GIPC3
Encyclopedia
PDZ domain-containing protein GIPC3 is a protein
that in humans is encoded by the GIPC3 gene
. GIPC3 is a member of the GIPC (GAIP-interacting protein C terminus) gene family that also includes GIPC1
and GIPC2
. The encoded protein, GIPC3, features a centrally located PDZ domain
, which is flanked on each side by a single GIPC-homology domain.
.
s that give raise to a open reading frame of 639 nucleotide
s encoding the GIPC3 protein of 312 amino acid
s. A single PDZ domain is located at amino acid position 122-189.
In the mouse, Gipc3 is located on chromosome 10 at cytogenetic band qC1. The genomic
region covers a distance of 5.5 kbp. The six coding exons encode a protein of 297 amino acids. The PDZ domain is located at amino acid position 107-174.
in Gipc3 (c.343G>A) leads to a non-synonymous amino acid replacement (p.G115R) in the loop connecting two beta strands of the PDZ domain. Glycine
115 is conserved in all GIPC proteins.
Missense (c.785C>T; p. L262R) and nonsense
(c.903G>A, p.W301X) mutations in human GIPC3 cause congenital sensorineural hearing impairment in families segregating non-syndromic hearing loss DFNB15 and DFNB95.
. A genetic locus conferring susceptibility was identified (juvenile audiogenic monogenic seizures1, jams1) on chromosome 10. A positional cloning approach aimed to decipher the genetic basis of both the hearing loss and audiogenic seizure susceptibility subsequently identified the glycine
to arginine
substitution in Gipc3 as the underlying cause.
In humans, individuals with the p.W301X missense mutation (DFNB95) exhibit bilateral sensorineural hearing loss with threshold shifts of 70-80 dB hearing levels as early as 11 months of age.
of GIPC family proteins interact with:
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the GIPC3 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. GIPC3 is a member of the GIPC (GAIP-interacting protein C terminus) gene family that also includes GIPC1
GIPC1
GIPC PDZ domain containing family, member 1 is a protein that in humans is encoded by the GIPC1 gene.-Interactions:GIPC1 has been shown to interact with Beta-1 adrenergic receptor, ITGA5, ITGA6, TPBG, RGS19, TYRP1, GLUT1, Actinin, alpha 1, KIF1B, LRP2, Luteinizing hormone/choriogonadotropin...
and GIPC2
GIPC2
GIPC PDZ domain containing family, member 2 is a protein that in humans is encoded by the GIPC2 gene.-See also:GIPC PDZ domain containing family, member 2, GIPC1GIPC PDZ domain containing family, member 3, GIPC3-Further reading:...
. The encoded protein, GIPC3, features a centrally located PDZ domain
PDZ domain
The PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of bacteria, yeast, plants, viruses and animals...
, which is flanked on each side by a single GIPC-homology domain.
Function
GIPC3 is thought to be important for acoustic signal acquisition and propagation in hair cells of the mammalian cochleaCochlea
The cochlea is the auditory portion of the inner ear. It is a spiral-shaped cavity in the bony labyrinth, making 2.5 turns around its axis, the modiolus....
.
Gene
The human GIPC3 gene is located on the short arm of chromosome 19 at p13.3. The locus extends over ≈8 kbp and contains the six coding exonExon
An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...
s that give raise to a open reading frame of 639 nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
s encoding the GIPC3 protein of 312 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s. A single PDZ domain is located at amino acid position 122-189.
In the mouse, Gipc3 is located on chromosome 10 at cytogenetic band qC1. The genomic
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
region covers a distance of 5.5 kbp. The six coding exons encode a protein of 297 amino acids. The PDZ domain is located at amino acid position 107-174.
Genetics
In the mouse, a missense mutationMissense mutation
In genetics, a missense mutation is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid . This can render the resulting protein nonfunctional...
in Gipc3 (c.343G>A) leads to a non-synonymous amino acid replacement (p.G115R) in the loop connecting two beta strands of the PDZ domain. Glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
115 is conserved in all GIPC proteins.
Missense (c.785C>T; p. L262R) and nonsense
Nonsense mutation
In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and in a truncated, incomplete, and usually nonfunctional protein product. It differs from a missense mutation, which is a point mutation...
(c.903G>A, p.W301X) mutations in human GIPC3 cause congenital sensorineural hearing impairment in families segregating non-syndromic hearing loss DFNB15 and DFNB95.
Phenotypes
Mice of the Black Swiss strain develop early-onset slowly progressing sensorineural hearing loss. A genetic study identified two quantitative trait loci (QTL) that control hearing function. One QTL, named age-related hearing loss 5 (ahl5) localizes to chromosome 10 and accounted for ca. 60% of the variation in hearing thresholds. A second QTL, ahl6, localized to chromosome 18 and has a smaller effect size. Besides their hearing impairment, Black Swiss mice also are hypersensitive to acoustic stimulation, reacting with seizures (audiogenic seizures) to loud white noiseWhite noise
White noise is a random signal with a flat power spectral density. In other words, the signal contains equal power within a fixed bandwidth at any center frequency...
. A genetic locus conferring susceptibility was identified (juvenile audiogenic monogenic seizures1, jams1) on chromosome 10. A positional cloning approach aimed to decipher the genetic basis of both the hearing loss and audiogenic seizure susceptibility subsequently identified the glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
to arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
substitution in Gipc3 as the underlying cause.
In humans, individuals with the p.W301X missense mutation (DFNB95) exhibit bilateral sensorineural hearing loss with threshold shifts of 70-80 dB hearing levels as early as 11 months of age.
Interactions
The PDZ domainPDZ domain
The PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of bacteria, yeast, plants, viruses and animals...
of GIPC family proteins interact with:
- Frizzled-3 (FZD3FZD3Frizzled-3 is a protein that in humans is encoded by the FZD3 gene.-Further reading:...
) class of WNT receptor, - insulin-like growth factor-I receptor (IGF1R),
- receptor tyrosine kinase TrkA,
- TGF-beta type III receptor (TGF-beta RIII),
- integrin alpha6A (ITGA6ITGA6Integrin alpha-6 is a protein that in humans is encoded by the ITGA6 gene.-Interactions:ITGA6 has been shown to interact with TSPAN4 and GIPC1.-External links:* Info with links in the...
), - transmembrane glycoprotein TPBGTPBGTrophoblast glycoprotein, also known as TPBG or 5T4, is a human gene.5T4 is an antigen expressed in a number of carcinomas. It is an N-glycosylated transmembrane 72 kDa glycoprotein containing seven leucine-rich repeat regions...
, and - RGS19RGS19Regulator of G-protein signaling 19 is a protein that in humans is encoded by the RGS19 gene.-Interactions:RGS19 has been shown to interact with GNAO1, GIPC1, OSTM1, GNAI1, GNAI3 and GNAZ.-Further reading:...
/RGS-GAIP.
See also
- GIPC PDZ domain containing family, member 1, GIPC1GIPC1GIPC PDZ domain containing family, member 1 is a protein that in humans is encoded by the GIPC1 gene.-Interactions:GIPC1 has been shown to interact with Beta-1 adrenergic receptor, ITGA5, ITGA6, TPBG, RGS19, TYRP1, GLUT1, Actinin, alpha 1, KIF1B, LRP2, Luteinizing hormone/choriogonadotropin...
- GIPC PDZ domain containing family, member 2, GIPC2GIPC2GIPC PDZ domain containing family, member 2 is a protein that in humans is encoded by the GIPC2 gene.-See also:GIPC PDZ domain containing family, member 2, GIPC1GIPC PDZ domain containing family, member 3, GIPC3-Further reading:...