ATD3A_HUMAN
ID ATD3A_HUMAN Reviewed; 634 AA.
AC Q9NVI7; B3KPB3; D2K8Q1; G3V1I6; Q5SV23; Q8N275; Q96A50;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=ATPase family AAA domain-containing protein 3A {ECO:0000312|HGNC:HGNC:25567};
GN Name=ATAD3A {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; 250-256; 276-286; 339-346; 443-451; 479-487 AND
RP 606-616 (ISOFORMS 1/2), PROTEIN SEQUENCE OF 93-152 (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-539, 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, HOMOOLIGOMERIZATION, INDUCTION, SUBCELLULAR LOCATION, TOPOLOGY,
RP AND MUTAGENESIS OF LYS-406 AND ASP-459.
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-341; LEU-345 AND
RP 349-ILE-GLN-350.
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-369, 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 VARIANTS HAYOS ILE-53 AND TRP-528 (ISOFORM 2), 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 [21]
RP VARIANTS PHRINL ARG-77 AND 212-GLN--SER-634 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 [22]
RP VARIANT PHRINL ARG-454, INVOLVEMENT IN PHRINL, AND CHARACTERIZATION OF
RP VARIANT PHRINL ARG-454.
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
CC level. May play an important role in mitochondrial protein synthesis.
CC May also participate in mitochondrial DNA replication. May bind to
CC mitochondrial DNA D-loops and contribute to nucleoid stability.
CC Required for enhanced channeling of cholesterol for hormone-dependent
CC steroidogenesis. Involved in mitochondrial-mediated antiviral innate
CC immunity (PubMed:31522117). {ECO:0000269|PubMed:17210950,
CC ECO:0000269|PubMed:20154147, ECO:0000269|PubMed:22453275,
CC ECO:0000269|PubMed:31522117}.
CC -!- SUBUNIT: Can form homooligomers. Homodimer formation at the N-terminus
CC may be regulated by ATP and is required for the interaction with the
CC inner surface of the mitochondrial outer membrane and correct
CC mitochondrial homeostasis. Interacts with components of the
CC mitochondrial ribosome and with other proteins involved in
CC mitochondrial RNA metabolism. May also interact with protein involved
CC in lipid metabolism, including STARD9. May interact with FAM210A.
CC Interacts with GADD45GIP1. Interacts with S100B in a Ca(+2)- and
CC Zn(+2)-dependent manner; this interaction probably occurs in the
CC cytosol prior to mitochondrial targeting. S100B could assist ATAD3A
CC cytoplasmic processing, preventing aggregation and favoring
CC mitochondrial localization. Interacts with HSP60/HSPD1. Forms
CC heterooligomers with ATAD3B; this interaction may affect ATAD3A
CC activity. Interacts with CLPB (PubMed:31522117).
CC {ECO:0000269|PubMed:20351179, ECO:0000269|PubMed:22453275,
CC ECO:0000269|PubMed:22664726, ECO:0000269|PubMed:31522117}.
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:20349121,
CC PubMed:20154147). 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). {ECO:0000269|PubMed:18063578,
CC ECO:0000269|PubMed:20154147, ECO:0000269|PubMed:20349121}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9NVI7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NVI7-2; Sequence=VSP_015636;
CC Name=3;
CC IsoId=Q9NVI7-3; Sequence=VSP_044145, VSP_015636;
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 -!- MISCELLANEOUS: [Isoform 2]: May be the predominant ATAD3A form.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the AAA ATPase family. {ECO:0000305}.
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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_001170535.2. [Q9NVI7-2]
DR RefSeq; NP_001164007.1; NM_001170536.2. [Q9NVI7-3]
DR RefSeq; NP_060658.3; NM_018188.4. [Q9NVI7-1]
DR AlphaFoldDB; Q9NVI7; -.
DR SMR; Q9NVI7; -.
DR BioGRID; 120506; 283.
DR DIP; DIP-33194N; -.
DR IntAct; Q9NVI7; 254.
DR MINT; Q9NVI7; -.
DR STRING; 9606.ENSP00000368030; -.
DR GlyGen; Q9NVI7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NVI7; -.
DR MetOSite; Q9NVI7; -.
DR PhosphoSitePlus; Q9NVI7; -.
DR SwissPalm; Q9NVI7; -.
DR BioMuta; ATAD3A; -.
DR DMDM; 84028405; -.
DR EPD; Q9NVI7; -.
DR jPOST; Q9NVI7; -.
DR MassIVE; Q9NVI7; -.
DR MaxQB; Q9NVI7; -.
DR PaxDb; Q9NVI7; -.
DR PeptideAtlas; Q9NVI7; -.
DR PRIDE; Q9NVI7; -.
DR ProteomicsDB; 32346; -.
DR ProteomicsDB; 82815; -. [Q9NVI7-1]
DR ProteomicsDB; 82816; -. [Q9NVI7-2]
DR Antibodypedia; 26400; 165 antibodies from 24 providers.
DR DNASU; 55210; -.
DR Ensembl; ENST00000378755.9; ENSP00000368030.5; ENSG00000197785.14. [Q9NVI7-1]
DR Ensembl; ENST00000378756.8; ENSP00000368031.3; ENSG00000197785.14. [Q9NVI7-2]
DR Ensembl; ENST00000536055.6; ENSP00000439290.1; ENSG00000197785.14. [Q9NVI7-3]
DR GeneID; 55210; -.
DR KEGG; hsa:55210; -.
DR MANE-Select; ENST00000378756.8; ENSP00000368031.3; NM_001170535.3; NP_001164006.1. [Q9NVI7-2]
DR UCSC; uc001afz.3; human. [Q9NVI7-1]
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 neXtProt; NX_Q9NVI7; -.
DR OpenTargets; ENSG00000197785; -.
DR Orphanet; 496790; Ocular anomalies-axonal neuropathy-developmental delay syndrome.
DR PharmGKB; PA134872099; -.
DR VEuPathDB; HostDB:ENSG00000197785; -.
DR eggNOG; KOG0742; Eukaryota.
DR GeneTree; ENSGT00730000111059; -.
DR HOGENOM; CLU_011488_2_0_1; -.
DR InParanoid; Q9NVI7; -.
DR OMA; KTCSKMA; -.
DR OrthoDB; 357201at2759; -.
DR PhylomeDB; Q9NVI7; -.
DR TreeFam; TF313922; -.
DR PathwayCommons; Q9NVI7; -.
DR SignaLink; Q9NVI7; -.
DR BioGRID-ORCS; 55210; 43 hits in 1042 CRISPR screens.
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 177 other tissues.
DR ExpressionAtlas; Q9NVI7; baseline and differential.
DR Genevisible; Q9NVI7; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0140374; P:antiviral innate immune response; IMP:UniProtKB.
DR GO; GO:0007005; P:mitochondrion organization; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; IMP:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR039188; ATAD3.
DR InterPro; IPR021911; ATAD3_N.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR23075; PTHR23075; 1.
DR Pfam; PF00004; AAA; 1.
DR Pfam; PF12037; DUF3523; 2.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Coiled coil;
KW Direct protein sequencing; Disease variant; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Mitochondrion nucleoid; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.6"
FT CHAIN 2..634
FT /note="ATPase family AAA domain-containing protein 3A"
FT /id="PRO_0000084799"
FT TOPO_DOM 2..294
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..312
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 313..634
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255"
FT REGION 1..52
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 REGION 159..181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 338..353
FT /note="S100B-binding"
FT COILED 139..267
FT /evidence="ECO:0000255"
FT BINDING 400..407
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 369
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 539
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..79
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044145"
FT VAR_SEQ 95..142
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:20332122"
FT /id="VSP_015636"
FT VARIANT 15
FT /note="G -> D (in dbSNP:rs2274435)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_023526"
FT VARIANT 77
FT /note="L -> R (in PHRINL; dbSNP:rs1570319915)"
FT /evidence="ECO:0000269|PubMed:29053797"
FT /id="VAR_083867"
FT VARIANT 101
FT /note="S -> N (in dbSNP:rs1619896)"
FT /id="VAR_055468"
FT VARIANT 212..634
FT /note="Missing (in PHRINL; dbSNP:rs760826883)"
FT /evidence="ECO:0000269|PubMed:29053797"
FT /id="VAR_083868"
FT VARIANT 454
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 MUTAGEN 341
FT /note="V->S: Loss of S100B-binding; when associated with S-
FT 345."
FT /evidence="ECO:0000269|PubMed:20351179"
FT MUTAGEN 345
FT /note="L->S: Loss of S100B-binding; when associated with S-
FT 341."
FT /evidence="ECO:0000269|PubMed:20351179"
FT MUTAGEN 349..350
FT /note="Missing: Decrease in S100B-binding."
FT /evidence="ECO:0000269|PubMed:20351179"
FT MUTAGEN 406
FT /note="K->E: No effect on homooligomerization. Immediate
FT fragmentation of the mitochondrial network."
FT /evidence="ECO:0000269|PubMed:20154147"
FT MUTAGEN 459
FT /note="D->Q: No effect on homooligomerization. Immediate
FT fragmentation of the mitochondrial network."
FT /evidence="ECO:0000269|PubMed:20154147"
FT CONFLICT 224
FT /note="R -> Q (in Ref. 2; BAG51625)"
FT /evidence="ECO:0000305"
FT CONFLICT 255
FT /note="I -> T (in Ref. 2; BAC03595)"
FT /evidence="ECO:0000305"
FT VARIANT Q9NVI7-2:53
FT /note="T -> I (in HAYOS) (Ref.19; dbSNP:rs1057517687)"
FT /evidence="ECO:0000269|PubMed:27640307"
FT /id="VAR_082788"
FT VARIANT Q9NVI7-2:528
FT /note="R -> W (in HAYOS) (Ref.19; dbSNP:rs1057517686)"
FT /evidence="ECO:0000269|PubMed:27640307"
FT /id="VAR_082789"
SQ SEQUENCE 634 AA; 71369 MW; 47E765629B6F3267 CRC64;
MSWLFGINKG PKGEGAGPPP PLPPAQPGAE GGGDRGLGDR PAPKDKWSNF DPTGLERAAK
AARELEHSRY AKDALNLAQM QEQTLQLEQQ SKLKMRLEAL SLLHTLVWAW SLCRAGAVQT
QERLSGSASP EQVPAGECCA LQEYEAAVEQ LKSEQIRAQA EERRKTLSEE TRQHQARAQY
QDKLARQRYE DQLKQQQLLN EENLRKQEES VQKQEAMRRA TVEREMELRH KNEMLRVEAE
ARARAKAERE NADIIREQIR LKAAEHRQTV LESIRTAGTL FGEGFRAFVT DWDKVTATVA
GLTLLAVGVY SAKNATLVAG RFIEARLGKP SLVRETSRIT VLEALRHPIQ VSRRLLSRPQ
DALEGVVLSP SLEARVRDIA IATRNTKKNR SLYRNILMYG PPGTGKTLFA KKLALHSGMD
YAIMTGGDVA PMGREGVTAM HKLFDWANTS RRGLLLFVDE ADAFLRKRAT EKISEDLRAT
LNAFLYRTGQ HSNKFMLVLA SNQPEQFDWA INDRINEMVH FDLPGQEERE RLVRMYFDKY
VLKPATEGKQ RLKLAQFDYG RKCSEVARLT EGMSGREIAQ LAVSWQATAY ASEDGVLTEA
MMDTRVQDAV QQHQQKMCWL KAEGPGRGDE PSPS
