CCHL_HUMAN
ID CCHL_HUMAN Reviewed; 268 AA.
AC P53701; B3KUS1; Q502X8;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Holocytochrome c-type synthase {ECO:0000305|PubMed:23150584, ECO:0000305|PubMed:8661044};
DE EC=4.4.1.17 {ECO:0000269|PubMed:23150584};
DE AltName: Full=Cytochrome c-type heme lyase {ECO:0000305|PubMed:23150584};
GN Name=HCCS {ECO:0000312|HGNC:HGNC:4837}; Synonyms=CCHL;
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].
RX PubMed=8661044; DOI=10.1006/geno.1996.0261;
RA Schaefer L., Ballabio A., Zoghbi H.Y.;
RT "Cloning and characterization of a putative human holocytochrome c-type
RT synthetase gene (HCCS) isolated from the critical region for microphthalmia
RT with linear skin defects (MLS).";
RL Genomics 34:166-172(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9674913;
RX DOI=10.1002/(sici)1096-8628(19980630)78:2<179::aid-ajmg17>3.3.co;2-3;
RA van den Veyver I.B., Subramanian S., Zoghbi H.Y.;
RT "Genomic structure of a human holocytochrome c-type synthetase gene in
RT Xp22.3 and mutation analysis in patients with Rett syndrome.";
RL Am. J. Med. Genet. 78:179-181(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Ovary;
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, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP HIS-154 AND HIS-211.
RX PubMed=23150584; DOI=10.1073/pnas.1213897109;
RA San Francisco B., Bretsnyder E.C., Kranz R.G.;
RT "Human mitochondrial holocytochrome c synthase's heme binding, maturation
RT determinants, and complex formation with cytochrome c.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E788-E797(2013).
RN [8]
RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=25255805; DOI=10.1038/ncomms5919;
RA Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., Wright M.H.,
RA Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.;
RT "Global profiling of co- and post-translationally N-myristoylated proteomes
RT in human cells.";
RL Nat. Commun. 5:4919-4919(2014).
RN [9]
RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=25807930; DOI=10.1002/anie.201500342;
RA Broncel M., Serwa R.A., Ciepla P., Krause E., Dallman M.J., Magee A.I.,
RA Tate E.W.;
RT "Multifunctional reagents for quantitative proteome-wide analysis of
RT protein modification in human cells and dynamic profiling of protein
RT lipidation during vertebrate development.";
RL Angew. Chem. Int. Ed. 54:5948-5951(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 LSDMCA1 197-ARG--SER-268 DEL AND CYS-217, CHARACTERIZATION OF
RP VARIANTS LSDMCA1 197-ARG--SER-268 DEL AND CYS-217, AND SUBCELLULAR
RP LOCATION.
RX PubMed=17033964; DOI=10.1086/508474;
RA Wimplinger I., Morleo M., Rosenberger G., Iaconis D., Orth U., Meinecke P.,
RA Lerer I., Ballabio A., Gal A., Franco B., Kutsche K.;
RT "Mutations of the mitochondrial holocytochrome c-type synthase in X-linked
RT dominant microphthalmia with linear skin defects syndrome.";
RL Am. J. Hum. Genet. 79:878-889(2006).
CC -!- FUNCTION: Lyase that catalyzes the covalent linking of the heme group
CC to the cytochrome C apoprotein to produce the mature functional
CC cytochrome. {ECO:0000269|PubMed:23150584}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=holo-[cytochrome c] = apo-[cytochrome c] + heme b;
CC Xref=Rhea:RHEA:22648, Rhea:RHEA-COMP:10725, Rhea:RHEA-COMP:10726,
CC ChEBI:CHEBI:29950, ChEBI:CHEBI:60344, ChEBI:CHEBI:83739; EC=4.4.1.17;
CC Evidence={ECO:0000269|PubMed:23150584};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22650;
CC Evidence={ECO:0000305|PubMed:23150584};
CC -!- INTERACTION:
CC P53701; P06307: CCK; NbExp=3; IntAct=EBI-10763431, EBI-6624398;
CC P53701; Q9UHD4: CIDEB; NbExp=3; IntAct=EBI-10763431, EBI-7062247;
CC P53701; Q9HC62: SENP2; NbExp=3; IntAct=EBI-10763431, EBI-714881;
CC P53701; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-10763431, EBI-2623095;
CC P53701; Q13596: SNX1; NbExp=3; IntAct=EBI-10763431, EBI-2822329;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000305|PubMed:17033964}. Membrane {ECO:0000269|PubMed:23150584};
CC Lipid-anchor {ECO:0000305|PubMed:25255805,
CC ECO:0000305|PubMed:25807930}.
CC -!- DISEASE: Linear skin defects with multiple congenital anomalies 1
CC (LSDMCA1) [MIM:309801]: A disorder characterized by dermal, ocular,
CC neurological and cardiac abnormalities. LSDMCA1 main features are
CC unilateral or bilateral microphthalmia, linear skin defects in affected
CC females, and in utero lethality for males. Skin defects are limited to
CC the face and neck, consisting of areas of aplastic skin that heal with
CC age to form hyperpigmented areas. Additional features in female
CC patients include agenesis of the corpus callosum, sclerocornea,
CC chorioretinal abnormalities, infantile seizures, congenital heart
CC defect, intellectual disability, and diaphragmatic hernia.
CC Microphthalmia is a disorder of eye formation, ranging from small size
CC of a single eye to complete bilateral absence of ocular tissues
CC (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in
CC association with syndromes that include non-ocular abnormalities.
CC {ECO:0000269|PubMed:17033964}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the cytochrome c-type heme lyase family.
CC {ECO:0000305}.
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DR EMBL; U36787; AAB19007.1; -; mRNA.
DR EMBL; AF053015; AAC35274.1; -; Genomic_DNA.
DR EMBL; AF053010; AAC35274.1; JOINED; Genomic_DNA.
DR EMBL; AF053011; AAC35274.1; JOINED; Genomic_DNA.
DR EMBL; AF053012; AAC35274.1; JOINED; Genomic_DNA.
DR EMBL; AF053013; AAC35274.1; JOINED; Genomic_DNA.
DR EMBL; AF053014; AAC35274.1; JOINED; Genomic_DNA.
DR EMBL; AK097815; BAG53533.1; -; mRNA.
DR EMBL; CH471074; EAW98783.1; -; Genomic_DNA.
DR EMBL; BC001691; AAH01691.1; -; mRNA.
DR EMBL; BC095455; AAH95455.1; -; mRNA.
DR CCDS; CCDS14139.1; -.
DR PIR; G02133; G02133.
DR RefSeq; NP_001116080.1; NM_001122608.2.
DR RefSeq; NP_001165462.1; NM_001171991.2.
DR RefSeq; NP_005324.3; NM_005333.4.
DR AlphaFoldDB; P53701; -.
DR BioGRID; 109302; 118.
DR IntAct; P53701; 51.
DR MINT; P53701; -.
DR STRING; 9606.ENSP00000326579; -.
DR GlyGen; P53701; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P53701; -.
DR PhosphoSitePlus; P53701; -.
DR SwissPalm; P53701; -.
DR BioMuta; HCCS; -.
DR DMDM; 1705694; -.
DR EPD; P53701; -.
DR jPOST; P53701; -.
DR MassIVE; P53701; -.
DR MaxQB; P53701; -.
DR PaxDb; P53701; -.
DR PeptideAtlas; P53701; -.
DR PRIDE; P53701; -.
DR ProteomicsDB; 56613; -.
DR Antibodypedia; 479; 316 antibodies from 32 providers.
DR DNASU; 3052; -.
DR Ensembl; ENST00000321143.8; ENSP00000326579.4; ENSG00000004961.15.
DR Ensembl; ENST00000380762.5; ENSP00000370139.4; ENSG00000004961.15.
DR Ensembl; ENST00000380763.7; ENSP00000370140.3; ENSG00000004961.15.
DR GeneID; 3052; -.
DR KEGG; hsa:3052; -.
DR MANE-Select; ENST00000380762.5; ENSP00000370139.4; NM_005333.5; NP_005324.3.
DR UCSC; uc004cuj.4; human.
DR CTD; 3052; -.
DR DisGeNET; 3052; -.
DR GeneCards; HCCS; -.
DR GeneReviews; HCCS; -.
DR HGNC; HGNC:4837; HCCS.
DR HPA; ENSG00000004961; Low tissue specificity.
DR MalaCards; HCCS; -.
DR MIM; 300056; gene.
DR MIM; 309801; phenotype.
DR neXtProt; NX_P53701; -.
DR OpenTargets; ENSG00000004961; -.
DR Orphanet; 2556; Microphthalmia with linear skin defects syndrome.
DR PharmGKB; PA29214; -.
DR VEuPathDB; HostDB:ENSG00000004961; -.
DR eggNOG; KOG3996; Eukaryota.
DR GeneTree; ENSGT00390000004175; -.
DR HOGENOM; CLU_048602_2_1_1; -.
DR InParanoid; P53701; -.
DR OMA; EGAWDEI; -.
DR OrthoDB; 1282808at2759; -.
DR PhylomeDB; P53701; -.
DR TreeFam; TF105185; -.
DR BioCyc; MetaCyc:HS00120-MON; -.
DR BRENDA; 4.4.1.17; 2681.
DR PathwayCommons; P53701; -.
DR SignaLink; P53701; -.
DR BioGRID-ORCS; 3052; 89 hits in 714 CRISPR screens.
DR ChiTaRS; HCCS; human.
DR GeneWiki; HCCS_(gene); -.
DR GenomeRNAi; 3052; -.
DR Pharos; P53701; Tbio.
DR PRO; PR:P53701; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P53701; protein.
DR Bgee; ENSG00000004961; Expressed in skeletal muscle tissue of biceps brachii and 199 other tissues.
DR ExpressionAtlas; P53701; baseline and differential.
DR Genevisible; P53701; HS.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:ProtInc.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0004408; F:holocytochrome-c synthase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc.
DR GO; GO:0018063; P:cytochrome c-heme linkage; IDA:UniProtKB.
DR InterPro; IPR000511; Holocyt_c/c1_synthase.
DR PANTHER; PTHR12743; PTHR12743; 1.
DR Pfam; PF01265; Cyto_heme_lyase; 1.
DR PROSITE; PS00821; CYTO_HEME_LYASE_1; 1.
DR PROSITE; PS00822; CYTO_HEME_LYASE_2; 1.
PE 1: Evidence at protein level;
KW Disease variant; Heme; Iron; Lipoprotein; Lyase; Membrane; Metal-binding;
KW Microphthalmia; Mitochondrion; Mitochondrion inner membrane; Myristate;
KW Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:25255805,
FT ECO:0000269|PubMed:25807930"
FT CHAIN 2..268
FT /note="Holocytochrome c-type synthase"
FT /id="PRO_0000121712"
FT REPEAT 24..29
FT /note="HRM 1"
FT REPEAT 34..39
FT /note="HRM 2"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:25255805,
FT ECO:0000269|PubMed:25807930"
FT VARIANT 197..268
FT /note="Missing (in LSDMCA1; loss of function; loss of
FT localization to mitochondrion)"
FT /evidence="ECO:0000269|PubMed:17033964"
FT /id="VAR_083982"
FT VARIANT 217
FT /note="R -> C (in LSDMCA1; loss of function; no effect on
FT localization to mitochondrion; dbSNP:rs121917889)"
FT /evidence="ECO:0000269|PubMed:17033964"
FT /id="VAR_030823"
FT MUTAGEN 154
FT /note="H->A,G,Y: Loss of holocytochrome C synthase
FT activity. Loss of heme-binding. Loss of interaction with
FT cytochrome C."
FT /evidence="ECO:0000269|PubMed:23150584"
FT MUTAGEN 211
FT /note="H->A,G,C,Y: No effect on holocytochrome C synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:23150584"
SQ SEQUENCE 268 AA; 30602 MW; 8DC4DA47E444B2FB CRC64;
MGLSPSAPAV AVQASNASAS PPSGCPMHEG KMKGCPVNTE PSGPTCEKKT YSVPAHQERA
YEYVECPIRG TAAENKENLD PSNLMPPPNQ TPAPDQPFAL STVREESSIP RADSEKKWVY
PSEQMFWNAM LKKGWKWKDE DISQKDMYNI IRIHNQNNEQ AWKEILKWEA LHAAECPCGP
SLIRFGGKAK EYSPRARIRS WMGYELPFDR HDWIINRCGT EVRYVIDYYD GGEVNKDYQF
TILDVRPALD SLSAVWDRMK VAWWRWTS
