AT132_HUMAN
ID AT132_HUMAN Reviewed; 1180 AA.
AC Q9NQ11; O75700; Q5JXY1; Q5JXY2; Q6S9Z9;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Polyamine-transporting ATPase 13A2 {ECO:0000305|PubMed:31996848};
DE EC=7.6.2.- {ECO:0000269|PubMed:31996848};
GN Name=ATP13A2 {ECO:0000312|HGNC:HGNC:30213};
GN Synonyms=PARK9 {ECO:0000303|PubMed:21542062};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RA Rhodes S., Huckle E.;
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Liu J.-P., Li H.;
RT "Homo sapiens putative ATPase (N-ATPase) mRNA.";
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC TISSUE=Brain, and Fetus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 705-1180 (ISOFORM A).
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 855-1180 (ISOFORM B).
RA Casciano I., Volpi E.V., De Ambrosis A., Marchi J.M., Romani M.;
RT "YAC analysis and genes identification at a site of viral integration in
RT the 1p36.1-36.2 chromosomal site.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=22186024; DOI=10.1093/hmg/ddr606;
RA Ramonet D., Podhajska A., Stafa K., Sonnay S., Trancikova A., Tsika E.,
RA Pletnikova O., Troncoso J.C., Glauser L., Moore D.J.;
RT "PARK9-associated ATP13A2 localizes to intracellular acidic vesicles and
RT regulates cation homeostasis and neuronal integrity.";
RL Hum. Mol. Genet. 21:1725-1743(2012).
RN [10]
RP INVOLVEMENT IN KRS.
RX PubMed=16964263; DOI=10.1038/ng1884;
RA Ramirez A., Heimbach A., Gruendemann J., Stiller B., Hampshire D.,
RA Cid L.P., Goebel I., Mubaidin A.F., Wriekat A.-L., Roeper J., Al-Din A.,
RA Hillmer A.M., Karsak M., Liss B., Woods C.G., Behrens M.I., Kubisch C.;
RT "Hereditary parkinsonism with dementia is caused by mutations in ATP13A2,
RT encoding a lysosomal type 5 P-type ATPase.";
RL Nat. Genet. 38:1184-1191(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=24603074; DOI=10.1093/hmg/ddu099;
RA Kong S.M., Chan B.K., Park J.S., Hill K.J., Aitken J.B., Cottle L.,
RA Farghaian H., Cole A.R., Lay P.A., Sue C.M., Cooper A.A.;
RT "Parkinson's disease-linked human PARK9/ATP13A2 maintains zinc homeostasis
RT and promotes alpha-Synuclein externalization via exosomes.";
RL Hum. Mol. Genet. 23:2816-2833(2014).
RN [13]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25392495; DOI=10.1523/jneurosci.1629-14.2014;
RA Tsunemi T., Hamada K., Krainc D.;
RT "ATP13A2/PARK9 regulates secretion of exosomes and alpha-synuclein.";
RL J. Neurosci. 34:15281-15287(2014).
RN [14]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, DOMAIN, TOPOLOGY,
RP AUTOPHOSPHORYLATION, ACTIVE SITE, GLYCOSYLATION AT ASN-1033, AND
RP MUTAGENESIS OF GLY-59; 66-ARG--LYS-68; 74-ARG--ARG-78; 160-LYS--ARG-164 AND
RP ASN-1033.
RX PubMed=26134396; DOI=10.1073/pnas.1508220112;
RA Holemans T., Soerensen D.M., van Veen S., Martin S., Hermans D.,
RA Kemmer G.C., Van den Haute C., Baekelandt V., Guenther Pomorski T.,
RA Agostinis P., Wuytack F., Palmgren M., Eggermont J., Vangheluwe P.;
RT "A lipid switch unlocks Parkinson's disease-associated ATP13A2.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:9040-9045(2015).
RN [15]
RP FUNCTION.
RX PubMed=31132336; DOI=10.1016/j.bbamem.2019.05.015;
RA Marcos A.L., Corradi G.R., Mazzitelli L.R., Casali C.I.,
RA Fernandez Tome M.D.C., Adamo H.P., de Tezanos Pinto F.;
RT "The Parkinson-associated human P5B-ATPase ATP13A2 modifies lipid
RT homeostasis.";
RL Biochim. Biophys. Acta 1861:182993-182993(2019).
RN [16]
RP FUNCTION, INTERACTION WITH HDAC6, AND CHARACTERIZATION OF VARIANTS KRS
RP LEU-182 AND ARG-504.
RX PubMed=30538141; DOI=10.1083/jcb.201804165;
RA Wang R., Tan J., Chen T., Han H., Tian R., Tan Y., Wu Y., Cui J., Chen F.,
RA Li J., Lv L., Guan X., Shang S., Lu J., Zhang Z.;
RT "ATP13A2 facilitates HDAC6 recruitment to lysosome to promote
RT autophagosome-lysosome fusion.";
RL J. Cell Biol. 218:267-284(2019).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, CHARACTERIZATION OF VARIANTS KRS MET-12; ARG-533; THR-746 AND
RP ARG-877, CHARACTERIZATION OF VARIANT SPG8 ILE-517, AND MUTAGENESIS OF
RP GLU-348; ALA-472; ASP-513; ASP-967 AND LYS-1067.
RX PubMed=31996848; DOI=10.1038/s41586-020-1968-7;
RA van Veen S., Martin S., Van den Haute C., Benoy V., Lyons J., Vanhoutte R.,
RA Kahler J.P., Decuypere J.P., Gelders G., Lambie E., Zielich J.,
RA Swinnen J.V., Annaert W., Agostinis P., Ghesquiere B., Verhelst S.,
RA Baekelandt V., Eggermont J., Vangheluwe P.;
RT "ATP13A2 deficiency disrupts lysosomal polyamine export.";
RL Nature 578:419-424(2020).
RN [18]
RP VARIANT KRS ARG-504, AND VARIANTS MET-12 AND ARG-533.
RX PubMed=17485642; DOI=10.1212/01.wnl.0000260963.08711.08;
RA Di Fonzo A., Chien H.F., Socal M., Giraudo S., Tassorelli C., Iliceto G.,
RA Fabbrini G., Marconi R., Fincati E., Abbruzzese G., Marini P.,
RA Squitieri F., Horstink M.W., Montagna P., Libera A.D., Stocchi F.,
RA Goldwurm S., Ferreira J.J., Meco G., Martignoni E., Lopiano L.,
RA Jardim L.B., Oostra B.A., Barbosa E.R., Bonifati V.;
RT "ATP13A2 missense mutations in juvenile parkinsonism and young onset
RT Parkinson disease.";
RL Neurology 68:1557-1562(2007).
RN [19]
RP VARIANT KRS LEU-182.
RX PubMed=18413573; DOI=10.1212/01.wnl.0000310427.72236.68;
RA Ning Y.P., Kanai K., Tomiyama H., Li Y., Funayama M., Yoshino H., Sato S.,
RA Asahina M., Kuwabara S., Takeda A., Hattori T., Mizuno Y., Hattori N.;
RT "PARK9-linked parkinsonism in eastern Asia: mutation detection in ATP13A2
RT and clinical phenotype.";
RL Neurology 70:1491-1493(2008).
RN [20]
RP VARIANT THR-746.
RX PubMed=19015489; DOI=10.1212/01.wnl.0000335167.72412.68;
RA Lin C.H., Tan E.K., Chen M.L., Tan L.C., Lim H.Q., Chen G.S., Wu R.M.;
RT "Novel ATP13A2 variant associated with Parkinson disease in Taiwan and
RT Singapore.";
RL Neurology 71:1727-1732(2008).
RN [21]
RP VARIANTS SER-49; GLN-294; LEU-389; GLY-578; TRP-762; ILE-776 AND PHE-946.
RX PubMed=19085912; DOI=10.1002/humu.20877;
RA Vilarino-Guell C., Soto A.I., Lincoln S.J., Ben Yahmed S., Kefi M.,
RA Heckman M.G., Hulihan M.M., Chai H., Diehl N.N., Amouri R., Rajput A.,
RA Mash D.C., Dickson D.W., Middleton L.T., Gibson R.A., Hentati F.,
RA Farrer M.J.;
RT "ATP13A2 variability in Parkinson disease.";
RL Hum. Mutat. 30:406-410(2009).
RN [22]
RP INVOLVEMENT IN KRS.
RX PubMed=20683840; DOI=10.1002/mds.22996;
RA Behrens M.I., Bruggemann N., Chana P., Venegas P., Kagi M., Parrao T.,
RA Orellana P., Garrido C., Rojas C.V., Hauke J., Hahnen E., Gonzalez R.,
RA Seleme N., Fernandez V., Schmidt A., Binkofski F., Kompf D., Kubisch C.,
RA Hagenah J., Klein C., Ramirez A.;
RT "Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with
RT ATP13A2 mutations.";
RL Mov. Disord. 25:1929-1937(2010).
RN [23]
RP VARIANT KRS ARG-1059, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT
RP KRS ARG-1059.
RX PubMed=21542062; DOI=10.1002/humu.21527;
RA Park J.S., Mehta P., Cooper A.A., Veivers D., Heimbach A., Stiller B.,
RA Kubisch C., Fung V.S., Krainc D., Mackay-Sim A., Sue C.M.;
RT "Pathogenic effects of novel mutations in the P-type ATPase ATP13A2 (PARK9)
RT causing Kufor-Rakeb syndrome, a form of early-onset parkinsonism.";
RL Hum. Mutat. 32:956-964(2011).
RN [24]
RP VARIANT KRS ARG-877.
RX PubMed=20853184; DOI=10.1007/s10048-010-0259-0;
RA Santoro L., Breedveld G.J., Manganelli F., Iodice R., Pisciotta C.,
RA Nolano M., Punzo F., Quarantelli M., Pappata S., Di Fonzo A., Oostra B.A.,
RA Bonifati V.;
RT "Novel ATP13A2 (PARK9) homozygous mutation in a family with marked
RT phenotype variability.";
RL Neurogenetics 12:33-39(2011).
RN [25]
RP VARIANT KRS ARG-854.
RX PubMed=22388936; DOI=10.1093/hmg/dds089;
RA Bras J., Verloes A., Schneider S.A., Mole S.E., Guerreiro R.J.;
RT "Mutation of the parkinsonism gene ATP13A2 causes neuronal ceroid-
RT lipofuscinosis.";
RL Hum. Mol. Genet. 21:2646-2650(2012).
RN [26]
RP VARIANT KRS VAL-522, AND FUNCTION.
RX PubMed=22296644; DOI=10.1016/j.neurobiolaging.2011.12.035;
RA Gruenewald A., Arns B., Seibler P., Rakovic A., Muenchau A., Ramirez A.,
RA Sue C.M., Klein C.;
RT "ATP13A2 mutations impair mitochondrial function in fibroblasts from
RT patients with Kufor-Rakeb syndrome.";
RL Neurobiol. Aging 33:1843.E1-1843.E7(2012).
RN [27]
RP FUNCTION, CHARACTERIZATION OF VARIANTS KRS MET-12; LEU-182; ARG-504;
RP ARG-533; THR-746 AND ARG-877, AND SUBCELLULAR LOCATION.
RX PubMed=22768177; DOI=10.1371/journal.pone.0039942;
RA Podhajska A., Musso A., Trancikova A., Stafa K., Moser R., Sonnay S.,
RA Glauser L., Moore D.J.;
RT "Common pathogenic effects of missense mutations in the P-type ATPase
RT ATP13A2 (PARK9) associated with early-onset parkinsonism.";
RL PLoS ONE 7:E39942-E39942(2012).
RN [28]
RP FUNCTION, AND INTERACTION WITH MYCBP2.
RX PubMed=27278822; DOI=10.1038/ncomms11803;
RA Bento C.F., Ashkenazi A., Jimenez-Sanchez M., Rubinsztein D.C.;
RT "The Parkinson's disease-associated genes ATP13A2 and SYT11 regulate
RT autophagy via a common pathway.";
RL Nat. Commun. 7:11803-11803(2016).
RN [29]
RP INVOLVEMENT IN SPG78.
RX PubMed=27217339; DOI=10.1093/brain/aww111;
RA Kara E., Tucci A., Manzoni C., Lynch D.S., Elpidorou M., Bettencourt C.,
RA Chelban V., Manole A., Hamed S.A., Haridy N.A., Federoff M., Preza E.,
RA Hughes D., Pittman A., Jaunmuktane Z., Brandner S., Xiromerisiou G.,
RA Wiethoff S., Schottlaender L., Proukakis C., Morris H., Warner T.,
RA Bhatia K.P., Korlipara L.V., Singleton A.B., Hardy J., Wood N.W.,
RA Lewis P.A., Houlden H.;
RT "Genetic and phenotypic characterization of complex hereditary spastic
RT paraplegia.";
RL Brain 139:1904-1918(2016).
RN [30]
RP INVOLVEMENT IN SPG78, VARIANT SPG78 ILE-517, CHARACTERIZATION OF VARIANT
RP KRS LEU-182, CHARACTERIZATION OF VARIANT SPG78 ILE-517, CHARACTERIZATION OF
RP VARIANT ARG-533, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, AND MUTAGENESIS
RP OF ASP-513.
RX PubMed=28137957; DOI=10.1093/brain/aww307;
RA Estrada-Cuzcano A., Martin S., Chamova T., Synofzik M., Timmann D.,
RA Holemans T., Andreeva A., Reichbauer J., De Rycke R., Chang D.I.,
RA van Veen S., Samuel J., Schoels L., Poeppel T., Mollerup Soerensen D.,
RA Asselbergh B., Klein C., Zuchner S., Jordanova A., Vangheluwe P.,
RA Tournev I., Schuele R.;
RT "Loss-of-function mutations in the ATP13A2/PARK9 gene cause complicated
RT hereditary spastic paraplegia (SPG78).";
RL Brain 140:287-305(2017).
RN [31]
RP VARIANTS KRS PHE-441 AND THR-1069.
RX PubMed=29903538; DOI=10.1016/j.braindev.2018.05.017;
RA Suleiman J., Hamwi N., El-Hattab A.W.;
RT "ATP13A2 novel mutations causing a rare form of juvenile-onset Parkinson
RT disease.";
RL Brain Dev. 40:824-826(2018).
CC -!- FUNCTION: ATPase which acts as a lysosomal polyamine exporter with high
CC affinity for spermine (PubMed:31996848). Also stimulates cellular
CC uptake of polyamines and protects against polyamine toxicity
CC (PubMed:31996848). Plays a role in intracellular cation homeostasis and
CC the maintenance of neuronal integrity (PubMed:22186024). Contributes to
CC cellular zinc homeostasis (PubMed:24603074). Confers cellular
CC protection against Mn(2+) and Zn(2+) toxicity and mitochondrial stress
CC (PubMed:26134396). Required for proper lysosomal and mitochondrial
CC maintenance (PubMed:22296644, PubMed:28137957). Regulates the
CC autophagy-lysosome pathway through the control of SYT11 expression at
CC both transcriptional and post-translational levels (PubMed:27278822).
CC Facilitates recruitment of deacetylase HDAC6 to lysosomes to
CC deacetylate CTTN, leading to actin polymerization, promotion of
CC autophagosome-lysosome fusion and completion of autophagy
CC (PubMed:30538141). Promotes secretion of exosomes as well as secretion
CC of SCNA via exosomes (PubMed:25392495, PubMed:24603074). Plays a role
CC in lipid homeostasis (PubMed:31132336). {ECO:0000269|PubMed:22186024,
CC ECO:0000269|PubMed:22296644, ECO:0000269|PubMed:24603074,
CC ECO:0000269|PubMed:25392495, ECO:0000269|PubMed:26134396,
CC ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:28137957,
CC ECO:0000269|PubMed:30538141, ECO:0000269|PubMed:31132336,
CC ECO:0000269|PubMed:31996848}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + spermidine(out) = ADP + H(+) + phosphate +
CC spermidine(in); Xref=Rhea:RHEA:29999, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57834, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:31996848};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + spermine(out) = ADP + H(+) + phosphate +
CC spermine(in); Xref=Rhea:RHEA:63368, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:45725, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:31996848};
CC -!- ACTIVITY REGULATION: Accumulates in an inactive autophosphorylated
CC state (PubMed:26134396). The presence of spermine results in a dose-
CC dependent reduction in autophosphorylation (PubMed:31996848).
CC {ECO:0000269|PubMed:26134396, ECO:0000269|PubMed:31996848}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=76 uM for spermine {ECO:0000269|PubMed:31996848};
CC Vmax=159 nmol/min/mg enzyme {ECO:0000269|PubMed:31996848};
CC -!- SUBUNIT: Interacts with MYCBP2; the interaction inhibits the
CC ubiquitination of TSC2 by MYCBP2 (PubMed:27278822). Interacts with
CC HDAC6; the interaction results in recruitment of HDAC6 to lysosomes to
CC promote CTTN deacetylation (PubMed:30538141).
CC {ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:30538141}.
CC -!- INTERACTION:
CC Q9NQ11; Q2M2I8: AAK1; NbExp=2; IntAct=EBI-6308763, EBI-1383433;
CC Q9NQ11; O60238: BNIP3L; NbExp=2; IntAct=EBI-6308763, EBI-849893;
CC Q9NQ11; O14976: GAK; NbExp=2; IntAct=EBI-6308763, EBI-714707;
CC Q9NQ11; Q9UBN7: HDAC6; NbExp=2; IntAct=EBI-6308763, EBI-301697;
CC Q9NQ11; P11142: HSPA8; NbExp=2; IntAct=EBI-6308763, EBI-351896;
CC Q9NQ11; Q9BT88: SYT11; NbExp=2; IntAct=EBI-6308763, EBI-751770;
CC Q9NQ11; O95070: YIF1A; NbExp=2; IntAct=EBI-6308763, EBI-2799703;
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:21542062,
CC ECO:0000269|PubMed:22186024, ECO:0000269|PubMed:22768177,
CC ECO:0000269|PubMed:24603074, ECO:0000269|PubMed:26134396,
CC ECO:0000269|PubMed:28137957}; Multi-pass membrane protein
CC {ECO:0000255}. Late endosome membrane {ECO:0000269|PubMed:24603074,
CC ECO:0000269|PubMed:25392495, ECO:0000269|PubMed:26134396}; Multi-pass
CC membrane protein {ECO:0000255}. Endosome, multivesicular body membrane
CC {ECO:0000269|PubMed:24603074, ECO:0000269|PubMed:25392495}; Multi-pass
CC membrane protein {ECO:0000255}. Cytoplasmic vesicle, autophagosome
CC membrane {ECO:0000269|PubMed:24603074}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=A;
CC IsoId=Q9NQ11-1; Sequence=Displayed;
CC Name=B;
CC IsoId=Q9NQ11-2; Sequence=VSP_007310, VSP_007311, VSP_007312;
CC Name=3;
CC IsoId=Q9NQ11-3; Sequence=VSP_007310;
CC -!- TISSUE SPECIFICITY: Expressed in brain; protein levels are markedly
CC increased in brain from subjects with Parkinson disease and subjects
CC with dementia with Lewy bodies. Detected in pyramidal neurons located
CC throughout the cingulate cortex (at protein level). In the substantia
CC nigra, it is found in neuromelanin-positive dopaminergic neurons (at
CC protein level). {ECO:0000269|PubMed:22186024}.
CC -!- DOMAIN: The N-terminal region is required for targeting to late
CC endosomes/lysosomes. It does not traverse the membrane but contains a
CC membrane-embedded intramembrane domain and interacts with the lipids
CC phosphatidic acid (PA) and phosphatidylinositol 3,5-bisphosphate
CC (PI(3,5)P2) (PubMed:26134396). PA and PI(3,5)P2 are required for the
CC protective effect against mitochondrial stress (PubMed:26134396).
CC {ECO:0000269|PubMed:26134396}.
CC -!- PTM: Autophosphorylated (PubMed:26134396, PubMed:28137957). Accumulates
CC in an inactive autophosphorylated state and autophosphorylation is
CC stimulated by phosphatidic acid and phosphatidylinositol 3,5-
CC bisphosphate but not by Mn(2+) or Zn(2+) (PubMed:26134396). The
CC presence of spermine results in a dose-dependent reduction in
CC autophosphorylation (PubMed:31996848). {ECO:0000269|PubMed:26134396,
CC ECO:0000269|PubMed:31996848, ECO:0000305|PubMed:28137957}.
CC -!- DISEASE: Kufor-Rakeb syndrome (KRS) [MIM:606693]: A rare form of
CC autosomal recessive juvenile or early-onset, levodopa-responsive
CC parkinsonism. In addition to typical parkinsonian signs, clinical
CC manifestations of Kufor-Rakeb syndrome include behavioral problems,
CC facial tremor, pyramidal tract dysfunction, supranuclear gaze palsy,
CC and dementia. {ECO:0000269|PubMed:16964263,
CC ECO:0000269|PubMed:17485642, ECO:0000269|PubMed:18413573,
CC ECO:0000269|PubMed:20683840, ECO:0000269|PubMed:20853184,
CC ECO:0000269|PubMed:21542062, ECO:0000269|PubMed:22296644,
CC ECO:0000269|PubMed:22388936, ECO:0000269|PubMed:22768177,
CC ECO:0000269|PubMed:28137957, ECO:0000269|PubMed:29903538,
CC ECO:0000269|PubMed:30538141, ECO:0000269|PubMed:31996848}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry. KRS has also been referred to as neuronal ceroid lipofuscinosis
CC 12 (CLN12), due to neuronal and glial lipofuscin deposits detected in
CC the cortex, basal nuclei and cerebellum of some patients.
CC {ECO:0000269|PubMed:22388936}.
CC -!- DISEASE: Spastic paraplegia 78, autosomal recessive (SPG78)
CC [MIM:617225]: A form of spastic paraplegia, a neurodegenerative
CC disorder characterized by a slow, gradual, progressive weakness and
CC spasticity of the lower limbs. Rate of progression and the severity of
CC symptoms are quite variable. Initial symptoms may include difficulty
CC with balance, weakness and stiffness in the legs, muscle spasms, and
CC dragging the toes when walking. In some forms of the disorder, bladder
CC symptoms (such as incontinence) may appear, or the weakness and
CC stiffness may spread to other parts of the body.
CC {ECO:0000269|PubMed:27217339, ECO:0000269|PubMed:28137957}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type V subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA08912.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AL354615; CAB89728.1; -; mRNA.
DR EMBL; AY461712; AAR23423.1; -; mRNA.
DR EMBL; AK290210; BAF82899.1; -; mRNA.
DR EMBL; AL049569; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471134; EAW94825.1; -; Genomic_DNA.
DR EMBL; CH471134; EAW94827.1; -; Genomic_DNA.
DR EMBL; BC030267; AAH30267.1; -; mRNA.
DR EMBL; AL833966; CAD38813.2; -; mRNA.
DR EMBL; AJ009947; CAA08912.1; ALT_FRAME; mRNA.
DR CCDS; CCDS175.1; -. [Q9NQ11-1]
DR CCDS; CCDS44072.1; -. [Q9NQ11-2]
DR CCDS; CCDS44073.1; -. [Q9NQ11-3]
DR RefSeq; NP_001135445.1; NM_001141973.2. [Q9NQ11-3]
DR RefSeq; NP_001135446.1; NM_001141974.2. [Q9NQ11-2]
DR RefSeq; NP_071372.1; NM_022089.3. [Q9NQ11-1]
DR PDB; 7M5V; EM; 2.90 A; A=1-1180.
DR PDB; 7M5X; EM; 2.70 A; A=1-1180.
DR PDB; 7M5Y; EM; 3.00 A; A=1-1180.
DR PDB; 7N70; EM; 2.80 A; A=1-1180.
DR PDB; 7N72; EM; 2.50 A; A=1-1180.
DR PDB; 7N73; EM; 2.90 A; A=1-1180.
DR PDB; 7N74; EM; 2.80 A; A=1-1180.
DR PDB; 7N75; EM; 2.90 A; A=1-1180.
DR PDB; 7N76; EM; 2.90 A; A=1-1180.
DR PDB; 7N77; EM; 3.20 A; A=1-1180.
DR PDB; 7N78; EM; 3.00 A; A=1-1180.
DR PDB; 7VPI; EM; 3.50 A; A=1-1180.
DR PDB; 7VPJ; EM; 3.50 A; A=1-1180.
DR PDB; 7VPK; EM; 3.50 A; A=1-1180.
DR PDB; 7VPL; EM; 3.50 A; A=1-1180.
DR PDBsum; 7M5V; -.
DR PDBsum; 7M5X; -.
DR PDBsum; 7M5Y; -.
DR PDBsum; 7N70; -.
DR PDBsum; 7N72; -.
DR PDBsum; 7N73; -.
DR PDBsum; 7N74; -.
DR PDBsum; 7N75; -.
DR PDBsum; 7N76; -.
DR PDBsum; 7N77; -.
DR PDBsum; 7N78; -.
DR PDBsum; 7VPI; -.
DR PDBsum; 7VPJ; -.
DR PDBsum; 7VPK; -.
DR PDBsum; 7VPL; -.
DR AlphaFoldDB; Q9NQ11; -.
DR SMR; Q9NQ11; -.
DR BioGRID; 116973; 103.
DR IntAct; Q9NQ11; 65.
DR MINT; Q9NQ11; -.
DR STRING; 9606.ENSP00000327214; -.
DR TCDB; 3.A.3.10.7; the p-type atpase (p-atpase) superfamily.
DR GlyGen; Q9NQ11; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NQ11; -.
DR PhosphoSitePlus; Q9NQ11; -.
DR BioMuta; ATP13A2; -.
DR DMDM; 14285364; -.
DR EPD; Q9NQ11; -.
DR jPOST; Q9NQ11; -.
DR MassIVE; Q9NQ11; -.
DR MaxQB; Q9NQ11; -.
DR PaxDb; Q9NQ11; -.
DR PeptideAtlas; Q9NQ11; -.
DR PRIDE; Q9NQ11; -.
DR ProteomicsDB; 63479; -.
DR ProteomicsDB; 82052; -. [Q9NQ11-1]
DR ProteomicsDB; 82053; -. [Q9NQ11-2]
DR ProteomicsDB; 82054; -. [Q9NQ11-3]
DR Antibodypedia; 29290; 198 antibodies from 24 providers.
DR DNASU; 23400; -.
DR Ensembl; ENST00000326735.13; ENSP00000327214.8; ENSG00000159363.19. [Q9NQ11-1]
DR Ensembl; ENST00000341676.9; ENSP00000341115.5; ENSG00000159363.19. [Q9NQ11-2]
DR Ensembl; ENST00000452699.5; ENSP00000413307.1; ENSG00000159363.19. [Q9NQ11-3]
DR GeneID; 23400; -.
DR KEGG; hsa:23400; -.
DR MANE-Select; ENST00000326735.13; ENSP00000327214.8; NM_022089.4; NP_071372.1.
DR UCSC; uc001baa.3; human. [Q9NQ11-1]
DR CTD; 23400; -.
DR DisGeNET; 23400; -.
DR GeneCards; ATP13A2; -.
DR HGNC; HGNC:30213; ATP13A2.
DR HPA; ENSG00000159363; Tissue enhanced (brain).
DR MalaCards; ATP13A2; -.
DR MIM; 606693; phenotype.
DR MIM; 610513; gene.
DR MIM; 617225; phenotype.
DR neXtProt; NX_Q9NQ11; -.
DR OpenTargets; ENSG00000159363; -.
DR Orphanet; 314632; ATP13A2-related juvenile neuronal ceroid lipofuscinosis.
DR Orphanet; 513436; Autosomal recessive spastic paraplegia type 78.
DR Orphanet; 306674; Kufor-Rakeb syndrome.
DR PharmGKB; PA134897221; -.
DR VEuPathDB; HostDB:ENSG00000159363; -.
DR eggNOG; KOG0208; Eukaryota.
DR GeneTree; ENSGT00940000159714; -.
DR HOGENOM; CLU_001828_0_0_1; -.
DR InParanoid; Q9NQ11; -.
DR OMA; SGWKDPL; -.
DR OrthoDB; 172453at2759; -.
DR PhylomeDB; Q9NQ11; -.
DR TreeFam; TF300331; -.
DR PathwayCommons; Q9NQ11; -.
DR Reactome; R-HSA-936837; Ion transport by P-type ATPases.
DR SignaLink; Q9NQ11; -.
DR BioGRID-ORCS; 23400; 14 hits in 1076 CRISPR screens.
DR ChiTaRS; ATP13A2; human.
DR GeneWiki; ATP13A2; -.
DR GenomeRNAi; 23400; -.
DR Pharos; Q9NQ11; Tbio.
DR PRO; PR:Q9NQ11; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9NQ11; protein.
DR Bgee; ENSG00000159363; Expressed in right frontal lobe and 164 other tissues.
DR ExpressionAtlas; Q9NQ11; baseline and differential.
DR Genevisible; Q9NQ11; HS.
DR GO; GO:0005776; C:autophagosome; IDA:ParkinsonsUK-UCL.
DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:1905103; C:integral component of lysosomal membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0016021; C:integral component of membrane; NAS:ParkinsonsUK-UCL.
DR GO; GO:0005770; C:late endosome; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031902; C:late endosome membrane; IDA:UniProtKB.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005771; C:multivesicular body; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032585; C:multivesicular body membrane; NAS:ParkinsonsUK-UCL.
DR GO; GO:0043005; C:neuron projection; IDA:ParkinsonsUK-UCL.
DR GO; GO:0043025; C:neuronal cell body; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030133; C:transport vesicle; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031982; C:vesicle; IDA:ParkinsonsUK-UCL.
DR GO; GO:0015417; F:ABC-type polyamine transporter activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; NAS:ParkinsonsUK-UCL.
DR GO; GO:0019829; F:ATPase-coupled cation transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:1903135; F:cupric ion binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0030145; F:manganese ion binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0140358; F:P-type transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0070300; F:phosphatidic acid binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0008270; F:zinc ion binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:1905037; P:autophagosome organization; IDA:ParkinsonsUK-UCL.
DR GO; GO:0061909; P:autophagosome-lysosome fusion; IMP:UniProtKB.
DR GO; GO:0006914; P:autophagy; IMP:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030003; P:cellular cation homeostasis; TAS:ParkinsonsUK-UCL.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0071287; P:cellular response to manganese ion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:ParkinsonsUK-UCL.
DR GO; GO:0071294; P:cellular response to zinc ion; TAS:ParkinsonsUK-UCL.
DR GO; GO:0006882; P:cellular zinc ion homeostasis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0097734; P:extracellular exosome biogenesis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR GO; GO:0055088; P:lipid homeostasis; IMP:UniProtKB.
DR GO; GO:0007041; P:lysosomal transport; IMP:UniProtKB.
DR GO; GO:1905166; P:negative regulation of lysosomal protein catabolic process; TAS:ParkinsonsUK-UCL.
DR GO; GO:1901215; P:negative regulation of neuron death; ISS:ParkinsonsUK-UCL.
DR GO; GO:1990938; P:peptidyl-aspartic acid autophosphorylation; IMP:ParkinsonsUK-UCL.
DR GO; GO:1902047; P:polyamine transmembrane transport; IDA:ParkinsonsUK-UCL.
DR GO; GO:1903543; P:positive regulation of exosomal secretion; IDA:ParkinsonsUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0046777; P:protein autophosphorylation; TAS:ParkinsonsUK-UCL.
DR GO; GO:0061462; P:protein localization to lysosome; IMP:UniProtKB.
DR GO; GO:0016243; P:regulation of autophagosome size; IDA:ParkinsonsUK-UCL.
DR GO; GO:1903146; P:regulation of autophagy of mitochondrion; TAS:ParkinsonsUK-UCL.
DR GO; GO:1904714; P:regulation of chaperone-mediated autophagy; TAS:ParkinsonsUK-UCL.
DR GO; GO:0052548; P:regulation of endopeptidase activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:1905123; P:regulation of glucosylceramidase activity; IEA:Ensembl.
DR GO; GO:0033157; P:regulation of intracellular protein transport; NAS:ParkinsonsUK-UCL.
DR GO; GO:1905165; P:regulation of lysosomal protein catabolic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0016241; P:regulation of macroautophagy; IMP:ParkinsonsUK-UCL.
DR GO; GO:0010821; P:regulation of mitochondrion organization; IDA:ParkinsonsUK-UCL.
DR GO; GO:1900180; P:regulation of protein localization to nucleus; IMP:UniProtKB.
DR GO; GO:2000152; P:regulation of ubiquitin-specific protease activity; IMP:UniProtKB.
DR GO; GO:1903710; P:spermine transmembrane transport; IMP:UniProtKB.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR GO; GO:0055069; P:zinc ion homeostasis; IMP:ParkinsonsUK-UCL.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR023299; ATPase_P-typ_cyto_dom_N.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR006544; P-type_TPase_V.
DR InterPro; IPR001757; P_typ_ATPase.
DR InterPro; IPR044492; P_typ_ATPase_HD_dom.
DR Pfam; PF12409; P5-ATPase; 1.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81660; SSF81660; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 2.
DR TIGRFAMs; TIGR01657; P-ATPase-V; 1.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cytoplasmic vesicle;
KW Disease variant; Endosome; Glycoprotein; Hereditary spastic paraplegia;
KW Lipid-binding; Lysosome; Magnesium; Membrane; Metal-binding;
KW Neurodegeneration; Neuronal ceroid lipofuscinosis; Nucleotide-binding;
KW Parkinsonism; Phosphoprotein; Reference proteome; Translocase;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1180
FT /note="Polyamine-transporting ATPase 13A2"
FT /id="PRO_0000046423"
FT TOPO_DOM 1..44
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:26134396"
FT INTRAMEM 45..65
FT /evidence="ECO:0000255"
FT TOPO_DOM 66..235
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:26134396"
FT TRANSMEM 236..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 254..256
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:26134396"
FT TRANSMEM 257..276
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 277..427
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:26134396"
FT TRANSMEM 428..448
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 449..463
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:26134396"
FT TRANSMEM 464..484
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 485..930
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:26134396"
FT TRANSMEM 931..951
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 952..957
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:26134396"
FT TRANSMEM 958..978
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 979..994
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:26134396"
FT TRANSMEM 995..1015
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1016..1048
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:26134396"
FT TRANSMEM 1049..1069
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1070..1080
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:26134396"
FT TRANSMEM 1081..1101
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1102..1117
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:26134396"
FT TRANSMEM 1118..1138
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1139..1180
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:26134396"
FT ACT_SITE 513
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000269|PubMed:26134396"
FT BINDING 878
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 882
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT MOD_RES 151
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CARBOHYD 1033
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:26134396"
FT CARBOHYD 1110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 155..159
FT /note="Missing (in isoform B and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2,
FT ECO:0000303|Ref.8"
FT /id="VSP_007310"
FT VAR_SEQ 805..843
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.8"
FT /id="VSP_007311"
FT VAR_SEQ 1079..1180
FT /note="VPFLVALALLSSVLVGLVLVPGLLQGPLALRNITDTGFKLLLLGLVTLNFVG
FT AFMLESVLDQCLPACLRRLRPKRASKKRFKQLERELAEQPWPPLPAGPLR -> ERARP
FT VPPRLPAPPPAQAGLQEALQAAGTRAGRAALAAAARRPPEVVQAHGHPRHWNSLPLSHQ
FT LDPSPATPPPPPPTSLRLATVYTPPPRPPPPWGSVDYCPLPWTIPRRGGSPQLPSVLLS
FT V (in isoform B)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.8"
FT /id="VSP_007312"
FT VARIANT 12
FT /note="T -> M (in KRS; no effect on stability; no effect on
FT location; decreased ATPase activity; dbSNP:rs151117874)"
FT /evidence="ECO:0000269|PubMed:17485642,
FT ECO:0000269|PubMed:22768177, ECO:0000269|PubMed:31996848"
FT /id="VAR_058451"
FT VARIANT 49
FT /note="G -> S (in dbSNP:rs56379718)"
FT /evidence="ECO:0000269|PubMed:19085912"
FT /id="VAR_058452"
FT VARIANT 182
FT /note="F -> L (in KRS; decreased protein stability; loss of
FT autophosphorylation; increased degradation by proteasome;
FT novel location to endoplasmic reticulum; loss of lysosomal
FT membrane location; impaired autophagosome-lysosome fusion;
FT impaired degradation of protein aggregates)"
FT /evidence="ECO:0000269|PubMed:18413573,
FT ECO:0000269|PubMed:22768177, ECO:0000269|PubMed:28137957,
FT ECO:0000269|PubMed:30538141"
FT /id="VAR_066019"
FT VARIANT 294
FT /note="R -> Q (in dbSNP:rs56367069)"
FT /evidence="ECO:0000269|PubMed:19085912"
FT /id="VAR_058453"
FT VARIANT 389
FT /note="P -> L (in dbSNP:rs56275621)"
FT /evidence="ECO:0000269|PubMed:19085912"
FT /id="VAR_058454"
FT VARIANT 441
FT /note="I -> F (in KRS; unknown pathological significance;
FT associated in cis with Thr-1069 in one individual;
FT dbSNP:rs772446950)"
FT /evidence="ECO:0000269|PubMed:29903538"
FT /id="VAR_083537"
FT VARIANT 504
FT /note="G -> R (in KRS; decreased protein stability;
FT increased degradation by proteasome; novel location to
FT endoplasmic reticulum; loss of lysosomal membrane location;
FT impaired autophagosome-lysosome fusion; impaired
FT degradation of protein aggregates; dbSNP:rs121918227)"
FT /evidence="ECO:0000269|PubMed:17485642,
FT ECO:0000269|PubMed:22768177, ECO:0000269|PubMed:30538141"
FT /id="VAR_058455"
FT VARIANT 517
FT /note="T -> I (in SPG78; no effect on protein stability;
FT loss of autophosphorylation; loss of lysosomal location;
FT loss of ATPase activity; dbSNP:rs1057519291)"
FT /evidence="ECO:0000269|PubMed:28137957,
FT ECO:0000269|PubMed:31996848"
FT /id="VAR_078055"
FT VARIANT 522
FT /note="G -> V (in KRS; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:22296644"
FT /id="VAR_078056"
FT VARIANT 533
FT /note="G -> R (in a patient with early onset Parkinson
FT disease and KRS; decreased ATPase activity; no effect on
FT autophosphorylation; no effect on stability; no effect on
FT location)"
FT /evidence="ECO:0000269|PubMed:17485642,
FT ECO:0000269|PubMed:22768177, ECO:0000269|PubMed:28137957,
FT ECO:0000269|PubMed:31996848"
FT /id="VAR_058456"
FT VARIANT 578
FT /note="V -> G (in dbSNP:rs56186751)"
FT /evidence="ECO:0000269|PubMed:19085912"
FT /id="VAR_058457"
FT VARIANT 746
FT /note="A -> T (in KRS; decreased ATPase activity; no effect
FT on stability; no effect on location; dbSNP:rs147277743)"
FT /evidence="ECO:0000269|PubMed:19015489,
FT ECO:0000269|PubMed:22768177, ECO:0000269|PubMed:31996848"
FT /id="VAR_058458"
FT VARIANT 762
FT /note="R -> W (in dbSNP:rs55635527)"
FT /evidence="ECO:0000269|PubMed:19085912"
FT /id="VAR_058459"
FT VARIANT 776
FT /note="V -> I (in dbSNP:rs56170027)"
FT /evidence="ECO:0000269|PubMed:19085912"
FT /id="VAR_058460"
FT VARIANT 854
FT /note="M -> R (in KRS; some patients manifest
FT neuropathologic findings suggestive of neuronal ceroid
FT lipofuscinosis; dbSNP:rs587777053)"
FT /evidence="ECO:0000269|PubMed:22388936"
FT /id="VAR_070194"
FT VARIANT 877
FT /note="G -> R (in KRS; found in two affected brothers also
FT carrying C-481 in FBXO7; decreased protein stability;
FT increased degradation by proteasome; novel location to
FT endoplasmic reticulum; loss of ATPase activity; loss of
FT autophosphorylation; dbSNP:rs144701072)"
FT /evidence="ECO:0000269|PubMed:20853184,
FT ECO:0000269|PubMed:22768177, ECO:0000269|PubMed:31996848"
FT /id="VAR_066020"
FT VARIANT 946
FT /note="I -> F (in dbSNP:rs55708915)"
FT /evidence="ECO:0000269|PubMed:19085912"
FT /id="VAR_058461"
FT VARIANT 1059
FT /note="L -> R (in KRS; the mutant protein is retained in
FT the endoplasmic reticulum; dbSNP:rs137853967)"
FT /evidence="ECO:0000269|PubMed:21542062"
FT /id="VAR_066021"
FT VARIANT 1069
FT /note="A -> T (in KRS; unknown pathological significance;
FT associated in cis with Phe-441 in one individual;
FT dbSNP:rs774238872)"
FT /evidence="ECO:0000269|PubMed:29903538"
FT /id="VAR_083538"
FT MUTAGEN 59
FT /note="G->A: No effect on lipid binding."
FT /evidence="ECO:0000269|PubMed:26134396"
FT MUTAGEN 66..68
FT /note="RWK->AWA: Reduces lipid binding."
FT /evidence="ECO:0000269|PubMed:26134396"
FT MUTAGEN 74..78
FT /note="RLRLR->ALALA: Reduces lipid binding."
FT /evidence="ECO:0000269|PubMed:26134396"
FT MUTAGEN 160..164
FT /note="KRVLR->AAVLA: Reduces lipid binding."
FT /evidence="ECO:0000269|PubMed:26134396"
FT MUTAGEN 348
FT /note="E->A: Autophosphorylated but displays limited
FT spermine-induced ATPase activity and lacks spermine-induced
FT dephosphorylation."
FT /evidence="ECO:0000269|PubMed:31996848"
FT MUTAGEN 472
FT /note="A->V: Reduced spermine-induced ATPase activity and
FT lack of spermine-induced dephosphorylation."
FT /evidence="ECO:0000269|PubMed:31996848"
FT MUTAGEN 513
FT /note="D->N: Loss of ATPase function, autophosphorylation
FT and protection against mitochondrial stress."
FT /evidence="ECO:0000269|PubMed:26134396,
FT ECO:0000269|PubMed:28137957, ECO:0000269|PubMed:31996848"
FT MUTAGEN 967
FT /note="D->N: Reduced spermine-induced ATPase activity."
FT /evidence="ECO:0000269|PubMed:31996848"
FT MUTAGEN 1033
FT /note="N->A: Abolishes glycosylation."
FT /evidence="ECO:0000269|PubMed:26134396"
FT MUTAGEN 1067
FT /note="K->A: Reduced spermine-induced ATPase activity."
FT /evidence="ECO:0000269|PubMed:31996848"
FT CONFLICT 322
FT /note="Q -> R (in Ref. 6; AAH30267)"
FT /evidence="ECO:0000305"
FT CONFLICT 855..858
FT /note="APEQ -> IPRA (in Ref. 8; CAA08912)"
FT /evidence="ECO:0000305"
FT CONFLICT 861
FT /note="E -> V (in Ref. 8; CAA08912)"
FT /evidence="ECO:0000305"
FT STRAND 36..41
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 44..55
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 60..67
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 69..76
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:7N72"
FT TURN 82..84
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 86..91
FT /evidence="ECO:0007829|PDB:7N72"
FT TURN 95..98
FT /evidence="ECO:0007829|PDB:7VPK"
FT STRAND 102..106
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 164..168
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 171..176
FT /evidence="ECO:0007829|PDB:7N72"
FT TURN 177..180
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 181..184
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 185..187
FT /evidence="ECO:0007829|PDB:7N72"
FT TURN 188..191
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 194..199
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 200..202
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 206..216
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 228..235
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 239..253
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 257..289
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 294..299
FT /evidence="ECO:0007829|PDB:7N72"
FT TURN 300..302
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 303..308
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 309..311
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 317..320
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 322..327
FT /evidence="ECO:0007829|PDB:7VPI"
FT STRAND 329..341
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 343..346
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 350..355
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 361..363
FT /evidence="ECO:0007829|PDB:7N72"
FT TURN 366..369
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 370..372
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 379..384
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 386..397
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 399..401
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 403..412
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 422..449
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 454..468
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 473..491
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 493..497
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 498..505
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 508..512
FT /evidence="ECO:0007829|PDB:7N72"
FT TURN 516..518
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 524..529
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 533..535
FT /evidence="ECO:0007829|PDB:7VPK"
FT STRAND 540..542
FT /evidence="ECO:0007829|PDB:7N78"
FT HELIX 543..545
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 550..557
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 562..564
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 567..570
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 572..581
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 584..586
FT /evidence="ECO:0007829|PDB:7VPL"
FT STRAND 593..596
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 600..604
FT /evidence="ECO:0007829|PDB:7VPI"
FT STRAND 622..628
FT /evidence="ECO:0007829|PDB:7N72"
FT TURN 632..634
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 636..642
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 644..647
FT /evidence="ECO:0007829|PDB:7VPK"
FT STRAND 650..655
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 657..660
FT /evidence="ECO:0007829|PDB:7N72"
FT TURN 661..663
FT /evidence="ECO:0007829|PDB:7N72"
FT TURN 666..668
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 673..681
FT /evidence="ECO:0007829|PDB:7N72"
FT TURN 682..684
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 686..694
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 701..704
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 709..713
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 714..725
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 732..741
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 745..749
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 754..763
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 765..767
FT /evidence="ECO:0007829|PDB:7N70"
FT STRAND 771..779
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 783..785
FT /evidence="ECO:0007829|PDB:7VPK"
FT STRAND 788..794
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 821..826
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 827..836
FT /evidence="ECO:0007829|PDB:7N72"
FT TURN 838..840
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 841..847
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 848..853
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 856..868
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 873..877
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 880..882
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 883..888
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 889..894
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 897..900
FT /evidence="ECO:0007829|PDB:7N72"
FT TURN 901..903
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 905..912
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 915..953
FT /evidence="ECO:0007829|PDB:7N72"
FT TURN 954..956
FT /evidence="ECO:0007829|PDB:7VPI"
FT HELIX 960..967
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 969..978
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 995..998
FT /evidence="ECO:0007829|PDB:7N74"
FT HELIX 999..1024
FT /evidence="ECO:0007829|PDB:7N72"
FT STRAND 1026..1028
FT /evidence="ECO:0007829|PDB:7N75"
FT STRAND 1034..1036
FT /evidence="ECO:0007829|PDB:7N73"
FT TURN 1038..1041
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 1045..1065
FT /evidence="ECO:0007829|PDB:7N72"
FT TURN 1069..1071
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 1075..1077
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 1079..1097
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 1100..1102
FT /evidence="ECO:0007829|PDB:7VPI"
FT TURN 1103..1107
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 1114..1149
FT /evidence="ECO:0007829|PDB:7N72"
FT HELIX 1158..1168
FT /evidence="ECO:0007829|PDB:7N72"
SQ SEQUENCE 1180 AA; 128794 MW; 98D13745D3B615BE CRC64;
MSADSSPLVG STPTGYGTLT IGTSIDPLSS SVSSVRLSGY CGSPWRVIGY HVVVWMMAGI
PLLLFRWKPL WGVRLRLRPC NLAHAETLVI EIRDKEDSSW QLFTVQVQTE AIGEGSLEPS
PQSQAEDGRS QAAVGAVPEG AWKDTAQLHK SEEAVSVGQK RVLRYYLFQG QRYIWIETQQ
AFYQVSLLDH GRSCDDVHRS RHGLSLQDQM VRKAIYGPNV ISIPVKSYPQ LLVDEALNPY
YGFQAFSIAL WLADHYYWYA LCIFLISSIS ICLSLYKTRK QSQTLRDMVK LSMRVCVCRP
GGEEEWVDSS ELVPGDCLVL PQEGGLMPCD AALVAGECMV NESSLTGESI PVLKTALPEG
LGPYCAETHR RHTLFCGTLI LQARAYVGPH VLAVVTRTGF CTAKGGLVSS ILHPRPINFK
FYKHSMKFVA ALSVLALLGT IYSIFILYRN RVPLNEIVIR ALDLVTVVVP PALPAAMTVC
TLYAQSRLRR QGIFCIHPLR INLGGKLQLV CFDKTGTLTE DGLDVMGVVP LKGQAFLPLV
PEPRRLPVGP LLRALATCHA LSRLQDTPVG DPMDLKMVES TGWVLEEEPA ADSAFGTQVL
AVMRPPLWEP QLQAMEEPPV PVSVLHRFPF SSALQRMSVV VAWPGATQPE AYVKGSPELV
AGLCNPETVP TDFAQMLQSY TAAGYRVVAL ASKPLPTVPS LEAAQQLTRD TVEGDLSLLG
LLVMRNLLKP QTTPVIQALR RTRIRAVMVT GDNLQTAVTV ARGCGMVAPQ EHLIIVHATH
PERGQPASLE FLPMESPTAV NGVKDPDQAA SYTVEPDPRS RHLALSGPTF GIIVKHFPKL
LPKVLVQGTV FARMAPEQKT ELVCELQKLQ YCVGMCGDGA NDCGALKAAD VGISLSQAEA
SVVSPFTSSM ASIECVPMVI REGRCSLDTS FSVFKYMALY SLTQFISVLI LYTINTNLGD
LQFLAIDLVI TTTVAVLMSR TGPALVLGRV RPPGALLSVP VLSSLLLQMV LVTGVQLGGY
FLTLAQPWFV PLNRTVAAPD NLPNYENTVV FSLSSFQYLI LAAAVSKGAP FRRPLYTNVP
FLVALALLSS VLVGLVLVPG LLQGPLALRN ITDTGFKLLL LGLVTLNFVG AFMLESVLDQ
CLPACLRRLR PKRASKKRFK QLERELAEQP WPPLPAGPLR
