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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.
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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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