P37172 · ACVR1_MOUSE
- ProteinActivin receptor type-1
- GeneAcvr1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids509 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Bone morphogenetic protein (BMP) type I receptor that is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation (PubMed:10479450, PubMed:15531373, PubMed:21945937).
As a type I receptor, forms heterotetrameric receptor complexes with the type II receptors AMHR2, ACVR2A ors ACVR2B. Upon binding of ligands such as BMP7 or BMP9 to the heteromeric complexes, type II receptors transphosphorylate ACVR1 intracellular domain. In turn, ACVR1 kinase domain is activated and subsequently phosphorylates SMAD1/5/8 proteins that transduce the signal. In addition to its role in mediating BMP pathway-specific signaling, suppresses TGFbeta/activin pathway signaling by interfering with the binding of activin to its type II receptor. Besides canonical SMAD signaling, can activate non-canonical pathways such as p38 mitogen-activated protein kinases/MAPKs (By similarity) (PubMed:10479450, PubMed:15531373, PubMed:21945937, PubMed:25413979).
May promote the expression of HAMP, potentially via its interaction with BMP6 (PubMed:31800957).
As a type I receptor, forms heterotetrameric receptor complexes with the type II receptors AMHR2, ACVR2A ors ACVR2B. Upon binding of ligands such as BMP7 or BMP9 to the heteromeric complexes, type II receptors transphosphorylate ACVR1 intracellular domain. In turn, ACVR1 kinase domain is activated and subsequently phosphorylates SMAD1/5/8 proteins that transduce the signal. In addition to its role in mediating BMP pathway-specific signaling, suppresses TGFbeta/activin pathway signaling by interfering with the binding of activin to its type II receptor. Besides canonical SMAD signaling, can activate non-canonical pathways such as p38 mitogen-activated protein kinases/MAPKs (By similarity) (PubMed:10479450, PubMed:15531373, PubMed:21945937, PubMed:25413979).
May promote the expression of HAMP, potentially via its interaction with BMP6 (PubMed:31800957).
Catalytic activity
- ATP + L-threonyl-[receptor-protein] = ADP + H+ + O-phospho-L-threonyl-[receptor-protein]
Cofactor
Mn2+ (UniProtKB | Rhea| CHEBI:29035 )
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameActivin receptor type-1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP37172
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Single-pass type I membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 21-123 | Extracellular | ||||
Sequence: VEDEKPKVNQKLYMCVCEGLSCGNEDHCEGQQCFSSLSINDGFHVYQKGCFQVYEQGKMTCKTPPSPGQAVECCQGDWCNRNITAQLPTKGKSFPGTQNFHLE | ||||||
Transmembrane | 124-146 | Helical | ||||
Sequence: VGLIILSVVFAVCLLACILGVAL | ||||||
Topological domain | 147-509 | Cytoplasmic | ||||
Sequence: RKFKRRNQERLNPRDVEYGTIEGLITTNVGDSTLAELLDHSCTSGSGSGLPFLVQRTVARQITLLECVGKGRYGEVWRGSWQGENVAVKIFSSRDEKSWFRETELYNTVMLRHENILGFIASDMTSRHSSTQLWLITHYHEMGSLYDYLQLTTLDTVSCLRIVLSIASGLAHLHIEIFGTQGKSAIAHRDLKSKNILVKKNGQCCIADLGLAVMHSQSTNQLDVGNNPRVGTKRYMAPEVLDETIQVDCFDSYKRVDIWAFGLVLWEVARRMVSNGIVEDYKPPFYDVVPNDPSFEDMRKVVCVDQQRPNIPNRWFSDPTLTSLAKLMKECWYQNPSARLTALRIKKTLTKIDNSLDKLKTDC |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Deletion mutants show a recessive embryonic lethality. At 7.0 dpc, mutant embryos did not show any special abnormalities except a smaller size. However, at 8.0 dpc, mesoderm formation is initiated but its development is arrested around the mid/late streak stage (PubMed:10479450).
In an osteoblast-specific manner loss of BMP signaling via ACVR1 directs osteoblasts to increase endogenous bone mass (PubMed:21945937).
Additionally, mice lacking ACVR1 in cartilage show reduced SMAD responses, but also decreased p38 MAPK activation (PubMed:25413979).
In an osteoblast-specific manner loss of BMP signaling via ACVR1 directs osteoblasts to increase endogenous bone mass (PubMed:21945937).
Additionally, mice lacking ACVR1 in cartilage show reduced SMAD responses, but also decreased p38 MAPK activation (PubMed:25413979).
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 20 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for signal, chain, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-20 | |||||
Sequence: MVDGVMILPVLMMMAFPSPS | ||||||
Chain | PRO_0000024395 | 21-509 | Activin receptor type-1 | |||
Sequence: VEDEKPKVNQKLYMCVCEGLSCGNEDHCEGQQCFSSLSINDGFHVYQKGCFQVYEQGKMTCKTPPSPGQAVECCQGDWCNRNITAQLPTKGKSFPGTQNFHLEVGLIILSVVFAVCLLACILGVALRKFKRRNQERLNPRDVEYGTIEGLITTNVGDSTLAELLDHSCTSGSGSGLPFLVQRTVARQITLLECVGKGRYGEVWRGSWQGENVAVKIFSSRDEKSWFRETELYNTVMLRHENILGFIASDMTSRHSSTQLWLITHYHEMGSLYDYLQLTTLDTVSCLRIVLSIASGLAHLHIEIFGTQGKSAIAHRDLKSKNILVKKNGQCCIADLGLAVMHSQSTNQLDVGNNPRVGTKRYMAPEVLDETIQVDCFDSYKRVDIWAFGLVLWEVARRMVSNGIVEDYKPPFYDVVPNDPSFEDMRKVVCVDQQRPNIPNRWFSDPTLTSLAKLMKECWYQNPSARLTALRIKKTLTKIDNSLDKLKTDC | ||||||
Glycosylation | 102 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 501 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in bone during developmental stages (PubMed:21945937).
Expressed in normal parenchymal cells, endothelial cells, fibroblasts and tumor-derived epithelial cells
Expressed in normal parenchymal cells, endothelial cells, fibroblasts and tumor-derived epithelial cells
Developmental stage
Highly expressed in the node and midline and weakly expressed in 8.5 dpc embryos and in the lateral plate mesoderm.
Gene expression databases
Interaction
Subunit
Interacts with FKBP1A (By similarity).
Interacts with FCHO1 (By similarity).
Interacts with CLU. Interacts with type II receptors AMHR2 and ACVR2A (By similarity).
Interacts with BMP7 (By similarity).
Interacts with BMP9 (By similarity).
Interacts with BMP6 (when glycosylated); the interaction may induce HAMP expression (PubMed:31800957).
Interacts with TSC22D1/TSC-22 (By similarity).
Interacts with FCHO1 (By similarity).
Interacts with CLU. Interacts with type II receptors AMHR2 and ACVR2A (By similarity).
Interacts with BMP7 (By similarity).
Interacts with BMP9 (By similarity).
Interacts with BMP6 (when glycosylated); the interaction may induce HAMP expression (PubMed:31800957).
Interacts with TSC22D1/TSC-22 (By similarity).
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 178-207 | GS | ||||
Sequence: STLAELLDHSCTSGSGSGLPFLVQRTVARQ | ||||||
Domain | 208-502 | Protein kinase | ||||
Sequence: ITLLECVGKGRYGEVWRGSWQGENVAVKIFSSRDEKSWFRETELYNTVMLRHENILGFIASDMTSRHSSTQLWLITHYHEMGSLYDYLQLTTLDTVSCLRIVLSIASGLAHLHIEIFGTQGKSAIAHRDLKSKNILVKKNGQCCIADLGLAVMHSQSTNQLDVGNNPRVGTKRYMAPEVLDETIQVDCFDSYKRVDIWAFGLVLWEVARRMVSNGIVEDYKPPFYDVVPNDPSFEDMRKVVCVDQQRPNIPNRWFSDPTLTSLAKLMKECWYQNPSARLTALRIKKTLTKIDNSL |
Sequence similarities
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length509
- Mass (Da)57,226
- Last updated2006-10-17 v2
- Checksum05BCFC22C5740028
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
B1AW87 | B1AW87_MOUSE | Acvr1 | 130 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 27 | in Ref. 3; BAE29239/BAE29286 | ||||
Sequence: K → E | ||||||
Sequence conflict | 60 | in Ref. 1; AAA40495 | ||||
Sequence: N → Y |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L15436 EMBL· GenBank· DDBJ | AAA40495.1 EMBL· GenBank· DDBJ | mRNA | ||
AF332087 EMBL· GenBank· DDBJ | AAK56115.1 EMBL· GenBank· DDBJ | mRNA | ||
AF332088 EMBL· GenBank· DDBJ | AAK56116.1 EMBL· GenBank· DDBJ | mRNA | ||
AK150014 EMBL· GenBank· DDBJ | BAE29239.1 EMBL· GenBank· DDBJ | mRNA | ||
AK150075 EMBL· GenBank· DDBJ | BAE29286.1 EMBL· GenBank· DDBJ | mRNA | ||
BC058718 EMBL· GenBank· DDBJ | AAH58718.1 EMBL· GenBank· DDBJ | mRNA |