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FLASH GENE

Symbol

FLRT3

contributors: mct - updated : 04-10-2022

HGNC name	fibronectin leucine rich transmembrane protein 3
HGNC id	3762

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	HH21 hypogonadotropic hypogonadism 21 with anosmia
Location	20p12.1      Physical location : 14.304.639 - 14.318.313
Synonym symbol(s)	KIAA1469

DNA

TYPE	functioning gene
STRUCTURE	14.63 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_013281 2 - 3830 NP_037413 - 649 - 1999 10644439 NM_198391 3 - 4024 NP_938205 - 649 - 1999 10644439

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Endocrine parathyroid       highly Hearing/Equilibrium ear       highly Nervous brain basal nuclei         brain hindbrain cerebellum       brain limbic system hippocampus     Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, pregnancy

Text	placenta
	widely expressed in the developing embryo, particularly highly expressed initially in the midbrain, and later expressed in the developing pharyngeal region

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	ten leucine rich repeats flanked by N and C terminal cysteine rich regions
	two fibronectin-collagen-like domains
	a transmembrane segment (TM1) and an intracellular tail

conjugated

GlycoP

HOMOLOGY

intraspecies	homolog to ECM small leucine-rich proteoglycans
	paralog to FLRT1
	paralog to FLRT2

Homologene

FAMILY

fibronectin leucine rich transmembrane protein (FLRT) family

CATEGORY

adhesion , receptor membrane

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic
text	type I membrane protein

basic FUNCTION	functioning in cell adhesion and/or receptor signaling
	may contribute to regeneration following axonal injury
	putative cell surface receptor implicated in both the development of the nervous system and in the regeneration of the peripheral nervous system (PNS)
	FLRT1, FLRT2, FLRT3 have a dual role, promoting FGF signalling and modulating homotypic cell adhesion
	FLRT proteins act potentially as regulators of FGF signalling, being induced by the signal and then able to interact with the signalling receptor, in many tissues
	important roles for FLRT2 and FLRT3 in mediating events such as neural crest cell migration, chondrogenesis and epithelial-mesenchymal interactions during craniofacial development
	having dual properties as regulators of cell adhesion and potentiators of fibroblast growth factor (FGF) mediated signalling
	FLRT2 or FLRT3 are potentially required in the epicardium to promote heart morphogenesis
	axon guidance-related factor connected to the regulation of neuronal cell outgrowth and morphogenesis
	bifunctional role of FLRT3 in repulsive vs. adhesive cell signaling has been already detected during embryogenesis and neuronal growth, and depends on its interactions either with UNC5B or another FLRT3 expressed by adjacent cells
	is a modulator of neurite outgrowth, axon pathfinding, and cell adhesion, which is upregulated in the dorsal horn following peripheral nerve injury
	FLRT2, FLRT3 are required for the proper distribution of interneurons within the cortical migratory streams and for the final laminar allocation in the postnatal cortex
	neuropathic pain induction is a novel function of FLRT3

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

vitamin

signaling

signal transduction

a component	constituent of extracellular membrane
	PCDH8 and FLRT3 form a functional complex with cadherins

INTERACTION

DNA

RNA

small molecule

protein	interacting with PCDH8 (functions as a molecular "governor" to maintain FLRT3 activity at the optimal level for physiological regulation of C-cadherin adhesion, cell sorting, and morphogenesis)
	UNC5B was recently shown to bind FLRT3
	BMP signal can down-regulate FGF pathway via inhibition of FLRT3 expression for anterior neural formation
	UNC5A, UNC5B, UNC5C, UNC5D and ADGRL3 can simultaneously bind to FLRT3, forming a trimeric complex, and FLRT3 may form transsynaptic complexes with both ADGRL3 and UNC5
	ADGRL3 regulate excitatory synapse number through trans interactions with fibronectin leucine-rich repeat transmembrane 3 (FLRT3)
	TBX2, which is a target gene of BMP signal, down-regulates FGF8 signaling by inhibiting the expression of FLRT3, a positive regulator of this pathway

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

HH21

Susceptibility

to congenital Hypogonadotropic Hypogonadism

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS