ID ATD3A_HUMAN Reviewed; 586 AA. AC Q9NVI7; B3KPB3; D2K8Q1; G3V1I6; Q5SV23; Q8N275; Q96A50; DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot. DT 09-APR-2025, sequence version 3. DT 28-JAN-2026, entry version 205. DE RecName: Full=ATPase family AAA domain-containing protein 3A {ECO:0000305}; DE EC=3.6.1.- {ECO:0000269|PubMed:20154147, ECO:0000305|PubMed:39116259}; GN Name=ATAD3A {ECO:0000303|PubMed:37832546, GN ECO:0000312|HGNC:HGNC:25567}; 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 [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RC TISSUE=Lung adenocarcinoma; RX PubMed=20332122; DOI=10.1242/jcs.062034; RA Fang H.Y., Chang C.L., Hsu S.H., Huang C.Y., Chiang S.F., Chiou S.H., RA Huang C.H., Hsiao Y.T., Lin T.Y., Chiang I.P., Hsu W.H., Sugano S., RA Chen C.Y., Lin C.Y., Ko W.J., Chow K.C.; RT "ATPase family AAA domain-containing 3A is a novel anti-apoptotic factor in RT lung adenocarcinoma cells."; RL J. Cell Sci. 123:1171-1180(2010). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Teratocarcinoma, and Tongue; 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 [3] 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ASP-15. RC TISSUE=Brain, and Skin; 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 [6] RP PROTEIN SEQUENCE OF 2-9; 202-208; 228-238; 291-298; 395-403; 431-439 AND RP 558-568 (ISOFORMS 1/2), PROTEIN SEQUENCE OF 93-104 (ISOFORM 2), CLEAVAGE OF RP INITIATOR METHIONINE, ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Colon carcinoma; RA Bienvenut W.V., Heiserich L., Boulahbel H., Gottlieb E.; RL Submitted (JUL-2007) to UniProtKB. RN [7] RP FUNCTION, SUBCELLULAR LOCATION, AND ASSOCIATION WITH NUCLEOIDS. RX PubMed=17210950; DOI=10.1083/jcb.200609158; RA He J., Mao C.C., Reyes A., Sembongi H., Di Re M., Granycome C., RA Clippingdale A.B., Fearnley I.M., Harbour M., Robinson A.J., Reichelt S., RA Spelbrink J.N., Walker J.E., Holt I.J.; RT "The AAA+ protein ATAD3 has displacement loop binding properties and is RT involved in mitochondrial nucleoid organization."; RL J. Cell Biol. 176:141-146(2007). RN [8] RP SUBCELLULAR LOCATION, TOPOLOGY, AND ASSOCIATION WITH NUCLEOIDS. RX PubMed=18063578; DOI=10.1074/jbc.m708444200; RA Bogenhagen D.F., Rousseau D., Burke S.; RT "The layered structure of human mitochondrial DNA nucleoids."; RL J. Biol. Chem. 283:3665-3675(2008). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-491, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [11] RP SUBCELLULAR LOCATION, AND TOPOLOGY. RX PubMed=20349121; DOI=10.1007/s10863-010-9269-8; RA Hubstenberger A., Merle N., Charton R., Brandolin G., Rousseau D.; RT "Topological analysis of ATAD3A insertion in purified human mitochondria."; RL J. Bioenerg. Biomembr. 42:143-150(2010). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, HOMOOLIGOMERIZATION, INDUCTION, SUBCELLULAR RP LOCATION, TOPOLOGY, AND MUTAGENESIS OF LYS-358 AND ASP-411. RX PubMed=20154147; DOI=10.1128/mcb.00007-10; RA Gilquin B., Taillebourg E., Cherradi N., Hubstenberger A., Gay O., RA Merle N., Assard N., Fauvarque M.O., Tomohiro S., Kuge O., Baudier J.; RT "The AAA+ ATPase ATAD3A controls mitochondrial dynamics at the interface of RT the inner and outer membranes."; RL Mol. Cell. Biol. 30:1984-1996(2010). RN [13] RP INTERACTION WITH S100B, AND MUTAGENESIS OF VAL-293; LEU-297 AND RP 301-ILE-GLN-302. RX PubMed=20351179; DOI=10.1128/mcb.01468-09; RA Gilquin B., Cannon B.R., Hubstenberger A., Moulouel B., Falk E., Merle N., RA Assard N., Kieffer S., Rousseau D., Wilder P.T., Weber D.J., Baudier J.; RT "The calcium-dependent interaction between S100B and the mitochondrial AAA RT ATPase ATAD3A and the role of this complex in the cytoplasmic processing of RT ATAD3A."; RL Mol. Cell. Biol. 30:2724-2736(2010). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [15] RP INTERACTION WITH ATAD3B AND HSPD1. RX PubMed=22664726; DOI=10.1016/j.mito.2012.05.005; RA Merle N., Feraud O., Gilquin B., Hubstenberger A., Kieffer-Jacquinot S., RA Assard N., Bennaceur-Griscelli A., Honnorat J., Baudier J.; RT "ATAD3B is a human embryonic stem cell specific mitochondrial protein, re- RT expressed in cancer cells, that functions as dominant negative for the RT ubiquitous ATAD3A."; RL Mitochondrion 12:441-448(2012). RN [16] RP FUNCTION, INTERACTION WITH PROTEINS INVOLVED IN MITOCHONDRIAL TRANSLATION; RP RNA METABOLISM; LIPID METABOLISM; GADD45GIP1 AND FAM210A, AND INDUCTION. RX PubMed=22453275; DOI=10.1093/nar/gks266; RA He J., Cooper H.M., Reyes A., Di Re M., Sembongi H., Litwin T.R., Gao J., RA Neuman K.C., Fearnley I.M., Spinazzola A., Walker J.E., Holt I.J.; RT "Mitochondrial nucleoid interacting proteins support mitochondrial protein RT synthesis."; RL Nucleic Acids Res. 40:6109-6121(2012). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-321, 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 [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [19] RP INTERACTION WITH CLPB, AND FUNCTION. RX PubMed=31522117; DOI=10.1016/j.isci.2019.08.056; RA Yoshinaka T., Kosako H., Yoshizumi T., Furukawa R., Hirano Y., Kuge O., RA Tamada T., Koshiba T.; RT "Structural Basis of Mitochondrial Scaffolds by Prohibitin Complexes: RT Insight into a Role of the Coiled-Coil Region."; RL IScience 19:1065-1078(2019). RN [20] RP FUNCTION. RX PubMed=37832546; DOI=10.1016/j.molcel.2023.09.026; RA Fu Y., Sacco O., DeBitetto E., Kanshin E., Ueberheide B., Sfeir A.; RT "Mitochondrial DNA breaks activate an integrated stress response to RT reestablish homeostasis."; RL Mol. Cell 83:3740-3753(2023). RN [21] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH EIF2AK3, AND MUTAGENESIS RP OF GLU-412. RX PubMed=39116259; DOI=10.1126/science.adp7114; RA Brar K.K., Hughes D.T., Morris J.L., Subramanian K., Krishna S., Gao F., RA Rieder L.S., Uhrig S., Freeman J., Smith H.L., Jukes-Jones R., Avezov E., RA Nunnari J., Prudent J., Butcher A.J., Mallucci G.R.; RT "PERK-ATAD3A interaction provides a subcellular safe haven for protein RT synthesis during ER stress."; RL Science 0:0-0(2024). RN [22] RP VARIANTS HAYOS ILE-53 AND TRP-528, AND INVOLVEMENT IN HAYOS. RX PubMed=27640307; DOI=10.1016/j.ajhg.2016.08.007; RG Baylor-Hopkins Center for Mendelian Genomics; RG University of Washington Center for Mendelian Genomics; RA Harel T., Yoon W.H., Garone C., Gu S., Coban-Akdemir Z., Eldomery M.K., RA Posey J.E., Jhangiani S.N., Rosenfeld J.A., Cho M.T., Fox S., Withers M., RA Brooks S.M., Chiang T., Duraine L., Erdin S., Yuan B., Shao Y., RA Moussallem E., Lamperti C., Donati M.A., Smith J.D., McLaughlin H.M., RA Eng C.M., Walkiewicz M., Xia F., Pippucci T., Magini P., Seri M., RA Zeviani M., Hirano M., Hunter J.V., Srour M., Zanigni S., Lewis R.A., RA Muzny D.M., Lotze T.E., Boerwinkle E., Gibbs R.A., Hickey S.E., RA Graham B.H., Yang Y., Buhas D., Martin D.M., Potocki L., Graziano C., RA Bellen H.J., Lupski J.R.; RT "Recurrent de novo and biallelic variation of ATAD3A, encoding a RT mitochondrial membrane protein, Results in distinct neurological RT syndromes."; RL Am. J. Hum. Genet. 99:831-845(2016). RN [23] RP VARIANTS PHRINL ARG-77 AND 164-GLN--SER-586 DEL, AND INVOLVEMENT IN PHRINL. RX PubMed=29053797; DOI=10.1093/brain/awx239; RA Peeters-Scholte C.M.P.C.D., Adama van Scheltema P.N., Klumper F.J.C.M., RA Everwijn S.M.P., Koopmans M., Hoffer M.J.V., Koopmann T.T., RA Ruivenkamp C.A.L., Steggerda S.J., van der Knaap M.S., Santen G.W.E.; RT "Genotype-phenotype correlation in ATAD3A deletions: not just of scientific RT relevance."; RL Brain 140:e66-e66(2017). RN [24] RP VARIANT PHRINL ARG-406, INVOLVEMENT IN PHRINL, AND CHARACTERIZATION OF RP VARIANT PHRINL ARG-406. RX PubMed=31727539; DOI=10.1016/j.ymgme.2019.10.012; RA Peralta S., Gonzalez-Quintana A., Ybarra M., Delmiro A., Perez-Perez R., RA Docampo J., Arenas J., Blazquez A., Ugalde C., Martin M.A.; RT "Novel ATAD3A recessive mutation associated to fatal cerebellar hypoplasia RT with multiorgan involvement and mitochondrial structural abnormalities."; RL Mol. Genet. Metab. 128:452-462(2019). CC -!- FUNCTION: Essential for mitochondrial network organization, CC mitochondrial metabolism and cell growth at organism and cellular level CC (PubMed:17210950, PubMed:20154147, PubMed:22453275, PubMed:31522117, CC PubMed:37832546, PubMed:39116259). May play an important role in CC mitochondrial protein synthesis (PubMed:22453275). May also participate CC in mitochondrial DNA replication (PubMed:17210950). May bind to CC mitochondrial DNA D-loops and contribute to nucleoid stability CC (PubMed:17210950). Required for enhanced channeling of cholesterol for CC hormone-dependent steroidogenesis (PubMed:22453275). Involved in CC mitochondrial-mediated antiviral innate immunity (PubMed:31522117). CC Required to protect mitochondria from the PERK-mediated unfolded CC protein response: specifically inhibits the activity of EIF2AK3/PERK at CC mitochondria-endoplasmic reticulum contact sites, thereby providing a CC safe haven for mitochondrial protein translation during endoplasmic CC reticulum stress (PubMed:39116259). Ability to inhibit EIF2AK3/PERK is CC independent of its ATPase activity (PubMed:39116259). Also involved in CC the mitochondrial DNA damage response by promoting signaling between CC damaged genomes and the mitochondrial membrane, leading to activation CC of the integrated stress response (ISR) (PubMed:37832546). CC {ECO:0000269|PubMed:17210950, ECO:0000269|PubMed:20154147, CC ECO:0000269|PubMed:22453275, ECO:0000269|PubMed:31522117, CC ECO:0000269|PubMed:37832546, ECO:0000269|PubMed:39116259}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + phosphate + H(+); Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; CC Evidence={ECO:0000269|PubMed:20154147, ECO:0000305|PubMed:39116259}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; CC Evidence={ECO:0000269|PubMed:20154147, ECO:0000305|PubMed:39116259}; CC -!- SUBUNIT: Can form homooligomers (PubMed:20154147). Homodimer formation CC at the N-terminus may be regulated by ATP and is required for the CC interaction with the inner surface of the mitochondrial outer membrane CC and correct mitochondrial homeostasis (PubMed:20154147). Interacts with CC components of the mitochondrial ribosome and with other proteins CC involved in mitochondrial RNA metabolism (PubMed:22453275). May also CC interact with protein involved in lipid metabolism, including STARD9 CC (PubMed:22453275). May interact with FAM210A (PubMed:22453275). CC Interacts with GADD45GIP1 (PubMed:22453275). Interacts with S100B in a CC Ca(+2)- and Zn(+2)-dependent manner; this interaction probably occurs CC in the cytosol prior to mitochondrial targeting (PubMed:20351179). CC S100B could assist ATAD3A cytoplasmic processing, preventing CC aggregation and favoring mitochondrial localization (PubMed:20351179). CC Interacts with HSP60/HSPD1 (PubMed:22664726). Forms heterooligomers CC with ATAD3B; this interaction may affect ATAD3A activity CC (PubMed:22664726). Interacts with CLPB (PubMed:31522117). Interacts CC with EIF2AK3/PERK; ATAD3A and EIF2S1/eIF-2-alpha occupy a common CC binding site within the cytoplasmic loop of EIF2AK3/PERK, leading to CC prevent EIF2AK3/PERK association with its substrate EIF2S1/eIF-2-alpha CC (PubMed:39116259). {ECO:0000269|PubMed:20154147, CC ECO:0000269|PubMed:20351179, ECO:0000269|PubMed:22453275, CC ECO:0000269|PubMed:22664726, ECO:0000269|PubMed:31522117, CC ECO:0000269|PubMed:39116259}. CC -!- INTERACTION: CC Q9NVI7; O00429: DNM1L; NbExp=4; IntAct=EBI-352007, EBI-724571; CC Q9NVI7; P10809: HSPD1; NbExp=4; IntAct=EBI-352007, EBI-352528; CC Q9NVI7-2; Q9NVI7-2: ATAD3A; NbExp=2; IntAct=EBI-5456381, EBI-5456381; CC Q9NVI7-2; O00429: DNM1L; NbExp=5; IntAct=EBI-5456381, EBI-724571; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:18063578, ECO:0000269|PubMed:20154147, CC ECO:0000269|PubMed:20332122, ECO:0000269|PubMed:20349121}; Single-pass CC membrane protein {ECO:0000269|PubMed:20154147, CC ECO:0000269|PubMed:20349121}. Mitochondrion matrix, mitochondrion CC nucleoid {ECO:0000269|PubMed:17210950, ECO:0000269|PubMed:18063578}. CC Note=In the mitochondrial inner membrane, enriched in sites with the CC potential to form contacts with the outer membrane (PubMed:20154147, CC PubMed:20349121). The N-terminal domain interacts with the inner CC surface of the mitochondrial outer membrane and the C-terminal domain CC localizes in a specific matrix compartment, where it is associated with CC nucleoids (PubMed:18063578). Also present at mitochondria-endoplasmic CC reticulum contact sites; where it interacts with EIF2AK3/PERK CC (PubMed:39116259). {ECO:0000269|PubMed:18063578, CC ECO:0000269|PubMed:20154147, ECO:0000269|PubMed:20349121, CC ECO:0000269|PubMed:39116259}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=2; CC IsoId=Q9NVI7-2; Sequence=Displayed; CC Name=1; CC IsoId=Q9NVI7-1; Sequence=VSP_062536; CC Name=3; CC IsoId=Q9NVI7-3; Sequence=VSP_062535; CC -!- TISSUE SPECIFICITY: Overexpressed in lung adenocarcinomas (at protein CC level). {ECO:0000269|PubMed:20332122}. CC -!- INDUCTION: Up-regulated by Angiotensin/AGT. CC {ECO:0000269|PubMed:20154147, ECO:0000269|PubMed:22453275}. CC -!- DOMAIN: The transmembrane domain and a C-terminal adjacent region CC contain all information necessary for mitochondrial targeting. CC {ECO:0000269|PubMed:20154147}. CC -!- DISEASE: Harel-Yoon syndrome (HAYOS) [MIM:617183]: A syndrome CC characterized by global developmental delay, hypotonia, intellectual CC disability, and axonal neuropathy. Some patients have optic atrophy and CC hypertrophic cardiomyopathy. HAYOS inheritance can be autosomal CC dominant or autosomal recessive. {ECO:0000269|PubMed:27640307}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Pontocerebellar hypoplasia, hypotonia, and respiratory CC insufficiency syndrome, neonatal lethal (PHRINL) [MIM:618810]: An CC autosomal recessive multisystem disorder with onset in utero and death CC in the neonatal period. Affected infants show respiratory insufficiency CC and almost no spontaneous movement at birth. Additional features CC include corneal clouding, seizures, dysmorphic facies, contractures, CC and progressive pontocerebellar hypoplasia with simplified gyral CC pattern and white matter abnormalities. Some patients may have cardiac CC anomalies or cardiac hypertrophy. {ECO:0000269|PubMed:29053797, CC ECO:0000269|PubMed:31727539}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the AAA ATPase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; GU189416; ACZ80514.1; -; mRNA. DR EMBL; AK001571; BAA91764.1; -; mRNA. DR EMBL; AK056099; BAG51625.1; -; mRNA. DR EMBL; AK091144; BAC03595.1; -; mRNA. DR EMBL; AL645728; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471183; EAW56187.1; -; Genomic_DNA. DR EMBL; CH471183; EAW56190.1; -; Genomic_DNA. DR EMBL; BC007803; AAH07803.1; -; mRNA. DR EMBL; BC011814; AAH11814.1; -; mRNA. DR EMBL; BC014101; AAH14101.1; -; mRNA. DR EMBL; BC033109; AAH33109.1; -; mRNA. DR EMBL; BC063607; AAH63607.1; -; mRNA. DR CCDS; CCDS31.1; -. [Q9NVI7-1] DR CCDS; CCDS53259.1; -. [Q9NVI7-2] DR CCDS; CCDS53260.1; -. [Q9NVI7-3] DR RefSeq; NP_001164006.1; NM_001170535.3. [Q9NVI7-2] DR RefSeq; NP_001164007.1; NM_001170536.3. [Q9NVI7-3] DR RefSeq; NP_060658.3; NM_018188.4. [Q9NVI7-1] DR AlphaFoldDB; Q9NVI7; -. DR SMR; Q9NVI7; -. DR BioGRID; 120506; 374. DR DIP; DIP-33194N; -. DR FunCoup; Q9NVI7; 2296. DR IntAct; Q9NVI7; 295. DR MINT; Q9NVI7; -. DR STRING; 9606.ENSP00000368030; -. DR iPTMnet; Q9NVI7; -. DR MetOSite; Q9NVI7; -. DR PhosphoSitePlus; Q9NVI7; -. DR SwissPalm; Q9NVI7; -. DR BioMuta; ATAD3A; -. DR DMDM; 84028405; -. DR jPOST; Q9NVI7; -. DR MassIVE; Q9NVI7; -. DR PaxDb; 9606-ENSP00000368030; -. DR PeptideAtlas; Q9NVI7; -. DR PRIDE; Q9NVI7; -. DR ProteomicsDB; 32346; -. DR ProteomicsDB; 82815; -. [Q9NVI7-1] DR ProteomicsDB; 82816; -. [Q9NVI7-2] DR Pumba; Q9NVI7; -. DR Antibodypedia; 26400; 166 antibodies from 25 providers. DR DNASU; 55210; -. DR Ensembl; ENST00000378755.9; ENSP00000368030.5; ENSG00000197785.15. [Q9NVI7-1] DR Ensembl; ENST00000378756.8; ENSP00000368031.3; ENSG00000197785.15. [Q9NVI7-2] DR Ensembl; ENST00000536055.6; ENSP00000439290.1; ENSG00000197785.15. [Q9NVI7-3] DR GeneID; 55210; -. DR KEGG; hsa:55210; -. DR MANE-Select; ENST00000378756.8; ENSP00000368031.3; NM_001170535.3; NP_001164006.1. DR UCSC; uc001afz.3; human. [Q9NVI7-2] DR AGR; HGNC:25567; -. DR ClinPGx; PA134872099; -. DR CTD; 55210; -. DR DisGeNET; 55210; -. DR GeneCards; ATAD3A; -. DR HGNC; HGNC:25567; ATAD3A. DR HPA; ENSG00000197785; Low tissue specificity. DR MalaCards; ATAD3A; -. DR MIM; 612316; gene. DR MIM; 617183; phenotype. DR MIM; 618810; phenotype. DR OpenTargets; ENSG00000197785; -. DR Orphanet; 656279; 1p36.33 duplication syndrome. DR Orphanet; 615983; Lethal pontocerebellar hypoplasia-hypotonia-respiratory insufficiency syndrome due to a point mutation. DR Orphanet; 615986; Lethal pontocerebellar hypoplasia-hypotonia-respiratory insufficiency syndrome due to biallelic deletions in the ATAD3 gene cluster. DR Orphanet; 496790; Ocular anomalies-axonal neuropathy-developmental delay syndrome. DR VEuPathDB; HostDB:ENSG00000197785; -. DR eggNOG; KOG0742; Eukaryota. DR GeneTree; ENSGT00730000111059; -. DR HOGENOM; CLU_011488_2_0_1; -. DR InParanoid; Q9NVI7; -. DR OMA; HKSITGG; -. DR OrthoDB; 199596at2759; -. DR PAN-GO; Q9NVI7; 2 GO annotations based on evolutionary models. DR PhylomeDB; Q9NVI7; -. DR PathwayCommons; Q9NVI7; -. DR SignaLink; Q9NVI7; -. DR Agora; ENSG00000197785; -. DR BioGRID-ORCS; 55210; 46 hits in 1120 CRISPR screens. DR CD-CODE; 232F8A39; P-body. DR CD-CODE; 91857CE7; Nucleolus. DR CD-CODE; DEE660B4; Stress granule. DR ChiTaRS; ATAD3A; human. DR GenomeRNAi; 55210; -. DR Pharos; Q9NVI7; Tbio. DR PRO; PR:Q9NVI7; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9NVI7; protein. DR Bgee; ENSG00000197785; Expressed in sural nerve and 179 other cell types or tissues. DR ExpressionAtlas; Q9NVI7; baseline and differential. DR GO; GO:0044233; C:mitochondria-associated endoplasmic reticulum membrane contact site; IDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0042645; C:mitochondrial nucleoid; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005524; F:ATP binding; IMP:FlyBase. DR GO; GO:0016887; F:ATP hydrolysis activity; IMP:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IDA:UniProtKB. DR GO; GO:0140374; P:antiviral innate immune response; IMP:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0140468; P:HRI-mediated signaling; IDA:UniProtKB. DR GO; GO:0007005; P:mitochondrion organization; IMP:FlyBase. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:1903898; P:negative regulation of PERK-mediated unfolded protein response; IDA:UniProtKB. DR GO; GO:0001558; P:regulation of cell growth; IMP:UniProtKB. DR CDD; cd19512; RecA-like_ATAD3-like; 1. DR FunFam; 3.40.50.300:FF:000470; ATPase family, AAA domain containing 3A; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR021911; ATAD3_N. DR InterPro; IPR003959; ATPase_AAA_core. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR23075:SF5; ATPASE FAMILY AAA DOMAIN-CONTAINING PROTEIN 3A; 1. DR PANTHER; PTHR23075; PUTATIVE ATP-ASE; 1. DR Pfam; PF00004; AAA; 1. DR Pfam; PF12037; ATAD3_N; 1. DR SMART; SM00382; AAA; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; ATP-binding; Coiled coil; KW Direct protein sequencing; Disease variant; Hydrolase; Membrane; KW Mitochondrion; Mitochondrion inner membrane; Mitochondrion nucleoid; KW Nucleotide-binding; Phosphoprotein; Proteomics identification; KW Reference proteome; Transmembrane; Transmembrane helix. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.6" FT CHAIN 2..586 FT /note="ATPase family AAA domain-containing protein 3A" FT /id="PRO_0000084799" FT TOPO_DOM 2..246 FT /note="Mitochondrial intermembrane" FT /evidence="ECO:0000255" FT TRANSMEM 247..264 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 265..586 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000255" FT REGION 1..55 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2..50 FT /note="Required for interaction with the inner surface of FT the mitochondrial outer membrane" FT /evidence="ECO:0000269|PubMed:18063578" FT REGION 111..134 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 290..305 FT /note="S100B-binding" FT /evidence="ECO:0000269|PubMed:20351179" FT COILED 86..219 FT /evidence="ECO:0000255" FT COMPBIAS 17..26 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 32..48 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 111..125 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 352..359 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000269|Ref.6" FT MOD_RES 321 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 491 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VAR_SEQ 1..79 FT /note="Missing (in isoform 3)" FT /id="VSP_062535" FT VAR_SEQ 94 FT /note="K -> KMRLEALSLLHTLVWAWSLCRAGAVQTQERLSGSASPEQVPAGECCA FT LQ (in isoform 1)" FT /id="VSP_062536" FT VARIANT 15 FT /note="G -> D (in dbSNP:rs2274435)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_023526" FT VARIANT 53 FT /note="T -> I (in HAYOS; dbSNP:rs1057517687)" FT /evidence="ECO:0000269|PubMed:27640307" FT /id="VAR_082788" FT VARIANT 77 FT /note="L -> R (in PHRINL; dbSNP:rs1570319915)" FT /evidence="ECO:0000269|PubMed:29053797" FT /id="VAR_083867" FT VARIANT 164..586 FT /note="Missing (in PHRINL; dbSNP:rs760826883)" FT /evidence="ECO:0000269|PubMed:29053797" FT /id="VAR_083868" FT VARIANT 406 FT /note="L -> R (in PHRINL; decreased protein levels in FT patient cells; dbSNP:rs1570345942)" FT /evidence="ECO:0000269|PubMed:31727539" FT /id="VAR_083869" FT VARIANT 528 FT /note="R -> W (in HAYOS; dbSNP:rs1057517686)" FT /evidence="ECO:0000269|PubMed:27640307" FT /id="VAR_082789" FT MUTAGEN 293 FT /note="V->S: Loss of S100B-binding; when associated with FT S-297." FT /evidence="ECO:0000269|PubMed:20351179" FT MUTAGEN 297 FT /note="L->S: Loss of S100B-binding; when associated with FT S-293." FT /evidence="ECO:0000269|PubMed:20351179" FT MUTAGEN 301..302 FT /note="Missing: Decrease in S100B-binding." FT /evidence="ECO:0000269|PubMed:20351179" FT MUTAGEN 358 FT /note="K->E: No effect on homooligomerization. Immediate FT fragmentation of the mitochondrial network." FT /evidence="ECO:0000269|PubMed:20154147" FT MUTAGEN 411 FT /note="D->Q: No effect on homooligomerization. Immediate FT fragmentation of the mitochondrial network." FT /evidence="ECO:0000269|PubMed:20154147" FT MUTAGEN 412 FT /note="E->Q: Abolished ATPase activity without affecting FT its ability to interact with and inhibit EIF2AK3/PERK." FT /evidence="ECO:0000269|PubMed:39116259" FT CONFLICT 176 FT /note="R -> Q (in Ref. 2; BAG51625)" FT /evidence="ECO:0000305" FT CONFLICT 207 FT /note="I -> T (in Ref. 2; BAC03595)" FT /evidence="ECO:0000305" SQ SEQUENCE 586 AA; 66218 MW; 1E83D08AE33D550F CRC64; MSWLFGINKG PKGEGAGPPP PLPPAQPGAE GGGDRGLGDR PAPKDKWSNF DPTGLERAAK AARELEHSRY AKDALNLAQM QEQTLQLEQQ SKLKEYEAAV EQLKSEQIRA QAEERRKTLS EETRQHQARA QYQDKLARQR YEDQLKQQQL LNEENLRKQE ESVQKQEAMR RATVEREMEL RHKNEMLRVE AEARARAKAE RENADIIREQ IRLKAAEHRQ TVLESIRTAG TLFGEGFRAF VTDWDKVTAT VAGLTLLAVG VYSAKNATLV AGRFIEARLG KPSLVRETSR ITVLEALRHP IQVSRRLLSR PQDALEGVVL SPSLEARVRD IAIATRNTKK NRSLYRNILM YGPPGTGKTL FAKKLALHSG MDYAIMTGGD VAPMGREGVT AMHKLFDWAN TSRRGLLLFV DEADAFLRKR ATEKISEDLR ATLNAFLYRT GQHSNKFMLV LASNQPEQFD WAINDRINEM VHFDLPGQEE RERLVRMYFD KYVLKPATEG KQRLKLAQFD YGRKCSEVAR LTEGMSGREI AQLAVSWQAT AYASEDGVLT EAMMDTRVQD AVQQHQQKMC WLKAEGPGRG DEPSPS //