3.A.3.10.20
Probable divalent cation transporting ATPase 13A4, ATP13A4, of 1196 aas and 10 TMSs. This protein had been suggested to be a Mg2+ transporter, but the evidence is equivocal (Schäffers et al. 2018). It may be a Mn2+/Ca2+ exporter. This protein as well as ATP13A2 has been implicated in Parkinson's disease and autism spectrum disorder (Sørensen et al. 2018). ATPA2 - 5 are all in compartments of the endosomal system and all have 10 TMSs with overlapping functions, often in different amounts in different tissues (Sørensen et al. 2018). Dysregulation of polyamine homeostasis strongly associates with human
diseases. ATP13A2 is mutated in juvenile-onset Parkinson's
disease and autosomal recessive spastic paraplegia 78. It is a
transporter that balances the polyamine concentration between the
lysosome and the cytosol. Single-particle cryo-EM solved high-resolution
structures of human ATP13A2 in six intermediate states, including the
putative E2 structure for the P5 subfamily of P-type ATPases. These
structures comprise a nearly complete conformational cycle spanning the
polyamine transport process and capture multiple substrate binding sites
distributed along the transmembrane regions, suggesting a potential
polyamine transport pathway (Mu et al. 2023).
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| Accession Number: | Q4VNC1 |
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| Protein Name: | Probable cation-transporting ATPase 13A4 |
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| Length: | 1196 |
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| Molecular Weight: | 133987.00 |
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| Species: | Homo sapiens (Human) [9606] |
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| Number of TMSs: | 8 |
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| Location1 / Topology2 / Orientation3: |
Membrane1 / Multi-pass membrane protein2 |
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| Substrate |
metal cation, magnesium(2+), polyamine macromolecule |
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1: MGHFEKGQHA LLNEGEENEM EIFGYRTQGC RKSLCLAGSI FSFGILPLVF YWRPAWHVWA
61: HCVPCSLQEA DTVLLRTTDE FQIYSWKKVI WIYLSALNSA FGLTPDHPLM TDEEYIINRA
121: IRKPDLKVRC IKVQKIRYVW NYLEGQFQKI GSLEDWLSSA KIHQKFGSGL TREEQEIRRL
181: ICGPNTIDVE VTPIWKLLIK EVLNPFYIFQ LFSVCLWFSE DYKEYAFAII IMSIISISLT
241: VYDLREQSVK LHHLVESHNS ITVSVCGRKA GVQELESRVL VPGDLLILTG NKVLMPCDAV
301: LIEGSCVVDE GMLTGESIPV TKTPLPKMDS SVPWKTQSEA DYKRHVLFCG TEVIQAKAAC
361: SGTVRAVVLQ TGFNTAKGDL VRSILYPKPV NFQLYRDAIR FLLCLVGTAT IGMIYTLCVY
421: VLSGEPPEEV VRKALDVITI AVPPALPAAL TTGIIYAQRR LKKRGIFCIS PQRINVCGQL
481: NLVCFDKTGT LTRDGLDLWG VVSCDRNGFQ EVHSFASGQA LPWGPLCAAM ASCHSLILLD
541: GTIQGDPLDL KMFEATTWEM AFSGDDFHIK GVPAHAMVVK PCRTASQVPV EGIAILHQFP
601: FSSALQRMTV IVQEMGGDRL AFMKGAPERV ASFCQPETVP TSFVSELQIY TTQGFRVIAL
661: AYKKLENDHH ATTLTRETVE SDLIFLGLLI LENRLKEETK PVLEELISAR IRTVMITGDN
721: LQTAITVARK SGMVSESQKV ILIEANETTG SSSASISWTL VEEKKHIMYG NQDNYINIRD
781: EVSDKGREGS YHFALTGKSF HVISQHFSSL LPKILINGTI FARMSPGQKS SLVEEFQKLD
841: YFVGMCGDGA NDCGALKMAH VGISLSEQEA SVASPFTSKT PNIECVPHLI KEGRAALVTS
901: FCMFKYMALY SMIQYVGVLL LYWETNSLSN YQFLFQDLAI TTLIGVTMNL NGAYPKLVPF
961: RPAGRLISPP LLLSVIFNIL LSLAMHIAGF ILVQRQPWYS VEIHSACTVQ NESISELTMS
1021: PTAPEKMESN STFTSFENTT VWFLGTINCI TVALVFSKGK PFRQPTYTNY IFVLVLIIQL
1081: GVCLFILFAD IPELYRRLDL LCTPVLWRAS IVIMLSLNFI VSLVAEEAVI ENRALWMMIK
1141: RCFGYQSKSQ YRIWQRDLAN DPSWPPLNQT SHSDMPECGR GVSYSNPVFE SNEEQL