ZDHHC17 Membrane Protein Introduction

Introduction of ZDHHC17

Palmitoyltransferase ZDHHC17 is encoded by the ZDHHC17 gene. ZDHHC17 has two distinct features compared with other DHHCs, it has seven cytoplasmic ankyrin repeats at the N terminus and six predicted transmembrane helices instead of four. DHHC17 is localized to the Golgi membrane, and in humans, it is highly expressed in the brain. DHHC17 has been shown to recruit via its seven-AR domain. It palmitoylates many synaptic proteins, including cysteine string protein (CSP), GluA1, GluA2, PSD95, synaptosomal-associated protein 25 (SNAP25), synaptotagmin 1 (SYT1), the HD disease-causing protein huntingtin (HTT).

Basic Information of ZDHHC17
Protein Name	Palmitoyltransferase ZDHHC17
Gene Name	ZDHHC17, HIP14, HSPC294
Aliases	Huntingtin yeast partner H, Huntingtin-interacting protein 14 (HIP-14), Huntingtin-interacting protein 3 (HIP-3), Huntingtin-interacting protein H, Putative MAPK-activating protein PM11, Putative NF-kappa-B-activating protein 205, Zinc finger DHHC domain-containing protein 17 (DHHC-17)
Organism	Homo sapiens (Human)
UniProt ID	Q8IUH5
Transmembrane Times	6
Length (aa)	632
Sequence	MQREEGFNTKMADGPDEYDTEAGCVPLLHPEEIKPQSHYNHGYGEPLGRKTHIDDYSTWDIVKATQYGIYERCRELVEAGYDVRQPDKENVTLLHWAAINNRIDLVKYYISKGAIVDQLGGDLNSTPLHWATRQGHLSMVVQLMKYGADPSLIDGEGCSCIHLAAQFGHTSIVAYLIAKGQDVDMMDQNGMTPLMWAAYRTHSVDPTRLLLTFNVSVNLGDKYHKNTALHWAVLAGNTTVISLLLEAGANVDAQNIKGESALDLAKQRKNVWMINHLQEARQAKGYDNPSFLRKLKADKEFRQKVMLGTPFLVIWLVGFIADLNIDSWLIKGLMYGGVWATVQFLSKSFFDHSMHSALPLGIYLATKFWMYVTWFFWFWNDLNFLFIHLPFLANSVALFYNFGKSWKSDPGIIKATEEQKKKTIVELAETGSLDLSIFCSTCLIRKPVRSKHCGVCNRCIAKFDHHCPWVGNCVGAGNHRYFMGYLFFLLFMICWMIYGCISYWGLHCETTYTKDGFWTYITQIATCSPWMFWMFLNSVFHFMWVAVLLMCQMYQISCLGITTNERMNARRYKHFKVTTTSIESPFNHGCVRNIIDFFEFRCCGLFRPVIVDWTRQYTIEYDQISGSGYQLV

Function of ZDHHC17 Membrane Protein

ZDHHC17 was recently identified as a key player in ischemic stroke and a regulator of neuronal cell death. In addition to its well-studied function in protein palmitoylation, other roles of ZDHHC17 need to be identified clearly, including the mediation of Mg²⁺ transport, regulation of Ca²⁺ channel functions and activation of c-Jun N-terminus kinase (JNK) pathways. Moreover, ZDHHC17 is responsible for palmitoylation of large-conductance calcium- and voltage-activated potassium (BK) channels, which control membrane potential and calcium influx. ZDHHC17 may be involved in the sorting or targeting of critical proteins involved in the initiating events of endocytosis at the plasma membrane. However, the roles and molecular mechanisms of ZDHHC17 in neuronal development and function are not yet fully understood.

ZDHHC17 Membrane Protein Introduction Fig.1 DHHC PAT domain structure and membrane topology. (Sanders, 2015)

Application of ZDHHC17 Membrane Protein in Literature

Shi W., et al. ZDHHC17 promotes axon outgrowth by regulating TrkA-tubulin complex formation. Molecular and Cellular Neuroscience. 2015, 68: 194-202. PubMed ID: 26232532

This article finds that ZDHHC17 is a neuron-intrinsic factor for axon growth that is crucial for TrkA-tubulin interaction, which regulates signal transmission, including ERK1/2 phosphorylation.
Lemonidis K., et al. Identification of a Novel Sequence Motif Recognized by the Ankyrin Repeat Domain of zDHHC17/13 S-Acyltransferases. Journal of Biological Chemistry. 2015, 290(36): 21939-50. PubMed ID: 26198635

This article identifies variations of a novel unstructured peptide motif in many proteins, which is specifically required for binding to the AR domains of zDHHC17 and zDHHC13.
Sanders S.S., et al. Huntingtin interacting proteins 14 and 14-like are required for chorioallantoic fusion during early placental development. Developmental Biology. 2015, 397(2): 257-66. PubMed ID: 25478910

This article suggests that none of the other DHHC PATs are compensating for the loss of Hip14 and Hip14l by up-regulation of expression at the mRNA level.
Sanders S.S., et al. Sudden death due to paralysis and synaptic and behavioral deficits when Hip14/Zdhhc17 is deleted in adult mice. BMC Biol. 2016, 14(1): 108. PubMed ID: 27927242

This article reveals that HIP14 is essential for the maintenance of life and neuronal integrity in the adult mouse.
Butland S.L., et al. The palmitoyl acyltransferase HIP14 shares a high proportion of interactors with huntingtin: implications for a role in the pathogenesis of Huntington's disease. Human Molecular Genetics. 2014, 23(15): 4142-60. PubMed ID: 24705354

This article suggests the involvement of multiple candidate HIP14 substrates and regulators in HD, highlighting the significance of palmitoylation by HIP14 is a key contributor to the pathogenesis of the disease.

ZDHHC17 Preparation Options

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During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are happy to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

Sanders S S and Hayden M R. (2015). Aberrant palmitoylation in Huntington disease. Biochemical Society Transactions. 43(2): 205-10.

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