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}.
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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 Genevisible; P36896; HS.
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.
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
//
