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2.A.30.1.8
Na+,K+,Cl--cotransporter, NKCC1or Slc12a2/a4, of 1136 aas and 12 TMSs.  Ion transport via an ortholog is oxygen-sensitive and is regulated by two different oxygen sensors in crucian carp (Carassius carassius) (Berenbrink et al. 2006). Chew et al. 2019 determined the cryo-EM structure which defined the architecture of this protein family and revealed how cytosolic and transmembrane domains are strategically positioned for communication. Structural analyses, functional characterizations and computational studies revealed the ion-translocation pathway, ion-binding sites and key residues involved in transport activity, thus providing insights into ion selectivity, coupling and translocation, and establishing a framework for understanding the physiological functions of CCCs as well as interpreting disease-related mutations (Chew et al. 2019). The 3-D structures of this protein and the humanKCC! (TC# 2.A.30.1.4) have been compared and reviewed (Delpire and Guo 2020). While cation-Cl- cotransporters share the overall architecture of carriers belonging to the amino acid-polyamine-organocation (APC) superfamily and some of their substrate binding sites, several new features have been revealed. (1) The large extracellular domain between TMSs 5 and 6 stabilizes the dimer and forms a cap that likely participates in extracellular gating. (2) Conservation of the K+ and Cl- binding sites and a second Cl- coordination site were revealed. (3) an extracellular gate is formed by conserved salt bridges between charged residues located toward the ends of TMSs 3 and 4, and there is an additional neighboring bridge in the hKCC1 structure. (4) Multiple points of contacts occur between the monomers forming the cotransporter homodimer units. These involve the TMSs, the COOH-terminal domains, and the large extracellular loop for hKCC1 (Delpire and Guo 2020).

Accession Number:Q6IQW8
Protein Name:Solute carrier family 12 (Potassium/chloride transporters), member 2
Length:1136
Molecular Weight:124123.00
Species:Danio rerio (Zebrafish) [7955]
Number of TMSs:12
Substrate

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MSASPPISAG DYLSAPEPDA LKPAGPTPSQ SRFQVDLVTE SAGDGETTVG FDSSPPEYVA 
61:	EPPPDGLRDS VSGGEKAKGR FRVVNFAASS PDAAPAETAQ NGDTVMSEGS LHSSTGGQQH 
121:	HHYDTHTNTY YLRTFGHNTI DAVPKIDFYR QTAAPLGEKL IRPTLSELHD ELDKEPFEDG 
181:	FANGEELTPA EESAAKDVSE SKGVVKFGWI KGVLVRCMLN IWGVMLFIRM TWIVGQAGIA 
241:	YSCIIVIMAT VVTTITGCST SAIATNGFVR GGGAYYLISR SLGPEFGGSI GLIFAFANAV 
301:	AVAMYVVGFA ETVVELLMDS GLLMIDQTND IRVIGTITVI LLLGISVAGM EWEAKAQIFL 
361:	LVILITAIFN YFIGSFIAVD SKKKFGFFSY DAGILAENFG PDFRGQTFFS VFSIFFPAAT 
421:	GILAGANISG DLADPQMAIP KGTLLAILIT GLVYVGVAIS AGACIVRDAT GIESNFTLIS 
481:	NCTDAACKYG YDFSSCRPTV EGEVSSCKFG LHNDFQVMSV VSGFSPLISA GIFSATLSSA 
541:	LASLVSAPKV FQALCKDNIY PGIAIFGKGY GKNNEPLRGY FLTFGIALAF ILIAELNVIA 
601:	PIISNFFLAS YALINFSVFH ASLANSPGWR PSFKYYNMWA SLAGAILCCV VMFIINWWAA 
661:	LLTNVIVLSL YIYVSYKKPD VNWGSSTQAL TYHQALTHSL QLCGVADHIK TFRPQCLVMT 
721:	GAPNSRPAIL HLVHAFTKNV GLMLCGHVRI SSRRPNFKEL NSDMLRYQRW LLNNNSKAFY 
781:	TCVVAEDLRQ GTQYMLQAAG LGRLRPNTLV IGFKNDWRIG DIKEVETYIN LIHDAFDFQY 
841:	GVVILRLREG LDISHIQGQD DSSGMKDVVV SVDISKDSDG DSSKPSSKAT SVQNSPAVQK 
901:	DEDDDGKAHT QPLLKKDKKS PTVPLNVADQ RLLDASQQFQ QKQGKGTVDV WWLFDDGGLT 
961:	LLIPYLIANK KKWKDCKIRV FIGGKINRID HDRRAMATLL SKFRIDFSDI TVLGDINTKP 
1021:	KSEGLTEFAE MIEPYKLRED DMEQEAAEKL KSEEPWRITD NELELYKAKG NRQIRLNELL 
1081:	KEHSSTANLI VMSMPLARKG AVSSALYMAW LDTLSKDLPP ILLVRGNHQS VLTFYS