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2.A.30.1.15
KCl symporter, KCC3 (Andermann Syndrome protein) of 1150 aas and 12 TMSs. Erythroid-specific inactivation of Slc12a6/Kcc3 by EpoR promoter-driven Cre expression reduces K-Cl cotransport activity in mouse erythrocytes (Shmukler et al. 2022). Both KCC3b and KCC3a seem to be needed for maintaining cell volume during enhanced inward cotransport of Na+-glucose in proximal tubules and Na+-HCO3- in intercalated cells (Ferdaus and Delpire 2023). In addition, apical KCC3a might couple to pendrin function to recycle Cl-, particularly in conditions of low salt diet and therefore low Cl- delivery to the distal tubule. This function is critical in alkalemia, and KCC3a function in the pendrin-expressing cells may contribute to the K+ loss which is observed in alkalemia (Ferdaus and Delpire 2023).

Accession Number:Q9UHW9
Protein Name:KCC3
Length:1150
Molecular Weight:127617.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate chloride, potassium(1+)

Cross database links:

RefSeq: NP_005126.1    NP_598408.1   
Entrez Gene ID: 9990   
Pfam: PF00324    PF03522   
OMIM: 218000  phenotype
604878  gene
KEGG: hsa:9990   

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:0006873 P:cellular ion homeostasis
GO:0006821 P:chloride transport
GO:0006813 P:potassium ion transport
GO:0008217 P:regulation of blood pressure
GO:0006814 P:sodium ion transport
GO:0055085 P:transmembrane transport
GO:0016323 C:basolateral plasma membrane
GO:0016021 C:integral to membrane
GO:0001525 P:angiogenesis
GO:0071477 P:cellular hypotonic salinity response

References (21)

[1] “Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporter.”  Race J.E.et.al.   10600773
[2] “Cloning, characterization, and chromosomal location of a novel human K+-Cl- cotransporter.”  Hiki K.et.al.   10187864
[3] “Cloning and characterization of KCC3 and KCC4, new members of the cation-chloride cotransporter gene family.”  Mount D.B.et.al.   10347194
[4] “The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum.”  Howard H.C.et.al.   12368912
[5] “The full-ORF clone resource of the German cDNA consortium.”  Bechtel S.et.al.   17974005
[6] “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
[7] “A quantitative atlas of mitotic phosphorylation.”  Dephoure N.et.al.   18669648
[8] “Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.”  Mayya V.et.al.   19690332
[9] “Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporter.”  Race J.E.et.al.   10600773
[10] “Cloning, characterization, and chromosomal location of a novel human K+-Cl- cotransporter.”  Hiki K.et.al.   10187864
[11] “Cloning and characterization of KCC3 and KCC4, new members of the cation-chloride cotransporter gene family.”  Mount D.B.et.al.   10347194
[12] “The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum.”  Howard H.C.et.al.   12368912
[13] “NH2-terminal heterogeneity in the KCC3 K+-Cl- cotransporter.”  Mercado A.et.al.   16048901
[14] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[15] “Analysis of the DNA sequence and duplication history of human chromosome 15.”  Zody M.C.et.al.   16572171
[16] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[17] “The full-ORF clone resource of the German cDNA consortium.”  Bechtel S.et.al.   17974005
[18] “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
[19] “A quantitative atlas of mitotic phosphorylation.”  Dephoure N.et.al.   18669648
[20] “Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.”  Mayya V.et.al.   19690332
[21] “Similar Effects of all WNK3 Variants upon SLC12 Cotransporters.”  Cruz-Rangel S.et.al.   21613606
Structure:
6Y5R   6Y5V     

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Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
FASTA formatted sequence 
1:	MHPPETTTKM ASVRFMVTPT KIDDIPGLSD TSPDLSSRSS SRVRFSSRES VPETSRSEPM 
61:	SEMSGATTSL ATVALDPPSD RTSHPQDVIE DLSQNSITGE HSQLLDDGHK KARNAYLNNS 
121:	NYEEGDEYFD KNLALFEEEM DTRPKVSSLL NRMANYTNLT QGAKEHEEAE NITEGKKKPT 
181:	KTPQMGTFMG VYLPCLQNIF GVILFLRLTW VVGTAGVLQA FAIVLICCCC TMLTAISMSA 
241:	IATNGVVPAG GSYFMISRAL GPEFGGAVGL CFYLGTTFAA AMYILGAIEI FLVYIVPRAA 
301:	IFHSDDALKE SAAMLNNMRV YGTAFLVLMV LVVFIGVRYV NKFASLFLAC VIVSILAIYA 
361:	GAIKSSFAPP HFPVCMLGNR TLSSRHIDVC SKTKEINNMT VPSKLWGFFC NSSQFFNATC 
421:	DEYFVHNNVT SIQGIPGLAS GIITENLWSN YLPKGEIIEK PSAKSSDVLG SLNHEYVLVD 
481:	ITTSFTLLVG IFFPSVTGIM AGSNRSGDLK DAQKSIPIGT ILAILTTSFV YLSNVVLFGA 
541:	CIEGVVLRDK FGDAVKGNLV VGTLSWPSPW VIVIGSFFST CGAGLQSLTG APRLLQAIAK 
601:	DNIIPFLRVF GHSKANGEPT WALLLTAAIA ELGILIASLD LVAPILSMFF LMCYLFVNLA 
661:	CALQTLLRTP NWRPRFRYYH WALSFMGMSI CLALMFISSW YYAIVAMVIA GMIYKYIEYQ 
721:	GAEKEWGDGI RGLSLSAARF ALLRLEEGPP HTKNWRPQLL VLLKLDEDLH VKHPRLLTFA 
781:	SQLKAGKGLT IVGSVIVGNF LENYGEALAA EQTIKHLMEA EKVKGFCQLV VAAKLREGIS 
841:	HLIQSCGLGG MKHNTVVMGW PNGWRQSEDA RAWKTFIGTV RVTTAAHLAL LVAKNISFFP 
901:	SNVEQFSEGN IDVWWIVHDG GMLMLLPFLL KQHKVWRKCS IRIFTVAQLE DNSIQMKKDL 
961:	ATFLYHLRIE AEVEVVEMHD SDISAYTYER TLMMEQRSQM LRHMRLSKTE RDREAQLVKD 
1021:	RNSMLRLTSI GSDEDEETET YQEKVHMTWT KDKYMASRGQ KAKSMEGFQD LLNMRPDQSN 
1081:	VRRMHTAVKL NEVIVNKSHE AKLVLLNMPG PPRNPEGDEN YMEFLEVLTE GLERVLLVRG 
1141:	GGSEVITIYS