ACVR1B

ACVR1B
已やめ知的ちてき結構けっこう
PDB	直系ちょっけい同どう源みなもと搜索そうさく: PDBe RCSB
PDBID列れつ表ひょう
	3H9R、3MTF、3OOM、3Q4U、4BGG、4C02、4DYM
識別しきべつ號ごう
别名	ACVR1B；, ACTRIB, ACVRLK4, ALK4, SKR2, activin A receptor type 1B
外部がいぶID	OMIM：601300 MGI：1338944 HomoloGene：20906 GeneCards：ACVR1B
基もと因いん位置いち（人ひと类）
染色せんしょく体たい	12號ごう染色せんしょく體たい
终止	51,997,078 bp
基もと因いん位置いち（小しょう鼠ねずみ）
染色せんしょく体たい	小しょう鼠ねずみ15号ごう染色せんしょく体たい
终止	101,111,565 bp
基もと因いん本體ほんたい
分子ぶんし功こう能のう	• 轉移てんい酶活性せい; • 核かく苷酸結合けつごう; • 蛋白たんぱく激げき酶活性せい; • growth factor binding; • activin binding; • 金屬きんぞく離はなれ子こ結合けつごう; • 激げき酶活性せい; • transmembrane receptor protein serine/threonine kinase activity; • inhibin binding; • 血ち浆蛋白しろ结合; • activin-activated receptor activity; • ATP結合けつごう; • 泛素蛋白たんぱく连接酶结合あい; • 蛋白たんぱく质丝氨酸/苏氨酸さん激げき酶活性せい; • activin receptor activity, type I; • SMAD binding; • transforming growth factor beta-activated receptor activity; • transforming growth factor beta receptor activity, type I;
細胞さいぼう組ぐみ分ぶん	• integral component of membrane; • 膜まく; • receptor complex; • 细胞膜まく; • integral component of plasma membrane; • activin receptor complex; • cell surface; • 细胞质基质;
生物せいぶつ學がく過程かてい	• hair follicle development; • regulation of transcription, DNA-templated; • positive regulation of erythrocyte differentiation; • extrinsic apoptotic signaling pathway; • 磷酸化か; • 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; • 自體じたい磷酸化か; • peptidyl-threonine phosphorylation; • 訊息傳でん遞; • 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
直系ちょっけい同どう源みなもと
	91
	11479
	ENSG00000135503
	ENSMUSG00000000532
	P36896
	Q61271
	NM_004302; NM_020327; NM_020328
	NM_007395
	NP_004293; NP_064732; NP_064733
	NP_031421
	維基數すう據よりどころ
檢視けんし/編輯へんしゅう人類じんるい	檢視けんし/編輯へんしゅう小しょう鼠ねずみ

1B型がた激げき活かつ素もと受体（Activin receptor type-1B），缩写为ACVR1B或あるALK-4，在ざい人体じんたい中ちゅう是ぜ一いち种由ACVR1B基もと因いん编码的てき蛋白たんぱく质^[5]^[6]。

ALK-4能のう够对激げき活かつ素もと或ある激げき活かつ素もと样配体たい（即そく抑制よくせい素もと）的てき信号しんごう进行转导。激げき活かつ素首そくび先さき与あずかACVR2A（英えい语：ACVR2A）或あるACVR2B（英えい语：ACVR2B）结合，之これ后きさき再さい与あずかALK-4形成けいせい复合物ぶつ。上述じょうじゅつ过程能のう够招募R-SMAD（英えい语：R-SMAD）、SMAD2（英えい语：SMAD2）或ある者ものSMAD3（英えい语：SMAD3）分子ぶんし^[7]。ALK-4也可以转导NODAL（英えい语：NODAL）、GDF-1、Vg1的てき信号しんごう。但ただし是ぜ，和わ激げき活かつ素もと不同ふどう，这些分子ぶんし（与あずかALK-4的てき结合）需要じゅようCripto（英えい语：Cripto）蛋白たんぱく等とう共ども受体^[8]。

功こう能のう[编辑]

激げき活かつ素もと是ぜ一类二聚体生长分化因子，属ぞく于TGF-βべーた蛋白たんぱく质超家族かぞく，一类结构上相关的信号蛋白。激げき活かつ素もと信号しんごう能のう够通过一个包含至少两分子1型がた以及两分子ぶんし2型がた受体的てき受体丝氨酸さん激げき酶异聚复合体がったい进行转导。这些受体都と属ぞく于跨膜まく蛋白たんぱく，包含ほうがん一いち个含有がんゆう丰富半はん胱氨酸さん区域くいき的てき细胞外がい配はい体たい结合结构域いき，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（即そく细胞质中的てき）（激げき酶）结构域いき。1型がた受体对信号ごう转导来らい说是必要ひつよう的てき，2型がた受体则对1型がた受体的てき表ひょう达以及配体たい的てき结合来らい说不可ふか或ある缺かけ。在ざい配はい体たい结合后きさき，1型がた受体以及2型がた受体能のう够形成けいせい一个稳定的复合物，并使1型がた受体被ひ2型がた受体磷酸化か^[6]。

基もと因いん结构与表ひょう达[编辑]

编码ALK-4基き因いん含有がんゆう11个外含子。可か变剪接せっ以及Poly(A)（多た聚腺嘌呤）尾お巴ともえ的てき变化使し该基因いん拥有多た个转录本，目前もくぜん已やめ有ゆう3个转录本得え到いた阐明，另外，此基因いん可能かのう存在そんざい第だい四よん个包含ほうがん8号ごう外そと显子，且8号外ごうがい显子与あずか11号外ごうがい显子缺乏けつぼう9号外ごうがい显子的てき转录本ほん，但ただし是ぜ这种转录本ほん对应的てきmRNA还没有ゆう得え到いた确认^[6]。

相互そうご作用さよう[编辑]

ALK能のう与あずかACVR2A、ACVR2B发生相互そうご作用さよう^[9]^[10]^[11]。

参考さんこう[编辑]

^ ^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. （原始げんし内容ないよう存そん档于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.

拓つぶせ展てん阅读[编辑]

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. （原始げんし内容ないよう存そん档于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.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]