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Identification
HMDB Protein ID HMDBP03029
Secondary Accession Numbers
  • 8554
  • HMDBP03520
Name Solute carrier family 12 member 4
Synonyms
  1. Electroneutral potassium-chloride cotransporter 1
  2. Erythroid K-Cl cotransporter 1
  3. hKCC1
Gene Name SLC12A4
Protein Type Transporter
Biological Properties
General Function Involved in transport
Specific Function Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia. Isoform 4 has no transport activity
Pathways Not Available
Reactions Not Available
GO Classification
Component
membrane
cell part
membrane part
intrinsic to membrane
integral to membrane
Function
transmembrane transporter activity
substrate-specific transmembrane transporter activity
ion transmembrane transporter activity
transporter activity
anion transmembrane transporter activity
anion:cation symporter activity
cation:chloride symporter activity
Process
sodium ion transport
establishment of localization
transport
chloride transport
transmembrane transport
anion transport
inorganic anion transport
monovalent inorganic cation transport
ion transport
cation transport
Cellular Location
  1. Membrane
  2. Multi-pass membrane protein
Gene Properties
Chromosome Location Chromosome:1
Locus 16q22.1
SNPs SLC12A4
Gene Sequence
>3258 bp
ATGCCTCACTTCACCGTGGTGCCAGTGGACGGGCCGAGGCGCGGCGACTATGACAACCTC
GAGGGGCTCAGTTGGGTGGACTACGGGGAGCGCGCCGAGCTGGATGACTCGGACGGACAT
GGCAACCACAGAGAGAGCAGCCCTTTTCTTTCCCCCTTGGAGGCTTCCAGAGGAATTGAC
TACTATGACAGGAACCTGGCACTGTTTGAGGAAGAGCTGGACATCCGCCCAAAGGTATCG
TCTCTTCTGGGAAAGCTCGTCAGCTACACCAACCTCACCCAGGGCGCCAAAGAGCATGAG
GAGGCCGAGAGTGGGGAGGGCACCCGCCGGAGGGCAGCCGAGGCACCCAGCATGGGCACC
CTCATGGGGGTGTACCTGCCCTGCCTGCAGAATATCTTTGGGGTTATCCTCTTCCTGCGG
CTGACCTGGATGGTGGGCACAGCAGGTGTGCTACAGGCCCTCCTCATCGTGCTTATCTGC
TGCTGTTGTACCCTGCTGACGGCCATCTCCATGAGTGCCATCGCCACCAACGGTGTGGTT
CCAGCTGGGGGCTCCTATTTCATGATCTCTCGTTCACTGGGGCCAGAATTTGGAGGTGCT
GTGGGCCTGTGCTTCTACCTGGGAACAACATTCGCAGCAGCCATGTACATCCTGGGGGCC
ATCGAGATCTTGCTGACCTACATTGCCCCACCAGCTGCCATTTTTTACCCATCGGGTGCT
CATGACACGTCGAATGCCACTTTGAACAATATGCGTGTGTATGGGACCATTTTCCTGACC
TTCATGACCCTGGTGGTGTTTGTGGGGGTCAAGTATGTGAACAAATTTGCCTCGCTCTTC
CTGGCCTGTGTGATCATCTCCATCCTCTCCATCTATGCTGGGGGCATAAAGTCTATATTT
GACCCTCCCGTGTTTCCGGTATGCATGCTGGGCAACAGGACCCTGTCCCGGGACCAGTTT
GACATCTGTGCCAAGACAGCTGTAGTGGACAATGAGACAGTGGCCACCCAGCTATGGAGT
TTCTTCTGCCACAGCCCCAACCTTACGACCGACTCCTGTGACCCCTACTTCATGCTCAAC
AATGTGACCGAGATCCCTGGCATCCCCGGGGCAGCTGCTGGTGTGCTCCAGGAAAACCTG
TGGAGCGCCTACCTGGAGAAGGGTGACATCGTGGAGAAGCATGGGCTGCCCTCCGCAGAT
GCCCCGAGCCTGAAGGAGAGCCTGCCTCTGTACGTGGTCGCTGACATCGCCACATCCTTC
ACCGTGCTGGTCGGCATCTTCTTCCCTTCTGTAACAGGCATCATGGCTGGCTCAAACCGC
TCTGGGGACCTTCGTGACGCCCAGAAGTCTATCCCTGTGGGGACCATTCTGGCCATCATT
ACAACTTCCCTCGTGTACTTCAGCAGTGTGGTTCTCTTTGGTGCCTGCATTGAGGGTGTG
GTTCTCCGGGACAAGTATGGCGATGGTGTCAGCAGGAACTTGGTGGTGGGCACACTGGCC
TGGCCTTCACCCTGGGTCATCGTCATCGGCTCCTTCTTTTCAACGTGTGGCGCTGGCCTC
CAGAGCCTCACAGGGGCACCACGCCTATTGCAGGCCATTGCCAAGGACAACATCATCCCC
TTCCTCCGGGTGTTTGGCCACGGGAAGGTGAATGGTGAACCCACATGGGCACTCCTCCTG
ACGGCACTCATCGCCGAGCTGGGCATCCTCATCGCCTCCCTCGACATGGTGGCCCCCATC
TTATCCATGTTCTTTCTGATGTGCTACCTGTTCGTGAACCTCGCCTGTGCGGTGCAGACA
CTCCTGAGGACCCCCAACTGGCGGCCCCGGTTCAAGTACTATCACTGGGCGCTGTCCTTC
CTGGGCATGAGTCTCTGCCTGGCCCTTATGTTTGTCTCCTCCTGGTACTATGCCCTGGTG
GCCATGCTCATCGCCGGCATGATCTACAAATACATCGAGTACCAAGGGGCTGAGAAGGAG
TGGGGTGACGGGATCCGAGGCCTGTCCCTGAGCGCTGCCCGCTACGCGCTGTTGCGGCTG
GAGGAGGGGCCTCCTCACACCAAGAACTGGCGGCCGCAGCTGCTGGTGCTGCTGAAGCTG
GACGAGGACCTCCACGTGAAGTACCCGCGGCTCCTCACCTTCGCCTCCCAGCTCAAGGCT
GGCAAGGGCCTGACCATTGTTGGTTCTGTCATCCAGGGGAGCTTCTTGGAGAGCTATGGC
GAGGCTCAGGCCGCCGAGCAGACCATCAAGAACATGATGGAAATTGAGAAGGTGAAGGGC
TTCTGCCAGGTGGTGGTGGCCAGCAAGGTGCGGGAGGGGCTGGCCCACCTCATCCAGTCC
TGTGGCCTGGGAGGCATGCGGCATAACTCCGTGGTGCTGGGCTGGCCCTACGGCTGGCGA
CAGAGCGAGGACCCCCGTGCCTGGAAGACCTTCATTGACACCGTGCGCTGCACTACGGCT
GCCCACCTGGCCCTGCTCGTGCCCAAGAACATCGCCTTCTACCCCAGCAACCACGAGCGC
TACCTGGAGGGCCACATAGACGTGTGGTGGATCGTGCACGATGGTGGCATGCTCATGCTT
CTGCCCTTCCTGCTGCGCCAGCATAAGGTCTGGAGGAAGTGCCGGATGCGCATCTTCACA
GTGGCCCAGATGGATGACAACAGCATCCAGATGAAGAAGGACCTGGCTGTCTTTCTGTAC
CATCTGCGCCTTGAGGCCGAGGTGGAGGTGGTGGAGATGCATAACAGTGACATCTCTGCA
TACACCTACGAGCGGACGCTGATGATGGAGCAGCGGTCGCAGATGCTGCGGCAGATGAGA
CTGACCAAGACTGAGCGGGAGCGAGAAGCCCAGCTGGTCAAGGATCGGCACTCGGCCCTG
CGGCTGGAGAGCCTGTACTCGGACGAGGAAGATGAGTCTGCAGTGGGGGCTGACAAGATC
CAGATGACGTGGACCAGGGACAAGTACATGACTGAGACCTGGGACCCCAGCCATGCCCCT
GACAATTTCCGGGAGCTGGTGCACATTAAGCCGGACCAATCCAATGTGCGGCGCATGCAC
ACTGCTGTGAAGCTCAATGAAGTCATTGTCACGCGCTCCCACGACGCCCGCCTGGTTCTC
CTAAACATGCCTGGCCCACCCAGGAACAGTGAGGGCGACGAGAACTACATGGAGTTCCTC
GAGGTGCTGACCGAGGGCCTTGAGCGGGTGCTGTTGGTGCGCGGTGGTGGCCGTGAAGTC
ATCACCATCTACTCCTGA
Protein Properties
Number of Residues 1085
Molecular Weight 120648.7
Theoretical pI 6.41
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 119-139
  • 149-169
  • 215-235
  • 253-273
  • 276-296
  • 356-376
  • 408-428
  • 453-473
  • 494-514
  • 567-587
  • 628-648
  • 845-865
Protein Sequence
>Solute carrier family 12 member 4
MPHFTVVPVDGPRRGDYDNLEGLSWVDYGERAELDDSDGHGNHRESSPFLSPLEASRGID
YYDRNLALFEEELDIRPKVSSLLGKLVSYTNLTQGAKEHEEAESGEGTRRRAAEAPSMGT
LMGVYLPCLQNIFGVILFLRLTWMVGTAGVLQALLIVLICCCCTLLTAISMSAIATNGVV
PAGGSYFMISRSLGPEFGGAVGLCFYLGTTFAAAMYILGAIEILLTYIAPPAAIFYPSGA
HDTSNATLNNMRVYGTIFLTFMTLVVFVGVKYVNKFASLFLACVIISILSIYAGGIKSIF
DPPVFPVCMLGNRTLSRDQFDICAKTAVVDNETVATQLWSFFCHSPNLTTDSCDPYFMLN
NVTEIPGIPGAAAGVLQENLWSAYLEKGDIVEKHGLPSADAPSLKESLPLYVVADIATSF
TVLVGIFFPSVTGIMAGSNRSGDLRDAQKSIPVGTILAIITTSLVYFSSVVLFGACIEGV
VLRDKYGDGVSRNLVVGTLAWPSPWVIVIGSFFSTCGAGLQSLTGAPRLLQAIAKDNIIP
FLRVFGHGKVNGEPTWALLLTALIAELGILIASLDMVAPILSMFFLMCYLFVNLACAVQT
LLRTPNWRPRFKYYHWALSFLGMSLCLALMFVSSWYYALVAMLIAGMIYKYIEYQGAEKE
WGDGIRGLSLSAARYALLRLEEGPPHTKNWRPQLLVLLKLDEDLHVKYPRLLTFASQLKA
GKGLTIVGSVIQGSFLESYGEAQAAEQTIKNMMEIEKVKGFCQVVVASKVREGLAHLIQS
CGLGGMRHNSVVLGWPYGWRQSEDPRAWKTFIDTVRCTTAAHLALLVPKNIAFYPSNHER
YLEGHIDVWWIVHDGGMLMLLPFLLRQHKVWRKCRMRIFTVAQMDDNSIQMKKDLAVFLY
HLRLEAEVEVVEMHNSDISAYTYERTLMMEQRSQMLRQMRLTKTEREREAQLVKDRHSAL
RLESLYSDEEDESAVGADKIQMTWTRDKYMTETWDPSHAPDNFRELVHIKPDQSNVRRMH
TAVKLNEVIVTRSHDARLVLLNMPGPPRNSEGDENYMEFLEVLTEGLERVLLVRGGGREV
ITIYS
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q9UP95
UniProtKB/Swiss-Prot Entry Name S12A4_HUMAN
PDB IDs Not Available
GenBank Gene ID U55054
GeneCard ID SLC12A4
GenAtlas ID SLC12A4
HGNC ID HGNC:10913
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  3. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  4. Gillen CM, Brill S, Payne JA, Forbush B 3rd: Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human. A new member of the cation-chloride cotransporter family. J Biol Chem. 1996 Jul 5;271(27):16237-44. [PubMed:8663127 ]
  5. Pellegrino CM, Rybicki AC, Musto S, Nagel RL, Schwartz RS: Molecular identification and expression of erythroid K:Cl cotransporter in human and mouse erythroleukemic cells. Blood Cells Mol Dis. 1998 Mar;24(1):31-40. [PubMed:9516379 ]
  6. Casula S, Shmukler BE, Wilhelm S, Stuart-Tilley AK, Su W, Chernova MN, Brugnara C, Alper SL: 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 Nov 9;276(45):41870-8. Epub 2001 Sep 10. [PubMed:11551954 ]
  7. Su W, Shmukler BE, Chernova MN, Stuart-Tilley AK, de Franceschi L, Brugnara C, Alper SL: Mouse K-Cl cotransporter KCC1: cloning, mapping, pathological expression, and functional regulation. Am J Physiol. 1999 Nov;277(5 Pt 1):C899-912. [PubMed:10564083 ]