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 25-APR-2018, entry version 124. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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- RT structural 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., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA 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., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., 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 RT project: 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., 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 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 RT CHCHD2."; RL Nucleic Acids Res. 41:2255-2266(2013). RN [8] RP SUBCELLULAR LOCATION, INVOLVEMENT IN PARK22, VARIANTS PARK22 ILE-61 RP AND GLN-145, AND CHARACTERIZATION OF VARIANTS PARK22 ILE-61 AND RP 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 RT disease: a 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., RA Ayoub D., 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., RA Siuda J., Opala G., Rudzinska M., Krygowska-Wajs A., Barcikowska M., RA Czyzewski K., Puschmann A., Nishioka K., Funayama M., Hattori N., RA Parisi J.E., Petersen R.C., Graff-Radford N.R., Boeve B.F., RA Springer W., Wszolek Z.K., Dickson D.W., Ross O.A.; RT "Mitochondrial targeting sequence variants of the CHCHD2 gene are a RT risk for Lewy body disorders."; RL Neurology 85:2016-2025(2015). CC -!- FUNCTION: Transcription factor. Binds to the oxygen responsive CC element of COX4I2 and activates its transcription under hypoxia CC conditions (4% oxygen), as well as normoxia conditions (20% CC oxygen) (PubMed:23303788). {ECO:0000269|PubMed:23303788}. CC -!- SUBUNIT: Interacts with RBPJ. {ECO:0000269|PubMed:23303788}. CC -!- INTERACTION: CC Q6UY14-3:ADAMTSL4; NbExp=3; IntAct=EBI-2321769, EBI-10173507; CC P05813:CRYBA1; NbExp=4; IntAct=EBI-2321769, EBI-7043337; CC A2ABF9:EHMT2; NbExp=3; IntAct=EBI-2321769, EBI-10174566; CC Q08379:GOLGA2; NbExp=5; IntAct=EBI-2321769, EBI-618309; CC Q9UKT9:IKZF3; NbExp=3; IntAct=EBI-2321769, EBI-747204; CC Q0VD86:INCA1; NbExp=3; IntAct=EBI-2321769, EBI-6509505; CC Q15323:KRT31; NbExp=3; IntAct=EBI-2321769, EBI-948001; CC Q6A162:KRT40; NbExp=3; IntAct=EBI-2321769, EBI-10171697; CC Q969G2:LHX4; NbExp=3; IntAct=EBI-2321769, EBI-2865388; CC O43482:OIP5; NbExp=4; IntAct=EBI-2321769, EBI-536879; CC Q04864:REL; NbExp=3; IntAct=EBI-2321769, EBI-307352; CC P15884:TCF4; NbExp=3; IntAct=EBI-2321769, EBI-533224; CC Q9BYV2:TRIM54; NbExp=3; IntAct=EBI-2321769, EBI-2130429; 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 localised in the intermembrane space. CC {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 CC ethnic origin. {ECO:0000269|PubMed:26067113, CC 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 CC involves the loss of dopaminergic neurons in the substantia nigra CC and the presence of Lewy bodies (intraneuronal accumulations of CC aggregated proteins), in surviving neurons in various areas of the CC brain. {ECO:0000269|PubMed:25662902}. Note=The gene represented in CC this entry may be involved in disease pathogenesis. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 UniGene; Hs.389996; -. DR UniGene; Hs.547257; -. DR ProteinModelPortal; Q9Y6H1; -. DR SMR; Q9Y6H1; -. DR BioGrid; 119326; 146. DR IntAct; Q9Y6H1; 36. DR MINT; Q9Y6H1; -. DR STRING; 9606.ENSP00000378812; -. DR iPTMnet; Q9Y6H1; -. DR PhosphoSitePlus; Q9Y6H1; -. DR BioMuta; CHCHD2; -. DR DMDM; 62510521; -. DR EPD; Q9Y6H1; -. DR MaxQB; Q9Y6H1; -. DR PaxDb; Q9Y6H1; -. DR PeptideAtlas; Q9Y6H1; -. DR PRIDE; Q9Y6H1; -. DR TopDownProteomics; Q9Y6H1; -. DR DNASU; 51142; -. DR Ensembl; ENST00000395422; ENSP00000378812; ENSG00000106153. DR GeneID; 51142; -. DR KEGG; hsa:51142; -. DR UCSC; uc003tsa.4; human. DR CTD; 51142; -. DR DisGeNET; 51142; -. DR EuPathDB; HostDB:ENSG00000106153.12; -. DR GeneCards; CHCHD2; -. DR HGNC; HGNC:21645; CHCHD2. DR HPA; HPA027407; -. DR HPA; HPA052510; -. DR MalaCards; CHCHD2; -. DR MIM; 616244; gene. DR MIM; 616710; phenotype. DR neXtProt; NX_Q9Y6H1; -. DR OpenTargets; ENSG00000106153; -. DR PharmGKB; PA134974636; -. DR eggNOG; KOG4090; Eukaryota. DR eggNOG; ENOG41126E7; LUCA. DR GeneTree; ENSGT00440000038159; -. DR HOGENOM; HOG000194088; -. DR HOVERGEN; HBG059852; -. DR InParanoid; Q9Y6H1; -. DR OMA; ICNWYLE; -. DR OrthoDB; EOG091G114W; -. DR PhylomeDB; Q9Y6H1; -. DR TreeFam; TF318060; -. DR Reactome; R-HSA-1268020; Mitochondrial protein import. DR ChiTaRS; CHCHD2; human. DR GenomeRNAi; 51142; -. DR PRO; PR:Q9Y6H1; -. DR Proteomes; UP000005640; Chromosome 7. DR Bgee; ENSG00000106153; -. DR CleanEx; HS_CHCHD2; -. 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:0043565; F:sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB. DR GO; GO:0007005; P:mitochondrion organization; IBA:GO_Central. 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 GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR InterPro; IPR010625; CHCH. DR Pfam; PF06747; CHCH; 1. DR PROSITE; PS51808; CHCH; 1. PE 1: Evidence at protein level; KW Activator; Complete proteome; Disulfide bond; Mitochondrion; KW Neurodegeneration; Nucleus; Parkinson disease; Parkinsonism; KW Polymorphism; Reference proteome; Transcription. FT CHAIN 1 151 Coiled-coil-helix-coiled-coil-helix FT domain-containing protein 2. FT /FTId=PRO_0000129160. FT DOMAIN 111 151 CHCH. {ECO:0000255|PROSITE- FT ProRule:PRU01150}. FT MOTIF 114 124 Cx9C motif 1. {ECO:0000255|PROSITE- FT ProRule:PRU01150}. FT MOTIF 134 144 Cx9C motif 2. {ECO:0000255|PROSITE- FT ProRule:PRU01150}. FT DISULFID 114 144 {ECO:0000255|PROSITE-ProRule:PRU01150}. FT DISULFID 124 134 {ECO:0000255|PROSITE-ProRule:PRU01150}. FT VARIANT 2 2 P -> L (rare polymorphism; may influence FT risk for Lewy body disorders; FT dbSNP:rs142444896). FT {ECO:0000269|PubMed:26561290}. FT /FTId=VAR_076293. FT VARIANT 4 4 G -> R (rare polymorphism; may influence FT risk for Lewy body disorders; FT dbSNP:rs778328496). FT {ECO:0000269|PubMed:26561290}. FT /FTId=VAR_076294. FT VARIANT 14 14 P -> S (rare polymorphism; may influence FT risk for Lewy body disorders; FT dbSNP:rs137965562). FT {ECO:0000269|PubMed:26561290}. FT /FTId=VAR_076295. FT VARIANT 34 34 P -> L (rare polymorphism; may influence FT risk for Lewy body disorders; FT dbSNP:rs371198317). FT {ECO:0000269|PubMed:26561290}. FT /FTId=VAR_076296. FT VARIANT 37 37 A -> V (rare polymorphism; may influence FT risk for Lewy body disorders). FT {ECO:0000269|PubMed:26561290}. FT /FTId=VAR_076297. FT VARIANT 49 49 A -> V (rare polymorphism; may influence FT risk for Lewy body disorders; FT dbSNP:rs151213700). FT {ECO:0000269|PubMed:26561290}. FT /FTId=VAR_076298. FT VARIANT 61 61 T -> I (in PARK22; does not affect FT subcellular location; dbSNP:rs864309650). FT {ECO:0000269|PubMed:25662902}. FT /FTId=VAR_076299. FT VARIANT 78 78 H -> N (in dbSNP:rs11546418). FT /FTId=VAR_048699. FT VARIANT 93 93 A -> V (rare polymorphism; may influence FT risk for Lewy body disorders; FT dbSNP:rs748182315). FT {ECO:0000269|PubMed:26561290}. FT /FTId=VAR_076300. FT VARIANT 145 145 R -> Q (in PARK22; unknown pathological FT significance; does not affect subcellular FT location; dbSNP:rs752169833). FT {ECO:0000269|PubMed:25662902}. FT /FTId=VAR_076301. FT CONFLICT 54 54 G -> V (in Ref. 5; AAH66331). FT {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 //