Solute carrier family 12 member 7 (SLC12A7)

The protein contains 1083 amino acids for an estimated molecular weight of 119106 Da.

 

Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May mediate K(+) uptake into Deiters' cells in the cochlea and contribute to K(+) recycling in the inner ear. Important for the survival of cochlear outer and inner hair cells and the maintenance of the organ of Corti. May be required for basolateral Cl(-) extrusion in the kidney and contribute to renal acidification (By similarity). (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 0%
Model score: 0
No model available.

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VariantDescription
dbSNP:rs4526148

No binding partner found

The reference OMIM entry for this protein is 604879

Solute carrier family 12 (potassium/chloride transporter), member 7; slc12a7
Potassium-chloride cotransporter 4; kcc4

Cation chloride cotransporters, including the potassium-chloride cotransporters (KCCs), are involved in the electroneutral movement of ions across the plasma membrane. Under most physiologic conditions, KCCs function as efflux pathways (Mount et al., 1999).

CLONING

By searching EST databases, Mount et al. (1999) identified a cDNA encoding SLC12A7, which they initially termed KCC3 but later renamed KCC4. The deduced 1,083-amino acid SLC12A7 protein contains 12 membrane-spanning segments, 8 phosphorylation sites, 7 of which are in the C terminus, and 4 potential N-glycosylation sites. SLC12A7 shares 65% amino acid identity with SLC12A4 (604119) and 66% identity with SLC12A6 (604878). Northern blot analysis detected a 5.3-kb SLC12A7 transcript in most tissues tested, with highest expression in heart and kidney and little or no expression in adult brain. Functional analysis confirmed that SLC12A7 is a KCC.

MAPPING

By radiation hybrid and somatic cell hybrid analyses, Mount et al. (1999) mapped the SLC12A7 gene, which contains marker D5S110, to 5p15.3.

ANIMAL MODEL

Boettger et al. (2002) generated mice constitutively lacking KCC4, which is predominantly expressed in kidney, heart, lung, and liver. Kcc4 -/- mice were born at the expected mendelian ratio. They were viable and fertile; however, their body weight was roughly 90% that of their littermates. Mice had normal hearing loss at postnatal day 14, indicated by normal auditory brainstem responses. Hearing deteriorated quickly during the following week, after which mice were nearly deaf, with a hearing loss of 70 to 80 decibels. Histologic analysis revealed that the inner ear developed normally and could not be distinguished from those of wildtype animals at postnatal day 14. At postnatal day 21, however, outer hair cells of basal turns of the cochlea were almost totally absent, whereas inner hair cells were still present. The degeneration proceeded from basal to apical turns. In adult knockout mice, the organ of Corti was lost completely in basal turns. In apical turns, some hair cells survived, accounting for the residual hearing ability in adult mice. Even in adult mice, there was no collapse of the Reissner membrane, which separates the scala media from the scala vestibuli, suggesting that Kcc4 is not essential for endolymph production. Outer hair cells of Kcc4 -/- mice degenerated before Deiters cells were lost, although Deiters cells and not outer hair cells normally express Kcc4 at this stage. This is consistent with a disturbance of extracellular homeostasis due to impaired salt uptake by Deiters cells, and may lead to death of outer hair cells by osmotic stress or membrane depolarization. Deafness in Kcc4 -/- mice was associated with renal tubular acidosis. The urine of knockout mice was more alkaline than that of wildtype littermates, whereas concentrations of sodium, potassium, and chloride were not changed. Blood gas analysis indicated a compensated metabolic acidosis with significantly decreased base excess. Immunofluorescence revealed that Kcc4 is expressed in basolateral membranes of several nephron segments. Intracellular chloride concentration was increased in proximal tubules and particularly in alpha-intercalated cells of knockout mice. Considering the prominent chloride/bicarbonate exchange activity in alpha-intercalated cells, the rise in intracellular chloride predicts a more alkaline intracellular pH in the knockout mice. This will dec ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604879 was added.