UniProt functional annotation for Q8BLU0



	UniProt functional annotation for Q8BLU0

UniProt code: Q8BLU0.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Functions in cell-cell adhesion, cell migration and axon guidance. Mediates cell-cell adhesion via its interactions with ADGRL3 and probably also other latrophilins that are expressed at the surface of adjacent cells (PubMed:21350012, PubMed:25728924 PubMed:25374360). May play a role in the migration of cortical neurons during brain development via its interaction with UNC5D (PubMed:21673655). Mediates axon growth cone collapse and plays a repulsive role in neuron guidance via its interaction with UNC5D, and possibly also other UNC-5 family members (PubMed:21673655, PubMed:25728924). Plays a role in fibroblast growth factor-mediated signaling cascades (PubMed:16872596). Required for normal organization of the cardiac basement membrane during embryogenesis, and for normal embryonic epicardium and heart morphogenesis (PubMed:21350012). {ECO:0000269|PubMed:16872596, ECO:0000269|PubMed:21350012, ECO:0000269|PubMed:21673655, ECO:0000269|PubMed:25374360, ECO:0000269|PubMed:25728924}.

Subunit: Self-associates (via leucine-rich repeats), giving rise to homooligomers (PubMed:25374360). Interacts with FGFR1 (PubMed:16872596). Interacts with FGFR2 (PubMed:21765038). Interacts (via extracellular domain) with ADGRL1/LPHN1 (PubMed:22405201). Interacts (via extracellular domain) with ADGRL3 (via olfactomedin-like domain)(PubMed:22405201, PubMed:25728924). Interacts (via extracellular domain) with UNC5D (via the first Ig-like domain) (PubMed:21673655, PubMed:25374360). Can also interact (via extracellular domain) with UNC5B, but with much lower affinity (PubMed:21673655). Interacts (via extracellular domain) with FN1 (PubMed:24585683). {ECO:0000269|PubMed:16872596, ECO:0000269|PubMed:21673655, ECO:0000269|PubMed:21765038, ECO:0000269|PubMed:22405201, ECO:0000269|PubMed:24585683, ECO:0000269|PubMed:25374360, ECO:0000269|PubMed:25728924}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:16872596, ECO:0000269|PubMed:22405201, ECO:0000269|PubMed:24585683, ECO:0000269|PubMed:25374360}; Single-pass membrane protein {ECO:0000305}. Endoplasmic reticulum membrane {ECO:0000305|PubMed:16872596, ECO:0000305|PubMed:24585683}. Cell junction, focal adhesion {ECO:0000269|PubMed:16872596}. Secreted, extracellular space, extracellular matrix {ECO:0000269|PubMed:24585683}. Cell junction, synapse, synaptosome {ECO:0000250|UniProtKB:D3ZTV3}. Microsome membrane {ECO:0000269|PubMed:24585683}. Secreted {ECO:0000269|PubMed:21673655}. Note=Proteolytic cleavage gives rise to a shedded ectodomain. {ECO:0000269|PubMed:21673655}.

Tissue specificity: Detected in adult brain (at protein level). {ECO:0000269|PubMed:21350012}.

Developmental stage: Detected in embryonic brain at 13 dpc. Levels in brain decrease gradually after 15 dpc, but expression continues after birth (PubMed:21673655). Detected in embryonic myocardium, body wall and pro-epicardial organ at 9.5 dpc. Detected in the epicardial cell layer and throughout the myocardium at 10.5 dpc. Highly expressed in embryonic and neonate heart, but after that levels decrease strongly, and the protein is barely detectable 3 weeks after birth, with even lower levels after 7 and 15 weeks (at protein level) (PubMed:21350012). Detected in the anterior endoderm at 7.5 dpc. Detected on anterior somites, the allantois and mesenchymal tissue behind the developing heart at 8.5 dpc (PubMed:18448090). Detected in the cephalic mesenchyme and in tissue posterior to the developing heart at 9.5 and 10.5 dpc. Detected in the developing stomach and in a subset of the trunk sclerotome at 10.5 dpc. At 11 dpc, detected also in branchial arches, eyes and limbs (PubMed:16872596, PubMed:18448090). {ECO:0000269|PubMed:16872596, ECO:0000269|PubMed:18448090, ECO:0000269|PubMed:21350012, ECO:0000269|PubMed:21673655}.

Induction: Up-regulated by FGF2. {ECO:0000269|PubMed:16872596}.

Ptm: N-glycosylated. {ECO:0000269|PubMed:16872596, ECO:0000269|PubMed:21673655}.

Ptm: Proteolytic cleavage in the juxtamembrane region gives rise to a soluble ectodomain. Cleavage is probably effected by a metalloprotease. {ECO:0000269|PubMed:21673655}.

Disruption phenotype: Heterozygous mice are viable and fertile, but homozygous mice display nearly complete embryonic lethality. Most embryos die at about 12.5 dpc, probably due to impaired expansion of the ventricular myocardium during development, reduced endocardial volume and heart insufficiency. Contrary to wild-type, the epicardium appears ruffled and presents numerous holes, due to defective formation of cell-cell adhesions. Still, there is a very small percentage of life-born pups that survive at least up to weaning. {ECO:0000269|PubMed:21350012}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Functions in cell-cell adhesion, cell migration and axon guidance. Mediates cell-cell adhesion via its interactions with ADGRL3 and probably also other latrophilins that are expressed at the surface of adjacent cells (PubMed:21350012, PubMed:25728924 PubMed:25374360). May play a role in the migration of cortical neurons during brain development via its interaction with UNC5D (PubMed:21673655). Mediates axon growth cone collapse and plays a repulsive role in neuron guidance via its interaction with UNC5D, and possibly also other UNC-5 family members (PubMed:21673655, PubMed:25728924). Plays a role in fibroblast growth factor-mediated signaling cascades (PubMed:16872596). Required for normal organization of the cardiac basement membrane during embryogenesis, and for normal embryonic epicardium and heart morphogenesis (PubMed:21350012). {ECO:0000269\|PubMed:16872596, ECO:0000269\|PubMed:21350012, ECO:0000269\|PubMed:21673655, ECO:0000269\|PubMed:25374360, ECO:0000269\|PubMed:25728924}.


Subunit:		Self-associates (via leucine-rich repeats), giving rise to homooligomers (PubMed:25374360). Interacts with FGFR1 (PubMed:16872596). Interacts with FGFR2 (PubMed:21765038). Interacts (via extracellular domain) with ADGRL1/LPHN1 (PubMed:22405201). Interacts (via extracellular domain) with ADGRL3 (via olfactomedin-like domain)(PubMed:22405201, PubMed:25728924). Interacts (via extracellular domain) with UNC5D (via the first Ig-like domain) (PubMed:21673655, PubMed:25374360). Can also interact (via extracellular domain) with UNC5B, but with much lower affinity (PubMed:21673655). Interacts (via extracellular domain) with FN1 (PubMed:24585683). {ECO:0000269\|PubMed:16872596, ECO:0000269\|PubMed:21673655, ECO:0000269\|PubMed:21765038, ECO:0000269\|PubMed:22405201, ECO:0000269\|PubMed:24585683, ECO:0000269\|PubMed:25374360, ECO:0000269\|PubMed:25728924}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:16872596, ECO:0000269\|PubMed:22405201, ECO:0000269\|PubMed:24585683, ECO:0000269\|PubMed:25374360}; Single-pass membrane protein {ECO:0000305}. Endoplasmic reticulum membrane {ECO:0000305\|PubMed:16872596, ECO:0000305\|PubMed:24585683}. Cell junction, focal adhesion {ECO:0000269\|PubMed:16872596}. Secreted, extracellular space, extracellular matrix {ECO:0000269\|PubMed:24585683}. Cell junction, synapse, synaptosome {ECO:0000250\|UniProtKB:D3ZTV3}. Microsome membrane {ECO:0000269\|PubMed:24585683}. Secreted {ECO:0000269\|PubMed:21673655}. Note=Proteolytic cleavage gives rise to a shedded ectodomain. {ECO:0000269\|PubMed:21673655}.
Tissue specificity:		Detected in adult brain (at protein level). {ECO:0000269\|PubMed:21350012}.
Developmental stage:		Detected in embryonic brain at 13 dpc. Levels in brain decrease gradually after 15 dpc, but expression continues after birth (PubMed:21673655). Detected in embryonic myocardium, body wall and pro-epicardial organ at 9.5 dpc. Detected in the epicardial cell layer and throughout the myocardium at 10.5 dpc. Highly expressed in embryonic and neonate heart, but after that levels decrease strongly, and the protein is barely detectable 3 weeks after birth, with even lower levels after 7 and 15 weeks (at protein level) (PubMed:21350012). Detected in the anterior endoderm at 7.5 dpc. Detected on anterior somites, the allantois and mesenchymal tissue behind the developing heart at 8.5 dpc (PubMed:18448090). Detected in the cephalic mesenchyme and in tissue posterior to the developing heart at 9.5 and 10.5 dpc. Detected in the developing stomach and in a subset of the trunk sclerotome at 10.5 dpc. At 11 dpc, detected also in branchial arches, eyes and limbs (PubMed:16872596, PubMed:18448090). {ECO:0000269\|PubMed:16872596, ECO:0000269\|PubMed:18448090, ECO:0000269\|PubMed:21350012, ECO:0000269\|PubMed:21673655}.
Induction:		Up-regulated by FGF2. {ECO:0000269\|PubMed:16872596}.
Ptm:		N-glycosylated. {ECO:0000269\|PubMed:16872596, ECO:0000269\|PubMed:21673655}.
Ptm:		Proteolytic cleavage in the juxtamembrane region gives rise to a soluble ectodomain. Cleavage is probably effected by a metalloprotease. {ECO:0000269\|PubMed:21673655}.
Disruption phenotype:		Heterozygous mice are viable and fertile, but homozygous mice display nearly complete embryonic lethality. Most embryos die at about 12.5 dpc, probably due to impaired expansion of the ventricular myocardium during development, reduced endocardial volume and heart insufficiency. Contrary to wild-type, the epicardium appears ruffled and presents numerous holes, due to defective formation of cell-cell adhesions. Still, there is a very small percentage of life-born pups that survive at least up to weaning. {ECO:0000269\|PubMed:21350012}.