UniProt functional annotation for Q04771



	UniProt functional annotation for Q04771

UniProt code: Q04771.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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:20628059, PubMed:22977237). As a type I receptor, forms heterotetrameric receptor complexes with the type II receptors AMHR2, ACVR2A ors ACVR2B (PubMed:17911401). Upon binding of ligands such as BMP7 or GDF2/BMP9 to the heteromeric complexes, type II receptors transphosphorylate ACVR1 intracellular domain (PubMed:25354296). In turn, ACVR1 kinase domain is activated and subsequently phosphorylates SMAD1/5/8 proteins that transduce the signal (PubMed:9748228). 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 (PubMed:17911401). Besides canonical SMAD signaling, can activate non-canonical pathways such as p38 mitogen-activated protein kinases/MAPKs (By similarity). {ECO:0000250|UniProtKB:P15261, ECO:0000269|PubMed:17911401, ECO:0000269|PubMed:20628059, ECO:0000269|PubMed:22977237, ECO:0000269|PubMed:25354296, ECO:0000269|PubMed:9748228}.

Catalytic activity: Reaction=ATP + L-threonyl-[receptor-protein] = ADP + H(+) + O-phospho- L-threonyl-[receptor-protein]; Xref=Rhea:RHEA:44880, Rhea:RHEA- COMP:11024, Rhea:RHEA-COMP:11025, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.30;

Catalytic activity: Reaction=ATP + L-seryl-[receptor-protein] = ADP + H(+) + O-phospho-L- seryl-[receptor-protein]; Xref=Rhea:RHEA:18673, Rhea:RHEA-COMP:11022, Rhea:RHEA-COMP:11023, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.30; Evidence={ECO:0000269|PubMed:9748228};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};

Subunit: Interacts with FKBP1A (PubMed:22484487, Ref.12). Interacts with FCHO1 (PubMed:22484487). Interacts with CLU (PubMed:8555189). Interacts with type II receptors AMHR2 and ACVR2A (PubMed:17911401). Interacts with BMP7 (PubMed:9748228). Interacts with GDF2/BMP9 (PubMed:20628059). Interacts with BMP6 (PubMed:18070108). {ECO:0000269|PubMed:17911401, ECO:0000269|PubMed:18070108, ECO:0000269|PubMed:20628059, ECO:0000269|PubMed:22484487, ECO:0000269|PubMed:8555189, ECO:0000269|PubMed:9748228, ECO:0000269|Ref.12}.

Subcellular location: Membrane; Single-pass type I membrane protein.

Tissue specificity: Expressed in normal parenchymal cells, endothelial cells, fibroblasts and tumor-derived epithelial cells. {ECO:0000269|PubMed:8389764}.

Disease: Fibrodysplasia ossificans progressiva (FOP) [MIM:135100]: A rare autosomal dominant connective tissue disorder resulting in skeletal malformations and progressive extraskeletal ossification. Heterotopic ossification begins in childhood and can be induced by trauma or may occur without warning. Bone formation is episodic and progressive, leading to a debilitating ankylosis of all major joints of the axial and appendicular skeleton, rendering movement impossible. {ECO:0000269|PubMed:16642017, ECO:0000269|PubMed:19085907, ECO:0000269|PubMed:19330033}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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:20628059, PubMed:22977237). As a type I receptor, forms heterotetrameric receptor complexes with the type II receptors AMHR2, ACVR2A ors ACVR2B (PubMed:17911401). Upon binding of ligands such as BMP7 or GDF2/BMP9 to the heteromeric complexes, type II receptors transphosphorylate ACVR1 intracellular domain (PubMed:25354296). In turn, ACVR1 kinase domain is activated and subsequently phosphorylates SMAD1/5/8 proteins that transduce the signal (PubMed:9748228). 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 (PubMed:17911401). Besides canonical SMAD signaling, can activate non-canonical pathways such as p38 mitogen-activated protein kinases/MAPKs (By similarity). {ECO:0000250\|UniProtKB:P15261, ECO:0000269\|PubMed:17911401, ECO:0000269\|PubMed:20628059, ECO:0000269\|PubMed:22977237, ECO:0000269\|PubMed:25354296, ECO:0000269\|PubMed:9748228}.


Catalytic activity:		Reaction=ATP + L-threonyl-[receptor-protein] = ADP + H(+) + O-phospho- L-threonyl-[receptor-protein]; Xref=Rhea:RHEA:44880, Rhea:RHEA- COMP:11024, Rhea:RHEA-COMP:11025, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.30;
Catalytic activity:		Reaction=ATP + L-seryl-[receptor-protein] = ADP + H(+) + O-phospho-L- seryl-[receptor-protein]; Xref=Rhea:RHEA:18673, Rhea:RHEA-COMP:11022, Rhea:RHEA-COMP:11023, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.30; Evidence={ECO:0000269\|PubMed:9748228};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
Subunit:		Interacts with FKBP1A (PubMed:22484487, Ref.12). Interacts with FCHO1 (PubMed:22484487). Interacts with CLU (PubMed:8555189). Interacts with type II receptors AMHR2 and ACVR2A (PubMed:17911401). Interacts with BMP7 (PubMed:9748228). Interacts with GDF2/BMP9 (PubMed:20628059). Interacts with BMP6 (PubMed:18070108). {ECO:0000269\|PubMed:17911401, ECO:0000269\|PubMed:18070108, ECO:0000269\|PubMed:20628059, ECO:0000269\|PubMed:22484487, ECO:0000269\|PubMed:8555189, ECO:0000269\|PubMed:9748228, ECO:0000269\|Ref.12}.
Subcellular location:		Membrane; Single-pass type I membrane protein.
Tissue specificity:		Expressed in normal parenchymal cells, endothelial cells, fibroblasts and tumor-derived epithelial cells. {ECO:0000269\|PubMed:8389764}.
Disease:		Fibrodysplasia ossificans progressiva (FOP) [MIM:135100]: A rare autosomal dominant connective tissue disorder resulting in skeletal malformations and progressive extraskeletal ossification. Heterotopic ossification begins in childhood and can be induced by trauma or may occur without warning. Bone formation is episodic and progressive, leading to a debilitating ankylosis of all major joints of the axial and appendicular skeleton, rendering movement impossible. {ECO:0000269\|PubMed:16642017, ECO:0000269\|PubMed:19085907, ECO:0000269\|PubMed:19330033}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. {ECO:0000305}.