UniProt functional annotation for Q9NZU0



	UniProt functional annotation for Q9NZU0

UniProt code: Q9NZU0.

Organism: Homo sapiens (Human).

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

Function: Functions in cell-cell adhesion, cell migration and axon guidance, exerting an attractive or repulsive role depending on its interaction partners. Plays a role in the spatial organization of brain neurons. Plays a role in vascular development in the retina (By similarity). Plays a role in cell-cell adhesion via its interaction with ADGRL3 and probably also other latrophilins that are expressed at the surface of adjacent cells (PubMed:26235030). Interaction with the intracellular domain of ROBO1 mediates axon attraction towards cells expressing NTN1. Mediates axon growth cone collapse and plays a repulsive role in neuron guidance via its interaction with UNC5B, and possibly also other UNC-5 family members (By similarity). Promotes neurite outgrowth (in vitro) (PubMed:14706654). Mediates cell-cell contacts that promote an increase both in neurite number and in neurite length. Plays a role in the regulation of the density of glutamaergic synapses. Plays a role in fibroblast growth factor-mediated signaling cascades. Required for normal morphogenesis during embryonic development, but not for normal embryonic patterning. Required for normal ventral closure, headfold fusion and definitive endoderm migration during embryonic development. Required for the formation of a normal basement membrane and the maintenance of a normal anterior visceral endoderm during embryonic development (By similarity). {ECO:0000250|UniProtKB:B1H234, ECO:0000250|UniProtKB:Q8BGT1, ECO:0000269|PubMed:14706654, ECO:0000269|PubMed:26235030}.

Subunit: Monomer and homodimer. Self-associates (via leucine-rich repeats), giving rise to homooligomers (PubMed:26235030). Interacts with FGFR1. Interacts (via extracellular domain) with ADGRL1/LPHN1 and LPHN2 (via olfactomedin-like domain) (By similarity). Interacts (via extracellular domain) with ADGRL3 (via olfactomedin-like domain); the interaction is direct (PubMed:26235030). Interacts (via extracellular domain) with UNC5B and UNC5D (via extracellular domain); the interaction is direct (PubMed:26235030). Identified in complexes composed of FLRT3, ADGRL3 and UNC5B, respectively FLRT3, ADGRL3 and UNC5D (PubMed:26235030). May also interact (via extracellular domain) with UNC5A and UNC5C. Interacts (via cytoplasmic domain) with ROBO1 (By similarity). {ECO:0000250|UniProtKB:Q8BGT1, ECO:0000269|PubMed:26235030}.

Subcellular location: Cell membrane {ECO:0000250|UniProtKB:Q8BGT1}; Single-pass membrane protein {ECO:0000250|UniProtKB:Q8BGT1}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q8BGT1}. Cell junction, focal adhesion {ECO:0000250|UniProtKB:Q8BGT1}. Secreted {ECO:0000250|UniProtKB:Q8BGT1}. Cell projection, axon {ECO:0000250|UniProtKB:Q8BGT1}. Cell projection, growth cone membrane {ECO:0000250|UniProtKB:Q8BGT1}. Note=Detected on dendritic punctae that colocalize in part with glutamaergic synapses, but not with GABAergic synapses. Proteolytic cleavage in the juxtamembrane region gives rise to a shedded ectodomain. {ECO:0000250|UniProtKB:B1H234, ECO:0000250|UniProtKB:Q8BGT1}.

Tissue specificity: Expressed in kidney, brain, pancreas, skeletal muscle, lung, liver, placenta, and heart. {ECO:0000269|PubMed:10644439}.

Ptm: N-glycosylated. {ECO:0000250|UniProtKB:Q8BGT1}.

Ptm: Proteolytic cleavage in the juxtamembrane region gives rise to a soluble ectodomain. Cleavage is probably effected by a metalloprotease. {ECO:0000250|UniProtKB:Q8BGT1}.

Disease: Hypogonadotropic hypogonadism 21 with or without anosmia (HH21) [MIM:615271]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin- releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). {ECO:0000269|PubMed:23643382}. Note=The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in FLRT3 also have a mutation in another HH-associated gene including FGFR1, HS6ST1 and FGF17 (PubMed:23643382). {ECO:0000269|PubMed:23643382}.

Sequence caution: Sequence=BAA95993.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAB55282.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAB55303.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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:		Functions in cell-cell adhesion, cell migration and axon guidance, exerting an attractive or repulsive role depending on its interaction partners. Plays a role in the spatial organization of brain neurons. Plays a role in vascular development in the retina (By similarity). Plays a role in cell-cell adhesion via its interaction with ADGRL3 and probably also other latrophilins that are expressed at the surface of adjacent cells (PubMed:26235030). Interaction with the intracellular domain of ROBO1 mediates axon attraction towards cells expressing NTN1. Mediates axon growth cone collapse and plays a repulsive role in neuron guidance via its interaction with UNC5B, and possibly also other UNC-5 family members (By similarity). Promotes neurite outgrowth (in vitro) (PubMed:14706654). Mediates cell-cell contacts that promote an increase both in neurite number and in neurite length. Plays a role in the regulation of the density of glutamaergic synapses. Plays a role in fibroblast growth factor-mediated signaling cascades. Required for normal morphogenesis during embryonic development, but not for normal embryonic patterning. Required for normal ventral closure, headfold fusion and definitive endoderm migration during embryonic development. Required for the formation of a normal basement membrane and the maintenance of a normal anterior visceral endoderm during embryonic development (By similarity). {ECO:0000250\|UniProtKB:B1H234, ECO:0000250\|UniProtKB:Q8BGT1, ECO:0000269\|PubMed:14706654, ECO:0000269\|PubMed:26235030}.


Subunit:		Monomer and homodimer. Self-associates (via leucine-rich repeats), giving rise to homooligomers (PubMed:26235030). Interacts with FGFR1. Interacts (via extracellular domain) with ADGRL1/LPHN1 and LPHN2 (via olfactomedin-like domain) (By similarity). Interacts (via extracellular domain) with ADGRL3 (via olfactomedin-like domain); the interaction is direct (PubMed:26235030). Interacts (via extracellular domain) with UNC5B and UNC5D (via extracellular domain); the interaction is direct (PubMed:26235030). Identified in complexes composed of FLRT3, ADGRL3 and UNC5B, respectively FLRT3, ADGRL3 and UNC5D (PubMed:26235030). May also interact (via extracellular domain) with UNC5A and UNC5C. Interacts (via cytoplasmic domain) with ROBO1 (By similarity). {ECO:0000250\|UniProtKB:Q8BGT1, ECO:0000269\|PubMed:26235030}.
Subcellular location:		Cell membrane {ECO:0000250\|UniProtKB:Q8BGT1}; Single-pass membrane protein {ECO:0000250\|UniProtKB:Q8BGT1}. Endoplasmic reticulum membrane {ECO:0000250\|UniProtKB:Q8BGT1}. Cell junction, focal adhesion {ECO:0000250\|UniProtKB:Q8BGT1}. Secreted {ECO:0000250\|UniProtKB:Q8BGT1}. Cell projection, axon {ECO:0000250\|UniProtKB:Q8BGT1}. Cell projection, growth cone membrane {ECO:0000250\|UniProtKB:Q8BGT1}. Note=Detected on dendritic punctae that colocalize in part with glutamaergic synapses, but not with GABAergic synapses. Proteolytic cleavage in the juxtamembrane region gives rise to a shedded ectodomain. {ECO:0000250\|UniProtKB:B1H234, ECO:0000250\|UniProtKB:Q8BGT1}.
Tissue specificity:		Expressed in kidney, brain, pancreas, skeletal muscle, lung, liver, placenta, and heart. {ECO:0000269\|PubMed:10644439}.
Ptm:		N-glycosylated. {ECO:0000250\|UniProtKB:Q8BGT1}.
Ptm:		Proteolytic cleavage in the juxtamembrane region gives rise to a soluble ectodomain. Cleavage is probably effected by a metalloprotease. {ECO:0000250\|UniProtKB:Q8BGT1}.
Disease:		Hypogonadotropic hypogonadism 21 with or without anosmia (HH21) [MIM:615271]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin- releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). {ECO:0000269\|PubMed:23643382}. Note=The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in FLRT3 also have a mutation in another HH-associated gene including FGFR1, HS6ST1 and FGF17 (PubMed:23643382). {ECO:0000269\|PubMed:23643382}.
Sequence caution:		Sequence=BAA95993.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAB55282.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAB55303.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};