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2.A.36.6.5
K+:H+ antiporter NhaP2 (catalyzes K+:H+ and Na+:H+ exchange; Resch et al., 2010). (84% identical to 2.A.36.6.3). A cation binding pocket in the middle of the membrane and a pathway leading to it have been identified (Mourin et al. 2018). There are 3 NhaP types in Vibrio cholerae (Vc-NhaP1, 2, and 3).  They are critical for maintenance of K+ homeostasis in the cytoplasm, and all 3 are required for cell survival at low pHs, suggesting a role in acid tolerance (Mourin et al. 2019). The solution structure of the N-terminal cytoplasmic domain of ~200 aas has been solved (Orriss et al. 2020). It reveals a compact N-terminal domain which resembles a Regulator of Conductance of K+ channels (RCK) domain connected to a more open C-terminal domain via a flexible 20 amino acid linker. NMR titration experiments showed that the protein binds ATP through its N-terminal domain (Orriss et al. 2020). Modified amiloride analogs with promising binding properties have been developed. Four selected drugs interacted with functionally important amino acid residues located on the cytoplasmic side of TMS VI, the extended chain region of TMSs V and XII, and the loop region between TMSs VIIII and IX (Mourin et al. 2021).

Accession Number:Q9KNM9
Protein Name:Cell volume regulation protein A homolog
Length:581
Molecular Weight:62698.00
Species:Vibrio cholerae [666]
Number of TMSs:13
Location1 / Topology2 / Orientation3: Cell inner membrane1 / Multi-pass membrane protein2
Substrate sodium(1+), potassium(1+), hydron

Cross database links:

RefSeq: NP_232330.1   
Entrez Gene ID: 2615531   
Pfam: PF03471    PF00999    PF02080   
KEGG: vch:VC2703   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005886 C:plasma membrane
GO:0005488 F:binding
GO:0003824 F:catalytic activity
GO:0015299 F:solute:hydrogen antiporter activity
GO:0006884 P:cell volume homeostasis
GO:0008152 P:metabolic process
GO:0006813 P:potassium ion transport
GO:0055085 P:transmembrane transport

References (1)

[1] “DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae.”  Heidelberg J.F.et.al.   10952301

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MDAVTINSFF MIGALLIGIS VLLSPVSSKL GIPILLVFLA VGMLAGEDGI GQIAFDNYPV 
61:	AYLVSNLALA IILLDGGMRT RVASFRVAFW PSVSLATLGV AVTTLLTGLL AMWLFNLSLL 
121:	QGVLVGAIVG STDAAAVFSL LKGRSLNERV GATLEIESGT NDPMAVFLTV TLIAVLGSAE 
181:	TNLSAGFLLL SFIQQFGVGA LLGLAGGWIL WWLINRNQLP EGLYSILAVS GGLMIFALSN 
241:	ALGGSGILSI YLTGLLLGNR PTRSRHAILN VLDGMTWLAQ IGMFLVLGLL VTPSELMEIA 
301:	LPGLALAVGM ILFARPIAVW IGLAPFKSFT AREKWFVSWV GLRGAVPIIL AVFPMMAGLP 
361:	NAQLYFNLAF FVVMVSLVVQ GGTLTKAMSL AKVELPPKPE PISRTGVEIY PTSEWELFIY 
421:	KLKADKWCIG EPLRNLFMPE GTRIAAVFRD NQLLHPSGST ELCEGDTLCV MAQERDLESL 
481:	SRLFSEAPEK ASLARFFGDF FLDIEAKLQD VALLYGLDLG ELEADAKLKD LVLEHLGETP 
541:	VLGDYFEWHG LQWVVADVVD WKVTKIGLRL PPEEELQEGA E