ACVR1_RAT
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 03-AUG-2022, entry version 177.
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).
CC {ECO:0000250|UniProtKB:P15261, 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. Interacts with FCHO1. Interacts with
CC CLU. Interacts with type II receptors AMHR2 and ACVR2A. Interacts with
CC BMP7. Interacts with GDF2/BMP9. Interacts with BMP6.
CC {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}.
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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.ENSRNOP00000006963; -.
DR GlyGen; P80201; 1 site.
DR PhosphoSitePlus; P80201; -.
DR PaxDb; P80201; -.
DR GeneID; 79558; -.
DR KEGG; rno:79558; -.
DR UCSC; RGD:620200; rat.
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 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 tissues.
DR ExpressionAtlas; P80201; baseline and differential.
DR Genevisible; P80201; RN.
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:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
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: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; TAS: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:0061312; P:BMP signaling pathway involved in heart development; 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:0003274; P:endocardial cushion fusion; ISO:RGD.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; 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:0060389; P:pathway-restricted SMAD protein phosphorylation; ISO:RGD.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:RGD.
DR GO; GO:0060037; P:pharyngeal system development; ISO:RGD.
DR GO; GO:0030501; P:positive regulation of bone mineralization; 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:1905007; P:positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation; ISO:RGD.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:RGD.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISO:RGD.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; 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 Gene3D; 2.10.60.10; -; 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; PTHR23255; 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; SSF56112; 1.
DR SUPFAM; SSF57302; SSF57302; 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; 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
