UniProt functional annotation for Q9ES64



	UniProt functional annotation for Q9ES64

UniProt code: Q9ES64.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Anchoring/scaffolding protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal development and maintenance of cochlear hair cell bundles (PubMed:19447093). As part of the intermicrovillar adhesion complex/IMAC plays a role in brush border differentiation, controlling microvilli organization and length. Probably plays a central regulatory role in the assembly of the complex, recruiting CDHR2, CDHR5 and MYO7B to the microvilli tips (PubMed:24725409, PubMed:26812018). {ECO:0000269|PubMed:19447093, ECO:0000269|PubMed:24725409, ECO:0000269|PubMed:26812018}.

Subunit: Part of the IMAC/intermicrovillar adhesion complex/intermicrovillar tip-link complex composed of ANKS4B, MYO7B, USH1C, CDHR2 and CDHR5 (By similarity). Part of a complex composed of USH1C, USH1G and MYO7A (By similarity). Interacts with F-actin (PubMed:19447093). Interacts with USH2A (PubMed:16301217). Interacts with SLC4A7 (PubMed:16301216). Interacts (via PDZ1 domain) with the C- terminus of USHBP1 (By similarity). Interacts (via N-terminus and PDZ 2 domain) with CDH23 (PubMed:19447093). Interacts with USH1G (By similarity). Interacts with MYO7B (PubMed:26812017). Interacts with CDHR2 and CDHR5; may mediate their interaction with MYO7B at the microvilli tip (By similarity) (PubMed:26812017). Interacts (via PDZ 1 domain) with ANKS4B (PubMed:12588794, PubMed:15461667). Interacts (via PDZ 1 domain) with DOCK4 (By similarity). {ECO:0000250|UniProtKB:Q9Y6N9, ECO:0000269|PubMed:12588794, ECO:0000269|PubMed:15461667, ECO:0000269|PubMed:16301216, ECO:0000269|PubMed:16301217, ECO:0000269|PubMed:19447093, ECO:0000269|PubMed:26812017}.

Subcellular location: Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q9Y6N9}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:19447093}. Cell projection, microvillus {ECO:0000269|PubMed:24725409}. Note=Colocalizes with F-actin (PubMed:19447093). Detected at the tip of cochlear hair cell stereocilia (PubMed:19447093). Enriched in microvilli of the intestinal brush border (PubMed:24725409). {ECO:0000269|PubMed:19447093, ECO:0000269|PubMed:24725409}.

Tissue specificity: Detected in stereocilia of cochlear hair cells (at protein level). Isoform 1 is expressed in the eye, cochlea, vestibule, heart, kidney, small intestine and testis; it is barely visible in skeletal muscle, liver, and lung and is absent from the brain. Isoforms 2 and 3 are expressed in the cochlea and vestibule. {ECO:0000269|PubMed:10973247, ECO:0000269|PubMed:19447093, ECO:0000269|PubMed:24725409}.

Domain: The PDZ 1 domain mediates interaction with ANKS4B, USHBP1, USH1G, SLC4A7. {ECO:0000250|UniProtKB:Q9Y6N9, ECO:0000269|PubMed:15461667}.

Domain: The N-terminal region constitutes an independently folded domain that has structural similarity with the CCM2 C-terminus, despite very low sequence similarity. {ECO:0000250|UniProtKB:Q9Y6N9}.

Disruption phenotype: Mice lacking Ush1c display abnormal brush border morphology along the length of the intestinal tract. {ECO:0000269|PubMed:24725409}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Anchoring/scaffolding protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal development and maintenance of cochlear hair cell bundles (PubMed:19447093). As part of the intermicrovillar adhesion complex/IMAC plays a role in brush border differentiation, controlling microvilli organization and length. Probably plays a central regulatory role in the assembly of the complex, recruiting CDHR2, CDHR5 and MYO7B to the microvilli tips (PubMed:24725409, PubMed:26812018). {ECO:0000269\|PubMed:19447093, ECO:0000269\|PubMed:24725409, ECO:0000269\|PubMed:26812018}.


Subunit:		Part of the IMAC/intermicrovillar adhesion complex/intermicrovillar tip-link complex composed of ANKS4B, MYO7B, USH1C, CDHR2 and CDHR5 (By similarity). Part of a complex composed of USH1C, USH1G and MYO7A (By similarity). Interacts with F-actin (PubMed:19447093). Interacts with USH2A (PubMed:16301217). Interacts with SLC4A7 (PubMed:16301216). Interacts (via PDZ1 domain) with the C- terminus of USHBP1 (By similarity). Interacts (via N-terminus and PDZ 2 domain) with CDH23 (PubMed:19447093). Interacts with USH1G (By similarity). Interacts with MYO7B (PubMed:26812017). Interacts with CDHR2 and CDHR5; may mediate their interaction with MYO7B at the microvilli tip (By similarity) (PubMed:26812017). Interacts (via PDZ 1 domain) with ANKS4B (PubMed:12588794, PubMed:15461667). Interacts (via PDZ 1 domain) with DOCK4 (By similarity). {ECO:0000250\|UniProtKB:Q9Y6N9, ECO:0000269\|PubMed:12588794, ECO:0000269\|PubMed:15461667, ECO:0000269\|PubMed:16301216, ECO:0000269\|PubMed:16301217, ECO:0000269\|PubMed:19447093, ECO:0000269\|PubMed:26812017}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000250\|UniProtKB:Q9Y6N9}. Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:19447093}. Cell projection, microvillus {ECO:0000269\|PubMed:24725409}. Note=Colocalizes with F-actin (PubMed:19447093). Detected at the tip of cochlear hair cell stereocilia (PubMed:19447093). Enriched in microvilli of the intestinal brush border (PubMed:24725409). {ECO:0000269\|PubMed:19447093, ECO:0000269\|PubMed:24725409}.
Tissue specificity:		Detected in stereocilia of cochlear hair cells (at protein level). Isoform 1 is expressed in the eye, cochlea, vestibule, heart, kidney, small intestine and testis; it is barely visible in skeletal muscle, liver, and lung and is absent from the brain. Isoforms 2 and 3 are expressed in the cochlea and vestibule. {ECO:0000269\|PubMed:10973247, ECO:0000269\|PubMed:19447093, ECO:0000269\|PubMed:24725409}.
Domain:		The PDZ 1 domain mediates interaction with ANKS4B, USHBP1, USH1G, SLC4A7. {ECO:0000250\|UniProtKB:Q9Y6N9, ECO:0000269\|PubMed:15461667}.
Domain:		The N-terminal region constitutes an independently folded domain that has structural similarity with the CCM2 C-terminus, despite very low sequence similarity. {ECO:0000250\|UniProtKB:Q9Y6N9}.
Disruption phenotype:		Mice lacking Ush1c display abnormal brush border morphology along the length of the intestinal tract. {ECO:0000269\|PubMed:24725409}.