CHCH2_HUMAN
ID CHCH2_HUMAN Reviewed; 151 AA.
AC Q9Y6H1; Q498C3; Q6NZ50;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Coiled-coil-helix-coiled-coil-helix domain-containing protein 2;
DE AltName: Full=Aging-associated gene 10 protein;
DE AltName: Full=HCV NS2 trans-regulated protein;
DE Short=NS2TP;
GN Name=CHCHD2; Synonyms=C7orf17; ORFNames=AAG10;
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 [MRNA].
RC TISSUE=Pituitary;
RA Peng Y., Song H., Dai M., Huang Q., Mao Y., Zhang Q., Mao M., Fu G.,
RA Luo M., Chen J., Hu R.;
RT "Human 16.7Kd protein, complete cds.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhang L.-Y., Cheng J., Deng H., Liu Y., Wang L.;
RT "Cloning and identification of gene NS2TP transregulated by non-structural
RT protein 2 of hepatitis C virus.";
RL Shi Jie Hua Ren Xiao Hua Za Zhi 13:1700-1704(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kim J.W.;
RT "Identification of a human aging-associated gene.";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Colon, Lung, and PNS;
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 [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., 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 [7]
RP FUNCTION IN COX4I2 TRANSCRIPTION, INTERACTION WITH RBPJ, SUBCELLULAR
RP LOCATION, AND INDUCTION BY HYPOXIA.
RX PubMed=23303788; DOI=10.1093/nar/gks1454;
RA Aras S., Pak O., Sommer N., Finley R. Jr., Huttemann M., Weissmann N.,
RA Grossman L.I.;
RT "Oxygen-dependent expression of cytochrome c oxidase subunit 4-2 gene
RT expression is mediated by transcription factors RBPJ, CXXC5 and CHCHD2.";
RL Nucleic Acids Res. 41:2255-2266(2013).
RN [8]
RP SUBCELLULAR LOCATION, INVOLVEMENT IN PARK22, VARIANTS PARK22 ILE-61 AND
RP GLN-145, AND CHARACTERIZATION OF VARIANTS PARK22 ILE-61 AND GLN-145.
RX PubMed=25662902; DOI=10.1016/s1474-4422(14)70266-2;
RA Funayama M., Ohe K., Amo T., Furuya N., Yamaguchi J., Saiki S., Li Y.,
RA Ogaki K., Ando M., Yoshino H., Tomiyama H., Nishioka K., Hasegawa K.,
RA Saiki H., Satake W., Mogushi K., Sasaki R., Kokubo Y., Kuzuhara S.,
RA Toda T., Mizuno Y., Uchiyama Y., Ohno K., Hattori N.;
RT "CHCHD2 mutations in autosomal dominant late-onset Parkinson's disease: a
RT genome-wide linkage and sequencing study.";
RL Lancet Neurol. 14:274-282(2015).
RN [9]
RP CORRESPONDENCE ON INVOLVEMENT OF CHCHD2 IN PARKINSON'S DISEASE.
RX PubMed=26067113; DOI=10.1016/s1474-4422(15)00096-4;
RA Iqbal Z., Toft M.;
RT "CHCHD2 and Parkinson's disease.";
RL Lancet Neurol. 14:680-681(2015).
RN [10]
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 [11]
RP VARIANTS LEU-2; ARG-4; SER-14; LEU-34; VAL-37; VAL-49 AND VAL-93.
RX PubMed=26561290; DOI=10.1212/wnl.0000000000002170;
RA Ogaki K., Koga S., Heckman M.G., Fiesel F.C., Ando M., Labbe C.,
RA Lorenzo-Betancor O., Moussaud-Lamodiere E.L., Soto-Ortolaza A.I.,
RA Walton R.L., Strongosky A.J., Uitti R.J., McCarthy A., Lynch T., Siuda J.,
RA Opala G., Rudzinska M., Krygowska-Wajs A., Barcikowska M., Czyzewski K.,
RA Puschmann A., Nishioka K., Funayama M., Hattori N., Parisi J.E.,
RA Petersen R.C., Graff-Radford N.R., Boeve B.F., Springer W., Wszolek Z.K.,
RA Dickson D.W., Ross O.A.;
RT "Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk
RT for Lewy body disorders.";
RL Neurology 85:2016-2025(2015).
CC -!- FUNCTION: Transcription factor. Binds to the oxygen responsive element
CC of COX4I2 and activates its transcription under hypoxia conditions (4%
CC oxygen), as well as normoxia conditions (20% oxygen) (PubMed:23303788).
CC {ECO:0000269|PubMed:23303788}.
CC -!- SUBUNIT: Interacts with RBPJ. {ECO:0000269|PubMed:23303788}.
CC -!- INTERACTION:
CC Q9Y6H1; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-2321769, EBI-10173507;
CC Q9Y6H1; P18825: ADRA2C; NbExp=3; IntAct=EBI-2321769, EBI-12015266;
CC Q9Y6H1; Q8WYQ3: CHCHD10; NbExp=15; IntAct=EBI-2321769, EBI-16721660;
CC Q9Y6H1; P05813: CRYBA1; NbExp=3; IntAct=EBI-2321769, EBI-7043337;
CC Q9Y6H1; P78358: CTAG1B; NbExp=3; IntAct=EBI-2321769, EBI-1188472;
CC Q9Y6H1; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-2321769, EBI-3867333;
CC Q9Y6H1; A2ABF9: EHMT2; NbExp=3; IntAct=EBI-2321769, EBI-10174566;
CC Q9Y6H1; Q08379: GOLGA2; NbExp=6; IntAct=EBI-2321769, EBI-618309;
CC Q9Y6H1; P42858: HTT; NbExp=10; IntAct=EBI-2321769, EBI-466029;
CC Q9Y6H1; Q9UKT9: IKZF3; NbExp=4; IntAct=EBI-2321769, EBI-747204;
CC Q9Y6H1; Q0VD86: INCA1; NbExp=3; IntAct=EBI-2321769, EBI-6509505;
CC Q9Y6H1; Q15323: KRT31; NbExp=3; IntAct=EBI-2321769, EBI-948001;
CC Q9Y6H1; Q6A162: KRT40; NbExp=3; IntAct=EBI-2321769, EBI-10171697;
CC Q9Y6H1; Q969G2: LHX4; NbExp=4; IntAct=EBI-2321769, EBI-2865388;
CC Q9Y6H1; A9UHW6-2: MIF4GD; NbExp=3; IntAct=EBI-2321769, EBI-9118295;
CC Q9Y6H1; O43482: OIP5; NbExp=3; IntAct=EBI-2321769, EBI-536879;
CC Q9Y6H1; P07237: P4HB; NbExp=3; IntAct=EBI-2321769, EBI-395883;
CC Q9Y6H1; Q9BYU1: PBX4; NbExp=3; IntAct=EBI-2321769, EBI-10302990;
CC Q9Y6H1; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-2321769, EBI-742388;
CC Q9Y6H1; Q9Y2S7: POLDIP2; NbExp=7; IntAct=EBI-2321769, EBI-713000;
CC Q9Y6H1; Q04864: REL; NbExp=3; IntAct=EBI-2321769, EBI-307352;
CC Q9Y6H1; P15884: TCF4; NbExp=3; IntAct=EBI-2321769, EBI-533224;
CC Q9Y6H1; Q12933: TRAF2; NbExp=3; IntAct=EBI-2321769, EBI-355744;
CC Q9Y6H1; Q8IWZ5: TRIM42; NbExp=3; IntAct=EBI-2321769, EBI-5235829;
CC Q9Y6H1; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-2321769, EBI-2130429;
CC Q9Y6H1; Q86WV8: TSC1; NbExp=3; IntAct=EBI-2321769, EBI-12806590;
CC Q9Y6H1; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-2321769, EBI-11975223;
CC Q9Y6H1; Q9H0C1: ZMYND12; NbExp=3; IntAct=EBI-2321769, EBI-12030590;
CC Q9Y6H1; PRO_0000041302 [P08563]; Xeno; NbExp=3; IntAct=EBI-2321769, EBI-11478341;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23303788}.
CC Mitochondrion {ECO:0000269|PubMed:25662902}. Mitochondrion
CC intermembrane space {ECO:0000269|PubMed:25662902}. Note=Mainly
CC localized in the intermembrane space. {ECO:0000269|PubMed:25662902}.
CC -!- INDUCTION: Up-regulated by hypoxia (4% oxygen) (at protein level).
CC {ECO:0000269|PubMed:23303788}.
CC -!- POLYMORPHISM: Mutations in CHCHD2 are rare, and might vary by ethnic
CC origin. {ECO:0000269|PubMed:26067113, ECO:0000269|PubMed:26561290}.
CC -!- DISEASE: Parkinson disease 22 (PARK22) [MIM:616710]: An autosomal
CC dominant form of Parkinson disease, a complex neurodegenerative
CC disorder characterized by bradykinesia, resting tremor, muscular
CC rigidity and postural instability, as well as by a clinically
CC significant response to treatment with levodopa. The pathology involves
CC the loss of dopaminergic neurons in the substantia nigra and the
CC presence of Lewy bodies (intraneuronal accumulations of aggregated
CC proteins), in surviving neurons in various areas of the brain.
CC {ECO:0000269|PubMed:25662902}. Note=The gene represented in this entry
CC may be involved in disease pathogenesis.
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DR EMBL; AY605046; AAT35813.1; -; mRNA.
DR EMBL; AF078845; AAD44477.1; -; mRNA.
DR EMBL; AY633613; AAV33306.1; -; mRNA.
DR EMBL; AC006970; AAQ96886.1; -; Genomic_DNA.
DR EMBL; BC003079; AAH03079.1; -; mRNA.
DR EMBL; BC015639; AAH15639.1; -; mRNA.
DR EMBL; BC066331; AAH66331.1; -; mRNA.
DR EMBL; BC071985; AAH71985.1; -; mRNA.
DR EMBL; BC100275; AAI00276.1; -; mRNA.
DR CCDS; CCDS5526.1; -.
DR RefSeq; NP_057223.1; NM_016139.3.
DR AlphaFoldDB; Q9Y6H1; -.
DR SMR; Q9Y6H1; -.
DR BioGRID; 119326; 253.
DR IntAct; Q9Y6H1; 150.
DR MINT; Q9Y6H1; -.
DR STRING; 9606.ENSP00000378812; -.
DR iPTMnet; Q9Y6H1; -.
DR PhosphoSitePlus; Q9Y6H1; -.
DR BioMuta; CHCHD2; -.
DR DMDM; 62510521; -.
DR EPD; Q9Y6H1; -.
DR jPOST; Q9Y6H1; -.
DR MassIVE; Q9Y6H1; -.
DR MaxQB; Q9Y6H1; -.
DR PaxDb; Q9Y6H1; -.
DR PeptideAtlas; Q9Y6H1; -.
DR PRIDE; Q9Y6H1; -.
DR ProteomicsDB; 86678; -.
DR TopDownProteomics; Q9Y6H1; -.
DR Antibodypedia; 44807; 150 antibodies from 27 providers.
DR DNASU; 51142; -.
DR Ensembl; ENST00000395422.4; ENSP00000378812.3; ENSG00000106153.13.
DR GeneID; 51142; -.
DR KEGG; hsa:51142; -.
DR MANE-Select; ENST00000395422.4; ENSP00000378812.3; NM_016139.4; NP_057223.1.
DR UCSC; uc003tsa.4; human.
DR CTD; 51142; -.
DR DisGeNET; 51142; -.
DR GeneCards; CHCHD2; -.
DR HGNC; HGNC:21645; CHCHD2.
DR HPA; ENSG00000106153; Low tissue specificity.
DR MalaCards; CHCHD2; -.
DR MIM; 616244; gene.
DR MIM; 616710; phenotype.
DR neXtProt; NX_Q9Y6H1; -.
DR OpenTargets; ENSG00000106153; -.
DR PharmGKB; PA134974636; -.
DR VEuPathDB; HostDB:ENSG00000106153; -.
DR eggNOG; KOG4090; Eukaryota.
DR GeneTree; ENSGT00440000038159; -.
DR HOGENOM; CLU_093520_2_2_1; -.
DR InParanoid; Q9Y6H1; -.
DR OMA; CDADARN; -.
DR OrthoDB; 1611117at2759; -.
DR PhylomeDB; Q9Y6H1; -.
DR TreeFam; TF318060; -.
DR PathwayCommons; Q9Y6H1; -.
DR Reactome; R-HSA-1268020; Mitochondrial protein import.
DR SignaLink; Q9Y6H1; -.
DR BioGRID-ORCS; 51142; 116 hits in 1078 CRISPR screens.
DR ChiTaRS; CHCHD2; human.
DR GenomeRNAi; 51142; -.
DR Pharos; Q9Y6H1; Tbio.
DR PRO; PR:Q9Y6H1; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9Y6H1; protein.
DR Bgee; ENSG00000106153; Expressed in right adrenal gland cortex and 144 other tissues.
DR Genevisible; Q9Y6H1; HS.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IDA:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; IGI:FlyBase.
DR GO; GO:0007005; P:mitochondrion organization; IBA:GO_Central.
DR GO; GO:1905448; P:positive regulation of mitochondrial ATP synthesis coupled electron transport; IGI:FlyBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:1900037; P:regulation of cellular response to hypoxia; IDA:UniProtKB.
DR InterPro; IPR010625; CHCH.
DR Pfam; PF06747; CHCH; 1.
DR PROSITE; PS51808; CHCH; 1.
PE 1: Evidence at protein level;
KW Activator; Disulfide bond; Mitochondrion; Neurodegeneration; Nucleus;
KW Parkinson disease; Parkinsonism; Reference proteome; Transcription.
FT CHAIN 1..151
FT /note="Coiled-coil-helix-coiled-coil-helix domain-
FT containing protein 2"
FT /id="PRO_0000129160"
FT DOMAIN 111..151
FT /note="CHCH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 77..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 114..124
FT /note="Cx9C motif 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150"
FT MOTIF 134..144
FT /note="Cx9C motif 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150"
FT DISULFID 114..144
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150"
FT DISULFID 124..134
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150"
FT VARIANT 2
FT /note="P -> L (may influence risk for Lewy body disorders;
FT dbSNP:rs142444896)"
FT /evidence="ECO:0000269|PubMed:26561290"
FT /id="VAR_076293"
FT VARIANT 4
FT /note="G -> R (may influence risk for Lewy body disorders;
FT dbSNP:rs778328496)"
FT /evidence="ECO:0000269|PubMed:26561290"
FT /id="VAR_076294"
FT VARIANT 14
FT /note="P -> S (may influence risk for Lewy body disorders;
FT dbSNP:rs137965562)"
FT /evidence="ECO:0000269|PubMed:26561290"
FT /id="VAR_076295"
FT VARIANT 34
FT /note="P -> L (may influence risk for Lewy body disorders;
FT dbSNP:rs371198317)"
FT /evidence="ECO:0000269|PubMed:26561290"
FT /id="VAR_076296"
FT VARIANT 37
FT /note="A -> V (may influence risk for Lewy body disorders;
FT dbSNP:rs1427631250)"
FT /evidence="ECO:0000269|PubMed:26561290"
FT /id="VAR_076297"
FT VARIANT 49
FT /note="A -> V (may influence risk for Lewy body disorders;
FT dbSNP:rs151213700)"
FT /evidence="ECO:0000269|PubMed:26561290"
FT /id="VAR_076298"
FT VARIANT 61
FT /note="T -> I (in PARK22; does not affect subcellular
FT location; dbSNP:rs864309650)"
FT /evidence="ECO:0000269|PubMed:25662902"
FT /id="VAR_076299"
FT VARIANT 78
FT /note="H -> N (in dbSNP:rs11546418)"
FT /id="VAR_048699"
FT VARIANT 93
FT /note="A -> V (may influence risk for Lewy body disorders;
FT dbSNP:rs748182315)"
FT /evidence="ECO:0000269|PubMed:26561290"
FT /id="VAR_076300"
FT VARIANT 145
FT /note="R -> Q (in PARK22; unknown pathological
FT significance; does not affect subcellular location;
FT dbSNP:rs752169833)"
FT /evidence="ECO:0000269|PubMed:25662902"
FT /id="VAR_076301"
FT CONFLICT 54
FT /note="G -> V (in Ref. 5; AAH66331)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 151 AA; 15513 MW; 5403662D8DB4FB86 CRC64;
MPRGSRSRTS RMAPPASRAP QMRAAPRPAP VAQPPAAAPP SAVGSSAAAP RQPGLMAQMA
TTAAGVAVGS AVGHTLGHAI TGGFSGGSNA EPARPDITYQ EPQGTQPAQQ QQPCLYEIKQ
FLECAQNQGD IKLCEGFNEV LKQCRLANGL A
