The following text describes a protein:
Function:
Electroneutral sodium:proton antiporter that regulates intracellular pH of sperm along with capacitation and fertility. Activated in response to egg-derived chemoattractants, couples membrane voltage to sodium:proton exchange and transduces membrane hyperpolarization to cytoplasmic alkalization to cAMP signaling and ultimately to sperm motility.
Miscellaneous:
MISCELLANEOUS: The VSD and CNBD domains are not functional in mammalian SLC9 orthologs. In addition, the conserved Asn-Asp/Asp-Asp motif that coordinates sodium ions in NHEs is lacking in mammalian SLC9C1 and SLC9C2, suggesting alternative transport mechanisms and/or substrates.
Subcellular Localization:
Cell projection, cilium, flagellum membrane; Multi-pass membrane protein. Note=Observed primarily in sperm flagellum and at the tip of the sperm head.
Domain:
The dimer domain comprises TM1-TM3 and TM8-TM10 regions. The dimerization interface is formed predominantly by tight interactions between TM1 on one protomer and TM8 on the other. It contains an hydrophobic cavity that accomodates phosphatidic acids likely playing an allosteric role; The transport core domain (TM4-TM6 and TM11-TM13) displays a typical sodium:proton exchanger (NHE) fold with a six transmembrane helix inverted repeat topology. It contains an Asn-Asp (Asn-237-Asp-238) sodium-coordinating motif characteristic of electroneutral NHEs; The voltage sensor domain (VSD) produces gating currents in response to hyperpolarization. It consists of four helices S1-S4 arranged in a bundle within the membrane. The extended S4 helix is essential for voltage sensing. The transmembrane part of S4 (residues 796-822) contains seven gating-charge residues in a canonical pattern (R/K-XX)n and interacts via salt bridges and hydrogen bonds with other charged residues in S1-S3 segments to form the charge transfer center. The extramembrane part of S4 (residues 823-857) is embedded within a network of intracellular coupling helices and may mediate their movement upon hyperpolarization. Unlike voltage-gated channels, there is no linker to directly connect the voltage sensor to the transporter domain; The cNMP-binding domain responds to cyclic nucleotides shifting the activation voltage near resting membrane potential. Has higher affinity for cAMP than cGMP.
Sequence:
MKKRVVKLRELVPAVAALAVAVLIQSATGSSGGSGHTPTTQATHADDHDLTTHNGTEEHDDGHDDGHDDLHAHAPKVIVFISGSCLFGAISRSLFKKLPIPYTVVLLILGAILGVVASNVPLVEEHTRDVAHMDPHVLLQIFLPVLIFESAFAMDVHTFMRSFSQVCILALFGLVVASVLTAVLAMNLFNYNWNFSEAMMFGAIMSATDPVAVVALLKDLGASKQLGTIIEGESLLNDGCAIVIFNVFMKMVFFPQLTSTVGQNVLYFLQVAVAGPLWGYAVAKVTVFFLSHIFNDALVEITITLAATYLTYYIGDIWLEVSGVLAVVVLGLIVNAEKTSISPEVEVFLHRFWEMLAYLANTLIFMMVGVVVTQKALVAVDKMDWFYLIILYLAITIIRGMVISLFSPILSRIGYGLTWRNAVIMTWGGLRGAVGLALALVVENLAGNDVIGSKFLFHTAGIVVLTLVINATTIQTLLRILGMSDISIPKRLAMAGAVRRIHEGQNRTLNMLKSDRFLADADWDIATAACEISDPYSALSDDENAPADELTLGERKSVCPGCKAMVPNEPSPREFADMMEEARLRMLKAEKISYWKQFEHGMLAREALRLLVQHAEVAADEKDQFILVDDLKKSWQIKGIYPWLKRKLEDLISEKKIAAIPMPKYKLGKLMYKICHHMAFEVTINIAIVLNIVPIIMEFVVQDKMASVSTMAAPGSTVSSEPSSLQKIEDALRISNYVFFVIYAIEAIVKILGLGRHYIVSHWNKFDAFILVVALVDIIIAETLLKGSITINLSSIKVVKLFRLLRGLRMLRLTKALIPKLILVVNGKINNQLSLGYDVGKGYIIGEEEVGKIIDRMVDNKKILRELKHISETGRLQVVKELGLLQREHPGIAVSVKTRQAIRTILNHSRETIHELQGAGLLDEMEAHKLELTVEIKMKRLMNAPSSIPPPPPENLLKNVSWLAGDMKLIDFIKARASLLHFDYGEVIVREGDESDGLFLIVSGLVKLYGKSAFLDHDNPPVTAGSEENEVFEDYLTVGNVIGEMGVLTKKPRNATVTCETTVQVYFITAEDMNIAIDTFTLYPSLEYRLWRVVAIRIATPLIMEQMAFQGWTQEKVKLHLERGYLVDLAESHFQFNIDATLEDVILINGTAYNAHTREEIRSPCLISRTVHKLTFQYTATEEPRLFVVRNAEYNGPILDGRLDVDSKRSLISITEISSNMCLKHAAELRQKNSKVMLSRKSSGAAAKEEEDCIPNTSDVEQAAGVSPSVPTKTTPKPKSFLPSLGLSMSKERVNGEAVEESPVKTKQGEETPETEEGAAPRVNV