UniProt functional annotation for Q9UK05



	UniProt functional annotation for Q9UK05

UniProt code: Q9UK05.

Organism: Homo sapiens (Human).

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

Function: Potent circulating inhibitor of angiogenesis. Signals through the type I activin receptor ACVRL1 but not other Alks. Signaling through SMAD1 in endothelial cells requires TGF-beta coreceptor endoglin/ENG. {ECO:0000269|PubMed:18309101, ECO:0000269|PubMed:21710321, ECO:0000269|PubMed:22799562, ECO:0000269|PubMed:23300529, ECO:0000269|PubMed:25237187}.

Subunit: Homodimer; disulfide-linked (PubMed:25237187, PubMed:28564608). Detected in extracellular fluid as mature homodimer, and in complex with its propeptide (PubMed:21710321, PubMed:25237187). Interacts with ACVRL1, BMPR2 and ACVR2B with high affinity (in vitro) (PubMed:22799562, PubMed:22347366, PubMed:25237187, PubMed:25751889). Identified in a complex with ACVRL1 and ACVR2B (PubMed:22718755). Has ten times lower affinity for ACVR2A (in vitro) (PubMed:25751889). Interacts with ENG, forming a heterotetramer with a 2:2 stoichiometry (PubMed:21737454, PubMed:28564608). Can form a heteromeric complex with ENG and ACVRL1 (PubMed:28564608). Interacts with type I receptor ACVR1 (PubMed:20628059). {ECO:0000269|PubMed:15851468, ECO:0000269|PubMed:20628059, ECO:0000269|PubMed:21710321, ECO:0000269|PubMed:21737454, ECO:0000269|PubMed:22347366, ECO:0000269|PubMed:22718755, ECO:0000269|PubMed:22799562, ECO:0000269|PubMed:25751889, ECO:0000269|PubMed:28564608}.

Subcellular location: Secreted {ECO:0000269|PubMed:18309101, ECO:0000269|PubMed:21710321, ECO:0000269|PubMed:25237187}.

Tissue specificity: Detected in blood plasma (at protein level). {ECO:0000269|PubMed:21710321}.

Ptm: A reversible disulfide bond can be formed between the two subunits in the homodimer; this has no effect on GDF2 activity. {ECO:0000269|PubMed:25237187}.

Disease: Telangiectasia, hereditary hemorrhagic, 5 (HHT5) [MIM:615506]: A multisystemic vascular dysplasia leading to dilation of permanent blood vessels and arteriovenous malformations of skin, mucosa, and viscera. The disease is characterized by recurrent epistaxis and gastro-intestinal hemorrhage. Visceral involvement includes arteriovenous malformations of the lung, liver, and brain. {ECO:0000269|PubMed:23972370}. Note=The disease is caused by variants affecting the gene represented in this entry.

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:		Potent circulating inhibitor of angiogenesis. Signals through the type I activin receptor ACVRL1 but not other Alks. Signaling through SMAD1 in endothelial cells requires TGF-beta coreceptor endoglin/ENG. {ECO:0000269\|PubMed:18309101, ECO:0000269\|PubMed:21710321, ECO:0000269\|PubMed:22799562, ECO:0000269\|PubMed:23300529, ECO:0000269\|PubMed:25237187}.


Subunit:		Homodimer; disulfide-linked (PubMed:25237187, PubMed:28564608). Detected in extracellular fluid as mature homodimer, and in complex with its propeptide (PubMed:21710321, PubMed:25237187). Interacts with ACVRL1, BMPR2 and ACVR2B with high affinity (in vitro) (PubMed:22799562, PubMed:22347366, PubMed:25237187, PubMed:25751889). Identified in a complex with ACVRL1 and ACVR2B (PubMed:22718755). Has ten times lower affinity for ACVR2A (in vitro) (PubMed:25751889). Interacts with ENG, forming a heterotetramer with a 2:2 stoichiometry (PubMed:21737454, PubMed:28564608). Can form a heteromeric complex with ENG and ACVRL1 (PubMed:28564608). Interacts with type I receptor ACVR1 (PubMed:20628059). {ECO:0000269\|PubMed:15851468, ECO:0000269\|PubMed:20628059, ECO:0000269\|PubMed:21710321, ECO:0000269\|PubMed:21737454, ECO:0000269\|PubMed:22347366, ECO:0000269\|PubMed:22718755, ECO:0000269\|PubMed:22799562, ECO:0000269\|PubMed:25751889, ECO:0000269\|PubMed:28564608}.
Subcellular location:		Secreted {ECO:0000269\|PubMed:18309101, ECO:0000269\|PubMed:21710321, ECO:0000269\|PubMed:25237187}.
Tissue specificity:		Detected in blood plasma (at protein level). {ECO:0000269\|PubMed:21710321}.
Ptm:		A reversible disulfide bond can be formed between the two subunits in the homodimer; this has no effect on GDF2 activity. {ECO:0000269\|PubMed:25237187}.
Disease:		Telangiectasia, hereditary hemorrhagic, 5 (HHT5) [MIM:615506]: A multisystemic vascular dysplasia leading to dilation of permanent blood vessels and arteriovenous malformations of skin, mucosa, and viscera. The disease is characterized by recurrent epistaxis and gastro-intestinal hemorrhage. Visceral involvement includes arteriovenous malformations of the lung, liver, and brain. {ECO:0000269\|PubMed:23972370}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the TGF-beta family. {ECO:0000305}.