3.A.3.10.19
Mn2+-exporting ATPase, ATP13A1 of 1204 aas. Defects cause Mn2+-dependent neurological disorders. Orthologous to the yeast Mn2+-ATPase, Spf1 (Cohen et al. 2013). It is present in the endoplasmic reticulum while the other P5 ATPases, A2 - A5, are in overlapping compartments of the endosomal system (Sørensen et al. 2018). It complements the yeast ER ATPase, SPF1 (TC#3.A.3.10.3) although ATP13A2 - 5 do not, and unlike these latter proteins, it seems to have 12 (rather than 10) TMSs, with the two extra ones in an N-terminal domain (Sørensen et al. 2018). ATP13A1 (Spf1 in yeast) directly interacts with the TMSs of mitochondrial tail-anchored proteins (McKenna et al. 2020). P5A-ATPase mediates the extraction of mistargeted proteins from the endoplasmic reticulum (ER). Cryo-electron microscopy structures of Saccharomyces cerevisiae Spf1 (TC# 3.A.3.10.3) revealed a large, membrane-accessible substrate-binding pocket that alternately faced the ER lumen and cytosol and an endogenous substrate resembling an alpha-helical TMS. Thus, the P5A-ATPase can dislocate misinserted hydrophobic helices flanked by short basic segments from the ER. TMS dislocation by the P5A-ATPase establishes an additional class of P-type ATPase substrates and may correct mistakes in protein targeting or topogenesis (McKenna et al. 2020). It has been designated as a transmembrane islocase (Dederer and Lemberg 2021).
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| Accession Number: | Q9HD20 |
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| Protein Name: | Probable cation-transporting ATPase 13A1 |
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| Length: | 1204 |
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| Molecular Weight: | 132955.00 |
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| Species: | Homo sapiens (Human) [9606] |
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| Number of TMSs: | 12 |
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| Location1 / Topology2 / Orientation3: |
Membrane1 / Multi-pass membrane protein2 |
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| Substrate |
manganese(2+) |
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1: MAAAAAVGNA VPCGARPCGV RPDGQPKPGP QPRALLAAGP ALIANGDELV AAVWPYRRLA
61: LLRRLTVLPF AGLLYPAWLG AAAAGCWGWG SSWVQIPEAA LLVLATICLA HALTVLSGHW
121: SVHAHCALTC TPEYDPSKAT FVKVVPTPNN GSTELVALHR NEGEDGLEVL SFEFQKIKYS
181: YDALEKKQFL PVAFPVGNAF SYYQSNRGFQ EDSEIRAAEK KFGSNKAEMV VPDFSELFKE
241: RATAPFFVFQ VFCVGLWCLD EYWYYSVFTL SMLVAFEASL VQQQMRNMSE IRKMGNKPHM
301: IQVYRSRKWR PIASDEIVPG DIVSIGRSPQ ENLVPCDVLL LRGRCIVDEA MLTGESVPQM
361: KEPIEDLSPD RVLDLQADSR LHVIFGGTKV VQHIPPQKAT TGLKPVDSGC VAYVLRTGFN
421: TSQGKLLRTI LFGVKRVTAN NLETFIFILF LLVFAIAAAA YVWIEGTKDP SRNRYKLFLE
481: CTLILTSVVP PELPIELSLA VNTSLIALAK LYMYCTEPFR IPFAGKVEVC CFDKTGTLTS
541: DSLVVRGVAG LRDGKEVTPV SSIPVETHRA LASCHSLMQL DDGTLVGDPL EKAMLTAVDW
601: TLTKDEKVFP RSIKTQGLKI HQRFHFASAL KRMSVLASYE KLGSTDLCYI AAVKGAPETL
661: HSMFSQCPPD YHHIHTEISR EGARVLALGY KELGHLTHQQ AREVKREALE CSLKFVGFIV
721: VSCPLKADSK AVIREIQNAS HRVVMITGDN PLTACHVAQE LHFIEKAHTL ILQPPSEKGR
781: QCEWRSIDGS IVLPLARGSP KALALEYALC LTGDGLAHLQ ATDPQQLLRL IPHVQVFARV
841: APKQKEFVIT SLKELGYVTL MCGDGTNDVG ALKHADVGVA LLANAPERVV ERRRRPRDSP
901: TLSNSGIRAT SRTAKQRSGL PPSEEQPTSQ RDRLSQVLRD LEDESTPIVK LGDASIAAPF
961: TSKLSSIQCI CHVIKQGRCT LVTTLQMFKI LALNALILAY SQSVLYLEGV KFSDFQATLQ
1021: GLLLAGCFLF ISRSKPLKTL SRERPLPNIF NLYTILTVML QFFVHFLSLV YLYREAQARS
1081: PEKQEQFVDL YKEFEPSLVN STVYIMAMAM QMATFAINYK GPPFMESLPE NKPLVWSLAV
1141: SLLAIIGLLL GSSPDFNSQF GLVDIPVEFK LVIAQVLLLD FCLALLADRV LQFFLGTPKL
1201: KVPS