CIA30_HUMAN
ID CIA30_HUMAN Reviewed; 327 AA.
AC Q9Y375; Q9BVZ5;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2002, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Complex I intermediate-associated protein 30, mitochondrial {ECO:0000305};
DE AltName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 1;
DE Flags: Precursor;
GN Name=NDUFAF1 {ECO:0000312|HGNC:HGNC:18828}; Synonyms=CIA30;
GN ORFNames=CGI-65;
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].
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANTS HIS-9; LEU-31;
RP LYS-176 AND GLY-314.
RX PubMed=11935339; DOI=10.1007/s00439-001-0673-3;
RA Janssen R., Smeitink J., Smeets R., van den Heuvel L.;
RT "CIA30 complex I assembly factor: a candidate for human complex I
RT deficiency?";
RL Hum. Genet. 110:264-270(2002).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16218961; DOI=10.1111/j.1742-4658.2005.04928.x;
RA Vogel R.O., Janssen R.J., Ugalde C., Grovenstein M., Huijbens R.J.,
RA Visch H.J., van den Heuvel L.P., Willems P.H., Zeviani M., Smeitink J.A.,
RA Nijtmans L.G.;
RT "Human mitochondrial complex I assembly is mediated by NDUFAF1.";
RL FEBS J. 272:5317-5326(2005).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INVOLVEMENT IN MC1DN11, AND
RP VARIANTS MC1DN11 PRO-207; 252-VAL-LYS-253 DEL AND ARG-253.
RX PubMed=17557076; DOI=10.1038/sj.emboj.7601748;
RA Dunning C.J., McKenzie M., Sugiana C., Lazarou M., Silke J., Connelly A.,
RA Fletcher J.M., Kirby D.M., Thorburn D.R., Ryan M.T.;
RT "Human CIA30 is involved in the early assembly of mitochondrial complex I
RT and mutations in its gene cause disease.";
RL EMBO J. 26:3227-3237(2007).
RN [6]
RP INTERACTION WITH ECSIT.
RX PubMed=17344420; DOI=10.1101/gad.408407;
RA Vogel R.O., Janssen R.J.R.J., van den Brand M.A.M., Dieteren C.E.J.,
RA Verkaart S., Koopman W.J.H., Willems P.H.G.M., Pluk W.,
RA van den Heuvel L.P.W.J., Smeitink J.A.M., Nijtmans L.G.J.;
RT "Cytosolic signaling protein Ecsit also localizes to mitochondria where it
RT interacts with chaperone NDUFAF1 and functions in complex I assembly.";
RL Genes Dev. 21:615-624(2007).
RN [7]
RP INTERACTION WITH ACAD9.
RX PubMed=20816094; DOI=10.1016/j.cmet.2010.08.002;
RA Nouws J., Nijtmans L., Houten S.M., van den Brand M., Huynen M.,
RA Venselaar H., Hoefs S., Gloerich J., Kronick J., Hutchin T., Willems P.,
RA Rodenburg R., Wanders R., van den Heuvel L., Smeitink J., Vogel R.O.;
RT "Acyl-CoA dehydrogenase 9 is required for the biogenesis of oxidative
RT phosphorylation complex I.";
RL Cell Metab. 12:283-294(2010).
RN [8]
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 [9]
RP INVOLVEMENT IN MC1DN11, AND VARIANTS MC1DN11 CYS-211 AND ARG-245.
RX PubMed=21931170; DOI=10.1136/jmedgenet-2011-100340;
RA Fassone E., Taanman J.W., Hargreaves I.P., Sebire N.J., Cleary M.A.,
RA Burch M., Rahman S.;
RT "Mutations in the mitochondrial complex I assembly factor NDUFAF1 cause
RT fatal infantile hypertrophic cardiomyopathy.";
RL J. Med. Genet. 48:691-697(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-318, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
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 [12]
RP IDENTIFICATION IN THE MCIA COMPLEX, AND FUNCTION.
RX PubMed=32320651; DOI=10.1016/j.celrep.2020.107541;
RA Formosa L.E., Muellner-Wong L., Reljic B., Sharpe A.J., Jackson T.D.,
RA Beilharz T.H., Stojanovski D., Lazarou M., Stroud D.A., Ryan M.T.;
RT "Dissecting the Roles of Mitochondrial Complex I Intermediate Assembly
RT Complex Factors in the Biogenesis of Complex I.";
RL Cell Rep. 31:107541-107541(2020).
RN [13]
RP INTERACTION WITH TMEM70 AND TMEM242.
RX PubMed=33753518; DOI=10.1073/pnas.2100558118;
RA Carroll J., He J., Ding S., Fearnley I.M., Walker J.E.;
RT "TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase
RT and interact with assembly factors for complex I.";
RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
CC -!- FUNCTION: As part of the MCIA complex, involved in the assembly of the
CC mitochondrial complex I. {ECO:0000269|PubMed:16218961,
CC ECO:0000269|PubMed:17557076, ECO:0000269|PubMed:32320651}.
CC -!- SUBUNIT: Part of the mitochondrial complex I assembly/MCIA complex that
CC comprises at least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9
CC and complement subunits such as COA1 and TMEM186 (PubMed:32320651).
CC Interacts with ECSIT (PubMed:17344420). Interacts with ACAD9
CC (PubMed:20816094). At early stages of complex I assembly, it is found
CC in intermediate subcomplexes that contain different subunits including
CC NDUFB6, NDUFA6, NDUFA9, NDUFS3, NDUFS7, ND1, ND2 and ND3
CC (PubMed:17557076). Interacts with TMEM70 and TMEM242 (PubMed:33753518).
CC {ECO:0000269|PubMed:17344420, ECO:0000269|PubMed:17557076,
CC ECO:0000269|PubMed:20816094, ECO:0000269|PubMed:32320651,
CC ECO:0000269|PubMed:33753518}.
CC -!- INTERACTION:
CC Q9Y375; P54315: PNLIPRP1; NbExp=3; IntAct=EBI-741874, EBI-8652812;
CC Q9Y375; Q9BRI3: SLC30A2; NbExp=3; IntAct=EBI-741874, EBI-8644112;
CC Q9Y375; Q9UNK0: STX8; NbExp=3; IntAct=EBI-741874, EBI-727240;
CC Q9Y375; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-741874, EBI-2548832;
CC Q9Y375; Q5BJF2: TMEM97; NbExp=3; IntAct=EBI-741874, EBI-12111910;
CC Q9Y375; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-741874, EBI-751210;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16218961,
CC ECO:0000269|PubMed:17557076}. Mitochondrion matrix
CC {ECO:0000305|PubMed:17557076}. Note=Peripherally associated with the
CC matrix face of the mitochondrial inner membrane.
CC {ECO:0000305|PubMed:17557076}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:11935339}.
CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 11 (MC1DN11)
CC [MIM:618234]: A form of mitochondrial complex I deficiency, the most
CC common biochemical signature of mitochondrial disorders, a group of
CC highly heterogeneous conditions characterized by defective oxidative
CC phosphorylation, which collectively affects 1 in 5-10000 live births.
CC Clinical disorders have variable severity, ranging from lethal neonatal
CC disease to adult-onset neurodegenerative disorders. Phenotypes include
CC macrocephaly with progressive leukodystrophy, non-specific
CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh
CC syndrome, Leber hereditary optic neuropathy, and some forms of
CC Parkinson disease. MC1DN11 transmission pattern is consistent with
CC autosomal recessive inheritance. {ECO:0000269|PubMed:17557076,
CC ECO:0000269|PubMed:21931170}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the CIA30 family. {ECO:0000305}.
CC -!- CAUTION: There is a putative pseudogene of CIA30 on chromosome 19
CC (19p12). {ECO:0000305}.
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DR EMBL; AF151823; AAD34060.1; -; mRNA.
DR EMBL; BC000780; AAH00780.1; -; mRNA.
DR CCDS; CCDS10075.1; -.
DR RefSeq; NP_057097.2; NM_016013.3.
DR RefSeq; XP_006720618.1; XM_006720555.2.
DR RefSeq; XP_011519960.1; XM_011521658.1.
DR AlphaFoldDB; Q9Y375; -.
DR SASBDB; Q9Y375; -.
DR SMR; Q9Y375; -.
DR BioGRID; 119292; 168.
DR ComplexPortal; CPX-6322; Mitochondrial complex I intermediate assembly (MCIA) complex.
DR CORUM; Q9Y375; -.
DR IntAct; Q9Y375; 57.
DR MINT; Q9Y375; -.
DR STRING; 9606.ENSP00000260361; -.
DR BindingDB; Q9Y375; -.
DR ChEMBL; CHEMBL2363065; -.
DR DrugCentral; Q9Y375; -.
DR iPTMnet; Q9Y375; -.
DR PhosphoSitePlus; Q9Y375; -.
DR BioMuta; NDUFAF1; -.
DR DMDM; 21542405; -.
DR EPD; Q9Y375; -.
DR jPOST; Q9Y375; -.
DR MassIVE; Q9Y375; -.
DR MaxQB; Q9Y375; -.
DR PaxDb; Q9Y375; -.
DR PeptideAtlas; Q9Y375; -.
DR PRIDE; Q9Y375; -.
DR ProteomicsDB; 85980; -.
DR Antibodypedia; 23296; 167 antibodies from 26 providers.
DR DNASU; 51103; -.
DR Ensembl; ENST00000260361.9; ENSP00000260361.4; ENSG00000137806.10.
DR Ensembl; ENST00000560978.2; ENSP00000453944.2; ENSG00000137806.10.
DR GeneID; 51103; -.
DR KEGG; hsa:51103; -.
DR MANE-Select; ENST00000260361.9; ENSP00000260361.4; NM_016013.4; NP_057097.2.
DR UCSC; uc001znx.4; human.
DR CTD; 51103; -.
DR DisGeNET; 51103; -.
DR GeneCards; NDUFAF1; -.
DR HGNC; HGNC:18828; NDUFAF1.
DR HPA; ENSG00000137806; Low tissue specificity.
DR MalaCards; NDUFAF1; -.
DR MIM; 606934; gene.
DR MIM; 618234; phenotype.
DR neXtProt; NX_Q9Y375; -.
DR OpenTargets; ENSG00000137806; -.
DR Orphanet; 2609; Isolated complex I deficiency.
DR PharmGKB; PA134934729; -.
DR VEuPathDB; HostDB:ENSG00000137806; -.
DR eggNOG; KOG2435; Eukaryota.
DR GeneTree; ENSGT00390000007200; -.
DR HOGENOM; CLU_059028_2_0_1; -.
DR InParanoid; Q9Y375; -.
DR OMA; TFWEREK; -.
DR OrthoDB; 1563319at2759; -.
DR PhylomeDB; Q9Y375; -.
DR TreeFam; TF314819; -.
DR PathwayCommons; Q9Y375; -.
DR Reactome; R-HSA-6799198; Complex I biogenesis.
DR SignaLink; Q9Y375; -.
DR BioGRID-ORCS; 51103; 208 hits in 1091 CRISPR screens.
DR ChiTaRS; NDUFAF1; human.
DR GeneWiki; NDUFAF1; -.
DR GenomeRNAi; 51103; -.
DR Pharos; Q9Y375; Tclin.
DR PRO; PR:Q9Y375; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9Y375; protein.
DR Bgee; ENSG00000137806; Expressed in apex of heart and 195 other tissues.
DR ExpressionAtlas; Q9Y375; baseline and differential.
DR Genevisible; Q9Y375; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005747; C:mitochondrial respiratory chain complex I; NAS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central.
DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; IDA:UniProtKB.
DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IBA:GO_Central.
DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB.
DR GO; GO:0010257; P:NADH dehydrogenase complex assembly; IBA:GO_Central.
DR GO; GO:0065003; P:protein-containing complex assembly; NAS:UniProtKB.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR013857; NADH-UbQ_OxRdtase-assoc_prot30.
DR InterPro; IPR039131; NDUFAF1.
DR PANTHER; PTHR13194; PTHR13194; 1.
DR Pfam; PF08547; CIA30; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
PE 1: Evidence at protein level;
KW Chaperone; Disease variant; Mitochondrion; Phosphoprotein;
KW Primary mitochondrial disease; Reference proteome; Transit peptide.
FT TRANSIT 1..24
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 25..327
FT /note="Complex I intermediate-associated protein 30,
FT mitochondrial"
FT /id="PRO_0000005464"
FT REGION 42..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 9
FT /note="R -> H (in dbSNP:rs1899)"
FT /evidence="ECO:0000269|PubMed:11935339"
FT /id="VAR_013559"
FT VARIANT 31
FT /note="R -> L (in dbSNP:rs3204853)"
FT /evidence="ECO:0000269|PubMed:11935339"
FT /id="VAR_013560"
FT VARIANT 176
FT /note="E -> K (in dbSNP:rs35227875)"
FT /evidence="ECO:0000269|PubMed:11935339"
FT /id="VAR_013561"
FT VARIANT 207
FT /note="T -> P (in MC1DN11; dbSNP:rs387906956)"
FT /evidence="ECO:0000269|PubMed:17557076"
FT /id="VAR_081445"
FT VARIANT 211
FT /note="R -> C (in MC1DN11; dbSNP:rs387906958)"
FT /evidence="ECO:0000269|PubMed:21931170"
FT /id="VAR_081446"
FT VARIANT 245
FT /note="G -> R (in MC1DN11; dbSNP:rs376344575)"
FT /evidence="ECO:0000269|PubMed:21931170"
FT /id="VAR_081447"
FT VARIANT 252..253
FT /note="Missing (in MC1DN11; due to a nucleotide
FT substitution located in the splice site consensus sequence
FT at the end of exon 3; patient cells contain transcripts
FT lacking the final 6 base pairs of exon 3 but also contain
FT normally spliced transcripts corresponding to protein
FT variant R-253)"
FT /evidence="ECO:0000269|PubMed:17557076"
FT /id="VAR_081448"
FT VARIANT 253
FT /note="K -> R (in MC1DN11; due to a nucleotide substitution
FT located in the splice site consensus sequence at the end of
FT exon 3; patient cells contain normally spliced transcripts
FT corresponding to protein variant R-253 but also transcripts
FT lacking the final 6 base pairs of exon 3 and corresponding
FT to protein variant 252-VK-253 del; dbSNP:rs387906957)"
FT /evidence="ECO:0000269|PubMed:17557076"
FT /id="VAR_081449"
FT VARIANT 314
FT /note="A -> G (in dbSNP:rs12900702)"
FT /evidence="ECO:0000269|PubMed:11935339"
FT /id="VAR_013562"
FT CONFLICT 178
FT /note="T -> S (in Ref. 1; AAD34060)"
FT /evidence="ECO:0000305"
FT CONFLICT 195
FT /note="E -> K (in Ref. 1; AAD34060)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 327 AA; 37764 MW; 13D76605CC50DFF7 CRC64;
MALVHKLLRG TYFLRKFSKP TSALYPFLGI RFAEYSSSLQ KPVASPGKAS SQRKTEGDLQ
GDHQKEVALD ITSSEEKPDV SFDKAIRDEA IYHFRLLKDE IVDHWRGPEG HPLHEVLLEQ
AKVVWQFRGK EDLDKWTVTS DKTIGGRSEV FLKMGKNNQS ALLYGTLSSE APQDGESTRS
GYCAMISRIP RGAFERKMSY DWSQFNTLYL RVRGDGRPWM VNIKEDTDFF QRTNQMYSYF
MFTRGGPYWQ EVKIPFSKFF FSNRGRIRDV QHELPLDKIS SIGFTLADKV DGPFFLEIDF
IGVFTDPAHT EEFAYENSPE LNPRLFK
