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SLC9A9 Membrane Protein Introduction

Introduction of SLC9A9

SLC9A9, the full protein name is solute carrier family 9 A9. It is also known as sodium/hydrogen exchanger 9 or sodium-hydrogen antiporter 9 (NHE-9), encoded by the gene SLC9A9. SLC9A9 is ubiquitously expressed in the lymph node, esophagus, and 24 other tissues. It functions as a Na+/H+ antiporter. Especially, SLC9A9 is localized in the late recycling endosomes and involved in cation homeostasis.

Basic Information of SLC9A9
Protein Name Sodium/hydrogen exchanger 9
Gene Name SLC9A9
Aliases Na(+)/H(+) exchanger 9, NHE9, Nbla00118
Organism Homo sapiens (Human)
UniProt ID Q8IVB4
Transmembrane Times 13
Length (aa) 645
Sequence MERQSRVMSEKDEYQFQHQGAVELLVFNFLLILTILTIWLFKNHRFRFLHETGGAMVYGLIMGLILRYATAPTDIESGTVYDCVKLTFSPSTLLVNITDQVYEYKYKREISQHNINPHQGNAILEKMTFDPEIFFNVLLPPIIFHAGYSLKKRHFFQNLGSILTYAFLGTAISCIVIGLIMYGFVKAMIHAGQLKNGDFHFTDCLFFGSLMSATDPVTVLAIFHELHVDPDLYTLLFGESVLNDAVAIVLTYSISIYSPKENPNAFDAAAFFQSVGNFLGIFAGSFAMGSAYAIITALLTKFTKLCEFPMLETGLFFLLSWSAFLSAEAAGLTGIVAVLFCGVTQAHYTYNNLSSDSKIRTKQLFEFMNFLAENVIFCYMGLALFTFQNHIFNALFILGAFLAIFVARACNIYPLSFLLNLGRKQKIPWNFQHMMMFSGLRGAIAFALAIRNTESQPKQMMFTTTLLLVFFTVWVFGGGTTPMLTWLQIRVGVDLDENLKEDPSSQHQEANNLDKNMTKAESARLFRMWYSFDHKYLKPILTHSGPPLTTTLPEWCGPISRLLTSPQAYGEQLKEDDVECIVNQDELAINYQEQASSPCSPPARLGLDQKASPQTPGKENIYEGDLGLGGYELKLEQTLGQSQLN

Function of SLC9A9 Membrane Protein

The major function of SLC9A9 is to mediate the sodium-ion transport by exchanging intracellular hydrogen ions to external sodium ions and plays an important role in cell pH regulation and cell volume. SLC9A9 perfectly modulates pH within the endosomal lumen. It’s localized to the late recycling endosomes and plays a critical role in cation homeostasis. It has been reported that mutations in SLC9A9 gene are related to attention deficit and hyperactivity disorder and autism susceptibility. In addition, SLC9A9 plays a role in glioblastoma cells by microRNA-135a by limiting EGFR trafficking. Also, SLC9A9 is identified as an oncogenic member which can promote tumor progression, and it can be a prognostic indicator and therapeutic target in colorectal cancer. This function is mediated by EGFR signaling. Moreover, SLC9A9 can regulate ion uptake at the blood-brain barrier.

Structural modeling of NHE9 and Nhx1. Fig.1 Structural modeling of NHE9 and Nhx1. (Kondapalli, 2013)

Application of SLC9A9 Membrane Protein in Literature

  1. Gomez Zubieta D.M., et al. MicroRNA-135a regulates NHE9 to inhibit proliferation and migration of glioblastoma cells. Cell Commun Signal. 2017, 15(1): 55. PubMed ID: 29268774

    This article indicates that SLC9A9 plays a functional role in the proliferation and migration of glioblastoma cells via microRNA-135a.

  2. Nishizawa D., et al. Genome-wide scan identifies candidate loci related to remifentanil requirements during laparoscopic-assisted colectomy. Pharmacogenomics. 2018, 19(2): 113-127. PubMed ID: 29207912

    This article shows that the identified SNPs within NHE9 are associated with intraoperative opioid requirements, and this is meaningful for personalized pain treatment.

  3. Prasad H., et al. Functional analysis of Na+/H+ exchanger 9 variants identified in patients with autism and epilepsy. Matters (Zur). 2017. PubMed ID: 28815171

    This article shows the functions of NHE9 variants which are identified in patients with autism and epilepsy.

  4. Ueda M., et al. Up-regulation of SLC9A9 Promotes Cancer Progression and Is Involved in Poor Prognosis in Colorectal Cancer. Anticancer Res. 2017, 37(5): 2255-2263. PubMed ID: 28476790

    This article shows that NHE9 up-regulation promotes tumor progression, and indicates that NHE9 can be a prognostic indicator in colorectal cancer.

  5. Beydoun R., et al. Na+/H+ Exchanger 9 Regulates Iron Mobilization at the Blood-Brain Barrier in Response to Iron Starvation. J Biol Chem. 2017, 292(10): 4293-4301. PubMed ID: 28130443

    This article shows NHE9 plays an important regulatory role in iron mobilization pathway at the blood-brain barrier.

SLC9A9 Preparation Options

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Reference

  1. Kondapalli K C, et al. (2013). Functional evaluation of autism-associated mutations in NHE9. Nat Commun. 4:2510.

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