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FLASH GENE

Symbol

MYO7A

contributors: shn - updated : 21-06-2016

HGNC name	myosin VIIA
HGNC id	7606

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	DFNA11 neurosensory deafness 11 DFNB2 neurosensory deafness 2 USH1B Usher syndrome, type IB
Location	11q13.5      Physical location : 76.839.309 - 76.926.286
Synonym name	myosin VIIA, unconventional, apparently non filamentous
Synonym symbol(s)	USH1B, DFNA11, DFNB2, MYOVIIA, MYU7A, NSRD2, HM7A

DNA

TYPE	functioning gene
STRUCTURE	86.00 kb     49 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D11S1321 - D11S4179 - MYO7A - D11S4186 - D11S1789 - qter

RNA

TRANSCRIPTS	type	messenger

text	a strong enhancer in the intron 1 is sufficient to target the expression of MYO7A gene exclusively in sensory cells of the inner ear

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000260 49 splicing 7465 NP_000251 - 2215 inner and base of outer segments and synaptic ending region of photoreceptor cells 1996 8842737 transcript variant 1 NM_001127179 27 splicing 4079 NP_001120651 - 1178 inner and base of outer segments and synaptic ending region of photoreceptor cells 1996 8842737 transcript variant 3 NM_001127180 49 splicing 7339 NP_001120652 - 2175 inner and base of outer segments and synaptic ending region of photoreceptor cells 1996 8842737 transcript variant 2

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 Hearing/Equilibrium ear inner cochlea     Homo sapiens Nervous nerve       highly Reproductive female system placenta     highly   male system testis       Homo sapiens Respiratory lung         Homo sapiens Urinary kidney         Homo sapiens Visual eye retina     highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Epithelial barrier lining retinal pigment epithelium (RPE)   highly Homo sapiens Epithelial sensory visual

cells

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

cell lineage
cell lines	primary cultures of human and mouse RPE
fluid/secretion

at STAGE

physiological period

embryo

Text	developing sensory epithelia, cochlear and vestibular neuroepithelia, retinal pigment epithelium and photoreceptor cells

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal motor head domain containing ATP and actin-binding sites
	a neck containing five IQ calmodulin or calmodulin-like light chain binding domains
	a tail containing a coiled-coil region, two myosin IV like
	two C terminal talin-like domains (FERM, EPB41-ezrin-radixin-moesin), involved in the linkage of cytoplasmic proteins to the membrane, FERM domain binding to a novel transmembrane protein VEZT
	a putative SH3 domain

HOMOLOGY

interspecies	ortholog to Myo7a, Mus musculus
	ortholog to drosophila Crickled
	ortholog to Myo7a, Rattus norvegicus
	ortholog to myo7a, Danio rerio
	ortholog to MYO7A, Pan troglodytes

Homologene

FAMILY

CATEGORY

motor/contractile

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,lysosome
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton
text	Myosin VIIa and USH1G localization at stereocilia upper tip-link density

basic FUNCTION	might play a role in the trafficking of ribbon-synaptic vesicle complexes and the renewal processes of the outer photoreceptor disks
	mediating the transport of membrane cargo along actin filaments in the membrane of photoreceptor cilia
	putative protein kinase A (PRKAR1A)-anchoring protein that targets PRKA to subcellular sites of sensory cells
	can have a dual function in the connecting cilium : after the fusion of membranous vesicles with the apical surface of the inner segment discussed above, the membrane incorporated cargo translocates in the ciliary membrane to the outer segment
	anchored by vezatin to the cadherin-catenins complex, creates a tension force between adherens junctions and the actin cytoskeleton that is expected to strengthen cell-cell adhesion
	opsin transport through the photoreceptor cilium
	RAB27A, MYRIP and MYO7A bridges retinal melanosomes to the actin cytoskeleton and thereby mediates the local trafficking of these organelles
	essential to ensure the cohesion of the stereocilia
	required for the normal processing of ingested disk membranes in the RPE, primarily in the basal transport of phagosomes into the cell body where they then fuse with lysosomes
	required for the normal transport of opsin through the ciliary plasma membrane to the outer segment, and, in the RPE, it functions in the movement of melanosomes and phagosomes
	required for hair bundle growth
	plays a role in the positioning of melanosomes and other digestion organelles in the retinal pigment epithelium
	role for MYO7A in the translocation of RPE65, illustrating the involvement of a molecular motor in the spatiotemporal organization of the retinoid cycle in vision
	functions by mediating light-dependent translocation of RPE65
	MYO7A, USH1G, and USH1C form the core components of the stereocilia upper tip-link density molecular complex
	MYO7A functions as a selective barrier for membrane proteins at the distal end of the transition zone
	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
	can likely transport its cargo molecules, such as USH1 proteins, upon release of the tail-dependent inhibition
	MYO7A regulate caspases in their signalling roles
	MYO7A movement appears to be suitable for translocating USH1 proteins on stereocilia actin bundles in inner-ear hair cells

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

sensory transduction/hearing , sensory transduction/vision

a component	with harmonin (USH1C) and CDH23 can form a ternary complex, which suggests that myosin VIIa applies tension forces on hair bundle links
	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
	MYO7A forms a complex with PDZD7, a paralog of USH1C and WHRN

INTERACTION

DNA

RNA

small molecule

protein	adherens junctions transmembrane protein vezatin, VEZT
	type I alpha regulatory subunit (RI alpha) of protein kinase A, PRKAR1A
	calmodulin, CaM and microtubule-associated protein-2B, MAP-2B
	associated with specialized adhesion plaques termed ectoplasmic specializations (ES) that form between Sertoli cells and germ cells in testis
	synaptotagmin-like protein homologue lacking C2 domains-c, Slac2-c
	myosin VIIA and Rab interacting protein, MYRIP
	kelch-like ECH-associated protein 1, KEAP1
	harmonin b
	MYRIP mediates cellular activation of MYO5A and MYO7A via non-overlapping domains
	with harmonin and CDH23 bind to phosphorylated forms of phosphatidylinositol including phosphatidylinositol 4,5-bisphosphate
	whirlin, WHRN (
	associated with cathepsin D- and Rab7-positive lysosomes
	MYO7A and RPE65 appear to be associated with each other, suggesting that MYO7A functions in the localization of the visual cycle enzyme
	CNGA3 interacts with stereocilia tip-link CDH23 + exon 68 or alternatively with MYO7A, two proteins required for hair cell mechanotransduction
	MYO7A interacts with ITGB5 and selectively promotes integrin ITGAB5-mediated cell migration
	MYRIP accumulates granules in the cortical F-actin network not by direct interaction with MYO5A, but by indirect interaction with a specific form of MYO7A through its previously unknown binding partner, RIMBP2 (28673385)

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

DFNB2 , USH1B , DFNA11

related resource

Hereditary Hearing Loss Homepage Hereditary Hearing Loss Homepage

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target	shaker1 RPE in preclinical studies on therapies for Usher syndrome 1B do not undergo retinal degeneration and may be a valid preclinical test for potential therapeutic treatments

ANIMAL & CELL MODELS

	Myo7a mutant mice (shaker1) show hyperactivity, head-tossing and circling due to vestibular dysfunction, together with typical neuroepithelial-type cochlear defects involving dysfunction and progressive degeneration of the organ of Corti
	shaker-1 mice display defective melanosome distribution in the retinal pigment epithelium
	zebrafish defective in myosin VIIA (circler mutant mariner) display morphological and functional defects that are similar to those present in mouse shaker-1: defects specific to sensory hair cell function
	Myo7a null mice display abnormal phagocytosis of photoreceptor outer segment disks by the retinal pigment epithelium (RPE)