UniProt functional annotation for P18075



	UniProt functional annotation for P18075

UniProt code: P18075.

Organism: Homo sapiens (Human).

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

Function: Growth factor of the TGF-beta superfamily that plays important role in various biological processes, including embryogenesis, hematopoiesis, neurogenesis and skeletal morphogenesis (PubMed:31208997). Initiates the canonical BMP signaling cascade by associating with type I receptor ACVR1 and type II receptor ACVR2A (PubMed:9748228, PubMed:12667445). Once all three components are bound together in a complex at the cell surface, ACVR2A phosphorylates and activates ACVR1. In turn, ACVR1 propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes (PubMed:12478285). For specific functions such as growth cone collapse in developing spinal neurons and chemotaxis of monocytes, uses also BMPR2 as type II receptor (PubMed:31208997). Can also signal through non-canonical pathways such as P38 MAP kinase signaling cascade that promotes brown adipocyte differentiation through activation of target genes, including members of the SOX family of transcription factors (PubMed:27923061). {ECO:0000269|PubMed:12478285, ECO:0000269|PubMed:12667445, ECO:0000269|PubMed:27923061, ECO:0000269|PubMed:31208997, ECO:0000269|PubMed:9748228}.

Subunit: Homodimer; disulfide-linked. Interacts with SOSTDC1 (PubMed:15020244). Interacts with TWSG1 (By similarity). Interacts with FBN1 (via N-terminal domain) and FBN2 (PubMed:18339631). Interacts with type I receptor ACVR1 (PubMed:9748228). Interacts with type II receptor ACVR2A (PubMed:12667445). Interacts with NOG; this interaction inhibits canonical BMP signaling (PubMed:12478285). {ECO:0000250|UniProtKB:P23359, ECO:0000269|PubMed:12478285, ECO:0000269|PubMed:12667445, ECO:0000269|PubMed:18339631, ECO:0000269|PubMed:9748228}.

Subcellular location: Secreted.

Tissue specificity: Expressed in the kidney and bladder. Lower levels seen in the brain.

Developmental stage: Expressed in the developing eye, brain and ear during embryogenesis. {ECO:0000269|PubMed:20506283}.

Ptm: Several N-termini starting at positions 293, 300, 315 and 316 have been identified by direct sequencing resulting in secretion of different mature forms. {ECO:0000269|PubMed:17977014}.

Pharmaceutical: Available under the name Osigraft (Stryker). Its use is indicated in the treatment of tibial non-union of at least 9 months duration, secondary to trauma, in skeletally mature patients, in cases where autograft has failed or is unfeasible.

Similarity: Belongs to the TGF-beta family. {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:		Growth factor of the TGF-beta superfamily that plays important role in various biological processes, including embryogenesis, hematopoiesis, neurogenesis and skeletal morphogenesis (PubMed:31208997). Initiates the canonical BMP signaling cascade by associating with type I receptor ACVR1 and type II receptor ACVR2A (PubMed:9748228, PubMed:12667445). Once all three components are bound together in a complex at the cell surface, ACVR2A phosphorylates and activates ACVR1. In turn, ACVR1 propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes (PubMed:12478285). For specific functions such as growth cone collapse in developing spinal neurons and chemotaxis of monocytes, uses also BMPR2 as type II receptor (PubMed:31208997). Can also signal through non-canonical pathways such as P38 MAP kinase signaling cascade that promotes brown adipocyte differentiation through activation of target genes, including members of the SOX family of transcription factors (PubMed:27923061). {ECO:0000269\|PubMed:12478285, ECO:0000269\|PubMed:12667445, ECO:0000269\|PubMed:27923061, ECO:0000269\|PubMed:31208997, ECO:0000269\|PubMed:9748228}.


Subunit:		Homodimer; disulfide-linked. Interacts with SOSTDC1 (PubMed:15020244). Interacts with TWSG1 (By similarity). Interacts with FBN1 (via N-terminal domain) and FBN2 (PubMed:18339631). Interacts with type I receptor ACVR1 (PubMed:9748228). Interacts with type II receptor ACVR2A (PubMed:12667445). Interacts with NOG; this interaction inhibits canonical BMP signaling (PubMed:12478285). {ECO:0000250\|UniProtKB:P23359, ECO:0000269\|PubMed:12478285, ECO:0000269\|PubMed:12667445, ECO:0000269\|PubMed:18339631, ECO:0000269\|PubMed:9748228}.
Subcellular location:		Secreted.
Tissue specificity:		Expressed in the kidney and bladder. Lower levels seen in the brain.
Developmental stage:		Expressed in the developing eye, brain and ear during embryogenesis. {ECO:0000269\|PubMed:20506283}.
Ptm:		Several N-termini starting at positions 293, 300, 315 and 316 have been identified by direct sequencing resulting in secretion of different mature forms. {ECO:0000269\|PubMed:17977014}.
Pharmaceutical:		Available under the name Osigraft (Stryker). Its use is indicated in the treatment of tibial non-union of at least 9 months duration, secondary to trauma, in skeletally mature patients, in cases where autograft has failed or is unfeasible.
Similarity:		Belongs to the TGF-beta family. {ECO:0000305}.