ID ACV1B_HUMAN Reviewed; 505 AA. AC P36896; B7Z5L8; B7Z5W5; Q15479; Q15480; Q15481; Q15482; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 27-MAR-2024, entry version 239. DE RecName: Full=Activin receptor type-1B; DE EC=2.7.11.30; DE AltName: Full=Activin receptor type IB; DE Short=ACTR-IB; DE AltName: Full=Activin receptor-like kinase 4; DE Short=ALK-4; DE AltName: Full=Serine/threonine-protein kinase receptor R2; DE Short=SKR2; DE Flags: Precursor; GN Name=ACVR1B; Synonyms=ACVRLK4, ALK4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=8397373; RA ten Dijke P., Ichijo H., Franzen P., Schulz P., Saras J., Toyoshima H., RA Heldin C.-H., Miyazono K.; RT "Activin receptor-like kinases: a novel subclass of cell-surface receptors RT with predicted serine/threonine kinase activity."; RL Oncogene 8:2879-2887(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION IN AN ACTIVIN RP RECEPTOR COMPLEX, ACTIVIN-BINDING, AND FUNCTION. RC TISSUE=Kidney; RX PubMed=8196624; DOI=10.1128/mcb.14.6.3810-3821.1994; RA Carcamo J., Weis F.M., Ventura F., Wieser R., Wrana J.L., Attisano L., RA Massague J.; RT "Type I receptors specify growth-inhibitory and transcriptional responses RT to transforming growth factor beta and activin."; RL Mol. Cell. Biol. 14:3810-3821(1994). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 2 AND 3), AND RP ALTERNATIVE SPLICING. RC TISSUE=Liver; RX PubMed=8058741; DOI=10.1073/pnas.91.17.7957; RA Xu J., Matsuzaki K., McKeehan K., Wang F., Kan M., McKeehan W.L.; RT "Genomic structure and cloned cDNAs predict that four variants in the RT kinase domain of serine/threonine kinase receptors arise by alternative RT splicing and poly(A) addition."; RL Proc. Natl. Acad. Sci. U.S.A. 91:7957-7961(1994). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain, and Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP INTERACTION WITH ACVR2B, PHOSPHORYLATION BY ACVR2B, DOMAIN GS, AND RP MUTAGENESIS OF THR-206. RX PubMed=8622651; DOI=10.1128/mcb.16.3.1066; RA Attisano L., Wrana J.L., Montalvo E., Massague J.; RT "Activation of signalling by the activin receptor complex."; RL Mol. Cell. Biol. 16:1066-1073(1996). RN [9] RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH TYPE-2 ACTIVIN RECEPTORS. RX PubMed=9032295; DOI=10.1128/mcb.17.3.1682; RA Lebrun J.J., Vale W.W.; RT "Activin and inhibin have antagonistic effects on ligand-dependent RT heteromerization of the type I and type II activin receptors and human RT erythroid differentiation."; RL Mol. Cell. Biol. 17:1682-1691(1997). RN [10] RP INTERACTION WITH SMAD2; SMAD3 AND SMAD7, AND FUNCTION. RX PubMed=9892009; DOI=10.1210/mend.13.1.0218; RA Lebrun J.J., Takabe K., Chen Y., Vale W.; RT "Roles of pathway-specific and inhibitory Smads in activin receptor RT signaling."; RL Mol. Endocrinol. 13:15-23(1999). RN [11] RP INTERACTION WITH IGSF1, AND ACTIVITY REGULATION. RX PubMed=11266516; DOI=10.1210/mend.15.4.0616; RA Chapman S.C., Woodruff T.K.; RT "Modulation of activin signal transduction by inhibin B and inhibin-binding RT protein (INhBP)."; RL Mol. Endocrinol. 15:668-679(2001). RN [12] RP PHOSPHORYLATION, AND INTERACTION WITH SMAD7. RX PubMed=12023024; DOI=10.1016/s0014-5793(02)02718-7; RA Liu X., Nagarajan R.P., Vale W., Chen Y.; RT "Phosphorylation regulation of the interaction between Smad7 and activin RT type I receptor."; RL FEBS Lett. 519:93-98(2002). RN [13] RP FUNCTION, AND PHOSPHORYLATION. RX PubMed=12364468; DOI=10.1210/jc.2002-020527; RA Danila D.C., Zhang X., Zhou Y., Haidar J.N., Klibanski A.; RT "Overexpression of wild-type activin receptor alk4-1 restores activin RT antiproliferative effects in human pituitary tumor cells."; RL J. Clin. Endocrinol. Metab. 87:4741-4746(2002). RN [14] RP INTERACTION WITH CRIPTO, AND ACTIVITY REGULATION. RX PubMed=11909953; DOI=10.1128/mcb.22.8.2586-2597.2002; RA Bianco C., Adkins H.B., Wechselberger C., Seno M., Normanno N., De Luca A., RA Sun Y., Khan N., Kenney N., Ebert A., Williams K.P., Sanicola M., RA Salomon D.S.; RT "Cripto-1 activates nodal- and ALK4-dependent and -independent signaling RT pathways in mammary epithelial Cells."; RL Mol. Cell. Biol. 22:2586-2597(2002). RN [15] RP PHOSPHORYLATION AT TYR-380. RX PubMed=12112843; RX DOI=10.1002/1615-9861(200206)2:6<642::aid-prot642>3.0.co;2-i; RA Maguire P.B., Wynne K.J., Harney D.F., O'Donoghue N.M., Stephens G., RA Fitzgerald D.J.; RT "Identification of the phosphotyrosine proteome from thrombin activated RT platelets."; RL Proteomics 2:642-648(2002). RN [16] RP FUNCTION. RX PubMed=12639945; DOI=10.1210/en.2002-220978; RA Mukasa C., Nomura M., Tanaka T., Tanaka K., Nishi Y., Okabe T., Goto K., RA Yanase T., Nawata H.; RT "Activin signaling through type IB activin receptor stimulates aromatase RT activity in the ovarian granulosa cell-like human granulosa (KGN) cells."; RL Endocrinology 144:1603-1611(2003). RN [17] RP MUTAGENESIS OF LEU-40; ILE-70; VAL-73; LEU-75 AND PRO-77, AND RP ACTIVIN-BINDING. RX PubMed=12665502; DOI=10.1074/jbc.m302015200; RA Harrison C.A., Gray P.C., Koerber S.C., Fischer W., Vale W.; RT "Identification of a functional binding site for activin on the type I RT receptor ALK4."; RL J. Biol. Chem. 278:21129-21135(2003). RN [18] RP INTERACTION WITH FKBP1A AND SMAD7, AND UBIQUITINATION. RX PubMed=16720724; DOI=10.1677/jme.1.01966; RA Yamaguchi T., Kurisaki A., Yamakawa N., Minakuchi K., Sugino H.; RT "FKBP12 functions as an adaptor of the Smad7-Smurf1 complex on activin type RT I receptor."; RL J. Mol. Endocrinol. 36:569-579(2006). RN [19] RP FUNCTION, AND AUTOPHOSPHORYLATION. RX PubMed=18039968; DOI=10.1242/dev.000026; RA Esguerra C.V., Nelles L., Vermeire L., Ibrahimi A., Crawford A.D., RA Derua R., Janssens E., Waelkens E., Carmeliet P., Collen D., RA Huylebroeck D.; RT "Ttrap is an essential modulator of Smad3-dependent Nodal signaling during RT zebrafish gastrulation and left-right axis determination."; RL Development 134:4381-4393(2007). RN [20] RP FUNCTION. RX PubMed=20226172; DOI=10.1016/j.bbrc.2010.03.039; RA Suzuki K., Kobayashi T., Funatsu O., Morita A., Ikekita M.; RT "Activin A induces neuronal differentiation and survival via ALK4 in a RT SMAD-independent manner in a subpopulation of human neuroblastomas."; RL Biochem. Biophys. Res. Commun. 394:639-645(2010). RN [21] RP UBIQUITINATION. RX PubMed=20596523; DOI=10.1371/journal.pone.0011332; RA Del Rincon S.V., Rogers J., Widschwendter M., Sun D., Sieburg H.B., RA Spruck C.; RT "Development and validation of a method for profiling post-translational RT modification activities using protein microarrays."; RL PLoS ONE 5:E11332-E11332(2010). RN [22] RP INTERACTION WITH TSC22D1. RX PubMed=21791611; DOI=10.1128/mcb.05448-11; RA Yan X., Zhang J., Pan L., Wang P., Xue H., Zhang L., Gao X., Zhao X., RA Ning Y., Chen Y.G.; RT "TSC-22 promotes transforming growth factor beta-mediated cardiac RT myofibroblast differentiation by antagonizing Smad7 activity."; RL Mol. Cell. Biol. 31:3700-3709(2011). RN [23] RP INVOLVEMENT IN SYSTEMIC SCLEROSIS. RX PubMed=21377836; DOI=10.1016/j.jaut.2010.09.004; RA Takagi K., Kawaguchi Y., Kawamoto M., Ota Y., Tochimoto A., Gono T., RA Katsumata Y., Takagi M., Hara M., Yamanaka H.; RT "Activation of the activin A-ALK-Smad pathway in systemic sclerosis."; RL J. Autoimmun. 36:181-188(2011). RN [24] RP VARIANT [LARGE SCALE ANALYSIS] LEU-146, AND VARIANT [LARGE SCALE ANALYSIS] RP HIS-478 (ISOFORM 3). RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Transmembrane serine/threonine kinase activin type-1 receptor CC forming an activin receptor complex with activin receptor type-2 CC (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface CC to the cytoplasm and is thus regulating a many physiological and CC pathological processes including neuronal differentiation and neuronal CC survival, hair follicle development and cycling, FSH production by the CC pituitary gland, wound healing, extracellular matrix production, CC immunosuppression and carcinogenesis. Activin is also thought to have a CC paracrine or autocrine role in follicular development in the ovary. CC Within the receptor complex, type-2 receptors (ACVR2A and/or ACVR2B) CC act as a primary activin receptors whereas the type-1 receptors like CC ACVR1B act as downstream transducers of activin signals. Activin binds CC to type-2 receptor at the plasma membrane and activates its serine- CC threonine kinase. The activated receptor type-2 then phosphorylates and CC activates the type-1 receptor such as ACVR1B. Once activated, the type- CC 1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, CC on serine residues of the C-terminal tail. Soon after their association CC with the activin receptor and subsequent phosphorylation, SMAD2 and CC SMAD3 are released into the cytoplasm where they interact with the CC common partner SMAD4. This SMAD complex translocates into the nucleus CC where it mediates activin-induced transcription. Inhibitory SMAD7, CC which is recruited to ACVR1B through FKBP1A, can prevent the CC association of SMAD2 and SMAD3 with the activin receptor complex, CC thereby blocking the activin signal. Activin signal transduction is CC also antagonized by the binding to the receptor of inhibin-B via the CC IGSF1 inhibin coreceptor. ACVR1B also phosphorylates TDP2. CC {ECO:0000269|PubMed:12364468, ECO:0000269|PubMed:12639945, CC ECO:0000269|PubMed:18039968, ECO:0000269|PubMed:20226172, CC ECO:0000269|PubMed:8196624, ECO:0000269|PubMed:9032295, CC ECO:0000269|PubMed:9892009}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[receptor-protein] = ADP + H(+) + O-phospho- CC L-threonyl-[receptor-protein]; Xref=Rhea:RHEA:44880, Rhea:RHEA- CC COMP:11024, Rhea:RHEA-COMP:11025, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, CC ChEBI:CHEBI:456216; EC=2.7.11.30; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[receptor-protein] = ADP + H(+) + O-phospho-L- CC seryl-[receptor-protein]; Xref=Rhea:RHEA:18673, Rhea:RHEA-COMP:11022, CC Rhea:RHEA-COMP:11023, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; CC EC=2.7.11.30; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: Activin receptor type-2 (ACVR2A or ACVR2B) CC activates the type-1 receptor through phosphorylation of its regulatory CC GS domain. {ECO:0000269|PubMed:11266516, ECO:0000269|PubMed:11909953}. CC -!- SUBUNIT: Forms an activin receptor complex with activin receptor type-2 CC (ACVR2A or ACVR2B) (PubMed:8196624, PubMed:8622651, PubMed:9032295). CC Part of a complex consisting of MAGI2/ARIP1, ACVR2A, ACVR1B and SMAD3 CC (By similarity). Interacts with SMAD2 and SMAD3 (PubMed:9892009). CC Interacts with SMAD7 (PubMed:9892009, PubMed:12023024, CC PubMed:16720724). Interacts with FKBP1A (PubMed:16720724). Interacts CC with IGSF1 (PubMed:11266516). Interacts with CRIPTO (PubMed:11909953). CC Interacts with TDP2 (By similarity). Interacts with TSC22D1/TSC-22 CC (PubMed:21791611). {ECO:0000250|UniProtKB:Q61271, CC ECO:0000269|PubMed:11266516, ECO:0000269|PubMed:11909953, CC ECO:0000269|PubMed:12023024, ECO:0000269|PubMed:16720724, CC ECO:0000269|PubMed:21791611, ECO:0000269|PubMed:8196624, CC ECO:0000269|PubMed:8622651, ECO:0000269|PubMed:9032295, CC ECO:0000269|PubMed:9892009}. CC -!- INTERACTION: CC P36896; P62942: FKBP1A; NbExp=2; IntAct=EBI-1384128, EBI-1027571; CC P36896; P08238: HSP90AB1; NbExp=2; IntAct=EBI-1384128, EBI-352572; CC P36896; O15105: SMAD7; NbExp=2; IntAct=EBI-1384128, EBI-3861591; CC P36896; P27040: Acvr2b; Xeno; NbExp=4; IntAct=EBI-1384128, EBI-8571194; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I CC membrane protein {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; Synonyms=SKR2-1; CC IsoId=P36896-1; Sequence=Displayed; CC Name=2; Synonyms=SKR2-2; CC IsoId=P36896-2; Sequence=VSP_004954; CC Name=3; Synonyms=SKR2-3; CC IsoId=P36896-3; Sequence=VSP_004953; CC Name=4; CC IsoId=P36896-4; Sequence=VSP_041842; CC Name=5; CC IsoId=P36896-5; Sequence=VSP_041841; CC -!- TISSUE SPECIFICITY: Expressed in many tissues, most strongly in kidney, CC pancreas, brain, lung, and liver. CC -!- DOMAIN: The GS domain is a 30-amino-acid sequence adjacent to the N- CC terminal boundary of the kinase domain and highly conserved in all CC other known type-1 receptors but not in type-2 receptors. The GS domain CC is the site of activation through phosphorylation by the II receptors. CC {ECO:0000269|PubMed:8622651}. CC -!- PTM: Autophosphorylated. Phosphorylated by activin receptor type-2 CC (ACVR2A or ACVR2B) in response to activin-binding at serine and CC threonine residues in the GS domain. Phosphorylation of ACVR1B by CC activin receptor type-2 regulates association with SMAD7. CC {ECO:0000269|PubMed:12023024, ECO:0000269|PubMed:12112843, CC ECO:0000269|PubMed:12364468, ECO:0000269|PubMed:8622651}. CC -!- PTM: Ubiquitinated. Level of ubiquitination is regulated by the SMAD7- CC SMURF1 complex. CC -!- PTM: Ubiquitinated. CC -!- DISEASE: Note=ACVRIB is abundantly expressed in systemic sclerosis CC patient fibroblasts and production of collagen is also induced by CC activin-A/INHBA. This suggests that the activin/ACRV1B signaling CC mechanism is involved in systemic sclerosis. CC {ECO:0000269|PubMed:21377836}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr CC protein kinase family. TGFB receptor subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z22536; CAA80258.1; -; mRNA. DR EMBL; U14722; AAA50246.1; -; mRNA. DR EMBL; L10125; AAA60555.1; -; mRNA. DR EMBL; L10126; AAA60556.1; -; mRNA. DR EMBL; L31848; AAA53349.1; -; Genomic_DNA. DR EMBL; L31848; AAA53350.1; -; Genomic_DNA. DR EMBL; L31848; AAA53351.1; -; Genomic_DNA. DR EMBL; BT007072; AAP35735.1; -; mRNA. DR EMBL; AK299120; BAH12954.1; -; mRNA. DR EMBL; AK299496; BAH13051.1; -; mRNA. DR EMBL; AC025259; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000254; AAH00254.1; -; mRNA. DR EMBL; BC040531; AAH40531.1; -; mRNA. DR CCDS; CCDS44893.2; -. [P36896-5] DR CCDS; CCDS44894.2; -. [P36896-4] DR CCDS; CCDS8816.1; -. [P36896-1] DR PIR; I38859; I38859. DR PIR; I80182; I80182. DR PIR; I80183; I80183. DR RefSeq; NP_004293.1; NM_004302.4. [P36896-1] DR RefSeq; NP_064732.3; NM_020327.3. [P36896-5] DR RefSeq; NP_064733.3; NM_020328.3. [P36896-4] DR PDB; 7MRZ; X-ray; 3.00 A; C=24-126. DR PDB; 7OLY; X-ray; 3.27 A; K=24-126. DR PDBsum; 7MRZ; -. DR PDBsum; 7OLY; -. DR AlphaFoldDB; P36896; -. DR SMR; P36896; -. DR BioGRID; 106606; 131. DR DIP; DIP-427N; -. DR IntAct; P36896; 24. DR MINT; P36896; -. DR STRING; 9606.ENSP00000442656; -. DR BindingDB; P36896; -. DR ChEMBL; CHEMBL5310; -. DR DrugBank; DB00171; ATP. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; P36896; -. DR GuidetoPHARMACOLOGY; 1787; -. DR GlyCosmos; P36896; 1 site, No reported glycans. DR GlyGen; P36896; 1 site. DR iPTMnet; P36896; -. DR PhosphoSitePlus; P36896; -. DR BioMuta; ACVR1B; -. DR DMDM; 547775; -. DR EPD; P36896; -. DR jPOST; P36896; -. DR MassIVE; P36896; -. DR MaxQB; P36896; -. DR PaxDb; 9606-ENSP00000442656; -. DR PeptideAtlas; P36896; -. DR ProteomicsDB; 55229; -. [P36896-1] DR ProteomicsDB; 55230; -. [P36896-2] DR ProteomicsDB; 55231; -. [P36896-3] DR ProteomicsDB; 55232; -. [P36896-4] DR ProteomicsDB; 55233; -. [P36896-5] DR Antibodypedia; 14450; 621 antibodies from 37 providers. DR DNASU; 91; -. DR Ensembl; ENST00000257963.9; ENSP00000257963.4; ENSG00000135503.13. [P36896-1] DR Ensembl; ENST00000415850.6; ENSP00000397550.2; ENSG00000135503.13. [P36896-3] DR Ensembl; ENST00000426655.6; ENSP00000390477.2; ENSG00000135503.13. [P36896-2] DR Ensembl; ENST00000541224.5; ENSP00000442656.1; ENSG00000135503.13. [P36896-4] DR Ensembl; ENST00000542485.1; ENSP00000442885.1; ENSG00000135503.13. [P36896-5] DR GeneID; 91; -. DR KEGG; hsa:91; -. DR MANE-Select; ENST00000257963.9; ENSP00000257963.4; NM_004302.5; NP_004293.1. DR UCSC; uc001rzl.4; human. [P36896-1] DR AGR; HGNC:172; -. DR CTD; 91; -. DR DisGeNET; 91; -. DR GeneCards; ACVR1B; -. DR HGNC; HGNC:172; ACVR1B. DR HPA; ENSG00000135503; Low tissue specificity. DR MalaCards; ACVR1B; -. DR MIM; 601300; gene. DR neXtProt; NX_P36896; -. DR OpenTargets; ENSG00000135503; -. DR PharmGKB; PA24493; -. DR VEuPathDB; HostDB:ENSG00000135503; -. DR eggNOG; KOG2052; Eukaryota. DR GeneTree; ENSGT00940000157032; -. DR HOGENOM; CLU_000288_8_1_1; -. DR InParanoid; P36896; -. DR OMA; VRNTHCC; -. DR OrthoDB; 3900892at2759; -. DR PhylomeDB; P36896; -. DR TreeFam; TF314724; -. DR BRENDA; 2.7.10.2; 2681. DR PathwayCommons; P36896; -. DR Reactome; R-HSA-1181150; Signaling by NODAL. DR Reactome; R-HSA-1433617; Regulation of signaling by NODAL. DR Reactome; R-HSA-1502540; Signaling by Activin. DR SignaLink; P36896; -. DR SIGNOR; P36896; -. DR BioGRID-ORCS; 91; 23 hits in 1208 CRISPR screens. DR ChiTaRS; ACVR1B; human. DR GeneWiki; ACVR1B; -. DR GenomeRNAi; 91; -. DR Pharos; P36896; Tchem. DR PRO; PR:P36896; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P36896; Protein. DR Bgee; ENSG00000135503; Expressed in secondary oocyte and 205 other cell types or tissues. DR ExpressionAtlas; P36896; baseline and differential. DR GO; GO:0048179; C:activin receptor complex; IDA:BHF-UCL. DR GO; GO:0009986; C:cell surface; IDA:HGNC-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HGNC-UCL. DR GO; GO:0043235; C:receptor complex; IDA:BHF-UCL. DR GO; GO:0048185; F:activin binding; IEA:Ensembl. DR GO; GO:0017002; F:activin receptor activity; IDA:ARUK-UCL. DR GO; GO:0016361; F:activin receptor activity, type I; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IDA:HGNC-UCL. DR GO; GO:0070411; F:I-SMAD binding; IPI:BHF-UCL. DR GO; GO:0034711; F:inhibin binding; IPI:BHF-UCL. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0046332; F:SMAD binding; IDA:HGNC-UCL. DR GO; GO:0004675; F:transmembrane receptor protein serine/threonine kinase activity; NAS:HGNC-UCL. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:BHF-UCL. DR GO; GO:0032924; P:activin receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0071363; P:cellular response to growth factor stimulus; IBA:GO_Central. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IMP:BHF-UCL. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IDA:HGNC-UCL. DR GO; GO:0001942; P:hair follicle development; IEA:Ensembl. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0030308; P:negative regulation of cell growth; IDA:HGNC-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl. DR GO; GO:0007399; P:nervous system development; IBA:GO_Central. DR GO; GO:0038092; P:nodal signaling pathway; IGI:UniProtKB. DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:UniProtKB. DR GO; GO:0032927; P:positive regulation of activin receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IDA:HGNC-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl. DR GO; GO:1901165; P:positive regulation of trophoblast cell migration; IDA:BHF-UCL. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:HGNC-UCL. DR GO; GO:0007165; P:signal transduction; IDA:HGNC-UCL. DR GO; GO:0007178; P:transmembrane receptor protein serine/threonine kinase signaling pathway; TAS:ProtInc. DR CDD; cd14143; STKc_TGFbR1_ACVR1b_ACVR1c; 1. DR Gene3D; 2.10.60.10; CD59; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR000472; Activin_recp. DR InterPro; IPR003605; GS_dom. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR InterPro; IPR045860; Snake_toxin-like_sf. DR InterPro; IPR000333; TGFB_receptor. DR PANTHER; PTHR23255:SF22; ACTIVIN RECEPTOR TYPE-1B; 1. DR PANTHER; PTHR23255; TRANSFORMING GROWTH FACTOR-BETA RECEPTOR TYPE I AND II; 1. DR Pfam; PF01064; Activin_recp; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF08515; TGF_beta_GS; 1. DR SMART; SM00467; GS; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF57302; Snake toxin-like; 1. DR PROSITE; PS51256; GS; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; P36896; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; KW Glycoprotein; Kinase; Magnesium; Manganese; Membrane; Metal-binding; KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; KW Serine/threonine-protein kinase; Signal; Transferase; Transmembrane; KW Transmembrane helix; Ubl conjugation. FT SIGNAL 1..23 FT /evidence="ECO:0000255" FT CHAIN 24..505 FT /note="Activin receptor type-1B" FT /id="PRO_0000024417" FT TOPO_DOM 24..126 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 127..149 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 150..505 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 177..206 FT /note="GS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00585" FT DOMAIN 207..497 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT ACT_SITE 335 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 213..221 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 234 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 380 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:12112843" FT CARBOHYD 43 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 1..52 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_041841" FT VAR_SEQ 271 FT /note="D -> ADCSFLTLPWEVVMVSAAPKLRSLRLQYKGGRGRARFLFPLN (in FT isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_041842" FT VAR_SEQ 422..505 FT /note="VHEEYQLPYYDLVPSDPSIEEMRKVVCDQKLRPNIPNWWQSYEALRVMGKMM FT RECWYANGAARLTALRIKKTLSQLSVQEDVKI -> TFLFCLCSYLPFQDAGSPKAVLL FT PPFFLQPVGCLLPEPESSFKVAIKGVEVAVLRVRLFFRDQFVE (in isoform 3)" FT /evidence="ECO:0000303|PubMed:8058741" FT /id="VSP_004953" FT VAR_SEQ 465..505 FT /note="ALRVMGKMMRECWYANGAARLTALRIKKTLSQLSVQEDVKI -> VRSWPPA FT AFPSA (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8058741" FT /id="VSP_004954" FT VARIANT 146 FT /note="F -> L (in dbSNP:rs34488074)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041406" FT VARIANT 408 FT /note="L -> V (in dbSNP:rs928906)" FT /id="VAR_011716" FT MUTAGEN 40 FT /note="L->A: Increases binding to activin." FT /evidence="ECO:0000269|PubMed:12665502" FT MUTAGEN 70 FT /note="I->A: Decreases binding to activin." FT /evidence="ECO:0000269|PubMed:12665502" FT MUTAGEN 73 FT /note="V->A: Increases binding to activin." FT /evidence="ECO:0000269|PubMed:12665502" FT MUTAGEN 75 FT /note="L->A: Decreases binding to activin." FT /evidence="ECO:0000269|PubMed:12665502" FT MUTAGEN 77 FT /note="P->A: Decreases binding to activin." FT /evidence="ECO:0000269|PubMed:12665502" FT MUTAGEN 206 FT /note="T->V: Leads to constitutive activation." FT /evidence="ECO:0000269|PubMed:8622651" FT CONFLICT 56 FT /note="I -> F (in Ref. 3; AAA60555/AAA60556)" FT /evidence="ECO:0000305" FT CONFLICT 222..223 FT /note="WR -> MA (in Ref. 3; AAA60555/AAA60556)" FT /evidence="ECO:0000305" FT STRAND 32..34 FT /evidence="ECO:0007829|PDB:7OLY" FT HELIX 40..42 FT /evidence="ECO:0007829|PDB:7MRZ" FT STRAND 49..55 FT /evidence="ECO:0007829|PDB:7MRZ" FT STRAND 60..62 FT /evidence="ECO:0007829|PDB:7MRZ" FT STRAND 66..70 FT /evidence="ECO:0007829|PDB:7MRZ" FT TURN 72..74 FT /evidence="ECO:0007829|PDB:7MRZ" FT STRAND 77..80 FT /evidence="ECO:0007829|PDB:7MRZ" FT HELIX 82..84 FT /evidence="ECO:0007829|PDB:7MRZ" FT TURN 88..90 FT /evidence="ECO:0007829|PDB:7OLY" FT STRAND 94..96 FT /evidence="ECO:0007829|PDB:7MRZ" FT VARIANT P36896-3:478 FT /note="R -> H (in dbSNP:rs34050429)" FT /evidence="ECO:0000305" FT /id="VAR_082894" SQ SEQUENCE 505 AA; 56807 MW; 40A6C65CAA4C7573 CRC64; MAESAGASSF FPLVVLLLAG SGGSGPRGVQ ALLCACTSCL QANYTCETDG ACMVSIFNLD GMEHHVRTCI PKVELVPAGK PFYCLSSEDL RNTHCCYTDY CNRIDLRVPS GHLKEPEHPS MWGPVELVGI IAGPVFLLFL IIIIVFLVIN YHQRVYHNRQ RLDMEDPSCE MCLSKDKTLQ DLVYDLSTSG SGSGLPLFVQ RTVARTIVLQ EIIGKGRFGE VWRGRWRGGD VAVKIFSSRE ERSWFREAEI YQTVMLRHEN ILGFIAADNK DNGTWTQLWL VSDYHEHGSL FDYLNRYTVT IEGMIKLALS AASGLAHLHM EIVGTQGKPG IAHRDLKSKN ILVKKNGMCA IADLGLAVRH DAVTDTIDIA PNQRVGTKRY MAPEVLDETI NMKHFDSFKC ADIYALGLVY WEIARRCNSG GVHEEYQLPY YDLVPSDPSI EEMRKVVCDQ KLRPNIPNWW QSYEALRVMG KMMRECWYAN GAARLTALRI KKTLSQLSVQ EDVKI //