Full text data of UQCRC2
UQCRC2
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Cytochrome b-c1 complex subunit 2, mitochondrial (Complex III subunit 2; Core protein II; Ubiquinol-cytochrome-c reductase complex core protein 2; Flags: Precursor)
Cytochrome b-c1 complex subunit 2, mitochondrial (Complex III subunit 2; Core protein II; Ubiquinol-cytochrome-c reductase complex core protein 2; Flags: Precursor)
UniProt
P22695
ID QCR2_HUMAN Reviewed; 453 AA.
AC P22695; B3KSN4; Q9BQ05;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 11-JUL-2002, sequence version 3.
DT 22-JAN-2014, entry version 141.
DE RecName: Full=Cytochrome b-c1 complex subunit 2, mitochondrial;
DE AltName: Full=Complex III subunit 2;
DE AltName: Full=Core protein II;
DE AltName: Full=Ubiquinol-cytochrome-c reductase complex core protein 2;
DE Flags: Precursor;
GN Name=UQCRC2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLN-183.
RX PubMed=2547763;
RA Hosokawa Y., Suzuki H., Toda H., Nishikimi M., Ozawa T.;
RT "Complementary DNA encoding core protein II of human mitochondrial
RT cytochrome bc1 complex. Substantial diversity in deduced primary
RT structure from its yeast counterpart.";
RL J. Biol. Chem. 264:13483-13488(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 43-60; 71-84 AND 200-217, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [6]
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.,
RA Buerckstuemmer T., 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 [7]
RP VARIANT [LARGE SCALE ANALYSIS] TYR-208.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
RN [8]
RP VARIANT MC3DN5 TRP-183.
RX PubMed=23281071; DOI=10.1002/humu.22257;
RA Miyake N., Yano S., Sakai C., Hatakeyama H., Matsushima Y., Shiina M.,
RA Watanabe Y., Bartley J., Abdenur J.E., Wang R.Y., Chang R.,
RA Tsurusaki Y., Doi H., Nakashima M., Saitsu H., Ogata K., Goto Y.,
RA Matsumoto N.;
RT "Mitochondrial complex III deficiency caused by a homozygous UQCRC2
RT mutation presenting with neonatal-onset recurrent metabolic
RT decompensation.";
RL Hum. Mutat. 34:446-452(2013).
CC -!- FUNCTION: This is a component of the ubiquinol-cytochrome c
CC reductase complex (complex III or cytochrome b-c1 complex), which
CC is part of the mitochondrial respiratory chain. The core protein 2
CC is required for the assembly of the complex.
CC -!- SUBUNIT: The bc1 complex contains 11 subunits: 3 respiratory
CC subunits (cytochrome b, cytochrome c1 and Rieske/UQCRFS1), 2 core
CC proteins (UQCRC1/QCR1 and UQCRC2/QCR2) and 6 low-molecular weight
CC proteins (UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9,
CC UQCR11/QCR10 and a cleavage product of Rieske/UQCRFS1).
CC -!- INTERACTION:
CC O00555:CACNA1A; NbExp=2; IntAct=EBI-1051424, EBI-766279;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral
CC membrane protein; Matrix side.
CC -!- DISEASE: Mitochondrial complex III deficiency, nuclear 5 (MC3DN5)
CC [MIM:615160]: A disorder of the mitochondrial respiratory chain
CC resulting in a highly variable phenotype depending on which
CC tissues are affected. Clinical features include mitochondrial
CC encephalopathy, psychomotor retardation, ataxia, severe failure to
CC thrive, liver dysfunction, renal tubulopathy, muscle weakness and
CC exercise intolerance. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase M16 family. UQCRC2/QCR2
CC subfamily.
CC -!- CAUTION: Does not seem to have a protease activity as it lack the
CC zinc-binding site.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; J04973; AAA35710.1; -; mRNA.
DR EMBL; AK094006; BAG52796.1; -; mRNA.
DR EMBL; CH471249; EAW50592.1; -; Genomic_DNA.
DR EMBL; BC003136; AAH03136.1; -; mRNA.
DR EMBL; BC000484; AAH00484.1; -; mRNA.
DR PIR; A32629; A32629.
DR RefSeq; NP_003357.2; NM_003366.2.
DR UniGene; Hs.528803; -.
DR ProteinModelPortal; P22695; -.
DR SMR; P22695; 32-453.
DR IntAct; P22695; 7.
DR MINT; MINT-2801885; -.
DR STRING; 9606.ENSP00000268379; -.
DR MEROPS; M16.974; -.
DR PhosphoSite; P22695; -.
DR DMDM; 21903482; -.
DR REPRODUCTION-2DPAGE; IPI00305383; -.
DR UCD-2DPAGE; P22695; -.
DR PaxDb; P22695; -.
DR PeptideAtlas; P22695; -.
DR PRIDE; P22695; -.
DR DNASU; 7385; -.
DR Ensembl; ENST00000268379; ENSP00000268379; ENSG00000140740.
DR GeneID; 7385; -.
DR KEGG; hsa:7385; -.
DR UCSC; uc002djx.3; human.
DR CTD; 7385; -.
DR GeneCards; GC16P021963; -.
DR HGNC; HGNC:12586; UQCRC2.
DR HPA; HPA007998; -.
DR HPA; HPA019146; -.
DR MIM; 191329; gene.
DR MIM; 615160; phenotype.
DR neXtProt; NX_P22695; -.
DR Orphanet; 1460; Isolated CoQ-cytochrome C reductase deficiency.
DR PharmGKB; PA37217; -.
DR eggNOG; COG0612; -.
DR HOGENOM; HOG000046923; -.
DR HOVERGEN; HBG055236; -.
DR InParanoid; P22695; -.
DR KO; K00415; -.
DR OMA; QFVQNNF; -.
DR OrthoDB; EOG79CXZF; -.
DR PhylomeDB; P22695; -.
DR Reactome; REACT_111217; Metabolism.
DR SignaLink; P22695; -.
DR ChiTaRS; UQCRC2; human.
DR GeneWiki; UQCRC2; -.
DR GenomeRNAi; 7385; -.
DR NextBio; 28916; -.
DR PRO; PR:P22695; -.
DR ArrayExpress; P22695; -.
DR Bgee; P22695; -.
DR CleanEx; HS_UQCRC2; -.
DR Genevestigator; P22695; -.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005750; C:mitochondrial respiratory chain complex III; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:InterPro.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0009060; P:aerobic respiration; TAS:ProtInc.
DR GO; GO:0006119; P:oxidative phosphorylation; TAS:ProtInc.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR GO; GO:0022904; P:respiratory electron transport chain; TAS:Reactome.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 3.30.830.10; -; 2.
DR InterPro; IPR011249; Metalloenz_LuxS/M16.
DR InterPro; IPR011237; Pept_M16_dom.
DR InterPro; IPR011765; Pept_M16_N.
DR InterPro; IPR001431; Pept_M16_Zn_BS.
DR InterPro; IPR007863; Peptidase_M16_C.
DR Pfam; PF00675; Peptidase_M16; 1.
DR Pfam; PF05193; Peptidase_M16_C; 1.
DR SUPFAM; SSF63411; SSF63411; 3.
DR PROSITE; PS00143; INSULINASE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Complete proteome; Direct protein sequencing;
KW Disease mutation; Electron transport; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Polymorphism; Reference proteome;
KW Respiratory chain; Transit peptide; Transport.
FT TRANSIT 1 14 Mitochondrion.
FT CHAIN 15 453 Cytochrome b-c1 complex subunit 2,
FT mitochondrial.
FT /FTId=PRO_0000026791.
FT MOD_RES 66 66 N6-acetyllysine (By similarity).
FT MOD_RES 199 199 N6-acetyllysine (By similarity).
FT MOD_RES 250 250 N6-acetyllysine (By similarity).
FT VARIANT 148 148 R -> S (in dbSNP:rs2228473).
FT /FTId=VAR_029336.
FT VARIANT 183 183 R -> Q (in dbSNP:rs4850).
FT /FTId=VAR_034582.
FT VARIANT 183 183 R -> W (in MC3DN5).
FT /FTId=VAR_069709.
FT VARIANT 208 208 F -> Y (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036479.
FT VARIANT 254 254 R -> H (in dbSNP:rs11863893).
FT /FTId=VAR_034583.
FT CONFLICT 360 360 T -> R (in Ref. 1; AAA35710).
SQ SEQUENCE 453 AA; 48443 MW; BFA655C24C07AF52 CRC64;
MKLLTRAGSF SRFYSLKVAP KVKATAAPAG APPQPQDLEF TKLPNGLVIA SLENYSPVSR
IGLFIKAGSR YEDFSNLGTT HLLRLTSSLT TKGASSFKIT RGIEAVGGKL SVTATRENMA
YTVECLRGDV DILMEFLLNV TTAPEFRRWE VADLQPQLKI DKAVAFQNPQ THVIENLHAA
AYRNALANPL YCPDYRIGKV TSEELHYFVQ NHFTSARMAL IGLGVSHPVL KQVAEQFLNM
RGGLGLSGAK ANYRGGEIRE QNGDSLVHAA FVAESAVAGS AEANAFSVLQ HVLGAGPHVK
RGSNTTSHLH QAVAKATQQP FDVSAFNASY SDSGLFGIYT ISQATAAGDV IKAAYNQVKT
IAQGNLSNTD VQAAKNKLKA GYLMSVESSE CFLEEVGSQA LVAGSYMPPS TVLQQIDSVA
NADIINAAKK FVSGQKSMAA SGNLGHTPFV DEL
//
ID QCR2_HUMAN Reviewed; 453 AA.
AC P22695; B3KSN4; Q9BQ05;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 11-JUL-2002, sequence version 3.
DT 22-JAN-2014, entry version 141.
DE RecName: Full=Cytochrome b-c1 complex subunit 2, mitochondrial;
DE AltName: Full=Complex III subunit 2;
DE AltName: Full=Core protein II;
DE AltName: Full=Ubiquinol-cytochrome-c reductase complex core protein 2;
DE Flags: Precursor;
GN Name=UQCRC2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLN-183.
RX PubMed=2547763;
RA Hosokawa Y., Suzuki H., Toda H., Nishikimi M., Ozawa T.;
RT "Complementary DNA encoding core protein II of human mitochondrial
RT cytochrome bc1 complex. Substantial diversity in deduced primary
RT structure from its yeast counterpart.";
RL J. Biol. Chem. 264:13483-13488(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 43-60; 71-84 AND 200-217, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [6]
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.,
RA Buerckstuemmer T., 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 [7]
RP VARIANT [LARGE SCALE ANALYSIS] TYR-208.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
RN [8]
RP VARIANT MC3DN5 TRP-183.
RX PubMed=23281071; DOI=10.1002/humu.22257;
RA Miyake N., Yano S., Sakai C., Hatakeyama H., Matsushima Y., Shiina M.,
RA Watanabe Y., Bartley J., Abdenur J.E., Wang R.Y., Chang R.,
RA Tsurusaki Y., Doi H., Nakashima M., Saitsu H., Ogata K., Goto Y.,
RA Matsumoto N.;
RT "Mitochondrial complex III deficiency caused by a homozygous UQCRC2
RT mutation presenting with neonatal-onset recurrent metabolic
RT decompensation.";
RL Hum. Mutat. 34:446-452(2013).
CC -!- FUNCTION: This is a component of the ubiquinol-cytochrome c
CC reductase complex (complex III or cytochrome b-c1 complex), which
CC is part of the mitochondrial respiratory chain. The core protein 2
CC is required for the assembly of the complex.
CC -!- SUBUNIT: The bc1 complex contains 11 subunits: 3 respiratory
CC subunits (cytochrome b, cytochrome c1 and Rieske/UQCRFS1), 2 core
CC proteins (UQCRC1/QCR1 and UQCRC2/QCR2) and 6 low-molecular weight
CC proteins (UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9,
CC UQCR11/QCR10 and a cleavage product of Rieske/UQCRFS1).
CC -!- INTERACTION:
CC O00555:CACNA1A; NbExp=2; IntAct=EBI-1051424, EBI-766279;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral
CC membrane protein; Matrix side.
CC -!- DISEASE: Mitochondrial complex III deficiency, nuclear 5 (MC3DN5)
CC [MIM:615160]: A disorder of the mitochondrial respiratory chain
CC resulting in a highly variable phenotype depending on which
CC tissues are affected. Clinical features include mitochondrial
CC encephalopathy, psychomotor retardation, ataxia, severe failure to
CC thrive, liver dysfunction, renal tubulopathy, muscle weakness and
CC exercise intolerance. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase M16 family. UQCRC2/QCR2
CC subfamily.
CC -!- CAUTION: Does not seem to have a protease activity as it lack the
CC zinc-binding site.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; J04973; AAA35710.1; -; mRNA.
DR EMBL; AK094006; BAG52796.1; -; mRNA.
DR EMBL; CH471249; EAW50592.1; -; Genomic_DNA.
DR EMBL; BC003136; AAH03136.1; -; mRNA.
DR EMBL; BC000484; AAH00484.1; -; mRNA.
DR PIR; A32629; A32629.
DR RefSeq; NP_003357.2; NM_003366.2.
DR UniGene; Hs.528803; -.
DR ProteinModelPortal; P22695; -.
DR SMR; P22695; 32-453.
DR IntAct; P22695; 7.
DR MINT; MINT-2801885; -.
DR STRING; 9606.ENSP00000268379; -.
DR MEROPS; M16.974; -.
DR PhosphoSite; P22695; -.
DR DMDM; 21903482; -.
DR REPRODUCTION-2DPAGE; IPI00305383; -.
DR UCD-2DPAGE; P22695; -.
DR PaxDb; P22695; -.
DR PeptideAtlas; P22695; -.
DR PRIDE; P22695; -.
DR DNASU; 7385; -.
DR Ensembl; ENST00000268379; ENSP00000268379; ENSG00000140740.
DR GeneID; 7385; -.
DR KEGG; hsa:7385; -.
DR UCSC; uc002djx.3; human.
DR CTD; 7385; -.
DR GeneCards; GC16P021963; -.
DR HGNC; HGNC:12586; UQCRC2.
DR HPA; HPA007998; -.
DR HPA; HPA019146; -.
DR MIM; 191329; gene.
DR MIM; 615160; phenotype.
DR neXtProt; NX_P22695; -.
DR Orphanet; 1460; Isolated CoQ-cytochrome C reductase deficiency.
DR PharmGKB; PA37217; -.
DR eggNOG; COG0612; -.
DR HOGENOM; HOG000046923; -.
DR HOVERGEN; HBG055236; -.
DR InParanoid; P22695; -.
DR KO; K00415; -.
DR OMA; QFVQNNF; -.
DR OrthoDB; EOG79CXZF; -.
DR PhylomeDB; P22695; -.
DR Reactome; REACT_111217; Metabolism.
DR SignaLink; P22695; -.
DR ChiTaRS; UQCRC2; human.
DR GeneWiki; UQCRC2; -.
DR GenomeRNAi; 7385; -.
DR NextBio; 28916; -.
DR PRO; PR:P22695; -.
DR ArrayExpress; P22695; -.
DR Bgee; P22695; -.
DR CleanEx; HS_UQCRC2; -.
DR Genevestigator; P22695; -.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005750; C:mitochondrial respiratory chain complex III; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:InterPro.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0009060; P:aerobic respiration; TAS:ProtInc.
DR GO; GO:0006119; P:oxidative phosphorylation; TAS:ProtInc.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR GO; GO:0022904; P:respiratory electron transport chain; TAS:Reactome.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 3.30.830.10; -; 2.
DR InterPro; IPR011249; Metalloenz_LuxS/M16.
DR InterPro; IPR011237; Pept_M16_dom.
DR InterPro; IPR011765; Pept_M16_N.
DR InterPro; IPR001431; Pept_M16_Zn_BS.
DR InterPro; IPR007863; Peptidase_M16_C.
DR Pfam; PF00675; Peptidase_M16; 1.
DR Pfam; PF05193; Peptidase_M16_C; 1.
DR SUPFAM; SSF63411; SSF63411; 3.
DR PROSITE; PS00143; INSULINASE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Complete proteome; Direct protein sequencing;
KW Disease mutation; Electron transport; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Polymorphism; Reference proteome;
KW Respiratory chain; Transit peptide; Transport.
FT TRANSIT 1 14 Mitochondrion.
FT CHAIN 15 453 Cytochrome b-c1 complex subunit 2,
FT mitochondrial.
FT /FTId=PRO_0000026791.
FT MOD_RES 66 66 N6-acetyllysine (By similarity).
FT MOD_RES 199 199 N6-acetyllysine (By similarity).
FT MOD_RES 250 250 N6-acetyllysine (By similarity).
FT VARIANT 148 148 R -> S (in dbSNP:rs2228473).
FT /FTId=VAR_029336.
FT VARIANT 183 183 R -> Q (in dbSNP:rs4850).
FT /FTId=VAR_034582.
FT VARIANT 183 183 R -> W (in MC3DN5).
FT /FTId=VAR_069709.
FT VARIANT 208 208 F -> Y (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036479.
FT VARIANT 254 254 R -> H (in dbSNP:rs11863893).
FT /FTId=VAR_034583.
FT CONFLICT 360 360 T -> R (in Ref. 1; AAA35710).
SQ SEQUENCE 453 AA; 48443 MW; BFA655C24C07AF52 CRC64;
MKLLTRAGSF SRFYSLKVAP KVKATAAPAG APPQPQDLEF TKLPNGLVIA SLENYSPVSR
IGLFIKAGSR YEDFSNLGTT HLLRLTSSLT TKGASSFKIT RGIEAVGGKL SVTATRENMA
YTVECLRGDV DILMEFLLNV TTAPEFRRWE VADLQPQLKI DKAVAFQNPQ THVIENLHAA
AYRNALANPL YCPDYRIGKV TSEELHYFVQ NHFTSARMAL IGLGVSHPVL KQVAEQFLNM
RGGLGLSGAK ANYRGGEIRE QNGDSLVHAA FVAESAVAGS AEANAFSVLQ HVLGAGPHVK
RGSNTTSHLH QAVAKATQQP FDVSAFNASY SDSGLFGIYT ISQATAAGDV IKAAYNQVKT
IAQGNLSNTD VQAAKNKLKA GYLMSVESSE CFLEEVGSQA LVAGSYMPPS TVLQQIDSVA
NADIINAAKK FVSGQKSMAA SGNLGHTPFV DEL
//
MIM
191329
*RECORD*
*FIELD* NO
191329
*FIELD* TI
*191329 UBIQUINOL-CYTOCHROME c REDUCTASE CORE PROTEIN II; UQCRC2
*FIELD* TX
DESCRIPTION
read more
The UQCRC2 gene encodes a subunit of mitochondrial complex III (Duncan
et al., 1993). See also UQCRC1 (191328).
MAPPING
By in situ hybridization to metaphase chromosomes, Duncan et al. (1993)
assigned the UQCRC2 gene to human chromosome 16p12, thus confirming that
it is encoded by the nuclear rather than the mitochondrial genome. Two
other subunits of mitochondrial complex III (CYC1, 123980; UQPC, 191330)
map to chromosome 8.
GENE FUNCTION
Wisloff et al. (2005) hypothesized that artificial selection of rats
based on low and high intrinsic exercise capacity would yield models
that also contrast for cardiovascular disease risk. After 11
generations, rats with low aerobic capacity scored higher on
cardiovascular risk factors that constitute the metabolic syndrome. The
decrease in aerobic capacity was associated with decreases in the
amounts of transcription factors required for mitochondrial biogenesis
and in the amounts of oxidative enzymes in skeletal muscle. Wisloff et
al. (2005) found that the amount of PPARG (601487), PPARG
coactivator-1-alpha (PPARGC1A; 604517), ubiquinol-cytochrome c
oxidoreductase core 2 subunit (UQCRC2), cytochrome c oxidase subunit I
(MTCO1; 516030), uncoupling protein-2 (UCP2; 601693), and ATP synthase
H(+)-transporting mitochondrial F1 complex (F1-ATP synthase; see 108729)
were markedly reduced in the low capacity runner rats in comparison with
the high capacity runners. The uniform decline in these proteins was
consistent with the hypothesis that reduced aerobic metabolism plays a
causal role in the development of the differences between the low
capacity runner and high capacity runner rats. Wisloff et al. (2005)
concluded that impairment of mitochondrial function may link reduced
fitness to cardiovascular and metabolic disease.
MOLECULAR GENETICS
In 3 affected individuals from a large consanguineous Mexican kindred
with mitochondrial complex III deficiency nuclear type 5 (MC3DN5;
615160), Miyake et al. (2013) identified a homozygous mutation in the
UQCRC2 gene (R183W; 191329.0001). Structural analysis indicated that the
substitution would disrupt the hydrophobic core at the interface of the
UQCRC2-containing complex, resulting in destabilization of complex III.
In vitro studies showed that the mutant protein localized properly to
the mitochondria but had decreased expression compared to wildtype,
suggesting protein instability. Complex III activity in one of the
patient's cells was decreased to 50% of normal, whereas complex I
activity was increased and complex IV activity was normal. The patient's
cells also showed severely decreased levels of complex III assembly and
decreased levels of the supercomplex formed from complexes I, III, and
IV. The patients had neonatal onset of severe metabolic acidosis
associated with hyperammonemia and hypoglycemia. Physical signs included
tachypnea and poor sucking. Two of the patients showed normal growth and
development by early childhood despite multiple episodes of metabolic
decompensation, usually associated with illness. The third patient had a
similar disease course, but showed mild development delay at age 18
months.
*FIELD* AV
.0001
MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 5
UQCRC2, ARG183TRP
In 3 affected individuals from a large consanguineous Mexican kindred
with mitochondrial complex III deficiency, nuclear type 5 (MC3DN5;
615160), Miyake et al. (2013) identified a homozygous 547C-T transition
in the UQCRC2 gene, resulting in an arg183-to-trp (R183W) substitution
at a highly conserved residue. The mutation, which was found by exome
sequencing and confirmed by Sanger sequencing, was not present in 80
Mexican or 750 Japanese control alleles. Three unaffected family members
were heterozygous for the mutation. Structural analysis indicated that
the substitution would disrupt the hydrophobic core at the interface of
the UQCRC2-containing complex, resulting in destabilization of complex
III. In vitro studies showed that the mutant protein localized properly
to the mitochondria but had decreased expression compared to wildtype,
suggesting protein instability. Complex III activity in one of the
patient's cells was decreased to 50% of normal, whereas complex I
activity was increased and complex IV activity was normal. Patients
cells also showed severely decreased levels of complex III assembly and
decreased levels of the supercomplex formed from complexes I, III, and
IV.
*FIELD* RF
1. Duncan, A. M. V.; Ozawa, T.; Suzuki, H.; Rozen, R.: Assignment
of the gene for the core protein II (UQCRC2) subunit of the mitochondrial
cytochrome bc1 complex to human chromosome 16p12. Genomics 18: 455-456,
1993.
2. Miyake, N.; Yano, S.; Sakai, C.; Hatakeyama, H.; Matsushima, Y.;
Shiina, M.; Watanabe, Y.; Bartley, J.; Abdenur, J. E.; Wang, R. Y.;
Chang, R.; Tsurusaki, Y.; Doi, H.; Nakashima, M.; Saitsu, H.; Ogata,
K.; Goto, Y.; Matsumoto, N.: Mitochondrial complex III deficiency
caused by a homozygous UQCRC2 mutation presenting with neonatal-onset
recurrent metabolic decompensation. Hum. Mutat. 34: 446-452, 2013.
3. Wisloff, U.; Najjar, S. M.; Ellingsen, O.; Haram, P. M.; Swoap,
S.; Al-Share, Q.; Fernstrom, M.; Rezaei, K.; Lee, S. J.; Koch, L.
G.; Britton, S. L.: Cardiovascular risk factors emerge after artificial
selection for low aerobic capacity. Science 307: 418-420, 2005.
*FIELD* CN
Cassandra L. Kniffin - updated: 4/8/2013
Ada Hamosh - updated: 2/2/2005
*FIELD* CD
Victor A. McKusick: 11/18/1993
*FIELD* ED
carol: 04/08/2013
ckniffin: 4/8/2013
alopez: 2/22/2005
terry: 2/2/2005
carol: 11/30/1993
carol: 11/18/1993
*RECORD*
*FIELD* NO
191329
*FIELD* TI
*191329 UBIQUINOL-CYTOCHROME c REDUCTASE CORE PROTEIN II; UQCRC2
*FIELD* TX
DESCRIPTION
read more
The UQCRC2 gene encodes a subunit of mitochondrial complex III (Duncan
et al., 1993). See also UQCRC1 (191328).
MAPPING
By in situ hybridization to metaphase chromosomes, Duncan et al. (1993)
assigned the UQCRC2 gene to human chromosome 16p12, thus confirming that
it is encoded by the nuclear rather than the mitochondrial genome. Two
other subunits of mitochondrial complex III (CYC1, 123980; UQPC, 191330)
map to chromosome 8.
GENE FUNCTION
Wisloff et al. (2005) hypothesized that artificial selection of rats
based on low and high intrinsic exercise capacity would yield models
that also contrast for cardiovascular disease risk. After 11
generations, rats with low aerobic capacity scored higher on
cardiovascular risk factors that constitute the metabolic syndrome. The
decrease in aerobic capacity was associated with decreases in the
amounts of transcription factors required for mitochondrial biogenesis
and in the amounts of oxidative enzymes in skeletal muscle. Wisloff et
al. (2005) found that the amount of PPARG (601487), PPARG
coactivator-1-alpha (PPARGC1A; 604517), ubiquinol-cytochrome c
oxidoreductase core 2 subunit (UQCRC2), cytochrome c oxidase subunit I
(MTCO1; 516030), uncoupling protein-2 (UCP2; 601693), and ATP synthase
H(+)-transporting mitochondrial F1 complex (F1-ATP synthase; see 108729)
were markedly reduced in the low capacity runner rats in comparison with
the high capacity runners. The uniform decline in these proteins was
consistent with the hypothesis that reduced aerobic metabolism plays a
causal role in the development of the differences between the low
capacity runner and high capacity runner rats. Wisloff et al. (2005)
concluded that impairment of mitochondrial function may link reduced
fitness to cardiovascular and metabolic disease.
MOLECULAR GENETICS
In 3 affected individuals from a large consanguineous Mexican kindred
with mitochondrial complex III deficiency nuclear type 5 (MC3DN5;
615160), Miyake et al. (2013) identified a homozygous mutation in the
UQCRC2 gene (R183W; 191329.0001). Structural analysis indicated that the
substitution would disrupt the hydrophobic core at the interface of the
UQCRC2-containing complex, resulting in destabilization of complex III.
In vitro studies showed that the mutant protein localized properly to
the mitochondria but had decreased expression compared to wildtype,
suggesting protein instability. Complex III activity in one of the
patient's cells was decreased to 50% of normal, whereas complex I
activity was increased and complex IV activity was normal. The patient's
cells also showed severely decreased levels of complex III assembly and
decreased levels of the supercomplex formed from complexes I, III, and
IV. The patients had neonatal onset of severe metabolic acidosis
associated with hyperammonemia and hypoglycemia. Physical signs included
tachypnea and poor sucking. Two of the patients showed normal growth and
development by early childhood despite multiple episodes of metabolic
decompensation, usually associated with illness. The third patient had a
similar disease course, but showed mild development delay at age 18
months.
*FIELD* AV
.0001
MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 5
UQCRC2, ARG183TRP
In 3 affected individuals from a large consanguineous Mexican kindred
with mitochondrial complex III deficiency, nuclear type 5 (MC3DN5;
615160), Miyake et al. (2013) identified a homozygous 547C-T transition
in the UQCRC2 gene, resulting in an arg183-to-trp (R183W) substitution
at a highly conserved residue. The mutation, which was found by exome
sequencing and confirmed by Sanger sequencing, was not present in 80
Mexican or 750 Japanese control alleles. Three unaffected family members
were heterozygous for the mutation. Structural analysis indicated that
the substitution would disrupt the hydrophobic core at the interface of
the UQCRC2-containing complex, resulting in destabilization of complex
III. In vitro studies showed that the mutant protein localized properly
to the mitochondria but had decreased expression compared to wildtype,
suggesting protein instability. Complex III activity in one of the
patient's cells was decreased to 50% of normal, whereas complex I
activity was increased and complex IV activity was normal. Patients
cells also showed severely decreased levels of complex III assembly and
decreased levels of the supercomplex formed from complexes I, III, and
IV.
*FIELD* RF
1. Duncan, A. M. V.; Ozawa, T.; Suzuki, H.; Rozen, R.: Assignment
of the gene for the core protein II (UQCRC2) subunit of the mitochondrial
cytochrome bc1 complex to human chromosome 16p12. Genomics 18: 455-456,
1993.
2. Miyake, N.; Yano, S.; Sakai, C.; Hatakeyama, H.; Matsushima, Y.;
Shiina, M.; Watanabe, Y.; Bartley, J.; Abdenur, J. E.; Wang, R. Y.;
Chang, R.; Tsurusaki, Y.; Doi, H.; Nakashima, M.; Saitsu, H.; Ogata,
K.; Goto, Y.; Matsumoto, N.: Mitochondrial complex III deficiency
caused by a homozygous UQCRC2 mutation presenting with neonatal-onset
recurrent metabolic decompensation. Hum. Mutat. 34: 446-452, 2013.
3. Wisloff, U.; Najjar, S. M.; Ellingsen, O.; Haram, P. M.; Swoap,
S.; Al-Share, Q.; Fernstrom, M.; Rezaei, K.; Lee, S. J.; Koch, L.
G.; Britton, S. L.: Cardiovascular risk factors emerge after artificial
selection for low aerobic capacity. Science 307: 418-420, 2005.
*FIELD* CN
Cassandra L. Kniffin - updated: 4/8/2013
Ada Hamosh - updated: 2/2/2005
*FIELD* CD
Victor A. McKusick: 11/18/1993
*FIELD* ED
carol: 04/08/2013
ckniffin: 4/8/2013
alopez: 2/22/2005
terry: 2/2/2005
carol: 11/30/1993
carol: 11/18/1993
MIM
615160
*RECORD*
*FIELD* NO
615160
*FIELD* TI
#615160 MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 5; MC3DN5
*FIELD* TX
A number sign (#) is used with this entry because mitochondrial complex
read moreIII deficiency nuclear type 5 (MC3DN5) can be caused by homozygous
mutation in the UQCRC2 gene (191329) on chromosome 16p12.
For a discussion of genetic heterogeneity of mitochondrial complex III
deficiency, see MC3DN1 (124000).
CLINICAL FEATURES
Miyake et al. (2013) reported 3 affected individuals from a large
consanguineous Mexican kindred with mitochondrial complex III deficiency
nuclear type 5. The patients had neonatal onset of severe metabolic
acidosis associated with hyperammonemia and hypoglycemia. Physical signs
included tachypnea and poor sucking. Two of the patients showed normal
growth and development by early childhood despite multiple episodes of
metabolic decompensation, usually associated with illness. The third
patient had a similar disease course but showed mild development delay
at age 18 months. Complex III activity in one of the patient's cells was
decreased to 50% of normal, whereas complex I activity was increased and
complex IV activity was normal. Patients cells also showed severely
decreased levels of complex III assembly and decreased levels of the
supercomplex formed from complexes I, III, and IV.
INHERITANCE
The transmission pattern in the family with MC3DN5 reported by Miyake et
al. (2013) was consistent with autosomal recessive inheritance.
MOLECULAR GENETICS
In 3 affected individuals from a large consanguineous Mexican kindred
with mitochondrial complex III deficiency nuclear type 5, Miyake et al.
(2013) identified a homozygous mutation in the UQCRC2 gene (R183W;
191329.0001). Structural analysis indicated that the substitution would
disrupt the hydrophobic core at the interface of the UQCRC2-containing
complex, resulting in destabilization of complex III. In vitro studies
showed the mutant protein localized properly to the mitochondria but had
decreased expression compared to wildtype, suggesting protein
instability.
*FIELD* RF
1. Miyake, N.; Yano, S.; Sakai, C.; Hatakeyama, H.; Matsushima, Y.;
Shiina, M.; Watanabe, Y.; Bartley, J.; Abdenur, J. E.; Wang, R. Y.;
Chang, R.; Tsurusaki, Y.; Doi, H.; Nakashima, M.; Saitsu, H.; Ogata,
K.; Goto, Y.; Matsumoto, N.: Mitochondrial complex III deficiency
caused by a homozygous UQCRC2 mutation presenting with neonatal-onset
recurrent metabolic decompensation. Hum. Mutat. 34: 446-452, 2013.
*FIELD* CS
INHERITANCE:
Autosomal recessive
NEUROLOGIC:
[Central nervous system];
Cognitive impairment, mild (1 patient)
METABOLIC FEATURES:
Metabolic acidosis
LABORATORY ABNORMALITIES:
Hyperammonemia;
Hypoglycemia;
Increased serum lactate;
Increased serum pyruvate;
Decreased mitochondrial complex III activity (in fibroblasts of 1
patient)
MISCELLANEOUS:
Onset in the neonatal period;
Episodic metabolic decompensation usually associated with illness;
Three patients from 1 Mexican family has been reported (last curated
April 2013)
MOLECULAR BASIS:
Caused by mutation in the ubiquinol-cytochrome c reductase core protein
II gene (UQCR2, 191329.0001)
*FIELD* CD
Cassandra L. Kniffin: 4/4/2013
*FIELD* ED
joanna: 10/03/2013
ckniffin: 4/8/2013
*FIELD* CD
Cassandra L. Kniffin: 4/4/2013
*FIELD* ED
carol: 04/08/2013
ckniffin: 4/8/2013
*RECORD*
*FIELD* NO
615160
*FIELD* TI
#615160 MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 5; MC3DN5
*FIELD* TX
A number sign (#) is used with this entry because mitochondrial complex
read moreIII deficiency nuclear type 5 (MC3DN5) can be caused by homozygous
mutation in the UQCRC2 gene (191329) on chromosome 16p12.
For a discussion of genetic heterogeneity of mitochondrial complex III
deficiency, see MC3DN1 (124000).
CLINICAL FEATURES
Miyake et al. (2013) reported 3 affected individuals from a large
consanguineous Mexican kindred with mitochondrial complex III deficiency
nuclear type 5. The patients had neonatal onset of severe metabolic
acidosis associated with hyperammonemia and hypoglycemia. Physical signs
included tachypnea and poor sucking. Two of the patients showed normal
growth and development by early childhood despite multiple episodes of
metabolic decompensation, usually associated with illness. The third
patient had a similar disease course but showed mild development delay
at age 18 months. Complex III activity in one of the patient's cells was
decreased to 50% of normal, whereas complex I activity was increased and
complex IV activity was normal. Patients cells also showed severely
decreased levels of complex III assembly and decreased levels of the
supercomplex formed from complexes I, III, and IV.
INHERITANCE
The transmission pattern in the family with MC3DN5 reported by Miyake et
al. (2013) was consistent with autosomal recessive inheritance.
MOLECULAR GENETICS
In 3 affected individuals from a large consanguineous Mexican kindred
with mitochondrial complex III deficiency nuclear type 5, Miyake et al.
(2013) identified a homozygous mutation in the UQCRC2 gene (R183W;
191329.0001). Structural analysis indicated that the substitution would
disrupt the hydrophobic core at the interface of the UQCRC2-containing
complex, resulting in destabilization of complex III. In vitro studies
showed the mutant protein localized properly to the mitochondria but had
decreased expression compared to wildtype, suggesting protein
instability.
*FIELD* RF
1. Miyake, N.; Yano, S.; Sakai, C.; Hatakeyama, H.; Matsushima, Y.;
Shiina, M.; Watanabe, Y.; Bartley, J.; Abdenur, J. E.; Wang, R. Y.;
Chang, R.; Tsurusaki, Y.; Doi, H.; Nakashima, M.; Saitsu, H.; Ogata,
K.; Goto, Y.; Matsumoto, N.: Mitochondrial complex III deficiency
caused by a homozygous UQCRC2 mutation presenting with neonatal-onset
recurrent metabolic decompensation. Hum. Mutat. 34: 446-452, 2013.
*FIELD* CS
INHERITANCE:
Autosomal recessive
NEUROLOGIC:
[Central nervous system];
Cognitive impairment, mild (1 patient)
METABOLIC FEATURES:
Metabolic acidosis
LABORATORY ABNORMALITIES:
Hyperammonemia;
Hypoglycemia;
Increased serum lactate;
Increased serum pyruvate;
Decreased mitochondrial complex III activity (in fibroblasts of 1
patient)
MISCELLANEOUS:
Onset in the neonatal period;
Episodic metabolic decompensation usually associated with illness;
Three patients from 1 Mexican family has been reported (last curated
April 2013)
MOLECULAR BASIS:
Caused by mutation in the ubiquinol-cytochrome c reductase core protein
II gene (UQCR2, 191329.0001)
*FIELD* CD
Cassandra L. Kniffin: 4/4/2013
*FIELD* ED
joanna: 10/03/2013
ckniffin: 4/8/2013
*FIELD* CD
Cassandra L. Kniffin: 4/4/2013
*FIELD* ED
carol: 04/08/2013
ckniffin: 4/8/2013