SLC12A4 Membrane Protein Introduction

Introduction of SLC12A4

Solute carrier family 12 member 4 (also known as KCC1) is a chloride potassium symporter. Most K-Cl cotransport in the erythrocyte is attributed to KCC1. KCC1 activity is volume-, pH-, and chloride-dependent. The regulating mechanisms include cell volume, pH, PO2, magnesium, calcium, and oxidative changes. Another regulatory pathway of KCC1 activity is a phosphorylation/ dephosphorylation cycle with phosphorylation of the transporter or a regulatory protein decreasing KCC activity and dephosphorylation increasing activity.

Basic Information of SLC12A4
Protein Name Solute carrier family 12 member 4
Gene Name SLC12A4/KCC1
Aliases Electroneutral potassium-chloride cotransporter 1, Erythroid K-Cl cotransporter 1(hKCC1)
Organism Homo sapiens (Human)
UniProt ID Q9UP95
Transmembrane Times 12
Length (aa) 1085

Function of SLC12A4 Membrane Protein

Solute carrier family 12 member 4 (SLC12A4) can mediate electroneutral potassium-chloride cotransport when it is activated by cell swelling. It may help to cell volume homeostasis in single cells and also be involved in the regulation of basolateral Cl- exit in NaCl absorbing epithelia. It is different from other isoforms, SLC12A4 has no transport activity. Moreover, it also influences cation-coupled chloride cotransporters in human.

Two astrocytic subpopulations differing in the gene expression levels of K+/Cl− channels. Fig.1 Two astrocytic subpopulations differing in the gene expression levels of K+/Cl channels. (Jana, 2012)

Application of SLC12A4 Membrane Protein in Literature

  1. Casula S., et al. A dominant negative mutant of the KCC1 K-Cl cotransporter: both N- and C-terminal cytoplasmic domains are required for K-Cl cotransport activity. J Biol Chem. 2001, 276(45):41870-8. PubMed ID: 11551954

    The authors show us the importance of the N- and C-terminal cytoplasmic domains to its K-Cl cotransport function expressed in Xenopus oocytes. They conclude that C-terminal loss-of-function mutants lack a dominant negative phenotype.

  2. Zhang S., et al. The up-regulation of KCC1 gene expression in cervical cancer cells by IGF-II through the ERK1/2MAPK and PI3K/AKT pathways and its significance. Eur J Gynaecol Oncol. 2009, 30(1):29-34. PubMed ID: 19317253

    This article shows us that IGF-II can boost KCC1 gene expression in cervical cancer cells through the ERK1/2MAPK and PI3K/AKT signal transduction pathways.

  3. Shmukler B.E., et al. Structure and genetic polymorphism of the mouse KCC1 gene. Biochim Biophys Acta. 2000, 1492(2-3):353-61. PubMed ID: 11004507

    In this article, authors find that the intron 1 (AC) repeat in CAST/Ei and SPRET/Ei is not only more divergent in length but also underwent additional sequence variation. An intron 17 B1 Alu-like SINE present in all musculus strains is found to be absent from intron 17 in SPRET/Ei.

  4. Brown F.C., et al. Activation of the erythroid K-Cl cotransporter Kcc1 enhances sickle cell disease pathology in a humanized mouse model. BLOOD. 2015, 126(26):2863-70. PubMed ID: 26450986

    This article finds that a single mutant allele of Kcc1 is able to induce widespread sickling and tissue damage. It provides in vivo evidence that increasing KCC activity worsens end-organ damage and diminishes survival in sickle cell disease.

  5. Casula S., et al. Chemical crosslinking studies with the mouse Kcc1 K-Cl cotransporter. Blood Cells Mol Dis. 2009, 42(3):233-40. PubMed ID: 19380103

    The article shows that Kcc1 cross-linking is time-dependent and is independent of protein concentration. Kcc1 cross-linking by the cleavable cross-linker DTME is reversible. They support the oligomeric state of KCC polypeptides.

SLC12A4 Preparation Options

Membrane protein studies have got great progress over the past few years. Based on our versatile Magic™ membrane protein production platform, we can provide a series of membrane protein preparation services in reconstitution forms as well as multiple active formats for worldwide customers. Besides, aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-SLC12A4 antibody development services.

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


  1. Jana B, et al. (2012). Distinct expression/function of potassium and chloride channels contributes to the diverse volume regulation in cortical astrocytes of GFAP/EGFP mice. PLoS One. 7(1):e29725.

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