ID ACV1B_RAT Reviewed; 505 AA. AC P80202; DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1993, sequence version 1. DT 27-MAR-2024, entry version 189. 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 Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Sprague-Dawley; TISSUE=Urogenital ridge; RX PubMed=8395914; DOI=10.1002/aja.1001960207; RA He W.-W., Gustafson M.L., Hirobe S., Donahoe P.K.; RT "Developmental expression of four novel serine/threonine kinase receptors RT homologous to the activin/transforming growth factor-beta type II receptor RT family."; RL Dev. Dyn. 196:133-142(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Pituitary; RX PubMed=7813622; DOI=10.1006/excr.1995.1026; RA Takumi T., Moustakas A., Lin H.Y., Lodish H.F.; RT "Molecular characterization of a type I serine-threonine kinase receptor RT for TGF-beta and activin in the rat pituitary tumor cell line GH3."; RL Exp. Cell Res. 216:208-214(1995). 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 (By CC similarity). {ECO:0000250}. 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:0000250}. CC -!- SUBUNIT: Forms an activin receptor complex with activin receptor type-2 CC (ACVR2A or ACVR2B) (By similarity). Part of a complex consisting of CC MAGI2/ARIP1, ACVR2A, ACVR1B and SMAD3 (By similarity). Interacts with CC SMAD2 and SMAD3 (By similarity). Interacts with SMAD7 (By similarity). CC Interacts with FKBP1A (By similarity). Interacts with IGSF1 (By CC similarity). Interacts with CRIPTO (By similarity). Interacts with TDP2 CC (By similarity). Interacts with TSC22D1/TSC-22 (By similarity). CC {ECO:0000250|UniProtKB:P36896, ECO:0000250|UniProtKB:Q61271}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I CC membrane protein {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Urogenital ridge, testis, ovary, brain and lungs. 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 (By similarity). {ECO:0000250}. 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 (By CC similarity). {ECO:0000250}. CC -!- PTM: Ubiquitinated. Level of ubiquitination is regulated by the SMAD7- CC SMURF1 complex (By similarity). {ECO:0000250}. CC -!- PTM: Ubiquitinated. {ECO:0000250}. 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; S76466; AAB33045.1; -; mRNA. DR RefSeq; NP_954700.1; NM_199230.1. DR AlphaFoldDB; P80202; -. DR SMR; P80202; -. DR BioGRID; 248033; 1. DR STRING; 10116.ENSRNOP00000009345; -. DR GlyCosmos; P80202; 1 site, No reported glycans. DR GlyGen; P80202; 1 site. DR iPTMnet; P80202; -. DR PhosphoSitePlus; P80202; -. DR PaxDb; 10116-ENSRNOP00000009345; -. DR Ensembl; ENSRNOT00000009345.8; ENSRNOP00000009345.6; ENSRNOG00000006934.8. DR Ensembl; ENSRNOT00055045464; ENSRNOP00055037258; ENSRNOG00055026359. DR Ensembl; ENSRNOT00060026649; ENSRNOP00060021324; ENSRNOG00060015573. DR Ensembl; ENSRNOT00065039368; ENSRNOP00065031998; ENSRNOG00065023030. DR GeneID; 29381; -. DR KEGG; rno:29381; -. DR UCSC; RGD:735207; rat. DR AGR; RGD:735207; -. DR CTD; 91; -. DR RGD; 735207; Acvr1b. DR eggNOG; KOG2052; Eukaryota. DR GeneTree; ENSGT00940000157032; -. DR HOGENOM; CLU_000288_8_1_1; -. DR InParanoid; P80202; -. DR OrthoDB; 3900892at2759; -. DR PhylomeDB; P80202; -. DR BRENDA; 2.7.10.2; 5301. DR Reactome; R-RNO-1502540; Signaling by Activin. DR PRO; PR:P80202; -. DR Proteomes; UP000002494; Chromosome 7. DR Bgee; ENSRNOG00000006934; Expressed in frontal cortex and 18 other cell types or tissues. DR GO; GO:0048179; C:activin receptor complex; ISO:RGD. DR GO; GO:0009986; C:cell surface; ISO:RGD. DR GO; GO:0005886; C:plasma membrane; ISO:RGD. DR GO; GO:0043235; C:receptor complex; ISO:RGD. DR GO; GO:0048185; F:activin binding; ISO:RGD. DR GO; GO:0017002; F:activin receptor activity; ISO:RGD. DR GO; GO:0016361; F:activin receptor activity, type I; ISO:RGD. DR GO; GO:0005524; F:ATP binding; ISO:RGD. DR GO; GO:0070411; F:I-SMAD binding; ISO:RGD. DR GO; GO:0034711; F:inhibin binding; ISO:RGD. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD. DR GO; GO:0046332; F:SMAD binding; ISO:RGD. DR GO; GO:0004675; F:transmembrane receptor protein serine/threonine kinase activity; TAS:RGD. DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD. DR GO; GO:0032924; P:activin receptor signaling pathway; IMP:RGD. DR GO; GO:0060936; P:cardiac fibroblast cell development; IMP:RGD. DR GO; GO:0071363; P:cellular response to growth factor stimulus; IBA:GO_Central. DR GO; GO:0046545; P:development of primary female sexual characteristics; IEP:RGD. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISO:RGD. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISO:RGD. DR GO; GO:0001942; P:hair follicle development; ISO:RGD. DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD. DR GO; GO:0030308; P:negative regulation of cell growth; ISO:RGD. DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD. DR GO; GO:0007399; P:nervous system development; IBA:GO_Central. DR GO; GO:0038092; P:nodal signaling pathway; ISO:RGD. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0032927; P:positive regulation of activin receptor signaling pathway; ISO:RGD. DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IMP:RGD. DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; ISO:RGD. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:RGD. DR GO; GO:1901165; P:positive regulation of trophoblast cell migration; ISO:RGD. DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISO:RGD. DR GO; GO:0009966; P:regulation of signal transduction; ISO:RGD. DR GO; GO:0014823; P:response to activity; IEP:RGD. DR GO; GO:0007165; P:signal transduction; ISO:RGD. 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 2: Evidence at transcript level; KW ATP-binding; Cell membrane; Glycoprotein; Kinase; Magnesium; Manganese; KW Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Receptor; KW Reference proteome; Serine/threonine-protein kinase; Signal; Transferase; KW Transmembrane; 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_0000024419" 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:0000250|UniProtKB:P36896" FT CARBOHYD 43 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" SQ SEQUENCE 505 AA; 56805 MW; 377F4A5C867B3860 CRC64; MAESAGASSF FPLVVLLLAG SGGSGPRGIQ ALLCACTSCL QTNYTCETDG ACMVSIFNLD GMEHHVRTCI PKVELVPAGK PFYCLSSEDL RNTHCCYIDF CNKIDLRVPS 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 KLRPNVPNWW QSYEALRVMG KMMRECWYAN GAARLTALRI KKTLSQLSVQ EDVKI //