3.A.3.10.3
The endoplasmic reticular ATPase, Spf1 or Cod1. PIt pays a role in ER Mn2+ homeostasis by pumping Mn2+ into the ER lumen (Cronin et al., 2002; Cohen et al. 2013). Deletion of the gene results in ER stress and lowered Mn2+ in the ER lumen (Cohen et al. 2013). This SPF1-ATPase is a transmembrane helix dislocase, used to remove some mislocated TM proteins from the outer membranes of mitochondria (McKenna et al. 2020). Spf1p exhibits unique structures at its N-terminus, including two putative additional transmembrane domains, and a large insertion connecting the P domain with transmembrane segment M5 (Petrovich et al. 2021). The Spf1p P5A-ATPase "arm-like" domain is not essential for ATP hydrolysis but its deletion impairs autophosphorylation (Grenon et al. 2021). Structures of this dismutase and Msp1 reveal how they remove mislocalized TA proteins from the ER and outer mitochondrial membranes, respectively (Sinning and McDowell 2022). ATP hydrolytic activity of purified Spf1p correlates with micellar lipid fluidity and is dependent on conserved residues in transmembrane helix M1. Free movement of the M1 helix represent an energetic constraint on catalysis, and this constraint is likely lost in the purified preparations, resulting in protein with intrinsic spontaneous ATP hydrolytic activity. Removal of the N-terminal part of the protein apparently removes this activity (Ipsen and Sørensen 2022). Inhibition of P5A-ATPases such as Spf1p could potentiate metal ion-induced ER stress and proteotoxicity (Petrovich et al. 2022).
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| Accession Number: | P39986 |
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| Protein Name: | Manganese-transporting ATPase 1 |
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| Length: | 1215 |
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| Molecular Weight: | 135269.00 |
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| Species: | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [559292] |
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| Number of TMSs: | 12 |
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| Location1 / Topology2 / Orientation3: |
Endoplasmic reticulum membrane1 / Multi-pass membrane protein2 |
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| Substrate |
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1: MTKKSFVSSP IVRDSTLLVP KSLIAKPYVL PFFPLYATFA QLYFQQYDRY IKGPEWTFVY
61: LGTLVSLNIL VMLMPAWNVK IKAKFNYSTT KNVNEATHIL IYTTPNNGSD GIVEIQRVTE
121: AGSLQTFFQF QKKRFLWHEN EQVFSSPKFL VDESPKIGDF QKCKGHSGDL THLKRLYGEN
181: SFDIPIPTFM ELFKEHAVAP LFVFQVFCVA LWLLDEFWYY SLFNLFMIIS MEAAAVFQRL
241: TALKEFRTMG IKPYTINVFR NKKWVALQTN ELLPMDLVSI TRTAEESAIP CDLILLDGSA
301: IVNEAMLSGE STPLLKESIK LRPSEDNLQL DGVDKIAVLH GGTKALQVTP PEHKSDIPPP
361: PDGGALAIVT KTGFETSQGS LVRVMIYSAE RVSVDNKEAL MFILFLLIFA VIASWYVWVE
421: GTKMGRIQSK LILDCILIIT SVVPPELPME LTMAVNSSLA ALAKFYVYCT EPFRIPFAGR
481: IDVCCFDKTG TLTGEDLVFE GLAGISADSE NIRHLYSAAE APESTILVIG AAHALVKLED
541: GDIVGDPMEK ATLKAVGWAV ERKNSNYREG TGKLDIIRRF QFSSALKRSA SIASHNDALF
601: AAVKGAPETI RERLSDIPKN YDEIYKSFTR SGSRVLALAS KSLPKMSQSK IDDLNRDDVE
661: SELTFNGFLI FHCPLKDDAI ETIKMLNESS HRSIMITGDN PLTAVHVAKE VGIVFGETLI
721: LDRAGKSDDN QLLFRDVEET VSIPFDPSKD TFDHSKLFDR YDIAVTGYAL NALEGHSQLR
781: DLLRHTWVYA RVSPSQKEFL LNTLKDMGYQ TLMCGDGTND VGALKQAHVG IALLNGTEEG
841: LKKLGEQRRL EGMKMMYIKQ TEFMARWNQP QPPVPEPIAH LFPPGPKNPH YLKALESKGT
901: VITPEIRKAV EEANSKPVEV IKPNGLSEKK PADLASLLLN SAGDAQGDEA PALKLGDASC
961: AAPFTSKLAN VSAVTNIIRQ GRCALVNTIQ MYKILALNCL ISAYSLSIIY MAGVKFGDGQ
1021: ATVSGLLLSV CFLSISRGKP LEKLSKQRPQ SGIFNVYIMG SILSQFAVHI ATLVYITTEI
1081: YKLEPREPQV DLEKEFAPSL LNTGIFIIQL VQQVSTFAVN YQGEPFRENI RSNKGMYYGL
1141: LGVTGLALAS ATEFLPELNE AMKFVPMTDD FKIKLTLTLL LDFFGSWGVE HFFKFFFMDD
1201: KPSDISVQQV KIASK