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FLASH GENE

Symbol

UNC119

contributors: mct/shn - updated : 31-08-2017

HGNC name	unc-119 homolog (C. elegans)
HGNC id	12565

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	IMD13 Immunodeficiency 13
Location	17q11.2      Physical location : 26.873.724 - 26.879.646
Synonym name	unc119 (C.elegans) homolog
	retinal protein 4
	POC7 centriolar protein homolog A (Chlamydomonas)
	POC7 centriolar protein homolog A
	protein unc-119 homolog A
Synonym symbol(s)	HRG4, RG4, POC7, POC7A, MRG4, UNC119a

DNA

TYPE	functioning gene
SPECIAL FEATURE	arranged in tandem
STRUCTURE	5.92 kb     5 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence

scaffold attachement regions/matrix attachement regions

MAPPING

cloned

Y

linked

status

confirmed

Map	cen - D17S1824 - D17S935 - UNC119 - D17S925 - D17S1873 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005148 5 splicing 1398 NP_005139 27 240 - 2003 12496276 NM_054035 4 splicing 1665 NP_473376 - 220 - 2003 12496276 NM_001330166 - - 1461 NP_001317095 - 145 - 2003 12496276

EXPRESSION

Type	restricted

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 Endocrine adrenal gland       lowly Homo sapiens Nervous brain hindbrain cerebellum   lowly Homo sapiens Urinary kidney       lowly Homo sapiens Visual eye retina     specific Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Visual cone photoreceptor Homo sapiens Visual rod photoreceptor Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text

retina

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	rich in glycine and proline and in its proximal part
	C-terminal domain of UNC119 sharing significant sequence and structural homology with PDE6D

HOMOLOGY

interspecies	homolog to C.elegans Unc119
	ortholog to Unc119, Mus musculus
	ortholog to Unc119, Rattus norvegicus
	ortholog to UNC119, pan troglodytes

intraspecies

paralog to PDE6D

Homologene

FAMILY

PDE6D/UNC119 family

CATEGORY

adaptor , receptor

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
text	expressed at high levels in photoreceptor ribbon synapses
	CABP4 and UNC119 colocalized in the photoreceptor synapse of adult retina and during postnatal retinal development
	localizes to the centrosome in interphase cells and begins to translocate from the spindle pole to the spindle midzone after the onset of mitosis

basic FUNCTION	receptor-associated activator of Src family tyrosine kinases
	involved in the mechanism of photoreceptor neurotransmitter release through the synaptic vesicle cycle
	role for UNC119 and CABP4 in neurotransmitter release and in the maintenance of the photoreceptor synapse
	essential for vision and synaptic transmission at photoreceptor ribbon synapses
	regulates myofibroblast differentiation through the activation of FYN and the MAPK14 pathway
	orchestrates the recruitment of the actin-based motor protein, myosin 5B, and the organization of multiprotein complexes on endosomes
	UNC119-regulated pathway is essential for immunological synapse formation and T cell activation
	adaptor protein that is involved in the development of the vertebrate nervous system
	role in clathrin- and caveolae-based endocytosis as well as macropinocytosis
	regulates various endocytic pathways through dynamin and sets a threshold point for vesicular trafficking
	playing an important role in fibrotic processes through myofibroblast differentiation
	adapter signaling molecule, which regulates activation of tyrosine kinases in T cells, eosinophils and fibroblasts
	activates the Src family and inhibits the Abl family of tyrosine kinases
	essential for transducin transport in darkness
	a G-alpha subunit cofactor essential for G protein trafficking in sensory cilia
	may play conserved inhibitory role in regulation of GPCR-G protein signaling in non-visual tissues
	in addition to transducin trafficking, may play important roles in regulation of vesicle and ciliary trafficking processes in photoreceptor cells
	apart from its role as a cofactor of G-protein trafficking in ciliary sensory cells, may modulate signal transduction from GPCRs to G proteins in different cell types and tissues
	UNC119/HRG4 is responsible for ciliary delivery of myristoylated cargo
	promotes cell proliferation and growth through Wnt/CTNNB1 signaling
	solubilising factor UNC119 sequesters myristoylated Src family protein tyrosine kinases (SFKs) to maintain its enrichment at the plasma membrane to enable signal transduction

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

text	may play an important role in vision

PATHWAY

metabolism

signaling

neurotransmission

synaptic transmission

a component

synaptic ribbon-associated component

INTERACTION

DNA

RNA

small molecule

protein	IL-5Ralpha and Src family tyrosine kinases
	ADP-ribosylation factor-like protein 2, ARL2
	interaction of CABP4 with UNC119
	CTBP2-interacting protein at photoreceptor ribbon synapses (can be recruited to synaptic ribbons via its interaction with CTBP2)
	interacts with dynamin, a key effector molecule of many endocytic processes (inhibits the GTPase activity of dynamin)
	through inhibition of Abl kinases, dampens IFNG production
	acylated G-alpha peptides, acylated Talpha N-terminal peptide, Talpha-GTP
	interaction with transducin is dependent on the N-acylation, but does not require the GTP-bound form of GNAT1
	bound the myristoylated N terminus of GNAT1 with much higher affinity than a prenylated substrate, and inhibit the GTPase activity of GNAT1
	may inhibit GPCR-dependent activation of the Gi family G proteins
	although ARL3 and ARL2 bind UNC119 with similar affinities, only ARL3 allosterically displaces cargo by accelerating its release by three orders of magnitude
	as a dominant partner, GNAT1 may potentially modulate the function of other known UNC119-interacting proteins involved in photoreceptor ciliary trafficking and synaptic regulation, in a light-dependent manner
	UNC119 interacts with a Src family kinase, FYN and is required for the activation of this kinase
	plays a key role in the FYN signal transduction pathway, which regulates the completion of cytokinesis via RAB11A
	in photoreceptors, ARL2 and ARL3 participate in the trafficking of lipidated membrane-associated proteins and colocalize in the inner segment with UNC119 and PDE6D
	GNAT1, NPHP3, and PKD1 bind with high affinity to UNC119 whereas a peptide derived from a non-ciliary localizing protein (SRC) has low affinity

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

IMD13

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       late onset cone rod dystrophy in a female heterozygous for a premature termination codon mutation constitutional     --other   enhanced in CD4 T cells from patients with asthma tumoral     --over   in hepatocellular carcinoma (HCC) tissues

Susceptibility

Variant & Polymorphism

Candidate gene	a strong candidate gene for retinal diseases (
Marker
Therapy target

ANIMAL & CELL MODELS

	transgenic mice carrying a premature termination codon mutation developed age-dependent fundus lesions with electroretinographic changes consistent with defects in photoreceptor synaptic transmission , and retinal degeneration (
	reduction in proteins associated with synaptic vesicles and a possible compensatory increase in proteins involved in docking-exocytosis and endocytosis were observed in both the outer and inner plexiform layers of the retina of the transgenic HRG4 mouse model (
	deletion of UNC119 gene in both mouse and C. elegans led to G protein mislocalization (