UQCC2

Last updated
UQCC2
Identifiers
Aliases UQCC2 , C6orf125, Cbp6, M19, MNF1, bA6B20.2, ubiquinol-cytochrome c reductase complex assembly factor 2, C6orf126, MC3DN7
External IDs OMIM: 614461 MGI: 1914517 HomoloGene: 12105 GeneCards: UQCC2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_032340

NM_026063
NM_001364944

RefSeq (protein)

NP_115716

NP_080339
NP_001351873

Location (UCSC) Chr 6: 33.69 – 33.71 Mb Chr 17: 27.34 – 27.35 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Ubiquinol-cytochrome c reductase complex assembly factor 2 is a protein that in humans is encoded by the UQCC2 gene. Located in the mitochondrial nucleoid, this protein is a complex III assembly factor, playing a role in cytochrome b biogenesis along with the UQCC1 protein. [5] It regulates insulin secretion and mitochondrial ATP production and oxygen consumption. [6] [7] In the sole recorded case, a mutation in the UQCC2 gene caused Complex III deficiency, characterized by intrauterine growth retardation, neonatal lactic acidosis, and renal tubular dysfunction. [8]

Contents

Structure

The UQCC2 gene is located on the p arm of chromosome 6 in position 21.31 and spans 14,990 base pairs. [5] The gene produces a 14.9 kDa protein composed of 126 amino acids. [9] [10] This protein has no homologous domains with other known proteins. It is associated with the mitochondrial nucleoid, likely located in the peripheral region. [7] This protein's distribution pattern is similar to other components of the mitochondrial nucleoid, like mtSSB and PHB1/PHB2. [11]

Function

This gene encodes a nucleoid protein localized to the mitochondrial inner membrane and sublocalized to the mitochondrial matrix. [11] The encoded protein permissively regulates insulin secretion in pancreatic beta cells, positively regulates mitochondrial ATP production and oxygen consumption, and is involved in late skeletal muscle differentiation through modulation of mitochondrial respiratory chain activity. [7] This protein is required for the assembly of the Complex III. Expression of this protein is decreased in cells with low mtDNA. [11]

Clinical Significance

In the sole recorded case, a homozygous mutation in intron 2 of the UQCC2 gene caused a splicing disruption; the patient presented with symptoms of nuclear type 7 Complex III deficiency, including neonatal lactic acidosis, renal tubulopathy, and severe intrauterine growth retardation. Additional clinical features included a dysmorphic facial appearance, delayed psychomotor development, autistic features, aggressive behavior, and mild sensorineural hearing loss. [6] Additionally, the patient had decreased levels of UQCC1. [8]

Interactions

This protein interacts with UQCC1. [6]

Related Research Articles

<span class="mw-page-title-main">Coenzyme Q – cytochrome c reductase</span> Class of enzymes

The coenzyme Q : cytochrome c – oxidoreductase, sometimes called the cytochrome bc1 complex, and at other times complex III, is the third complex in the electron transport chain, playing a critical role in biochemical generation of ATP. Complex III is a multisubunit transmembrane protein encoded by both the mitochondrial and the nuclear genomes. Complex III is present in the mitochondria of all animals and all aerobic eukaryotes and the inner membranes of most eubacteria. Mutations in Complex III cause exercise intolerance as well as multisystem disorders. The bc1 complex contains 11 subunits, 3 respiratory subunits, 2 core proteins and 6 low-molecular weight proteins.

<span class="mw-page-title-main">MT-CYB</span> A mitochondrial protein-coding gene whose product is involved in the respiratory chain

Cytochrome b is a protein that in humans is encoded by the MT-CYB gene. Its gene product is a subunit of the respiratory chain protein ubiquinol–cytochrome c reductase, which consists of the products of one mitochondrially encoded gene, MT-CYB, and ten nuclear genes—UQCRC1, UQCRC2, CYC1, UQCRFS1, UQCRB, "11kDa protein", UQCRH, Rieske protein presequence, "cyt c1 associated protein", and Rieske-associated protein.

<span class="mw-page-title-main">CYC1</span> Protein-coding gene in the species Homo sapiens

Cytochrome c1, heme protein, mitochondrial (CYC1), also known as UQCR4, MC3DN6, Complex III subunit 4, Cytochrome b-c1 complex subunit 4, or Ubiquinol-cytochrome-c reductase complex cytochrome c1 subunit is a protein that in humans is encoded by the CYC1 gene. CYC1 is a respiratory subunit of Ubiquinol Cytochrome c Reductase, which is located in the inner mitochondrial membrane and is part of the electron transport chain. Mutations in this gene may cause mitochondrial complex III deficiency, nuclear, type 6.

<span class="mw-page-title-main">UQCRC1</span> Protein-coding gene in the species Homo sapiens

Cytochrome b-c1 complex subunit 1, mitochondrial is a protein that in humans is encoded by the UQCRC1 gene.

<span class="mw-page-title-main">BCS1L</span> Protein-coding gene in the species Homo sapiens

Mitochondrial chaperone BCS1 (BCS1L), also known as BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone (h-BCS1), is a protein that in humans is encoded by the BCS1L gene. BCS1L is a chaperone protein involved in the assembly of Ubiquinol Cytochrome c Reductase, which is located in the inner mitochondrial membrane and is part of the electron transport chain. Mutations in this gene are associated with mitochondrial complex III deficiency, GRACILE syndrome, and Bjoernstad syndrome.

<span class="mw-page-title-main">NDUFS1</span> Protein-coding gene in the species Homo sapiens

NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial (NDUFS1) is an enzyme that in humans is encoded by the NDUFS1 gene. The encoded protein, NDUFS1, is the largest subunit of complex I, located on the inner mitochondrial membrane, and is important for mitochondrial oxidative phosphorylation. Mutations in this gene are associated with complex I deficiency.

<span class="mw-page-title-main">UCRC</span> Protein-coding gene in the species Homo sapiens

Ubiquinol-cytochrome c reductase complex , also known as UCRC or UQCR10, is a human gene.

<span class="mw-page-title-main">UQCRB</span> Protein

Ubiquinol-cytochrome c reductase binding protein, also known as UQCRB, Complex III subunit 7, QP-C, or Ubiquinol-cytochrome c reductase complex 14 kDa protein is a protein which in humans is encoded by the UQCRB gene. This gene encodes a subunit of the ubiquinol-cytochrome c oxidoreductase complex, which consists of one mitochondrial-encoded and 10 nuclear-encoded subunits. Mutations in this gene are associated with mitochondrial complex III deficiency. Alternatively spliced transcript variants have been found for this gene. Related pseudogenes have been identified on chromosomes 1, 5 and X.

<span class="mw-page-title-main">UQCRC2</span> Protein-coding gene in the species Homo sapiens

Cytochrome b-c1 complex subunit 2, mitochondrial (UQCRC2), also known as QCR2, UQCR2, or MC3DN5 is a protein that in humans is encoded by the UQCRC2 gene. The product of UQCRC2 is a subunit of the respiratory chain protein Ubiquinol Cytochrome c Reductase, which consists of the products of one mitochondrially encoded gene, MTCYTB and ten nuclear genes: UQCRC1, UQCRC2, Cytochrome c1, UQCRFS1, UQCRB, "11kDa protein", UQCRH, Rieske Protein presequence, "cyt. c1 associated protein", and "Rieske-associated protein." Defects in UQCRC2 are associated with mitochondrial complex III deficiency, nuclear, type 5.

<span class="mw-page-title-main">UQCRFS1</span> Protein-coding gene in the species Homo sapiens

Ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1, also known as UQCRFS1, Rieske iron-sulfur (Fe-S) protein, Cytochrome b-c1 complex subunit 5, or Complex III subunit 5 is a protein which in humans is encoded by the UQCRFS1 gene. UQCRFS1 is a subunit of the respiratory chain protein Ubiquinol Cytochrome c Reductase, which consists of the products of one mitochondrially encoded gene, MTCYTB and ten nuclear genes UQCRC1, UQCRC2, Cytochrome C1, UQCRFS1, UQCRB,UQCRQ, UQCRH, UCRC, and UQCR.

<span class="mw-page-title-main">NDUFB11</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial is an enzyme that in humans is encoded by the NDUFB11 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 11 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain. NDUFB11 mutations have been associated with linear skin defects with multiple congenital anomalies 3 and mitochondrial complex I deficiency.

<span class="mw-page-title-main">UQCR11</span> Protein-coding gene in the species Homo sapiens

UQCR11 is a protein that in humans is encoded by the UQCR11 gene. UQCR11 is the smallest known component of Complex III in the mitochondrial respiratory chain.

<span class="mw-page-title-main">UQCRQ</span> Protein-coding gene in the species Homo sapiens

Ubiquinol-cytochrome c reductase, complex III subunit VII, 9.5kDa is a protein that in humans is encoded by the UQCRQ gene. This ubiqinone-binding protein is a subunit of mitochondrial Complex III in the electron transport chain. A mutation in the UQCRQ gene has been shown to cause severe neurological disorders. Infection by Trypanosoma cruzi can cause oxidative modification of this protein in cardiac muscle tissue.

Tetratricopeptide repeat domain 19, also known as TPR repeat protein 19 or Tetratricopeptide repeat protein 19, mitochondrial is a protein that in humans is encoded by the TTC19 gene. This gene encodes a protein with a tetratricopeptide repeat (TPR) domain containing several TPRs of about 34 amino acids each. These repeats are found in a variety of organisms including bacteria, fungi and plants, and are involved in a variety of functions including protein-protein interactions. This protein is embedded in the inner mitochondrial membrane and is involved in the formation of the mitochondrial respiratory chain III. It has also been suggested that this protein plays a role in cytokinesis. Mutations in this gene cause mitochondrial complex III deficiency. Alternatively spliced transcript variants have been found for this gene.

LYR motif containing 7, also known as Complex III assembly factor LYRM7 or LYR motif-containing protein 7 is a protein that in humans is encoded by the LYRM7 gene. The protein encoded by this gene is a nuclear-encoded mitochondrial matrix protein that stabilizes UQCRFS1 and chaperones it to the CIII complex. Defects in this gene are a cause of mitochondrial complex III deficiency, nuclear type 8. Three transcript variants encoding two different isoforms have been found for this gene.

<span class="mw-page-title-main">UQCC3</span> Protein-coding gene in the species Homo sapiens

Ubiquinol-cytochrome c reductase complex assembly factor 3 is a protein that in humans is encoded by the UQCC3 gene. Located in mitochondria, this protein is involved in the assembly of mitochondrial Complex III, stabilizing supercomplexes containing Complex III. Mutations in the UQCC3 gene cause Complex III deficiency with symptoms of hypoglycemia, hypotonia, lactic acidosis, and developmental delays. This protein plays an important role as an antiviral factor, bolstering the ability of cells to inhibit viral replication, independent of interferon production. The UQCC3 protein can be cleaved by OMA1 metalloprotease during mitochondrial depolarization, targeting the cell for apoptosis. Depletion of this protein alters cardiolipin composition, causing cellular and mitochondrial defects.

<span class="mw-page-title-main">COX14</span> Protein-coding gene in humans

Cytochrome c oxidase assembly factor COX14 is a protein that in humans is encoded by the COX14 gene. This gene encodes a small single-pass transmembrane protein that localizes to mitochondria. This protein may play a role in coordinating the early steps of cytochrome c oxidase subunit assembly and, in particular, the synthesis and assembly of the COX I subunit of the holoenzyme. Mutations in this gene have been associated with mitochondrial complex IV deficiency. Alternative splicing results in multiple transcript variants.

<span class="mw-page-title-main">COA6</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase assembly factor 6 is a protein that in humans is encoded by the COA6 gene. Mitochondrial respiratory chain Complex IV, or cytochrome c oxidase, is the component of the respiratory chain that catalyzes the transfer of electrons from intermembrane space cytochrome c to molecular oxygen in the matrix and as a consequence contributes to the proton gradient involved in mitochondrial ATP synthesis. The COA6 gene encodes an assembly factor for mitochondrial complex IV and is a member of the cytochrome c oxidase subunit 6B family. This protein is located in the intermembrane space, associating with SCO2 and COX2. It stabilizes newly formed COX2 and is part of the mitochondrial copper relay system. Mutations in this gene result in fatal infantile cardioencephalomyopathy.

<span class="mw-page-title-main">PET100</span> Protein-coding gene in the species Homo sapiens

PET100 homolog is a protein that in humans is encoded by the PET100 gene. Mitochondrial complex IV, or cytochrome c oxidase, is a large transmembrane protein complex that is part of the respiratory electron transport chain of mitochondria. The small protein encoded by the PET100 gene plays a role in the biogenesis of mitochondrial complex IV. This protein localizes to the inner mitochondrial membrane and is exposed to the intermembrane space. Mutations in this gene are associated with mitochondrial complex IV deficiency. This gene has a pseudogene on chromosome 3. Alternative splicing results in multiple transcript variants.

<span class="mw-page-title-main">TMEM70</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 70 is a protein that in humans is encoded by the TMEM70 gene. It is a transmembrane protein located in the mitochondrial inner membrane involved in the assembly of the F1 and Fo structural subunits of ATP synthase. Mutations in this gene have been associated with neonatal mitochondrial encephalo-cardiomyopathy due to ATP synthase deficiency, causing a wide variety of symptoms including 3-methylglutaconic aciduria, lactic acidosis, mitochondrial myopathy, and cardiomyopathy.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000137288 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000024208 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 "Entrez Gene: Ubiquinol-cytochrome c reductase complex assembly factor 2" . Retrieved 2018-08-02.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  6. 1 2 3 "UQCC2 - Ubiquinol-cytochrome-c reductase complex assembly factor 2 precursor - Homo sapiens (Human) - UQCC2 gene & protein". www.uniprot.org. Retrieved 2018-08-03.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  7. 1 2 3 Cambier L, Rassam P, Chabi B, Mezghenna K, Gross R, Eveno E, Auffray C, Wrutniak-Cabello C, Lajoix AD, Pomiès P (2012-02-20). "M19 modulates skeletal muscle differentiation and insulin secretion in pancreatic β-cells through modulation of respiratory chain activity". PLOS ONE. 7 (2): e31815. Bibcode:2012PLoSO...731815C. doi: 10.1371/journal.pone.0031815 . PMC   3282743 . PMID   22363741.
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  9. Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC   4076475 . PMID   23965338.
  10. "UQCC2 - Ubiquinol-cytochrome-c reductase complex assembly factor 2". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  11. 1 2 3 Sumitani M, Kasashima K, Ohta E, Kang D, Endo H (November 2009). "Association of a novel mitochondrial protein M19 with mitochondrial nucleoids". Journal of Biochemistry. 146 (5): 725–32. doi:10.1093/jb/mvp118. PMID   19643811.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.