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    HCCS holocytochrome c synthase [ Homo sapiens (human) ]

    Gene ID: 3052, updated on 27-Nov-2024

    Summary

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    Official Symbol
    HCCSprovided by HGNC
    Official Full Name
    holocytochrome c synthaseprovided by HGNC
    Primary source
    HGNC:HGNC:4837
    See related
    Ensembl:ENSG00000004961 MIM:300056; AllianceGenome:HGNC:4837
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MLS; CCHL; MCOPS7; LSDMCA1
    Summary
    The protein encoded by this gene is an enzyme that covalently links a heme group to the apoprotein of cytochrome c. Defects in this gene are a cause of microphthalmia syndromic type 7 (MCOPS7). Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jan 2010]
    Expression
    Ubiquitous expression in heart (RPKM 12.9), colon (RPKM 8.9) and 25 other tissues See more
    Orthologs
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    Genomic context

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    See HCCS in Genome Data Viewer
    Location:
    Xp22.2
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (11111332..11123086)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (10693810..10705564)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (11129452..11141206)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124905244 Neighboring gene HCCS divergent transcript Neighboring gene Sharpr-MPRA regulatory region 6238 Neighboring gene uncharacterized LOC124905243 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:11025249-11025760 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29409 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29410 Neighboring gene Rho GTPase activating protein 6 Neighboring gene Sharpr-MPRA regulatory region 12683 Neighboring gene FAM9C pseudogene 1 Neighboring gene NANOG hESC enhancer GRCh37_chrX:11323088-11323736 Neighboring gene amelogenin X-linked

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. The genes for X-linked ocular albinism (OA1) and microphthalmia with linear skin defects (MLS): cloning and characterization of the critical regions. Wapenaar MC, et al. Hum Mol Genet, 1993 Jul. PMID 8364577
    2. Molecular Basis Behind Inability of Mitochondrial Holocytochrome c Synthase to Mature Bacterial Cytochromes: DEFINING A CRITICAL ROLE FOR CYTOCHROME c α HELIX-1. Babbitt SE, et al. J Biol Chem, 2016 Aug 19. PMID 27387500, Free PMC Article
    3. Conserved residues of the human mitochondrial holocytochrome c synthase mediate interactions with heme. Babbitt SE, et al. Biochemistry, 2014 Aug 19. PMID 25054239, Free PMC Article
    4. Familial cases of a submicroscopic Xp22.2 deletion: genotype-phenotype correlation in microphthalmia with linear skin defects syndrome. Vergult S, et al. Mol Vis, 2013. PMID 23401659, Free PMC Article
    5. Mechanisms of mitochondrial holocytochrome c synthase and the key roles played by cysteines and histidine of the heme attachment site, Cys-XX-Cys-His. Babbitt SE, et al. J Biol Chem, 2014 Oct 17. PMID 25170082, Free PMC Article

    See all (62) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The implication of holocytochrome c synthase mutation in Korean familial hypoplastic amelogenesis imperfecta.
      Title: The implication of holocytochrome c synthase mutation in Korean familial hypoplastic amelogenesis imperfecta.
    2. Data suggest that although HCCS mediates heme attachment to N-terminal cysteine in heme-attachment site (CXXXH) of cytochrome C variants, up to 50% of cytochrome C produced is modified in an oxygen-dependent manner, resulting in a mixed population of cytochrome c. [HCCS = holocytochrome c synthase]
      Title: Biosynthesis of Single Thioether c-Type Cytochromes Provides Insight into Mechanisms Intrinsic to Holocytochrome c Synthase (HCCS).
    3. Bacterial cyt c biogenesis pathways (Systems I and II) appear to recognize simply the CXXCH motif, not requiring alpha helix-1. Results here explain mechanistically how HCCS (System III) requires an extended region adjacent to CXXCH for maturation.
      Title: Molecular Basis Behind Inability of Mitochondrial Holocytochrome c Synthase to Mature Bacterial Cytochromes: DEFINING A CRITICAL ROLE FOR CYTOCHROME c α HELIX-1.
    4. cysteines and histidine of the heme attachment site, Cys-XX-Cys-His play a key role in mitochondrial holocytochrome c synthase
      Title: Mechanisms of mitochondrial holocytochrome c synthase and the key roles played by cysteines and histidine of the heme attachment site, Cys-XX-Cys-His.
    5. These data indicate that heme contacts mediated by residues within these domains modulate the dynamics of heme binding and contribute to the stability of the HCCS-heme-cytochrome c steady state ternary complex.
      Title: Conserved residues of the human mitochondrial holocytochrome c synthase mediate interactions with heme.
    6. Identification of a deletion in two patients, including HCCS, leads to the diagnosis of microphthalmia with linear skin defects syndrome
      Title: Familial cases of a submicroscopic Xp22.2 deletion: genotype-phenotype correlation in microphthalmia with linear skin defects syndrome.
    7. Spectroscopic analyses of HCCS alone and complexes of HCCS with site-directed variants of cytochrome c revealed the fundamental steps of heme attachment and maturation.
      Title: Human mitochondrial holocytochrome c synthase's heme binding, maturation determinants, and complex formation with cytochrome c.
    8. Missense mutation p.E159K of HCCS, leading to loss-of-function of encoded holocytochrome c-type synthase, in female with microphthalmia of both eyes and bilateral sclerocornea may suggest HCCS as candidate for severe ocular manifestations.
      Title: HCCS loss-of-function missense mutation in a female with bilateral microphthalmia and sclerocornea: a novel gene for severe ocular malformations?
    9. mutant proteins (R217C and Delta 197-268) were unable to complement a Saccharomyces cerevisiae mutant deficient for the HCCS orthologue Cyc3p, in contrast to wild-type HCCS
      Title: Mutations of the mitochondrial holocytochrome c-type synthase in X-linked dominant microphthalmia with linear skin defects syndrome.
    10. Through the study of genetically engineered mice, the loss of HCCS is demonstrated to cause the male lethality of microphthalmia with linear skin defects (MLS) syndrome.
      Title: Loss of holocytochrome c-type synthetase causes the male lethality of X-linked dominant microphthalmia with linear skin defects (MLS) syndrome.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • DKFZp779I1858

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables heme binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables holocytochrome-c synthase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables holocytochrome-c synthase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables holocytochrome-c synthase activity TAS
    Traceable Author Statement
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in animal organ morphogenesis TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in cytochrome c-heme linkage IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in respiratory electron transport chain TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial inner membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    holocytochrome c-type synthase
    Names
    cytochrome c heme-lyase
    cytochrome c-type heme lyase
    holocytochrome-c synthetase
    microphthalamia with linear skin defects
    microphthalmia with linear skin defects
    NP_001116080.1
    NP_001165462.1
    NP_005324.3

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_016460.1 RefSeqGene

      Range
      5038..16792
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001122608.3 → NP_001116080.1  holocytochrome c-type synthase

      See identical proteins and their annotated locations for NP_001116080.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein.
      Source sequence(s)
      AI027533, AK097815
      Consensus CDS
      CCDS14139.1
      UniProtKB/Swiss-Prot
      B3KUS1, P53701, Q502X8
      UniProtKB/TrEMBL
      Q68D50
      Related
      ENSP00000326579.4, ENST00000321143.8
      Conserved Domains (1) summary
      pfam01265
      Location:4 → 266
      Cyto_heme_lyase; Cytochrome c/c1 heme lyase

    2. NM_001171991.3 → NP_001165462.1  holocytochrome c-type synthase

      See identical proteins and their annotated locations for NP_001165462.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein.
      Source sequence(s)
      AI027533, BC001691, BC095455, DB253108
      Consensus CDS
      CCDS14139.1
      UniProtKB/Swiss-Prot
      B3KUS1, P53701, Q502X8
      UniProtKB/TrEMBL
      Q68D50
      Related
      ENSP00000370140.3, ENST00000380763.7
      Conserved Domains (1) summary
      pfam01265
      Location:4 → 266
      Cyto_heme_lyase; Cytochrome c/c1 heme lyase

    3. NM_005333.5 → NP_005324.3  holocytochrome c-type synthase

      See identical proteins and their annotated locations for NP_005324.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2 and 3 encode the same protein.
      Source sequence(s)
      AI027533, BC095455, DB253108
      Consensus CDS
      CCDS14139.1
      UniProtKB/Swiss-Prot
      B3KUS1, P53701, Q502X8
      UniProtKB/TrEMBL
      Q68D50
      Related
      ENSP00000370139.4, ENST00000380762.5
      Conserved Domains (1) summary
      pfam01265
      Location:4 → 266
      Cyto_heme_lyase; Cytochrome c/c1 heme lyase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      11111332..11123086
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      10693810..10705564
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P53701.1 GenPept UniProtKB/Swiss-Prot:P53701

    Gene LinkOut

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