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2.A.30.1.4
Bumetanide-sensitive NaCl/KCl symporter (basolateral), NKCC1 or SLC12A2 (may also transport NH4+ and water); (Worrell et al., 2008; Hamann et al., 2010). Loop diuretic and ion binding residues have been identified (Somasekharan et al., 2012).  NKCC1 is the major Cl--loader responsible for the depolarizing action of GABA/glycine receptors at postnatal days 3-5 in cochlear nucleus neurons (Witte et al. 2014). Its activity is stimulated by ammonia (Hertz et al. 2015).  NKCC maintains Cl- gradients to sustain pacemaker activity (TC# 1.A.1.5.10) in interstitial cells of Cajal (Zhu et al. 2016). It uses the existing Na+ and/or K+ gradients to move Cl- into or out of cells. NKCC1 plays fundamental roles in regulating trans-epithelial ion movement, cell volume, chloride homeostasis and neuronal excitability. Yang et al. 2020 reported a cryo-EM structure of human NKCC1 captured in a partially loaded, inward-open state. NKCC1 assembles into a dimer, with the first ten TMSs harboring the transport core and TM11-TM12 helices lining the dimer interface. TMSs 1 and 6 break alpha-helical geometry halfway across the lipid bilayer where ion binding sites are organized around these discontinuous regions. NKCC1 may harbor multiple extracellular entryways and intracellular exit sites, raising the possibility that K+, Na+, and Cl- ions may traverse along their own routes for translocation (Yang et al. 2020). It is present in the basolateral membrane of crypt epithelial cells and mediates uptake of these three ions into these cells (A. Quach, personal communication).

Accession Number:P55011
Protein Name:NKC1 aka SLC12A2 aka NKCC1
Length:1212
Molecular Weight:131447.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:11
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate

Cross database links:

RefSeq: NP_001037.1   
Entrez Gene ID: 6558   
Pfam: PF00324    PF08403   
OMIM: 600840  gene
KEGG: hsa:6558    hsa:6558   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005624 C:membrane fraction
GO:0051739 F:ammonia transmembrane transporter activity
GO:0008511 F:sodium:potassium:chloride symporter activity
GO:0006813 P:potassium ion transport
GO:0006814 P:sodium ion transport
GO:0070634 P:transepithelial ammonium transport
GO:0030321 P:transepithelial chloride transport
GO:0055085 P:transmembrane transport
GO:0016324 C:apical plasma membrane
GO:0016323 C:basolateral plasma membrane
GO:0060444 P:branching involved in mammary gland duct morphogenesis
GO:0050910 P:detection of mechanical stimulus involved in sensory perception of sound
GO:0060763 P:mammary duct terminal end bud growth
GO:0035264 P:multicellular organism growth

References (11)

[1] “Primary structure, functional expression, and chromosomal localization of the bumetanide-sensitive Na-K-Cl cotransporter in human colon.”  Payne J.A.et.al.   7629105
[2] “Quantitation of Na(+)-K(+)-2Cl(-) cotransport splice variants in human tissues using kinetic polymerase chain reaction.”  Vibat C.R.et.al.   11700976
[3] “ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.”  Matsuoka S.et.al.   17525332
[4] “Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.”  Cantin G.T.et.al.   18220336
[5] “A quantitative atlas of mitotic phosphorylation.”  Dephoure N.et.al.   18669648
[6] “Primary structure, functional expression, and chromosomal localization of the bumetanide-sensitive Na-K-Cl cotransporter in human colon.”  Payne J.A.et.al.   7629105
[7] “Quantitation of Na(+)-K(+)-2Cl(-) cotransport splice variants in human tissues using kinetic polymerase chain reaction.”  Vibat C.R.et.al.   11700976
[8] “ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.”  Matsuoka S.et.al.   17525332
[9] “Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.”  Cantin G.T.et.al.   18220336
[10] “A quantitative atlas of mitotic phosphorylation.”  Dephoure N.et.al.   18669648
[11] “Similar Effects of all WNK3 Variants upon SLC12 Cotransporters.”  Cruz-Rangel S.et.al.   21613606
Structure:
6PZT     

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MEPRPTAPSS GAPGLAGVGE TPSAAALAAA RVELPGTAVP SVPEDAAPAS RDGGGVRDEG 
61:	PAAAGDGLGR PLGPTPSQSR FQVDLVSENA GRAAAAAAAA AAAAAAAGAG AGAKQTPADG 
121:	EASGESEPAK GSEEAKGRFR VNFVDPAASS SAEDSLSDAA GVGVDGPNVS FQNGGDTVLS 
181:	EGSSLHSGGG GGSGHHQHYY YDTHTNTYYL RTFGHNTMDA VPRIDHYRHT AAQLGEKLLR 
241:	PSLAELHDEL EKEPFEDGFA NGEESTPTRD AVVTYTAESK GVVKFGWIKG VLVRCMLNIW 
301:	GVMLFIRLSW IVGQAGIGLS VLVIMMATVV TTITGLSTSA IATNGFVRGG GAYYLISRSL 
361:	GPEFGGAIGL IFAFANAVAV AMYVVGFAET VVELLKEHSI LMIDEINDIR IIGAITVVIL 
421:	LGISVAGMEW EAKAQIVLLV ILLLAIGDFV IGTFIPLESK KPKGFFGYKS EIFNENFGPD 
481:	FREEETFFSV FAIFFPAATG ILAGANISGD LADPQSAIPK GTLLAILITT LVYVGIAVSV 
541:	GSCVVRDATG NVNDTIVTEL TNCTSAACKL NFDFSSCESS PCSYGLMNNF QVMSMVSGFT 
601:	PLISAGIFSA TLSSALASLV SAPKIFQALC KDNIYPAFQM FAKGYGKNNE PLRGYILTFL 
661:	IALGFILIAE LNVIAPIISN FFLASYALIN FSVFHASLAK SPGWRPAFKY YNMWISLLGA 
721:	ILCCIVMFVI NWWAALLTYV IVLGLYIYVT YKKPDVNWGS STQALTYLNA LQHSIRLSGV 
781:	EDHVKNFRPQ CLVMTGAPNS RPALLHLVHD FTKNVGLMIC GHVHMGPRRQ AMKEMSIDQA 
841:	KYQRWLIKNK MKAFYAPVHA DDLREGAQYL MQAAGLGRMK PNTLVLGFKK DWLQADMRDV 
901:	DMYINLFHDA FDIQYGVVVI RLKEGLDISH LQGQEELLSS QEKSPGTKDV VVSVEYSKKS 
961:	DLDTSKPLSE KPITHKVEEE DGKTATQPLL KKESKGPIVP LNVADQKLLE ASTQFQKKQG 
1021:	KNTIDVWWLF DDGGLTLLIP YLLTTKKKWK DCKIRVFIGG KINRIDHDRR AMATLLSKFR 
1081:	IDFSDIMVLG DINTKPKKEN IIAFEEIIEP YRLHEDDKEQ DIADKMKEDE PWRITDNELE 
1141:	LYKTKTYRQI RLNELLKEHS STANIIVMSL PVARKGAVSS ALYMAWLEAL SKDLPPILLV 
1201:	RGNHQSVLTF YS