TTYH1 Membrane Protein Introduction

Introduction of TTYH1

TTYH1, a member of the Tweety homolog family, encodes a chloride channel restricted to neural tissue with an ill-defined role in neuron physiology. TTYH1 gene translates into a protein of 729 amino acids in human. This protein contains five transmembrane domains. Tweety homolog belongs to a family which includes three members, designated as TTYH1 (Tweety homologue 1), TTYH2 and TTYH3. Human TTYH1 gene is located at chromosome 19q13.42. It is expressed in brain, eye, ovary, and testis and at lower levels in muscle, placenta, liver and lung.

Basic Information of TTYH1
Protein Name	Protein tweety homolog 1 (hTTY1)
Gene Name	TTYH1
Aliases
Organism	Homo sapiens (Human)
UniProt ID	Q9H313
Transmembrane Times	5
Length (aa)	450
Sequence	MGAPPGYRPSAWVHLLHQLPRADFQLRPVPSVFAPQEQEYQQALLLVAALAGLGLGLSLIFIAVYLIRFCCCRPPEPPGSKIPSPGGGCVTWSCIVALLAGCTGIGIGFYGNSETSDGVSQLSSALLHANHTLSTIDHLVLETVERLGEAVRTELTTLEEVLEPRTELVAAARGARRQAEAAAQQLQGLAFWQGVPLSPLQVAENVSFVEEYRWLAYVLLLLLELLVCLFTLLGLAKQSKWLVIVMTVMSLLVLVLSWGSMGLEAATAVGLSDFCSNPDPYVLNLTQEETGLSSDILSYYLLCNRAVSNPFQQRLTLSQRALANIHSQLLGLEREAVPQFPSAQKPLLSLEETLNVTEGNFHQLVALLHCRSLHKDYGAALRGLCEDALEGLLFLLLFSLLSAGALATALCSLPRAWALFPPSDDYDDTDDDDPFNPQESKRFVQWQSSI

Function of TTYH1 Membrane Protein

The TTYH11 protein functions as a calcium-independent, chloride channel and may be involved in cell adhesion. TTYH1 is involved in early embryonic development. The expression of TTYH1 protein is neuronal and has also been detected in neurons in vivo and in vitro. The overexpression of TTYH1 protein in cell lines and neurons in vitro leads to excessive filopodia formation. The involvement of TTYH1 has been implicated in aberrant neuronal structural plasticity in vivo, as increased TTYH1 protein expression is observed in the molecular layer of the dentate gyrus during epileptogenesis. TTYH1 is confirmed to be a potent regulator of normal TM morphology and of TM-mediated tumor-cell invasion and proliferation.

Fig.1 Schematic illustration of the role of TTYH1 for TM functions and brain tumor progression. (Jung, 2017)

Application of TTYH1 Membrane Protein in Literature

Wiernasz E., et al. Ttyh1 protein is expressed in glia in vitro and shows elevated expression in activated astrocytes following status epilepticus. Neurochemical Research. 2014, 39(12):2516-26. PubMed ID: 25316497

This article finds that Ttyh1 might be involved in neuronal and glial cell functions. Particularly, the elevated expression of Ttyh1 in astrocytes following damaging brain insult implies some unknown role for Ttyh1 protein in brain pathology.
Kleinman C.L., et al. Fusion of TTYH1 with the C19MC microRNA cluster drives expression of a brain-specific DNMT3B isoform in the embryonal brain tumor ETMR. Nature Genetics. 2014, 46(1):39-44. PubMed ID: 24316981

This article suggests that DNMT3B would represent a clear candidate for future therapies targeting these deadly tumors, which have been described by pathologists as resembling undifferentiated neural tubes.
Halleran A.D., et al. Characterization of tweety gene (ttyh1-3) expression in Xenopus laevis during embryonic development. Gene Expression Patterns. 2015, 17(1):38-44. PubMed ID: 25541457

This article suggests that ttyh1, ttyh2, and ttyh3 may play distinct roles throughout embryonic development.
Stefaniuk M., et al. Expression of Ttyh1, a member of the Tweety family in neurons in vitro and in vivo and its potential role in brain pathology. Journal of Neurochemistry. 2010, 115(5):1183-94. PubMed ID: 20874767

This article reveals that Ttyh1 expression is increased in the dentate gyrus in an animal model of epilepsy and Ttyh1 is involved in brain pathology.
Kumada T., et al. Ttyh1, a Ca(2+)-binding protein localized to the endoplasmic reticulum, is required for early embryonic development. Developmental Dynamics. 2010, 239(8):2233-45. PubMed ID: 20568244

This article suggests that the Ttyh1 involves in early embryogenesis, possibly by maintaining Ca(2+) homeostasis in the endoplasmic reticulum.

TTYH1 Preparation Options

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Reference

Jung E, et al. (2017). Tweety-Homolog 1 Drives Brain Colonization of Gliomas. Journal of Neuroscience. 37(29): 6837-6850.

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