ACV1B_RAT
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 03-AUG-2022, entry version 180.
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). Interacts with TDP2 (By similarity). Interacts with
CC AIP1, FKBP1A, IGSF1, TDGF1, SMAD2, SMAD3 and SMAD7 (By similarity).
CC {ECO:0000250}.
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}.
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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 GlyGen; P80202; 1 site.
DR iPTMnet; P80202; -.
DR PhosphoSitePlus; P80202; -.
DR PaxDb; P80202; -.
DR PRIDE; P80202; -.
DR Ensembl; ENSRNOT00000009345; ENSRNOP00000009345; ENSRNOG00000006934.
DR GeneID; 29381; -.
DR KEGG; rno:29381; -.
DR UCSC; RGD:735207; rat.
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 OMA; VRNTHCC; -.
DR OrthoDB; 776697at2759; -.
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 tissues.
DR GO; GO:0048179; C:activin receptor complex; ISO:RGD.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0048185; F:activin binding; 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: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:0032924; P:activin receptor signaling pathway; ISO:RGD.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IBA:GO_Central.
DR GO; GO:0007417; P:central nervous system development; IEP:RGD.
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:0018107; P:peptidyl-threonine phosphorylation; ISO:RGD.
DR GO; GO:0032927; P:positive regulation of activin receptor signaling pathway; ISO: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:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IMP: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:0046777; P:protein autophosphorylation; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0009966; P:regulation of signal transduction; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0007165; P:signal transduction; ISO:RGD.
DR Gene3D; 2.10.60.10; -; 1.
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; PTHR23255; 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; 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; 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
