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2.A.36.2.2
The electroneutral Na+/Li+:H+ antiporter, Nha2. Catalyzes Na+:Li+ antiport; contributes to salt homeostasis. It correlates with heritable hypertension (Xiang et al., 2007) and is critical for insulin secretion (Deisl et al. 2013). Like electrogenic Na+/H+ exchangers, it has two conserved aspartyl residues in the Na+ binding site but seems to be electroneutral (Uzdavinys et al. 2017). The structure, mechanism and lipid-mediated remodeling of the mammalian Na+/H+ exchanger NHA2, linked to the pathogenesis of diabetes mellitus, have been described (Matsuoka et al. 2022). NHA2 consists of 14 TMSs, rather than the 13 previously observed in mammalian NHEs and related bacterial antiporters. The additional N-terminal helix in NHA2 forms a unique homodimer interface with a large intracellular gap between the protomers, which closes in the presence of phosphoinositol lipids. Possibly the additional N-terminal helix has evolved as a lipid-mediated remodeling switch for the regulation of NHA2 activity (Matsuoka et al. 2022).  

Accession Number:Q86UD5
Protein Name:Nha2
Length:537
Molecular Weight:57564.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:14
Location1 / Topology2 / Orientation3: Mitochondrion membrane1 / Multi-pass membrane protein2
Substrate lithium(1+), sodium(1+), hydron

Cross database links:

RefSeq: NP_849155.2   
Entrez Gene ID: 133308   
Pfam: PF00999   
OMIM: 611789  gene
KEGG: hsa:133308    hsa:133308   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0031966 C:mitochondrial membrane
GO:0015299 F:solute:hydrogen antiporter activity
GO:0015992 P:proton transport
GO:0006814 P:sodium ion transport
GO:0055085 P:transmembrane transport

References (8)

[1] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[2] “Generation and annotation of the DNA sequences of human chromosomes 2 and 4.”  Hillier L.W.et.al.   15815621
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[4] “A human Na+/H+ antiporter sharing evolutionary origins with bacterial NhaA may be a candidate gene for essential hypertension.”  Xiang M.et.al.   18000046
[5] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[6] “Generation and annotation of the DNA sequences of human chromosomes 2 and 4.”  Hillier L.W.et.al.   15815621
[7] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[8] “A human Na+/H+ antiporter sharing evolutionary origins with bacterial NhaA may be a candidate gene for essential hypertension.”  Xiang M.et.al.   18000046

External Searches:

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MGDEDKRITY EDSEPSTGMN YTPSMHQEAQ EETVMKLKGI DANEPTEGSI LLKSSEKKLQ 
61:	ETPTEANHVQ RLRQMLACPP HGLLDRVITN VTIIVLLWAV VWSITGSECL PGGNLFGIII 
121:	LFYCAIIGGK LLGLIKLPTL PPLPSLLGML LAGFLIRNIP VINDNVQIKH KWSSSLRSIA 
181:	LSIILVRAGL GLDSKALKKL KGVCVRLSMG PCIVEACTSA LLAHYLLGLP WQWGFILGFV 
241:	LGAVSPAVVV PSMLLLQGGG YGVEKGVPTL LMAAGSFDDI LAITGFNTCL GIAFSTGSTV 
301:	FNVLRGVLEV VIGVATGSVL GFFIQYFPSR DQDKLVCKRT FLVLGLSVLA VFSSVHFGFP 
361:	GSGGLCTLVM AFLAGMGWTS EKAEVEKIIA VAWDIFQPLL FGLIGAEVSI ASLRPETVGL 
421:	CVATVGIAVL IRILTTFLMV CFAGFNLKEK IFISFAWLPK ATVQAAIGSV ALDTARSHGE 
481:	KQLEDYGMDV LTVAFLSILI TAPIGSLLIG LLGPRLLQKV EHQNKDEEVQ GETSVQV