ID ACVR1_RAT Reviewed; 509 AA. AC P80201; DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1993, sequence version 1. DT 27-MAR-2024, entry version 185. DE RecName: Full=Activin receptor type-1; DE EC=2.7.11.30; DE AltName: Full=Activin receptor type I; DE Short=ACTR-I; DE AltName: Full=Serine/threonine-protein kinase receptor R1; DE Short=SKR1; DE AltName: Full=TGF-B superfamily receptor type I; DE Short=TSR-I; DE Flags: Precursor; GN Name=Acvr1; Synonyms=Acvrlk2; 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 STRAIN=Sprague-Dawley; RX PubMed=8248234; DOI=10.1073/pnas.90.23.11242; RA Tsuchida K.K.T., Vale W.W.; RT "Cloning and characterization of a transmembrane serine kinase that acts as RT an activin type I receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 90:11242-11246(1993). CC -!- FUNCTION: Bone morphogenetic protein (BMP) type I receptor that is CC involved in a wide variety of biological processes, including bone, CC heart, cartilage, nervous, and reproductive system development and CC regulation. As a type I receptor, forms heterotetrameric receptor CC complexes with the type II receptors AMHR2, ACVR2A ors ACVR2B. Upon CC binding of ligands such as BMP7 or GDF2/BMP9 to the heteromeric CC complexes, type II receptors transphosphorylate ACVR1 intracellular CC domain. In turn, ACVR1 kinase domain is activated and subsequently CC phosphorylates SMAD1/5/8 proteins that transduce the signal. In CC addition to its role in mediating BMP pathway-specific signaling, CC suppresses TGFbeta/activin pathway signaling by interfering with the CC binding of activin to its type II receptor (By similarity). Besides CC canonical SMAD signaling, can activate non-canonical pathways such as CC p38 mitogen-activated protein kinases/MAPKs (By similarity). May CC promote the expression of HAMP, potentially via its interaction with CC BMP6 (By similarity). {ECO:0000250|UniProtKB:P15261, CC ECO:0000250|UniProtKB:P37172, ECO:0000250|UniProtKB:Q04771}. 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 -!- SUBUNIT: Interacts with FKBP1A (By similarity). Interacts with FCHO1 CC (By similarity). Interacts with CLU. Interacts with type II receptors CC AMHR2 and ACVR2A (By similarity). Interacts with BMP7 (By similarity). CC Interacts with GDF2/BMP9 (By similarity). Interacts with BMP6 (when CC glycosylated); the interaction may induce HAMP expression (By CC similarity). Interacts with TSC22D1/TSC-22 (By similarity). CC {ECO:0000250|UniProtKB:P37172, ECO:0000250|UniProtKB:Q04771}. CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. CC -!- TISSUE SPECIFICITY: Urogenital ridge, testis, ovary, brain and lungs. 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; L19341; AAA40673.1; -; mRNA. DR PIR; A49664; A49664. DR RefSeq; NP_077812.1; NM_024486.1. DR RefSeq; XP_006234276.1; XM_006234214.3. DR AlphaFoldDB; P80201; -. DR SMR; P80201; -. DR BioGRID; 249474; 1. DR STRING; 10116.ENSRNOP00000072326; -. DR GlyCosmos; P80201; 1 site, No reported glycans. DR GlyGen; P80201; 1 site. DR PhosphoSitePlus; P80201; -. DR SwissPalm; P80201; -. DR PaxDb; 10116-ENSRNOP00000006963; -. DR Ensembl; ENSRNOT00055001286; ENSRNOP00055001033; ENSRNOG00055000748. DR Ensembl; ENSRNOT00060013471; ENSRNOP00060010254; ENSRNOG00060008142. DR Ensembl; ENSRNOT00065034692; ENSRNOP00065027836; ENSRNOG00065020511. DR GeneID; 79558; -. DR KEGG; rno:79558; -. DR UCSC; RGD:620200; rat. DR AGR; RGD:620200; -. DR CTD; 90; -. DR RGD; 620200; Acvr1. DR VEuPathDB; HostDB:ENSRNOG00000005033; -. DR eggNOG; KOG2052; Eukaryota. DR HOGENOM; CLU_000288_8_5_1; -. DR InParanoid; P80201; -. DR OrthoDB; 3900892at2759; -. DR PhylomeDB; P80201; -. DR TreeFam; TF314724; -. DR BRENDA; 2.7.10.2; 5301. DR PRO; PR:P80201; -. DR Proteomes; UP000002494; Chromosome 3. DR Bgee; ENSRNOG00000005033; Expressed in quadriceps femoris and 19 other cell types or tissues. DR ExpressionAtlas; P80201; baseline and differential. DR GO; GO:0048179; C:activin receptor complex; IDA:RGD. DR GO; GO:0045177; C:apical part of cell; ISO:RGD. DR GO; GO:0070724; C:BMP receptor complex; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; ISO:RGD. DR GO; GO:0048185; F:activin binding; ISO:RGD. DR GO; GO:0016361; F:activin receptor activity, type I; IDA:RGD. DR GO; GO:0005524; F:ATP binding; ISO:RGD. DR GO; GO:0098821; F:BMP receptor activity; ISO:RGD. DR GO; GO:0045296; F:cadherin binding; ISO:RGD. DR GO; GO:0019838; F:growth factor binding; ISO:RGD. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD. DR GO; GO:0004672; F:protein kinase activity; ISO:RGD. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD. DR GO; GO:1990782; F:protein tyrosine kinase binding; ISO:RGD. DR GO; GO:0046332; F:SMAD binding; ISO:RGD. DR GO; GO:0050431; F:transforming growth factor beta binding; ISO:RGD. DR GO; GO:0005025; F:transforming growth factor beta receptor activity, type I; ISO:RGD. DR GO; GO:0004675; F:transmembrane receptor protein serine/threonine kinase activity; ISO:RGD. DR GO; GO:0032924; P:activin receptor signaling pathway; ISO:RGD. DR GO; GO:0002526; P:acute inflammatory response; ISO:RGD. DR GO; GO:0003289; P:atrial septum primum morphogenesis; ISO:RGD. DR GO; GO:0003181; P:atrioventricular valve morphogenesis; ISO:RGD. DR GO; GO:0030509; P:BMP signaling pathway; ISO:RGD. DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; ISO:RGD. DR GO; GO:0060923; P:cardiac muscle cell fate commitment; ISO:RGD. DR GO; GO:0071773; P:cellular response to BMP stimulus; ISO:RGD. DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IEP:RGD. DR GO; GO:0071363; P:cellular response to growth factor stimulus; IBA:GO_Central. DR GO; GO:0007368; P:determination of left/right symmetry; ISO:RGD. DR GO; GO:0009953; P:dorsal/ventral pattern formation; IBA:GO_Central. DR GO; GO:0003143; P:embryonic heart tube morphogenesis; ISO:RGD. DR GO; GO:0061445; P:endocardial cushion cell fate commitment; ISO:RGD. DR GO; GO:0003272; P:endocardial cushion formation; ISO:RGD. DR GO; GO:0003274; P:endocardial cushion fusion; ISO:RGD. DR GO; GO:0007369; P:gastrulation; ISO:RGD. DR GO; GO:0001702; P:gastrulation with mouth forming second; ISO:RGD. DR GO; GO:0007281; P:germ cell development; ISO:RGD. DR GO; GO:0007507; P:heart development; ISO:RGD. DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD. DR GO; GO:0007498; P:mesoderm development; ISO:RGD. DR GO; GO:0001707; P:mesoderm formation; ISO:RGD. DR GO; GO:0003183; P:mitral valve morphogenesis; ISO:RGD. DR GO; GO:0032926; P:negative regulation of activin receptor signaling pathway; ISO:RGD. DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; ISO:RGD. DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; ISO:RGD. DR GO; GO:0009968; P:negative regulation of signal transduction; ISO:RGD. DR GO; GO:0001755; P:neural crest cell migration; ISO:RGD. DR GO; GO:0060037; P:pharyngeal system development; ISO:RGD. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0030501; P:positive regulation of bone mineralization; ISO:RGD. DR GO; GO:0062043; P:positive regulation of cardiac epithelial to mesenchymal transition; ISO:RGD. DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD. DR GO; GO:2000017; P:positive regulation of determination of dorsal identity; ISO:RGD. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:RGD. DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:RGD. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; ISO:RGD. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD. DR GO; GO:0030278; P:regulation of ossification; ISO:RGD. DR GO; GO:0048641; P:regulation of skeletal muscle tissue development; IEP:UniProtKB. DR GO; GO:0051145; P:smooth muscle cell differentiation; ISO:RGD. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0001655; P:urogenital system development; IMP:MGI. DR GO; GO:0060412; P:ventricular septum morphogenesis; ISO:RGD. DR CDD; cd14142; STKc_ACVR1_ALK1; 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; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR InterPro; IPR045860; Snake_toxin-like_sf. DR InterPro; IPR000333; TGFB_receptor. DR PANTHER; PTHR23255:SF69; ACTIVIN RECEPTOR TYPE-1; 1. DR PANTHER; PTHR23255; TRANSFORMING GROWTH FACTOR-BETA RECEPTOR TYPE I AND II; 1. DR Pfam; PF01064; Activin_recp; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF08515; TGF_beta_GS; 1. DR PRINTS; PR00653; ACTIVIN2R. 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; P80201; RN. PE 2: Evidence at transcript level; KW ATP-binding; Glycoprotein; Kinase; Magnesium; Manganese; Membrane; KW Metal-binding; Nucleotide-binding; Phosphoprotein; Receptor; KW Reference proteome; Serine/threonine-protein kinase; Signal; Transferase; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..20 FT /evidence="ECO:0000255" FT CHAIN 21..509 FT /note="Activin receptor type-1" FT /id="PRO_0000024396" FT TOPO_DOM 21..123 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 124..146 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 147..509 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 178..207 FT /note="GS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00585" FT DOMAIN 208..502 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT ACT_SITE 336 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 214..222 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 235 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 501 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04771" FT CARBOHYD 102 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" SQ SEQUENCE 509 AA; 57195 MW; 7A70A477784DCF87 CRC64; MVDGAMILSV LMMMALPSPS MEDEEPKVNP KLYMCVCEGL SCGNEDHCEG QQCFSSLSVN DGFRVYQKGC FQVYEQGKMT CKTPPSPGQA VECCQGDWCN RNVTARLPTK GKSFPGSQNF HLEVGLIILS VVFAVCLFAC ILGVALRKFK RRNQERLNPR DVEYGTIEGL ITTNVGDSTL AELLDHSCTS GSGSGLPFLV QRTVARQITL LECVGKGRYG EVWRGSWQGE NVAVKIFSSR DEKSWFRETE LYNTVMLRHE NILGFIASDM TSRHSSTQLW LITHYHEMGS LYDYLQLTTL DTVSCLRIVL SIASGLAHLH IEIFGTQGKS AIAHRDLKSK NILVKKNGQC CIADLGLAVM HSQSTNQLDV GNNPRVGTKR YMAPEVLDET IQVDCFDSYK RVDIWAFGLV LWEVARRMVS NGIVEDYKPP FYDVVPNDPS FEDMRKVVCV DQQRPNIPNR WFSDPTLTSL AKLMKECWYQ NPSARLTALR IKKTLTKIDN SLDKLKTDC //