BOLA3_HUMAN
ID BOLA3_HUMAN Reviewed; 107 AA.
AC Q53S33; G3XAB0;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=BolA-like protein 3 {ECO:0000305};
GN Name=BOLA3 {ECO:0000312|HGNC:HGNC:24415};
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 1).
RC TISSUE=Liver;
RA Zhou Y., Cao J., Han Z.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon;
RX PubMed=7566098;
RA Adams M.D., Kerlavage A.R., Fleischmann R.D., Fuldner R.A., Bult C.J.,
RA Lee N.H., Kirkness E.F., Weinstock K.G., Gocayne J.D., White O.;
RT "Initial assessment of human gene diversity and expression patterns based
RT upon 83 million nucleotides of cDNA sequence.";
RL Nature 377:3-174(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
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 [5]
RP TISSUE SPECIFICITY.
RX PubMed=18548201; DOI=10.1007/s11010-008-9809-2;
RA Zhou Y.B., Cao J.B., Wan B.B., Wang X.R., Ding G.H., Zhu H., Yang H.M.,
RA Wang K.S., Zhang X., Han Z.G.;
RT "hBolA, novel non-classical secreted proteins, belonging to different BolA
RT family with functional divergence.";
RL Mol. Cell. Biochem. 317:61-68(2008).
RN [6]
RP INVOLVEMENT IN MMDS2.
RX PubMed=21944046; DOI=10.1016/j.ajhg.2011.08.011;
RA Cameron J.M., Janer A., Levandovskiy V., Mackay N., Rouault T.A.,
RA Tong W.H., Ogilvie I., Shoubridge E.A., Robinson B.H.;
RT "Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a
RT fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase
RT enzymes.";
RL Am. J. Hum. Genet. 89:486-495(2011).
RN [7]
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=22746225; DOI=10.1089/ars.2011.4253;
RA Willems P., Wanschers B.F., Esseling J., Szklarczyk R., Kudla U.,
RA Duarte I., Forkink M., Nooteboom M., Swarts H., Gloerich J., Nijtmans L.,
RA Koopman W., Huynen M.A.;
RT "BOLA1 is an aerobic protein that prevents mitochondrial morphology changes
RT induced by glutathione depletion.";
RL Antioxid. Redox Signal. 18:129-138(2013).
RN [10]
RP STRUCTURE BY NMR OF 27-107, AND INTERACTION WITH NFU1.
RX PubMed=27532772; DOI=10.7554/elife.16673;
RA Uzarska M.A., Nasta V., Weiler B.D., Spantgar F., Ciofi-Baffoni S.,
RA Saviello M.R., Gonnelli L., Muehlenhoff U., Banci L., Lill R.;
RT "Mitochondrial Bol1 and Bol3 function as assembly factors for specific
RT iron-sulfur proteins.";
RL Elife 5:0-0(2016).
RN [11]
RP VARIANT MMDS2 ASN-67.
RX PubMed=22562699; DOI=10.1007/s10545-012-9489-7;
RA Haack T.B., Rolinski B., Haberberger B., Zimmermann F., Schum J.,
RA Strecker V., Graf E., Athing U., Hoppen T., Wittig I., Sperl W.,
RA Freisinger P., Mayr J.A., Strom T.M., Meitinger T., Prokisch H.;
RT "Homozygous missense mutation in BOLA3 causes multiple mitochondrial
RT dysfunctions syndrome in two siblings.";
RL J. Inherit. Metab. Dis. 36:55-62(2013).
RN [12]
RP VARIANT MMDS2 46-ARG--ARG-107 DEL.
RX PubMed=24334290; DOI=10.1093/brain/awt328;
RA Baker P.R. II, Friederich M.W., Swanson M.A., Shaikh T., Bhattacharya K.,
RA Scharer G.H., Aicher J., Creadon-Swindell G., Geiger E., MacLean K.N.,
RA Lee W.T., Deshpande C., Freckmann M.L., Shih L.Y., Wasserstein M.,
RA Rasmussen M.B., Lund A.M., Procopis P., Cameron J.M., Robinson B.H.,
RA Brown G.K., Brown R.M., Compton A.G., Dieckmann C.L., Collard R.,
RA Coughlin C.R. II, Spector E., Wempe M.F., Van Hove J.L.;
RT "Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3
RT and the novel gene GLRX5.";
RL Brain 137:366-379(2014).
RN [13]
RP VARIANT MMDS2 ARG-96.
RX PubMed=26741492; DOI=10.1371/journal.pgen.1005679;
RA Kohda M., Tokuzawa Y., Kishita Y., Nyuzuki H., Moriyama Y., Mizuno Y.,
RA Hirata T., Yatsuka Y., Yamashita-Sugahara Y., Nakachi Y., Kato H.,
RA Okuda A., Tamaru S., Borna N.N., Banshoya K., Aigaki T., Sato-Miyata Y.,
RA Ohnuma K., Suzuki T., Nagao A., Maehata H., Matsuda F., Higasa K.,
RA Nagasaki M., Yasuda J., Yamamoto M., Fushimi T., Shimura M.,
RA Kaiho-Ichimoto K., Harashima H., Yamazaki T., Mori M., Murayama K.,
RA Ohtake A., Okazaki Y.;
RT "A comprehensive genomic analysis reveals the genetic landscape of
RT mitochondrial respiratory chain complex deficiencies.";
RL PLoS Genet. 12:E1005679-E1005679(2016).
CC -!- FUNCTION: Acts as a mitochondrial iron-sulfur (Fe-S) cluster assembly
CC factor that facilitates (Fe-S) cluster insertion into a subset of
CC mitochondrial proteins. Probably acts together with NFU1
CC (PubMed:27532772). {ECO:0000250|UniProtKB:P39724,
CC ECO:0000305|PubMed:27532772}.
CC -!- SUBUNIT: Interacts with NFU1 (PubMed:27532772).
CC {ECO:0000269|PubMed:27532772}.
CC -!- INTERACTION:
CC Q53S33; O76003: GLRX3; NbExp=5; IntAct=EBI-12086950, EBI-374781;
CC Q53S33; Q86SX6: GLRX5; NbExp=7; IntAct=EBI-12086950, EBI-1049910;
CC Q53S33; PRO_0000141650 [Q86SX6]: GLRX5; NbExp=5; IntAct=EBI-12086950, EBI-27823755;
CC Q53S33; Q0VD86: INCA1; NbExp=3; IntAct=EBI-12086950, EBI-6509505;
CC Q53S33; O76011: KRT34; NbExp=3; IntAct=EBI-12086950, EBI-1047093;
CC Q53S33; P43360: MAGEA6; NbExp=3; IntAct=EBI-12086950, EBI-1045155;
CC Q53S33; Q9UMS0: NFU1; NbExp=2; IntAct=EBI-12086950, EBI-725252;
CC Q53S33; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-12086950, EBI-79165;
CC Q53S33; Q9H0T7: RAB17; NbExp=3; IntAct=EBI-12086950, EBI-721615;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:22746225}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q53S33-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q53S33-2; Sequence=VSP_045787;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:18548201}.
CC -!- DISEASE: Multiple mitochondrial dysfunctions syndrome 2 with
CC hyperglycinemia (MMDS2) [MIM:614299]: A severe disorder of systemic
CC energy metabolism, resulting in weakness, respiratory failure, lack of
CC neurologic development, lactic acidosis, hyperglycinemia and early
CC death. Some patients show failure to thrive, pulmonary hypertension,
CC hypotonia and irritability. Biochemical features include severe
CC combined deficiency of the 2-oxoacid dehydrogenases, defective lipoic
CC acid synthesis and reduction in activity of mitochondrial respiratory
CC chain complexes. {ECO:0000269|PubMed:21944046,
CC ECO:0000269|PubMed:22562699, ECO:0000269|PubMed:24334290,
CC ECO:0000269|PubMed:26741492}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the BolA/IbaG family. {ECO:0000305}.
CC -!- CAUTION: Was initially reported to be secreted via a non-classical
CC export pathway (PubMed:18548201). It was however later shown that it
CC localizes to mitochondria, in agreement with other members of the
CC family (PubMed:22746225). {ECO:0000269|PubMed:18548201,
CC ECO:0000269|PubMed:22746225}.
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DR EMBL; DQ225187; ABB04094.1; -; mRNA.
DR EMBL; AA316348; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC073263; AAX93059.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99700.1; -; Genomic_DNA.
DR CCDS; CCDS33224.1; -. [Q53S33-2]
DR CCDS; CCDS33225.1; -. [Q53S33-1]
DR RefSeq; NP_001030582.1; NM_001035505.1. [Q53S33-2]
DR RefSeq; NP_997717.2; NM_212552.2. [Q53S33-1]
DR PDB; 2NCL; NMR; -; A=27-107.
DR PDBsum; 2NCL; -.
DR AlphaFoldDB; Q53S33; -.
DR SMR; Q53S33; -.
DR BioGRID; 132922; 38.
DR ComplexPortal; CPX-6863; Mitochondrial BOLA3-GLRX5 iron-sulfur cluster assembly complex.
DR IntAct; Q53S33; 31.
DR STRING; 9606.ENSP00000331369; -.
DR iPTMnet; Q53S33; -.
DR MetOSite; Q53S33; -.
DR PhosphoSitePlus; Q53S33; -.
DR BioMuta; BOLA3; -.
DR DMDM; 74726650; -.
DR EPD; Q53S33; -.
DR jPOST; Q53S33; -.
DR MassIVE; Q53S33; -.
DR MaxQB; Q53S33; -.
DR PaxDb; Q53S33; -.
DR PeptideAtlas; Q53S33; -.
DR PRIDE; Q53S33; -.
DR ProteomicsDB; 33698; -.
DR ProteomicsDB; 62531; -. [Q53S33-1]
DR TopDownProteomics; Q53S33-1; -. [Q53S33-1]
DR Antibodypedia; 65208; 58 antibodies from 17 providers.
DR DNASU; 388962; -.
DR Ensembl; ENST00000295326.4; ENSP00000295326.4; ENSG00000163170.12. [Q53S33-2]
DR Ensembl; ENST00000327428.10; ENSP00000331369.5; ENSG00000163170.12. [Q53S33-1]
DR GeneID; 388962; -.
DR KEGG; hsa:388962; -.
DR MANE-Select; ENST00000327428.10; ENSP00000331369.5; NM_212552.3; NP_997717.2.
DR UCSC; uc002skc.2; human. [Q53S33-1]
DR CTD; 388962; -.
DR DisGeNET; 388962; -.
DR GeneCards; BOLA3; -.
DR HGNC; HGNC:24415; BOLA3.
DR HPA; ENSG00000163170; Tissue enhanced (tongue).
DR MalaCards; BOLA3; -.
DR MIM; 613183; gene.
DR MIM; 614299; phenotype.
DR neXtProt; NX_Q53S33; -.
DR OpenTargets; ENSG00000163170; -.
DR Orphanet; 401874; Multiple mitochondrial dysfunctions syndrome type 2.
DR PharmGKB; PA142672554; -.
DR VEuPathDB; HostDB:ENSG00000163170; -.
DR eggNOG; KOG3348; Eukaryota.
DR GeneTree; ENSGT00390000013048; -.
DR HOGENOM; CLU_109462_0_2_1; -.
DR InParanoid; Q53S33; -.
DR OMA; EIQNMHG; -.
DR OrthoDB; 1571278at2759; -.
DR PhylomeDB; Q53S33; -.
DR TreeFam; TF332952; -.
DR PathwayCommons; Q53S33; -.
DR SignaLink; Q53S33; -.
DR BioGRID-ORCS; 388962; 126 hits in 1045 CRISPR screens.
DR ChiTaRS; BOLA3; human.
DR GenomeRNAi; 388962; -.
DR Pharos; Q53S33; Tbio.
DR PRO; PR:Q53S33; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q53S33; protein.
DR Bgee; ENSG00000163170; Expressed in left ventricle myocardium and 185 other tissues.
DR Genevisible; Q53S33; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:1990229; C:iron-sulfur cluster assembly complex; IPI:ComplexPortal.
DR GO; GO:0005759; C:mitochondrial matrix; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0045454; P:cell redox homeostasis; IC:ComplexPortal.
DR GO; GO:0055072; P:iron ion homeostasis; IC:ComplexPortal.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; IC:ComplexPortal.
DR GO; GO:0106035; P:protein maturation by [4Fe-4S] cluster transfer; IBA:GO_Central.
DR Gene3D; 3.30.300.90; -; 1.
DR InterPro; IPR002634; BolA.
DR InterPro; IPR036065; BolA-like_sf.
DR Pfam; PF01722; BolA; 1.
DR SUPFAM; SSF82657; SSF82657; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Disease variant; Mitochondrion;
KW Primary mitochondrial disease; Reference proteome.
FT CHAIN 1..107
FT /note="BolA-like protein 3"
FT /id="PRO_0000245501"
FT VAR_SEQ 58..107
FT /note="GCGAMYEIKIESEEFKEKRTVQQHQMVNQALKEEIKEMHGLRIFTSVPKR
FT -> TKRRNQRDAWIADIYLCPQTLTTPWLHRCCCLRPWMNFTDIILP (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:7566098"
FT /id="VSP_045787"
FT VARIANT 46..107
FT /note="Missing (in MMDS2)"
FT /evidence="ECO:0000269|PubMed:24334290"
FT /id="VAR_077910"
FT VARIANT 67
FT /note="I -> N (in MMDS2; dbSNP:rs550855238)"
FT /evidence="ECO:0000269|PubMed:22562699"
FT /id="VAR_077911"
FT VARIANT 96
FT /note="H -> R (in MMDS2; dbSNP:rs148674363)"
FT /evidence="ECO:0000269|PubMed:26741492"
FT /id="VAR_076180"
FT HELIX 31..43
FT /evidence="ECO:0007829|PDB:2NCL"
FT STRAND 47..54
FT /evidence="ECO:0007829|PDB:2NCL"
FT TURN 57..59
FT /evidence="ECO:0007829|PDB:2NCL"
FT STRAND 63..69
FT /evidence="ECO:0007829|PDB:2NCL"
FT HELIX 70..74
FT /evidence="ECO:0007829|PDB:2NCL"
FT HELIX 77..89
FT /evidence="ECO:0007829|PDB:2NCL"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:2NCL"
SQ SEQUENCE 107 AA; 12114 MW; EF3BF21DF14BD136 CRC64;
MAAWSPAAAA PLLRGIRGLP LHHRMFATQT EGELRVTQIL KEKFPRATAI KVTDISGGCG
AMYEIKIESE EFKEKRTVQQ HQMVNQALKE EIKEMHGLRI FTSVPKR
