Le 2. Overview of rare polymorphism (Table two)Exon /Intron Exon5 Nucleotide Adjust c.G346A Minor Allele Frequency Amino Acid Domain Table 2. Overview with the 3 variants in KRGDB SGI TMPRSS3. Change UCSC 1000G p.V116M SRCR 0.0015 0 0 0 Amino Acid Changep.V116M p.V291L p.V291LPhenotype Profound Probably Phenotype pathogenicReferences [10,11] This Study
International Journal ofMolecular SciencesCommunicationA Cell Junctional protein Network Related with ConnexinAna C. Batissoco 1,two, ID , Rodrigo SalazarSilva 1 , Jeanne Oiticica two , Ricardo F. Bento two Regina C. MingroniNetto 1 and Luciana A. HaddadID,Human Genome and Stem Cell Analysis Center, Department of Genetics and Evolutionary Biology, A8031 smad Inhibitors MedChemExpress Instituto de Bioci cias, Universidade de S Paulo, 05508090 S Paulo, Brazil; [email protected] (R.S.S.); [email protected] (R.C.M.N.); [email protected] (L.A.H.) Laborat io de Otorrinolaringologia/LIM32, Hospital das Cl icas, Faculdade de Medicina, Universidade de S Paulo, 01246903 S Paulo, Brazil; [email protected] (J.O.); [email protected] (R.F.B.) Correspondence: [email protected]; Tel.: 5511Received: 17 July 2018; Accepted: 21 August 2018; Published: 27 AugustAbstract: GJB2 mutations are the top cause of nonsyndromic inherited hearing loss. GJB2 encodes connexin26 (CX26), which is a connexin (CX) family protein expressed in cochlea, skin, liver, and brain, displaying brief cytoplasmic Ntermini and Ctermini. We searched for CX26 Cterminus binding partners by affinity capture and identified 12 exclusive proteins connected with cell junctions or cytoskeleton (CGN, DAAM1, FLNB, GAPDH, HOMER2, MAP7, MAPRE2 (EB2), JUP, PTK2B, RAI14, TJP1, and VCL) by utilizing mass spectrometry. We show that, similar to other CX family members, CX26 cofractionates with TJP1, VCL, and EB2 (EB1 paralogue) as well because the membraneassociated protein ASS1. The Acid corrosion Inhibitors Related Products adaptor protein CGN (cingulin) coimmunoprecipitates with CX26, ASS1, and TJP1. Furthermore, CGN coimmunoprecipitation with CX30, CX31, and CX43 indicates that CX association is independent around the CX Cterminus length or sequence. CX26, CGN, FLNB, and DAMM1 have been shown to distribute towards the organ of Corti and hepatocyte plasma membrane. Within the mouse liver, CX26 and TJP1 colocalized in the plasma membrane. In conclusion, CX26 associates with elements of other membrane junctions that integrate using the cytoskeleton. Search phrases: connexin; connexin 26; GJB2 gene; deafness; proteinprotein interaction; TJP1; CGN; FLNB; DAAM1; organ of Corti1. Introduction The GJB2 gene encodes connexin 26 (CX26), which is a protein that plays central roles in hearing, promoting cochlear improvement, and sustaining auditory function inside the mature cochlea [1]. In addition to the cochlea, expression of CX26 can also be observed in the skin, the liver, the brain, the mammary gland, the salivary gland, the uterus, testis, the pancreas, lungs, the stomach, the thyroid, along with the parathyroid [5]. GJB2 mutations are the most frequent cause of nonsyndromic recessive hearing loss across diverse populations [6]. Also, some heterozygous GJB2 mutations behave inside a dominant style, which results in nonsyndromic autosomal dominant hearing loss or for the keratitisichthyosisdeafness syndrome [10]. In vertebrates, connexins (CX) assemble intercellular gap junctions (GJ), which outcome from the interaction amongst two distinct hemichannels from adjacent cells with every single composed of six CX units. GJ directly makes it possible for the passage of numerous sma.