激酶异聚复合体进行转导。这些受体都属于跨膜蛋白，包含一个含有丰富半胱氨酸区域的细胞外配体结合结构域，一个跨膜结构域，以及一个推测具有丝氨酸或苏氨酸专一性的细胞内（即细胞质中的）（激酶）结构域。1型受体对信号转导来说是必要的，2型受体则对1型受体的表达以及配体的结合来说不可或缺。在配体结合后，1型受体以及2型受体能够形成一个稳定的复合物，并使1型受体被2型受体磷酸化^[6]。

基因结构与表达

编码ALK-4基因含有11个外含子。可变剪接以及Poly(A)（多聚腺嘌呤）尾巴的变化使该基因拥有多个转录本，目前已有3个转录本得到阐明，另外，此基因可能存在第四个包含8号外显子，且8号外显子与11号外显子缺乏9号外显子的转录本，但是这种转录本对应的mRNA还没有得到确认^[6]。

相互作用

ALK能与ACVR2A、ACVR2B发生相互作用^[9]^[10]^[11]。

参考

^ ^1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000135503 - Ensembl, May 2017
^ ^2.0 ^2.1 ^2.2 GRCm38: Ensembl release 89: ENSMUSG00000000532 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ten Dijke P, Ichijo H, Franzén P, Schulz P, Saras J, Toyoshima H, Heldin CH, Miyazono K. Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity. Oncogene. October 1993, 8 (10): 2879–87. PMID 8397373.
^ ^6.0 ^6.1 ^6.2 Entrez Gene: ACVR1B activin A receptor, type IB. （原始内容存档于2019-09-18）.
^ Inman GJ, Nicolás FJ, Callahan JF, Harling JD, Gaster LM, Reith AD, Laping NJ, Hill CS. SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol. Pharmacol. 2002, 62 (1): 65–74. PMID 12065756. doi:10.1124/mol.62.1.65.
^ Harrison CA, Gray PC, Koerber SC, Fischer W, Vale W. Identification of a functional binding site for activin on the type I receptor ALK4. J. Biol. Chem. 2003, 278 (23): 21129–35. PMID 12665502. doi:10.1074/jbc.M302015200.
^ Lebrun JJ, Takabe K, Chen Y, Vale W. Roles of pathway-specific and inhibitory Smads in activin receptor signaling. Mol. Endocrinol. January 1999, 13 (1): 15–23. PMID 9892009. doi:10.1210/mend.13.1.0218.
^ Attisano L, Wrana JL, Montalvo E, Massagué J. Activation of signalling by the activin receptor complex. Mol. Cell. Biol. March 1996, 16 (3): 1066–73. PMC 231089 . PMID 8622651.
^ De Winter JP, De Vries CJ, Van Achterberg TA, Ameerun RF, Feijen A, Sugino H, De Waele P, Huylebroeck D, Verschueren K, Van Den Eijden-Van Raaij AJ. Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. receptors. Exp. Cell Res. May 1996, 224 (2): 323–34. PMID 8612709. doi:10.1006/excr.1996.0142.

拓展阅读

Welt CK. The physiology and pathophysiology of inhibin, activin and follistatin in female reproduction. Curr. Opin. Obstet. Gynecol. 2002, 14 (3): 317–23. PMID 12032389. doi:10.1097/00001703-200206000-00012.
Liu F, Ventura F, Doody J, Massagué J. Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs. Mol. Cell. Biol. 1995, 15 (7): 3479–86. PMC 230584 . PMID 7791754. doi:10.1128/mcb.15.7.3479.
Xu J, Matsuzaki K, McKeehan K, Wang F, Kan M, McKeehan WL. Genomic structure and cloned cDNAs predict that four variants in the kinase domain of serine/threonine kinase receptors arise by alternative splicing and poly(A) addition. Proc. Natl. Acad. Sci. U.S.A. 1994, 91 (17): 7957–61. PMC 44523 . PMID 8058741. doi:10.1073/pnas.91.17.7957.
Cárcamo J, Weis FM, Ventura F, Wieser R, Wrana JL, Attisano L, Massagué J. Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor beta and activin. Mol. Cell. Biol. 1994, 14 (6): 3810–21. PMC 358748 . PMID 8196624.
De Winter JP, De Vries CJ, Van Achterberg TA, Ameerun RF, Feijen A, Sugino H, De Waele P, Huylebroeck D, Verschueren K, Van Den Eijden-Van Raaij AJ. Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. receptors. Exp. Cell Res. 1996, 224 (2): 323–34. PMID 8612709. doi:10.1006/excr.1996.0142.
Attisano L, Wrana JL, Montalvo E, Massagué J. Activation of signalling by the activin receptor complex. Mol. Cell. Biol. 1996, 16 (3): 1066–73. PMC 231089 . PMID 8622651.
Lebrun JJ, Vale WW. Activin and inhibin have antagonistic effects on ligand-dependent heteromerization of the type I and type II activin receptors and human erythroid differentiation. Mol. Cell. Biol. 1997, 17 (3): 1682–91. PMC 231893 . PMID 9032295.
Röijer E, Miyazono K, Aström AK, Geurts van Kessel A, ten Dijke P, Stenman G. Chromosomal localization of three human genes encoding members of the TGF-beta superfamily of type I serine/threonine kinase receptors. Mamm. Genome. 1998, 9 (3): 266–8. PMID 9501322. doi:10.1007/s003359900745.
Souchelnytskyi S, Nakayama T, Nakao A, Morén A, Heldin CH, Christian JL, ten Dijke P. Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming growth factor-beta receptors. J. Biol. Chem. 1998, 273 (39): 25364–70. PMID 9738003. doi:10.1074/jbc.273.39.25364.
Hashimoto O, Yamato K, Koseki T, Ohguchi M, Ishisaki A, Shoji H, Nakamura T, Hayashi Y, Sugino H, Nishihara T. The role of activin type I receptors in activin A-induced growth arrest and apoptosis in mouse B-cell hybridoma cells. Cell. Signal. 1998, 10 (10): 743–9. PMID 9884026. doi:10.1016/S0898-6568(98)00021-7.
Lebrun JJ, Takabe K, Chen Y, Vale W. Roles of pathway-specific and inhibitory Smads in activin receptor signaling. Mol. Endocrinol. 1999, 13 (1): 15–23. PMID 9892009. doi:10.1210/mend.13.1.0218.
Gray PC, Greenwald J, Blount AL, Kunitake KS, Donaldson CJ, Choe S, Vale W. Identification of a binding site on the type II activin receptor for activin and inhibin. J. Biol. Chem. 2000, 275 (5): 3206–12. PMID 10652306. doi:10.1074/jbc.275.5.3206.
Zhou Y, Sun H, Danila DC, Johnson SR, Sigai DP, Zhang X, Klibanski A. Truncated activin type I receptor Alk4 isoforms are dominant negative receptors inhibiting activin signaling. Mol. Endocrinol. 2000, 14 (12): 2066–75. PMID 11117535. doi:10.1210/me.14.12.2066.
Su GH, Bansal R, Murphy KM, Montgomery E, Yeo CJ, Hruban RH, Kern SE. ACVR1B (ALK4, activin receptor type 1B) gene mutations in pancreatic carcinoma. Proc. Natl. Acad. Sci. U.S.A. 2001, 98 (6): 3254–7. PMC 30640 . PMID 11248065. doi:10.1073/pnas.051484398.
Chapman SC, Woodruff TK. Modulation of activin signal transduction by inhibin B and inhibin-binding protein (INhBP). Mol. Endocrinol. 2001, 15 (4): 668–79. PMID 11266516. doi:10.1210/me.15.4.668.
Wurthner JU, Frank DB, Felici A, Green HM, Cao Z, Schneider MD, McNally JG, Lechleider RJ, Roberts AB. Transforming growth factor-beta receptor-associated protein 1 is a Smad4 chaperone. J. Biol. Chem. 2001, 276 (22): 19495–502. PMID 11278302. doi:10.1074/jbc.M006473200.
Parks WT, Frank DB, Huff C, Renfrew Haft C, Martin J, Meng X, de Caestecker MP, McNally JG, Reddi A, Taylor SI, Roberts AB, Wang T, Lechleider RJ. Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases. J. Biol. Chem. 2001, 276 (22): 19332–9. PMID 11279102. doi:10.1074/jbc.M100606200.
Birkey Reffey S, Wurthner JU, Parks WT, Roberts AB, Duckett CS. X-linked inhibitor of apoptosis protein functions as a cofactor in transforming growth factor-beta signaling. J. Biol. Chem. 2001, 276 (28): 26542–9. PMID 11356828. doi:10.1074/jbc.M100331200.
Bianco C, Adkins HB, Wechselberger C, Seno M, Normanno N, De Luca A, Sun Y, Khan N, Kenney N, Ebert A, Williams KP, Sanicola M, Salomon DS. Cripto-1 activates nodal- and ALK4-dependent and -independent signaling pathways in mammary epithelial Cells. Mol. Cell. Biol. 2002, 22 (8): 2586–97. PMC 133714 . PMID 11909953. doi:10.1128/MCB.22.8.2586-2597.2002.

[refGRCh38Ensembl-1] 1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000135503 - Ensembl, May 2017

[refGRCm38Ensembl-2] 2.0 ^2.1 ^2.2 GRCm38: Ensembl release 89: ENSMUSG00000000532 - Ensembl, May 2017

[3] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8397373-5] ten Dijke P, Ichijo H, Franzén P, Schulz P, Saras J, Toyoshima H, Heldin CH, Miyazono K. Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity. Oncogene. October 1993, 8 (10): 2879–87. PMID 8397373.

[entrez-6] 6.0 ^6.1 ^6.2 Entrez Gene: ACVR1B activin A receptor, type IB. （原始内容存档于2019-09-18）.

[pmid12065756-7] Inman GJ, Nicolás FJ, Callahan JF, Harling JD, Gaster LM, Reith AD, Laping NJ, Hill CS. SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol. Pharmacol. 2002, 62 (1): 65–74. PMID 12065756. doi:10.1124/mol.62.1.65.

[pmid12665502-8] Harrison CA, Gray PC, Koerber SC, Fischer W, Vale W. Identification of a functional binding site for activin on the type I receptor ALK4. J. Biol. Chem. 2003, 278 (23): 21129–35. PMID 12665502. doi:10.1074/jbc.M302015200.

[pmid9892009-9] Lebrun JJ, Takabe K, Chen Y, Vale W. Roles of pathway-specific and inhibitory Smads in activin receptor signaling. Mol. Endocrinol. January 1999, 13 (1): 15–23. PMID 9892009. doi:10.1210/mend.13.1.0218.

[pmid8622651-10] Attisano L, Wrana JL, Montalvo E, Massagué J. Activation of signalling by the activin receptor complex. Mol. Cell. Biol. March 1996, 16 (3): 1066–73. PMC 231089 . PMID 8622651.

[pmid8612709-11] De Winter JP, De Vries CJ, Van Achterberg TA, Ameerun RF, Feijen A, Sugino H, De Waele P, Huylebroeck D, Verschueren K, Van Den Eijden-Van Raaij AJ. Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. receptors. Exp. Cell Res. May 1996, 224 (2): 323–34. PMID 8612709. doi:10.1006/excr.1996.0142.

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