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2.A.30.1.17
Solute carrier family 12 member 4 (Electroneutral potassium-chloride cotransporter 1, KCC1) (Erythroid K-Cl cotransporter 1) (hKCC1).  It is activated by cell swelling and may contribute to cell volume homeostasis as well as being involved in the regulation of basolateral Cl- exit in NaCl absorbing epithelia. Isoform 4 has no transport activity. The kinase, WNK3, activates NKCC1/2 and NCC but inhibits the KCCs (Cruz-Rangel et al. 2011).  Liu et al. 2019 presented cryo-EM structures of human KCC1 in potassium chloride or sodium chloride at 2.9- to 3.5-Å resolution. KCC1 exists as a dimer, with both extracellular and transmembrane domains involved in dimerization. The structural and functional analyses, along with computational studies, reveal one potassium site and two chloride sites in KCC1, which are all required for the ion transport activity. The structure reveals an inward-facing conformation, with the extracellular gate occluded. The KCC1 structures allowed the authors to model a potential ion transport mechanism in KCCs and provide a blueprint for drug design (Liu et al. 2019).

Accession Number:Q9UP95
Protein Name:Solute carrier family 12 member 4
Length:1085
Molecular Weight:120650.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate

Cross database links:

Genevestigator: Q9UP95
eggNOG: COG0531
HEGENOM: HOG000092644
Entrez Gene ID: 6560   
Pfam: PF00324    PF03522   
KEGG: hsa:6560   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005624 C:membrane fraction
GO:0015379 F:potassium:chloride symporter activity
GO:0006884 P:cell volume homeostasis
GO:0006813 P:potassium ion transport

References (8)

[1] “Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human. A new member of the cation-chloride cotransporter family.”  Gillen C.M.et.al.   8663127
[2] “Molecular identification and expression of erythroid K:Cl cotransporter in human and mouse erythroleukemic cells.”  Pellegrino C.M.et.al.   9516379
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[4] “A dominant negative mutant of the KCC1 K-Cl cotransporter: both N- and C-terminal cytoplasmic domains are required for K-Cl cotransport activity.”  Casula S.et.al.   11551954
[5] “Mouse K-Cl cotransporter KCC1: cloning, mapping, pathological expression, and functional regulation.”  Su W.et.al.   10564083
[6] “A quantitative atlas of mitotic phosphorylation.”  Dephoure N.et.al.   18669648
[7] “Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.”  Mayya V.et.al.   19690332
[8] “Similar Effects of all WNK3 Variants upon SLC12 Cotransporters.”  Cruz-Rangel S.et.al.   21613606

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FASTA formatted sequence
1:	MPHFTVVPVD GPRRGDYDNL EGLSWVDYGE RAELDDSDGH GNHRESSPFL SPLEASRGID 
61:	YYDRNLALFE EELDIRPKVS SLLGKLVSYT NLTQGAKEHE EAESGEGTRR RAAEAPSMGT 
121:	LMGVYLPCLQ NIFGVILFLR LTWMVGTAGV LQALLIVLIC CCCTLLTAIS MSAIATNGVV 
181:	PAGGSYFMIS RSLGPEFGGA VGLCFYLGTT FAAAMYILGA IEILLTYIAP PAAIFYPSGA 
241:	HDTSNATLNN MRVYGTIFLT FMTLVVFVGV KYVNKFASLF LACVIISILS IYAGGIKSIF 
301:	DPPVFPVCML GNRTLSRDQF DICAKTAVVD NETVATQLWS FFCHSPNLTT DSCDPYFMLN 
361:	NVTEIPGIPG AAAGVLQENL WSAYLEKGDI VEKHGLPSAD APSLKESLPL YVVADIATSF 
421:	TVLVGIFFPS VTGIMAGSNR SGDLRDAQKS IPVGTILAII TTSLVYFSSV VLFGACIEGV 
481:	VLRDKYGDGV SRNLVVGTLA WPSPWVIVIG SFFSTCGAGL QSLTGAPRLL QAIAKDNIIP 
541:	FLRVFGHGKV NGEPTWALLL TALIAELGIL IASLDMVAPI LSMFFLMCYL FVNLACAVQT 
601:	LLRTPNWRPR FKYYHWALSF LGMSLCLALM FVSSWYYALV AMLIAGMIYK YIEYQGAEKE 
661:	WGDGIRGLSL SAARYALLRL EEGPPHTKNW RPQLLVLLKL DEDLHVKYPR LLTFASQLKA 
721:	GKGLTIVGSV IQGSFLESYG EAQAAEQTIK NMMEIEKVKG FCQVVVASKV REGLAHLIQS 
781:	CGLGGMRHNS VVLGWPYGWR QSEDPRAWKT FIDTVRCTTA AHLALLVPKN IAFYPSNHER 
841:	YLEGHIDVWW IVHDGGMLML LPFLLRQHKV WRKCRMRIFT VAQMDDNSIQ MKKDLAVFLY 
901:	HLRLEAEVEV VEMHNSDISA YTYERTLMME QRSQMLRQMR LTKTEREREA QLVKDRHSAL 
961:	RLESLYSDEE DESAVGADKI QMTWTRDKYM TETWDPSHAP DNFRELVHIK PDQSNVRRMH 
1021:	TAVKLNEVIV TRSHDARLVL LNMPGPPRNS EGDENYMEFL EVLTEGLERV LLVRGGGREV 
1081:	ITIYS