HCCS holocytochrome c synthase [Homo sapiens (human)] - Gene

Summary

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: mouse all
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Genomic context

Location:: Xp22.2

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (11111332..11123086)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (10693810..10705564)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (11129452..11141206)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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).
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.
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.
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.
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.
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.
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?
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.
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

Associated conditions

Description	Tests
Linear skin defects with multiple congenital anomalies 1 MedGen: C0796070 OMIM: 309801 GeneReviews: Microphthalmia with Linear Skin Defects Syndrome	Compare labs

EBI GWAS Catalog

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

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

RH71227 (e-PCR)
- UniSTS:70722

SHGC-78640 (e-PCR)
- UniSTS:102096

RH91114 (e-PCR)
- UniSTS:90365

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 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	IBA Inferred from Biological aspect of Ancestor more info
involved_in cytochrome c-heme linkage	IDA Inferred from Direct Assay more info	PubMed

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	IEA Inferred from Electronic Annotation more info
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

EC 4.4.1.17

NP_001165462.1

EC 4.4.1.17

NP_005324.3

EC 4.4.1.17

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

NG_016460.1 RefSeqGene

Range

5038..16792

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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