[email protected] (受疫情影响,东南亚目前只开放曼谷诊所)
全周 (9AM - 5PM)


Extra info thumb
  • 总部: 泰国曼谷市巴吞汪区仑披尼分区 普勒吉路齐隆巷5号.
  • [email protected]


Alternative titles; symbolsTAX INTERACTION PROTEIN 1; TIP1HGNC Approved Gene Symbol: TAX1BP3Cytogenetic location: 17p13.2 Genomic coordinates (GRCh38): 17:3,...

Alternative titles; symbols


HGNC Approved Gene Symbol: TAX1BP3

Cytogenetic location: 17p13.2 Genomic coordinates (GRCh38): 17:3,662,894-3,668,577 (from NCBI)

▼ Description
TAX1BP3 is a PDZ domain-containing protein that influences plasma membrane protein content and membrane dynamics (Wang et al., 2014).

▼ Cloning and Expression
Using the C-terminal tail of the inwardly rectifying potassium channel KCNJ4 (600504) as bait in a yeast 2-hybrid screen of a human kidney cDNA library, followed by RT-PCR of human kidney mRNA, Alewine et al. (2006) cloned TAX1BP3, which they called TIP1. The deduced 124-amino acid protein consists of a PDZ domain flanked by 11 N-terminal and 14 C-terminal residues. Northern blot analysis detected a 1.4-kb transcript in the 6 human tissues examined. Immunohistochemical analysis of rat kidney showed cytoplasmic Tip1 localization, with most intense expression in distal convoluted tubule, connecting tubule, and collecting duct.

▼ Gene Structure
Touchman et al. (2000) determined that the TAX1BP3 gene contains 4 exons.

▼ Mapping
By BAC analysis, Touchman et al. (2000) mapped the TAX1BP3 gene to chromosome 17p13.

▼ Gene Function
Using yeast 2-hybrid and coimmunoprecipitation assays, Hampson et al. (2004) showed that TIP1 interacted with human papillomavirus (HPV)-16 E6 protein. Cervical carcinoma cells infected with HPV-16 E6 had higher levels of phosphorylated myosin light chain (see 609931) and increased cell motility compared with uninfected controls. The phenotype was inhibited by antisense silencing of TIP1 expression or inhibition of RhoA kinase (see 601702).

A complex made up of the PDZ proteins LIN7 (see LIN7A, 603380) and CASK (300172) coordinates polarized expression of KCNJ4 at renal basolateral membranes via a PDZ interaction. Alewine et al. (2006) found that TIP1 interacted directly with KCNJ4 and inhibited its interaction with LIN7/CASK, resulting in internalization and endosomal targeting of KCNJ4 in polarized rat and canine kidney cells. The interaction required the PDZ domains of TIP1 and KCNJ4. Alewine et al. (2006) proposed that TIP1 functions as a dominant-negative PDZ domain to counter the targeting of PDZ-interacting protein targets to basolateral membranes.

Oliver et al. (2011) showed that ARHGEF16 (618871) interacted with TIP1 through the C-terminal PDZ domain of TIP1. ARHGEF16 expression was upregulated by ectopic expression of HPV16 E6, and ARHGEF16, TIP1, and HPV16 E6 cooperated to activate CDC42 (116952).

Wang et al. (2014) reported that TIP1 interacted with ARHGEF7 (605477) and rhotekin (RTKN; 602288) and colocalized with ARHGEF7 at the leading edge of migrating T98G human glioblastoma cells. Knockdown of TIP1 via short hairpin RNA did not change the protein content of ARHGEF7 or RTKN in glioblastoma cell lines, but it caused their intracellular redistribution, changed the appearance of T98G cells toward a highly branched morphology, and inhibited cell migration. Knockdown of TIP1 was accompanied by activation of the Rho GTPases RHOA (165390), CDC42, and RAC1 (602048). Knockdown of TIP1 in D54 human glioblastoma cell xenografts greatly extended mouse survival following intracranial injection, and it reduced invasion and infiltration into surrounding brain tissue. Wang et al. (2014) also found elevated TIP1 in human glioblastomas, and elevated TIP1 correlated with advanced staging and poor prognosis in glioma patients.

▼ ALLELIC VARIANTS ( 1 Selected Example):

This variant is classified as a variant of unknown significance because its contribution to a syndrome consisting of dilated cardiomyopathy, septooptic dysplasia, hypogonadotropic hypogonadism, and dysmorphic features has not been confirmed.

Reinstein et al. (2015) studied a multiply consanguineous Bedouin family in which 2 brothers exhibited dilated cardiomyopathy, septooptic dysplasia, hypogonadotropic hypogonadism, and dysmorphic features. Chromosomal microarray in the older brother showed no copy number variants (CNVs), but multiple runs of homozygosity were detected. Whole-exome sequencing in the 2 affected sibs revealed homozygosity for a c.98T-C transition in the TAX1BP3 gene (c.98T-C, NM_014604.3), resulting in an ile33-to-thr (I33T) substitution at a highly conserved residue within the core of a hydrophobic binding pocket. The unaffected parents and 7 unaffected sibs were heterozygous for the mutation. Brain MRI in the affected brothers revealed agenesis of the corpus callosum and absence of the septum pellucidum in both; the older brother had a normal-sized sella with no evidence of pituitary adenoma or hypothalamic mass, whereas the younger brother had a thin pituitary gland. Funduscopy in the older sib revealed bilateral inferior segmental optic disc hypoplasia with an inferior double-ring sign, and optical coherence measurements showed thinning of the optic nerve fibers; no ophthalmologic features were reported for the younger brother. Both brothers were tall, with height above the 90th percentile. Dysmorphic features included macrocephaly, long face, midface hypoplasia, hypertelorism, downslanting palpebral fissures, broad nasal ridge and bridge, low-set posteriorly rotated and cupped ears, and dental anomalies, including dental crowding and single central incisor. Echocardiography showed severe dilated cardiomyopathy with prominent involvement of the right ventricle in both sibs. The younger brother died after cardiac transplantation at age 18 years; postmortem cardiac examination showed nonspecific ischemic cardiomyopathy, normal valves, normal coronary arteries, and multiple fibrotic scars in the left ventricle and septum.

Tags: 17p13.2