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FLASH GENE

Symbol

USH1C

contributors: shn/npt/pgu - updated : 07-12-2017

HGNC name	USH1 protein network component harmonin
HGNC id	12597

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	USH1C Usher syndrome, type IC
Location	11p15.1      Physical location : 17.515.442 - 17.565.963
Synonym name	harmonin
	autoimmune enteropathy related antigen 75kDa
	Usher syndrome 1C (autosomal recessive severe/harmonin,PDZ containing protein,harmonin)
	renal carcinoma antigen NY-REN-3
	antigen NY-CO-38/NY-CO-37
	protein PDZ-73
Synonym symbol(s)	PDZ73, harmonin, NY-CO-37, NY-CO-38, PDZ-73, AIE-75, DFNB18, PDZ-45, ush1cpst, PDZ-73, PDZD7C

DNA

TYPE	functioning gene
SPECIAL FEATURE	overlapping, gene in gene
text	overlapping with DNFB18
STRUCTURE	50.52 kb     28 Exon(s)

10 Kb 5' upstream gene genomic sequence study

motif	repetitive sequence   other
text structure	VNTR in intron 5

MAPPING

cloned

Y

linked

N

status

provisional

Map	pter - D11S921 - D11S902 - USH1C USH1C - D11S4138 - D11S4130 - cen

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005709 21 splicing 2237 NP_005700 73 552 cytoplasmic reactivity in epithelial cells of the small intestine, colon and kidney tubules - stereocilia of hair cells, and in the retina within the synapse of photoreceptor cell layer 2010 20142502 harmonin a an additional PDZ domain at its C terminus NM_153676 27 splicing 3246 NP_710142 - 899 stereocilia of hair cells, and in the retina within synapse of the photoreceptor cell layer 2010 20142502 harmonin b an additional PDZ domain at its C terminus also contains a Pro, Ser, Th-rich sequence (PST) domain preceding the C-terminal PDZ domain that is known to be responsible for binding to F-actin NM_001297764 20 - 2180 NP_001284693 - 533 - 2010 20142502 harmonin c contains an N-terminal globular domain , two PDZ domains, and one or two coiled-coil regions

EXPRESSION

Type

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 Digestive intestine small intestine jejunum crypt of Lieberkuhn     intestine large intestine colon     Hearing/Equilibrium ear inner cochlea Corti   Nervous brain         Reproductive male system testis       Urinary kidney nephron       Visual eye retina

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Epithelial sensory stato-auditory     Nervous central

cells

System Cell Pubmed Species Stage Rna symbol Hearing / Equilibrium cochlea cell Hearing / Equilibrium stereocilia Visual cone photoreceptor

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal domain and the first PDZ domain are tethered by a small-domain C-terminal to PDZ1 to form a structural and functional supramodule responsible for binding to USH1G, and PDZ2 domain binds to the cytoplasmic portion of cadherin 23
	three conserved domains PSD/DLG/ZO1 (PDZ) domains
	one or two coiled-coil region(s)
	a putative PEST protein degradation motif
	one C terminal PBI domain (PDZ- binding interface)

HOMOLOGY

interspecies	ortholog to Ush1c, Mus musculus
	ortholog to Ush1c, Rattus norvegicus
	ortholog to ush1c, Danio rerio
	ortholog to USH1C, Pan troglodytes

Homologene

FAMILY

CATEGORY

antigen

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton
text	USH2A, VLGR1 and NBC3 are co-expressed with the USH1-protein harmonin in the synaptic terminals of both retinal photoreceptors and inner ear hair cells

basic FUNCTION	autoantigen involved in intracellular signaling cascade
	cooperates with Myosin VIIaand cadherin 23 to shape the sensory hair cell bundle
	essential to ensure the cohesion of the stereocilia
	MYO7A, USH1G, and USH1C form the core components of the stereocilia upper tip-link density molecular complex
	USH1G, MYO7A, USH1C, CDH23, PCDH15 form an adhesion belt around the basolateral region of the photoreceptor outer segment, and defects in this structure cause the retinal degeneration in USH1 patients
	in contrast to other actin-bundling proteins such as ESPN, USH1C or EPS8, PLS1 is dispensable for the initial formation of stereocilia
	ANKS4B interacts with USH1C and MYO7B, which link protocadherins to the actin cytoskeleton, and ANKS4B and USH1C also bind to the MYO7B cargo-binding tail at distinct sites
	while PDZ protein USH1C is not involved, its paralogous USH2 proteins, PDZD7 and WHRN, function synergistically in USH2 complex assembly in cochlear hair cells

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

immunity/defense

PATHWAY

metabolism

signaling

sensory transduction/hearing , sensory transduction/vision

possible Rac-DOCK4-ABP harmonin-activated signaling pathway in regulating actin cytoskeleton organization in stereocilia

a component	complexing with CDH23, MYO7A, USH1C (with CDH23 and myosin VIIa can form a ternary complex, which suggests that myosin VIIa applies tension forces on hair bundle links)
	USH1C, ANKS4B, and MYO7B form a stable ternary complex for anchoring microvilli tip-link cadherins
	harmonin/Sans (USH1C/USH1G)complex may serve as a platform to interact with many other proteins related to the development of hearing and visual cells via a number of other unoccupied domains in the complex
	MYO7A, USH1G, and the upper tip-link density protein USH1C form a tripartite complex and that each protein is capable of interacting with one another independently
	polymeric CDH23/USH1C complex formed beneath the upper tip link membranes may serve as part of the stable rootlet structure for anchoring the tip links of stereocilia

INTERACTION

DNA

RNA

small molecule

protein	Usher syndrome 1C binding protein 1, USHBP1 (
	Usher syndrome proteins cadherin 23, CDH23 (
	Usher syndrome type I G, USH1G (
	harmonin-interacting ankyrin repeat-containing protein, Harp (
	myosin VIIA, MYO7A
	usher syndrome type-2A protein, USH2A; G protein-coupled receptor 98, GPR98 (also known as VLGR1 or USH2C) and solute carrier family 4, sodium bicarbonate cotransporter, member 8, SLC4A8 (otherwise known as NBC3)
	protocadherin-related 15, PCDH15
	dedicator of cytokinesis 4, DOCK4
	binding DOCK4, an unconventional guanine exchange factor for the Rho family of guanosine triphosphatases (Rho GEF GTPases)
	with CDH23 and myosin VIIa bind to phosphorylated forms of phosphatidylinositol including phosphatidylinositol 4,5-bisphosphate
	multifaceted presynaptic role of USH1C in cochlear inner hair cells (IHCs) in regulating CACNA1D channels and exocytosis
	ANKS4B interacts with USH1C and MYO7B, which link protocadherins to the actin cytoskeleton

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

USH1C , DFNB18

related resource

Genetics hearing impairment Retinal Information Network

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neurosensorial visual retina Commercial aminoglycosides and NB30 induced significant read-through of the USH1C-p.R31X nonsense mutation with ignificantly reduced toxicity and good biocompatibility

ANIMAL & CELL MODELS

	Ush1c mutant mice congenital exhibit deafness and severe balance deficits due to inner ear dysfunction, stereocilia of cochlear hair cells are disorganized and splayed (
	deaf circler mice (dfcr), which carry a 12.8kb intragenic deletion of Ush1c gene that eliminates the second and third PDZ domain, have a normal retinal structure, synaptic ultrastructure and ERGs (William et al, 2009)