UniProtKB - Q61271 (ACV1B_MOUSE)
Protein
Activin receptor type-1B
Gene
Acvr1b
Organism
Mus musculus (Mouse)
Status
Functioni
Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, type-2 receptors (ACVR2A and/or ACVR2B) act as a primary activin receptors whereas the type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine-threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor such as ACVR1B. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor. ACVR1B also phosphorylates TDP2.2 Publications
Catalytic activityi
Activity regulationi
Activin receptor type-2 (ACVR2A or ACVR2B) activates the type-1 receptor through phosphorylation of its regulatory GS domain.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 234 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 335 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 213 – 221 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- activin binding Source: MGI
- activin receptor activity, type I Source: MGI
- ATP binding Source: MGI
- growth factor binding Source: Ensembl
- inhibin binding Source: MGI
- metal ion binding Source: UniProtKB-KW
- protein serine/threonine kinase activity Source: UniProtKB
- SMAD binding Source: MGI
- transmembrane receptor protein serine/threonine kinase activity Source: MGI
GO - Biological processi
- activin receptor signaling pathway Source: MGI
- cell surface receptor signaling pathway Source: MGI
- cellular response to growth factor stimulus Source: GO_Central
- central nervous system development Source: Ensembl
- development of primary female sexual characteristics Source: Ensembl
- extrinsic apoptotic signaling pathway Source: MGI
- G1/S transition of mitotic cell cycle Source: MGI
- hair follicle development Source: MGI
- in utero embryonic development Source: MGI
- mesoderm development Source: MGI
- negative regulation of cell growth Source: MGI
- negative regulation of gene expression Source: MGI
- nervous system development Source: GO_Central
- nodal signaling pathway Source: MGI
- peptidyl-threonine phosphorylation Source: UniProtKB
- positive regulation of activin receptor signaling pathway Source: MGI
- positive regulation of erythrocyte differentiation Source: MGI
- positive regulation of gene expression Source: MGI
- positive regulation of pathway-restricted SMAD protein phosphorylation Source: MGI
- positive regulation of transcription by RNA polymerase II Source: MGI
- positive regulation of trophoblast cell migration Source: MGI
- protein autophosphorylation Source: MGI
- protein phosphorylation Source: MGI
- regulation of signal transduction Source: MGI
- regulation of transcription, DNA-templated Source: MGI
- signal transduction Source: MGI
Keywordsi
Molecular function | Kinase, Receptor, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-MMU-1502540, Signaling by Activin |
Names & Taxonomyi
Protein namesi | Recommended name: Activin receptor type-1B (EC:2.7.11.30)Alternative name(s): Activin receptor type IB Short name: ACTR-IB Activin receptor-like kinase 4 Short name: ALK-4 Serine/threonine-protein kinase receptor R2 Short name: SKR2 |
Gene namesi | Name:Acvr1b Synonyms:Alk4 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1338944, Acvr1b |
Subcellular locationi
Plasma membrane
- Cell membrane By similarity; Single-pass type I membrane protein By similarity
Cytosol
- cytosol Source: MGI
Plasma Membrane
- activin receptor complex Source: MGI
- integral component of plasma membrane Source: MGI
- plasma membrane Source: GO_Central
Other locations
- cell surface Source: MGI
- receptor complex Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 24 – 126 | ExtracellularSequence analysisAdd BLAST | 103 | |
Transmembranei | 127 – 149 | HelicalSequence analysisAdd BLAST | 23 | |
Topological domaini | 150 – 505 | CytoplasmicSequence analysisAdd BLAST | 356 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Disruption phenotypei
Leads to hair loss.1 Publication
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 23 | Sequence analysisAdd BLAST | 23 | |
ChainiPRO_0000024418 | 24 – 505 | Activin receptor type-1BAdd BLAST | 482 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 43 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 380 | PhosphotyrosineBy similarity | 1 |
Post-translational modificationi
Autophosphorylated. Phosphorylated by activin receptor type-2 (ACVR2A or ACVR2B) in response to activin-binding at serine and threonine residues in the GS domain. Phosphorylation of ACVR1B by activin receptor type-2 regulates association with SMAD7 (By similarity).By similarity
Ubiquitinated. Level of ubiquitination is regulated by the SMAD7-SMURF1 complex (By similarity).By similarity
Ubiquitinated.By similarity
Keywords - PTMi
Glycoprotein, Phosphoprotein, Ubl conjugationProteomic databases
MaxQBi | Q61271 |
PaxDbi | Q61271 |
PRIDEi | Q61271 |
PTM databases
GlyGeni | Q61271, 1 site |
iPTMneti | Q61271 |
PhosphoSitePlusi | Q61271 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000000532, Expressed in neocortex and 328 other tissues |
ExpressionAtlasi | Q61271, baseline and differential |
Genevisiblei | Q61271, MM |
Interactioni
Subunit structurei
Forms an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B).
Interacts with TDP2 (By similarity).
Interacts with AIP1, FKBP1A, IGSF1, TDGF1, SMAD2, SMAD3 and SMAD7 (By similarity).
By similarityGO - Molecular functioni
- growth factor binding Source: Ensembl
- inhibin binding Source: MGI
- SMAD binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 197954, 8 interactors |
CORUMi | Q61271 |
IntActi | Q61271, 1 interactor |
MINTi | Q61271 |
STRINGi | 10090.ENSMUSP00000000544 |
Chemistry databases
BindingDBi | Q61271 |
Miscellaneous databases
RNActi | Q61271, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 177 – 206 | GSPROSITE-ProRule annotationAdd BLAST | 30 | |
Domaini | 207 – 497 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 291 |
Domaini
The GS domain is a 30-amino-acid sequence adjacent to the N-terminal boundary of the kinase domain and highly conserved in all other known type-1 receptors but not in type-2 receptors. The GS domain is the site of activation through phosphorylation by the II receptors (By similarity).By similarity
Sequence similaritiesi
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.Curated
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2052, Eukaryota |
GeneTreei | ENSGT00940000157032 |
HOGENOMi | CLU_000288_8_1_1 |
InParanoidi | Q61271 |
OMAi | AALQCAC |
OrthoDBi | 776697at2759 |
PhylomeDBi | Q61271 |
TreeFami | TF314724 |
Family and domain databases
InterProi | View protein in InterPro IPR003605, GS_dom IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS IPR000333, TGFB_receptor |
PANTHERi | PTHR23255, PTHR23255, 1 hit |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit PF08515, TGF_beta_GS, 1 hit |
SMARTi | View protein in SMART SM00467, GS, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS51256, GS, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
Q61271-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAESAGASSF FPLVVLLLAG SGGSGPRGIQ ALLCACTSCL QTNYTCETDG
60 70 80 90 100
ACMVSIFNLD GVEHHVRTCI PKVELVPAGK PFYCLSSEDL RNTHCCYIDF
110 120 130 140 150
CNKIDLRVPS GHLKEPAHPS MWGPVELVGI IAGPVFLLFL IIIIVFLVIN
160 170 180 190 200
YHQRVYHNRQ RLDMEDPSCE MCLSKDKTLQ DLVYDLSTSG SGSGLPLFVQ
210 220 230 240 250
RTVARTIVLQ EIIGKGRFGE VWRGRWRGGD VAVKIFSSRE ERSWFREAEI
260 270 280 290 300
YQTVMLRHEN ILGFIAADNK DNGTWTQLWL VSDYHEHGSL FDYLNRYTVT
310 320 330 340 350
IEGMIKLALS AASGLAHLHM EIVGTQGKPG IAHRDLKSKN ILVKKNGMCA
360 370 380 390 400
IADLGLAVRH DAVTDTIDIA PNQRVGTKRY MAPEVLDETI NMKHFDSFKC
410 420 430 440 450
ADIYALGLVY WEIARRCNSG GVHEDYQLPY YDLVPSDPSI EEMRKVVCDQ
460 470 480 490 500
KLRPNVPNWW QSYEALRVMG KMMRECWYAN GAARLTALRI KKTLSQLSVQ
EDVKI
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Z31663 mRNA Translation: CAA83483.1 |
CCDSi | CCDS27846.1 |
RefSeqi | NP_031421.1, NM_007395.3 |
Genome annotation databases
Ensembli | ENSMUST00000000544; ENSMUSP00000000544; ENSMUSG00000000532 |
GeneIDi | 11479 |
KEGGi | mmu:11479 |
UCSCi | uc007xsr.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Z31663 mRNA Translation: CAA83483.1 |
CCDSi | CCDS27846.1 |
RefSeqi | NP_031421.1, NM_007395.3 |
3D structure databases
SMRi | Q61271 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 197954, 8 interactors |
CORUMi | Q61271 |
IntActi | Q61271, 1 interactor |
MINTi | Q61271 |
STRINGi | 10090.ENSMUSP00000000544 |
Chemistry databases
BindingDBi | Q61271 |
PTM databases
GlyGeni | Q61271, 1 site |
iPTMneti | Q61271 |
PhosphoSitePlusi | Q61271 |
Proteomic databases
MaxQBi | Q61271 |
PaxDbi | Q61271 |
PRIDEi | Q61271 |
Protocols and materials databases
Antibodypediai | 14450, 524 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000000544; ENSMUSP00000000544; ENSMUSG00000000532 |
GeneIDi | 11479 |
KEGGi | mmu:11479 |
UCSCi | uc007xsr.1, mouse |
Organism-specific databases
CTDi | 91 |
MGIi | MGI:1338944, Acvr1b |
Phylogenomic databases
eggNOGi | KOG2052, Eukaryota |
GeneTreei | ENSGT00940000157032 |
HOGENOMi | CLU_000288_8_1_1 |
InParanoidi | Q61271 |
OMAi | AALQCAC |
OrthoDBi | 776697at2759 |
PhylomeDBi | Q61271 |
TreeFami | TF314724 |
Enzyme and pathway databases
Reactomei | R-MMU-1502540, Signaling by Activin |
Miscellaneous databases
BioGRID-ORCSi | 11479, 3 hits in 18 CRISPR screens |
ChiTaRSi | Acvr1b, mouse |
PROi | PR:Q61271 |
RNActi | Q61271, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000000532, Expressed in neocortex and 328 other tissues |
ExpressionAtlasi | Q61271, baseline and differential |
Genevisiblei | Q61271, MM |
Family and domain databases
InterProi | View protein in InterPro IPR003605, GS_dom IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS IPR000333, TGFB_receptor |
PANTHERi | PTHR23255, PTHR23255, 1 hit |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit PF08515, TGF_beta_GS, 1 hit |
SMARTi | View protein in SMART SM00467, GS, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS51256, GS, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ACV1B_MOUSE | |
Accessioni | Q61271Primary (citable) accession number: Q61271 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 5, 2004 |
Last sequence update: | November 1, 1996 | |
Last modified: | February 10, 2021 | |
This is version 173 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human and mouse protein kinases
Human and mouse protein kinases: classification and index