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UQCC3
Adas2-9939-5190: Created page; added introduction, structure, function, clinical significance, and interactions sections, in addition to semantic linkages and citations.
'''Ubiquinol-cytochrome c reductase complex assembly factor 3''' is a [[protein]] that in humans is encoded by the ''UQCC3'' [[gene]].<ref name="entrez"></ref> Located in mitochondria, this protein is involved in the [[Protein biosynthesis#Events during or following protein translation|assembly]] of [[Mitochondrion|mitochondrial]] [[Coenzyme Q – cytochrome c reductase|Complex III]], stabilizing [[Respirasome|supercomplexes]] containing Complex III.<ref name=":1">Liquid error: wrong number of arguments (1 for 2)</ref> [[Mutation|Mutations]] in the ''UQCC3'' gene cause Complex III deficiency with symptoms of [[hypoglycemia]], [[hypotonia]], [[lactic acidosis]], and [[Developmental disability|developmental delays]].<ref name=":2">Liquid error: wrong number of arguments (1 for 2)</ref> This protein plays an important role as an [[Antiviral protein|antiviral factor]], bolstering the ability of cells to inhibit [[viral replication]], independent of [[interferon]] production.<ref name=":3">Liquid error: wrong number of arguments (1 for 2)</ref> The UQCC3 protein can be cleaved by [[OMA1|OMA1 metalloprotease]] during mitochondrial [[depolarization]], targeting the cell for [[apoptosis]]. Depletion of this protein alters [[cardiolipin]] composition, causing cellular and mitochondrial defects.<ref name=":1" />
== Structure ==
The ''UQCC3'' gene is located on the q arm of [[chromosome 11]] in position 12.3 and spans 2,036 base pairs.<ref name="entrez" /> The gene produces a 10.1 kDa protein composed of 93 [[amino acids]].<ref name="COPaKB">Liquid error: wrong number of arguments (1 for 2)</ref><ref name="url_COPaKB"></ref> This protein faces the [[Mitochondrion#Intermembrane space|intermembrane space]].<ref name=":1" /> It possesses an [[N-terminus|N-terminal]] [[signal peptide]] and a signal transmembrane structure, in addition to several [[phosphorylation]] sites. The [[Protein secondary structure|secondary structure]] of this protein is made up mostly of random [[Coiled coil|coils]] and [[Alpha helix|alpha helices]].<ref name=":0">Liquid error: wrong number of arguments (1 for 2)</ref> Alpha helices 2 and 3 bind to cardiolipin.<ref name=":1" />
== Function ==
The ''UQCC3'' gene encodes a protein that functions in complex III assembly, downstream of assembly factors [[UQCC1]] and [[UQCC2]]. This is evidenced by the observation that UQCC3 levels are reduced in cells with decreased levels of UQCC1 and UQCC2, but lack of the UQCC3 protein does not affect levels of UQCC1 and UQCC2.<ref name=":2" /> Predicted to be a secretary protein with small molecular weight, this protein has important functions in [[Cell growth|cellular proliferation]] and antiviral [[Innate immune system|innate immune regulation]]. [[Gene expression|Expression]] of this protein is ubiquitous in [[Carcinoma|carcinomas]], along with normal [[Tissue (biology)|tissues]].<ref name=":0" /> During the early stages of Complex III assembly, the UQCC3 protein stabilizes supercomplexes containing Complex III, most notably the III<sub>2</sub>/IV supercomplex.
== Clinical Significance ==
In the sole recorded case of a mutation in the ''UQCC3'' gene, a patient with a [[Zygosity#Homozygous|homozygous]] [[missense mutation]] presented with nuclear type 9 complex III deficiency, displaying symptoms of hypoglycemia, hypotonia, lactic acidosis, severe [[Psychomotor retardation|delayed psychomotor development]], and other developmental delay. The patient also had decreased levels of [[cytochrome b]] within Complex III.<ref name=":2" />
The UQCC3 protein also has a role as an antiviral factor, independent of interferon production. Levels of this protein increase in response to a [[Viral disease|viral infection]], improving the ability of cells to inhibit viral replication. Overexpression of the ''UQCC3'' gene increases transcription of OAS3 while knockdown of [[Ribonuclease L|RNase L]] or [[OAS3]] hampers the antiviral effect of UQCC3. Signaling from UQCC3 to the OAS-RNase L system is independent of interferon production.<ref name=":3" /> This protein is also [[Regulation of gene expression|regulated]] by expression of the double-stranded RNA-dependent [[Protein kinase R|protein kinase EIF2AK2]].<ref name=":0" />
Depleted levels of the UQCC3 protein cause impaired [[Cellular respiration|respiration]] and subtle yet significant alterations in cardiolipin composition, which then result in abnormal [[crista]] morphology, increased sensitivity to apoptosis, and decreased levels of [[Adenosine triphosphate|ATP]]. Furthermore, mitochondrial depolarization causes OMA1 metalloprotease to cleave the UQCC3 protein; effectively, this mechanism targets cells with damaged mitochondria for apoptosis.<ref name=":1" />
== Interactions ==
This protein associates with the rest of mitochondrial Complex III and has [[protein-protein interactions]] with [[PHLDA3]].
== References ==
== Further reading ==
*Liquid error: wrong number of arguments (1 for 2)
*Liquid error: wrong number of arguments (1 for 2)
== Structure ==
The ''UQCC3'' gene is located on the q arm of [[chromosome 11]] in position 12.3 and spans 2,036 base pairs.<ref name="entrez" /> The gene produces a 10.1 kDa protein composed of 93 [[amino acids]].<ref name="COPaKB">Liquid error: wrong number of arguments (1 for 2)</ref><ref name="url_COPaKB"></ref> This protein faces the [[Mitochondrion#Intermembrane space|intermembrane space]].<ref name=":1" /> It possesses an [[N-terminus|N-terminal]] [[signal peptide]] and a signal transmembrane structure, in addition to several [[phosphorylation]] sites. The [[Protein secondary structure|secondary structure]] of this protein is made up mostly of random [[Coiled coil|coils]] and [[Alpha helix|alpha helices]].<ref name=":0">Liquid error: wrong number of arguments (1 for 2)</ref> Alpha helices 2 and 3 bind to cardiolipin.<ref name=":1" />
== Function ==
The ''UQCC3'' gene encodes a protein that functions in complex III assembly, downstream of assembly factors [[UQCC1]] and [[UQCC2]]. This is evidenced by the observation that UQCC3 levels are reduced in cells with decreased levels of UQCC1 and UQCC2, but lack of the UQCC3 protein does not affect levels of UQCC1 and UQCC2.<ref name=":2" /> Predicted to be a secretary protein with small molecular weight, this protein has important functions in [[Cell growth|cellular proliferation]] and antiviral [[Innate immune system|innate immune regulation]]. [[Gene expression|Expression]] of this protein is ubiquitous in [[Carcinoma|carcinomas]], along with normal [[Tissue (biology)|tissues]].<ref name=":0" /> During the early stages of Complex III assembly, the UQCC3 protein stabilizes supercomplexes containing Complex III, most notably the III<sub>2</sub>/IV supercomplex.
== Clinical Significance ==
In the sole recorded case of a mutation in the ''UQCC3'' gene, a patient with a [[Zygosity#Homozygous|homozygous]] [[missense mutation]] presented with nuclear type 9 complex III deficiency, displaying symptoms of hypoglycemia, hypotonia, lactic acidosis, severe [[Psychomotor retardation|delayed psychomotor development]], and other developmental delay. The patient also had decreased levels of [[cytochrome b]] within Complex III.<ref name=":2" />
The UQCC3 protein also has a role as an antiviral factor, independent of interferon production. Levels of this protein increase in response to a [[Viral disease|viral infection]], improving the ability of cells to inhibit viral replication. Overexpression of the ''UQCC3'' gene increases transcription of OAS3 while knockdown of [[Ribonuclease L|RNase L]] or [[OAS3]] hampers the antiviral effect of UQCC3. Signaling from UQCC3 to the OAS-RNase L system is independent of interferon production.<ref name=":3" /> This protein is also [[Regulation of gene expression|regulated]] by expression of the double-stranded RNA-dependent [[Protein kinase R|protein kinase EIF2AK2]].<ref name=":0" />
Depleted levels of the UQCC3 protein cause impaired [[Cellular respiration|respiration]] and subtle yet significant alterations in cardiolipin composition, which then result in abnormal [[crista]] morphology, increased sensitivity to apoptosis, and decreased levels of [[Adenosine triphosphate|ATP]]. Furthermore, mitochondrial depolarization causes OMA1 metalloprotease to cleave the UQCC3 protein; effectively, this mechanism targets cells with damaged mitochondria for apoptosis.<ref name=":1" />
== Interactions ==
This protein associates with the rest of mitochondrial Complex III and has [[protein-protein interactions]] with [[PHLDA3]].
== References ==
== Further reading ==
*Liquid error: wrong number of arguments (1 for 2)
*Liquid error: wrong number of arguments (1 for 2)
August 07, 2018 at 06:54AM
