UQCC3_HUMAN
ID UQCC3_HUMAN Reviewed; 93 AA.
AC Q6UW78; Q5FVD5;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Ubiquinol-cytochrome-c reductase complex assembly factor 3 {ECO:0000312|HGNC:HGNC:34399};
DE AltName: Full=Assembly factor CBP4 homolog {ECO:0000303|PubMed:25008109};
GN Name=UQCC3 {ECO:0000312|HGNC:HGNC:34399};
GN Synonyms=C11orf83 {ECO:0000312|HGNC:HGNC:34399}; ORFNames=UNQ655/PRO1286;
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=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
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 [4]
RP PROTEIN SEQUENCE OF 24-37, AND CAUTION.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [5]
RP INVOLVEMENT IN MC3DN9, FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, CAUTION,
RP AND VARIANT MC3DN9 GLU-20.
RX PubMed=25008109; DOI=10.1093/hmg/ddu357;
RA Wanschers B.F., Szklarczyk R., van den Brand M.A., Jonckheere A.,
RA Suijskens J., Smeets R., Rodenburg R.J., Stephan K., Helland I.B.,
RA Elkamil A., Rootwelt T., Ott M., van den Heuvel L., Nijtmans L.G.,
RA Huynen M.A.;
RT "A mutation in the human CBP4 ortholog UQCC3 impairs complex III assembly,
RT activity and cytochrome b stability.";
RL Hum. Mol. Genet. 23:6356-6365(2014).
RN [6]
RP FUNCTION, LIPID-BINDING, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY,
RP PROTEOLYTIC PROCESSING, CAUTION, MUTAGENESIS OF 5-ARG-LYS-6, AND REGION.
RX PubMed=25605331; DOI=10.1128/mcb.01047-14;
RA Desmurs M., Foti M., Raemy E., Vaz F.M., Martinou J.C., Bairoch A.,
RA Lane L.;
RT "C11orf83, a mitochondrial cardiolipin-binding protein involved in bc1
RT complex assembly and supercomplex stabilization.";
RL Mol. Cell. Biol. 35:1139-1156(2015).
CC -!- FUNCTION: Required for the assembly of the ubiquinol-cytochrome c
CC reductase complex (mitochondrial respiratory chain complex III or
CC cytochrome b-c1 complex), mediating cytochrome b recruitment and
CC probably stabilization within the complex. Thereby, plays an important
CC role in ATP production by mitochondria. Cardiolipin-binding protein, it
CC may also control the cardiolipin composition of mitochondria membranes
CC and their morphology. {ECO:0000269|PubMed:25008109,
CC ECO:0000269|PubMed:25605331}.
CC -!- SUBUNIT: Associates with the ubiquinol-cytochrome c reductase complex
CC (mitochondrial respiratory chain complex III or cytochrome b-c1
CC complex). {ECO:0000269|PubMed:25605331}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:25008109, ECO:0000269|PubMed:25605331}; Single-pass
CC membrane protein {ECO:0000269|PubMed:25008109,
CC ECO:0000269|PubMed:25605331}.
CC -!- PTM: Probably cleaved by OMA1 under mitochondrial stress conditions.
CC {ECO:0000269|PubMed:25605331}.
CC -!- DISEASE: Mitochondrial complex III deficiency, nuclear 9 (MC3DN9)
CC [MIM:616111]: A form of mitochondrial complex III deficiency, a
CC disorder of the mitochondrial respiratory chain resulting in a highly
CC variable phenotype depending on which tissues are affected. MC3DN9
CC clinical features include feeding difficulties, hypoglycemia, severe
CC lactic acidosis, and delayed psychomotor development.
CC {ECO:0000269|PubMed:25008109}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the UQCC3 family. {ECO:0000305}.
CC -!- CAUTION: Was initially reported to be secreted (PubMed:15340161).
CC However, it was later shown to be localized in the inner mitochondrial
CC membrane (PubMed:25008109, PubMed:25605331).
CC {ECO:0000269|PubMed:25008109, ECO:0000269|PubMed:25605331,
CC ECO:0000303|PubMed:15340161}.
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DR EMBL; AY358935; AAQ89294.1; -; mRNA.
DR EMBL; AP001458; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC090057; AAH90057.1; -; mRNA.
DR CCDS; CCDS41658.1; -.
DR RefSeq; NP_001078841.1; NM_001085372.2.
DR AlphaFoldDB; Q6UW78; -.
DR SMR; Q6UW78; -.
DR BioGRID; 612915; 30.
DR IntAct; Q6UW78; 2.
DR STRING; 9606.ENSP00000432692; -.
DR iPTMnet; Q6UW78; -.
DR PhosphoSitePlus; Q6UW78; -.
DR BioMuta; UQCC3; -.
DR DMDM; 296434449; -.
DR EPD; Q6UW78; -.
DR jPOST; Q6UW78; -.
DR MassIVE; Q6UW78; -.
DR MaxQB; Q6UW78; -.
DR PaxDb; Q6UW78; -.
DR PeptideAtlas; Q6UW78; -.
DR PRIDE; Q6UW78; -.
DR ProteomicsDB; 67454; -.
DR TopDownProteomics; Q6UW78; -.
DR Antibodypedia; 63885; 10 antibodies from 9 providers.
DR DNASU; 790955; -.
DR Ensembl; ENST00000377953.4; ENSP00000367189.3; ENSG00000204922.5.
DR Ensembl; ENST00000531323.1; ENSP00000432692.1; ENSG00000204922.5.
DR GeneID; 790955; -.
DR KEGG; hsa:790955; -.
DR MANE-Select; ENST00000377953.4; ENSP00000367189.3; NM_001085372.3; NP_001078841.1.
DR UCSC; uc001nui.5; human.
DR CTD; 790955; -.
DR DisGeNET; 790955; -.
DR GeneCards; UQCC3; -.
DR HGNC; HGNC:34399; UQCC3.
DR HPA; ENSG00000204922; Low tissue specificity.
DR MalaCards; UQCC3; -.
DR MIM; 616097; gene.
DR MIM; 616111; phenotype.
DR neXtProt; NX_Q6UW78; -.
DR OpenTargets; ENSG00000204922; -.
DR Orphanet; 1460; Isolated complex III deficiency.
DR PharmGKB; PA162377760; -.
DR VEuPathDB; HostDB:ENSG00000204922; -.
DR eggNOG; ENOG502S9VI; Eukaryota.
DR GeneTree; ENSGT00390000001930; -.
DR HOGENOM; CLU_184624_0_0_1; -.
DR InParanoid; Q6UW78; -.
DR OMA; VAWRKDW; -.
DR PhylomeDB; Q6UW78; -.
DR TreeFam; TF339744; -.
DR PathwayCommons; Q6UW78; -.
DR SignaLink; Q6UW78; -.
DR BioGRID-ORCS; 790955; 58 hits in 1079 CRISPR screens.
DR ChiTaRS; UQCC3; human.
DR GenomeRNAi; 790955; -.
DR Pharos; Q6UW78; Tbio.
DR PRO; PR:Q6UW78; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q6UW78; protein.
DR Bgee; ENSG00000204922; Expressed in endothelial cell and 177 other tissues.
DR Genevisible; Q6UW78; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:1901612; F:cardiolipin binding; IDA:UniProtKB.
DR GO; GO:0070300; F:phosphatidic acid binding; IDA:UniProtKB.
DR GO; GO:0006754; P:ATP biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0042407; P:cristae formation; IMP:UniProtKB.
DR GO; GO:0006122; P:mitochondrial electron transport, ubiquinol to cytochrome c; IMP:UniProtKB.
DR GO; GO:0034551; P:mitochondrial respiratory chain complex III assembly; IMP:UniProtKB.
DR InterPro; IPR027896; UQCC3.
DR PANTHER; PTHR36465; PTHR36465; 1.
DR Pfam; PF15141; UQCC3; 1.
PE 1: Evidence at protein level;
KW ATP synthesis; Direct protein sequencing; Disease variant; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Primary mitochondrial disease;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..93
FT /note="Ubiquinol-cytochrome-c reductase complex assembly
FT factor 3"
FT /id="PRO_0000022611"
FT TOPO_DOM 1..7
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:25008109"
FT TRANSMEM 8..28
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 29..93
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:25008109,
FT ECO:0000269|PubMed:25605331"
FT REGION 23..80
FT /note="Mediates lipid-binding"
FT /evidence="ECO:0000269|PubMed:25605331"
FT VARIANT 20
FT /note="V -> E (in MC3DN9; decreases protein abundance;
FT reduces complex III formation; reduces complex III
FT activity; dbSNP:rs606231426)"
FT /evidence="ECO:0000269|PubMed:25008109"
FT /id="VAR_071864"
FT MUTAGEN 5..6
FT /note="RK->AA,DD: Loss of localization to the
FT mitochondria."
FT /evidence="ECO:0000269|PubMed:25605331"
FT CONFLICT 89
FT /note="G -> S (in Ref. 1; AAQ89294 and 3; AAH90057)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 93 AA; 10081 MW; 7E65D81280196F93 CRC64;
MDSLRKMLIS VAMLGAGAGV GYALLVIVTP GERRKQEMLK EMPLQDPRSR EEAARTQQLL
LATLQEAATT QENVAWRKNW MVGGEGGAGG RSP
