HSCB HscB mitochondrial iron-sulfur cluster cochaperone [Homo sapiens (human)] - Gene

Summary

Official Symbol: HSCBprovided by HGNC
Official Full Name: HscB mitochondrial iron-sulfur cluster cochaperoneprovided by HGNC
Primary source: HGNC:HGNC:28913
See related: Ensembl:ENSG00000100209 MIM:608142; AllianceGenome:HGNC:28913
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: JAC1; HSC20; SIDBA5; DNAJC20
Summary: This gene encodes a DnaJ-type co-chaperone and member of the heat shock cognate B (HscB) family of proteins. The encoded protein plays a role in the synthesis of iron-sulfur clusters, protein cofactors that are involved in the redox reactions of mitochondrial electron transport and other processes. Cells in which this gene is knocked down exhibit reduced activity of iron-sulfur cluster-dependent enzymes including succinate dehydrogenase and aconitase. The encoded protein may stimulate the ATPase activity of the mitochondrial stress-70 protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
Expression: Ubiquitous expression in ovary (RPKM 4.7), prostate (RPKM 4.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 22q12.1

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (28742032..28757510)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (29203667..29219144)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (29138020..29153498)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

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?

PI3K/HSCB axis facilitates FOG1 nuclear translocation to promote erythropoiesis and megakaryopoiesis.
Title: PI3K/HSCB axis facilitates FOG1 nuclear translocation to promote erythropoiesis and megakaryopoiesis.
Structural characterization of the human DjC20/HscB cochaperone in solution.
Title: Structural characterization of the human DjC20/HscB cochaperone in solution.
Cytosolic HSC20 is indispensable for cytoplasmic Fe-S assembly and delivery, which is initiated de novo in the cytosol.
Title: Cytosolic HSC20 integrates de novo iron-sulfur cluster biogenesis with the CIAO1-mediated transfer to recipients.
Nfu is shown to bind to both chaperone proteins with binding affinities similar to those observed for IscU binding to the homologous HSPA9 and Hsc20, while Nfu can also stimulate the ATPase activity of HSPA9
Title: Regulation of human Nfu activity in Fe-S cluster delivery-characterization of the interaction between Nfu and the HSPA9/Hsc20 chaperone complex.
The delivery of assembled Fe-S clusters to recipient proteins is a crucial step in the biogenesis of Fe-S proteins; review focuses on recent insights into the molecular mechanism of amino acid motif recognition and discrimination by the co-chaperone HSC20 and finds co-chaperone HSC20 binds to LYR motifs present in Fe-S recipient proteins or their binding partners. [Review]
Title: Mammalian Fe-S proteins: definition of a consensus motif recognized by the co-chaperone HSC20.
the crucial role of HSC20 in the assembly of the mitochondrial respiratory chain, is reported.
Title: A Single Adaptable Cochaperone-Scaffold Complex Delivers Nascent Iron-Sulfur Clusters to Mammalian Respiratory Chain Complexes I-III.
NFS1 binds preferentially to the D-state of ISCU while mtHSP70 binds preferentially to the D-state of ISCU and HSC20 binds preferentially to the S-state of ISCU.
Title: Human mitochondrial chaperone (mtHSP70) and cysteine desulfurase (NFS1) bind preferentially to the disordered conformation, whereas co-chaperone (HSC20) binds to the structured conformation of the iron-sulfur cluster scaffold protein (ISCU).
A cysteine-rich N-terminal domain, which clearly distinguishes hHSC20 from the specialized DnaJ type III proteins of fungi and most bacteria, was found to be important for the integrity and function of the human co-chaperone.
Title: Characterization of the human HSC20, an unusual DnaJ type III protein, involved in iron-sulfur cluster biogenesis.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
structural analysis of human J-type co-chaperone HscB reveals a tetracysteine metal-binding domain
Title: Structure of human J-type co-chaperone HscB reveals a tetracysteine metal-binding domain.

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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
Anemia, sideroblastic, 5 MedGen: C5561985 OMIM: 619523 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. 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

PMC111029P1 (e-PCR)
- UniSTS:270202

G32810 (e-PCR)
- UniSTS:117389

RH17891 (e-PCR)
- UniSTS:48546

NoName (e-PCR)
- UniSTS:483530

A009S23 (e-PCR)
- UniSTS:8144

stdJ366L4.X.6856 (e-PCR)
- UniSTS:181735

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATPase activator activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables molecular_function	ND No biological Data available more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-folding chaperone binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in [2Fe-2S] cluster assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in iron-sulfur cluster assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in primitive erythrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in primitive hemopoiesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein complex oligomerization	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in mitochondrion	HTP more info	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
located_in mitochondrion	TAS Traceable Author Statement more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: iron-sulfur cluster co-chaperone protein HscB

Names: DnaJ (Hsp40) homolog, subfamily C, member 20; HscB iron-sulfur cluster co-chaperone homolog; HscB mitochondrial iron-sulfur cluster co-chaperone; J-type co-chaperone HSC20; epididymis secretory sperm binding protein; iron-sulfur cluster co-chaperone protein HscB, mitochondrial

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.

mRNA and Protein(s)

NM_001318314.2 → NP_001305243.1 iron-sulfur cluster co-chaperone protein HscB isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate exon in the 3' coding region, which results in a frameshift and an early stop codon compared to variant 1. The encoded isoform (2) contains a shorter and distinct C-terminus compared to isoform 1.

Source sequence(s)

BC000004, CR979598

Conserved Domains (2) summary

PRK05014
Location:72 → 142

hscB; co-chaperone HscB; Provisional

pfam18256
Location:39 → 65

HscB_4_cys; Co-chaperone HscB tetracysteine metal binding motif
NM_001318315.2 → NP_001305244.1 iron-sulfur cluster co-chaperone protein HscB isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice site and lacks an alternate exon in the 3' coding region, which results in a frameshift and an early stop codon compared to variant 1. The encoded isoform (3) contains a shorter and distinct C-terminus compared to isoform 1. Variants 3 and 6 both encode the same isoform (3).

Source sequence(s)

BC000004, BQ054405

Consensus CDS

CCDS82704.1

UniProtKB/TrEMBL

A8MYY2, B0QYH2

Related

ENSP00000381914.2, ENST00000398941.6

Conserved Domains (2) summary

PRK05014
Location:72 → 143

hscB; co-chaperone HscB; Provisional

pfam18256
Location:39 → 65

HscB_4_cys; Co-chaperone HscB tetracysteine metal binding motif
NM_001318316.2 → NP_001305245.1 iron-sulfur cluster co-chaperone protein HscB isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon compared to variant 1. The encoded isoform (4) has a shorter N-terminus and lacks a predicted mitochondrial transit peptide compared to isoform 1.

Source sequence(s)

BC000004, DW414316, HY057929

Related

ENST00000495977.1

Conserved Domains (1) summary

pfam07743
Location:1 → 73

HSCB_C; HSCB C-terminal oligomerization domain
NM_001363856.1 → NP_001350785.1 iron-sulfur cluster co-chaperone protein HscB isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (6) differs in the 3' UTR and coding sequence compared to variant 1. The resulting isoform (3) has a shorter and distinct C-terminus compared to isoform 1. Variants 3 and 6 both encode the same isoform (3).

Source sequence(s)

AL117330

Consensus CDS

CCDS87014.1

UniProtKB/TrEMBL

A8MYY2, B0QYH2

Related

ENSP00000416679.1, ENST00000420442.5

Conserved Domains (2) summary

PRK05014
Location:72 → 143

hscB; co-chaperone HscB; Provisional

pfam18256
Location:39 → 65

HscB_4_cys; Co-chaperone HscB tetracysteine metal binding motif
NM_172002.5 → NP_741999.3 iron-sulfur cluster co-chaperone protein HscB isoform 1 precursor

See identical proteins and their annotated locations for NP_741999.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

BC000004

Consensus CDS

CCDS13845.1

UniProtKB/Swiss-Prot

Q8IWL3, Q9BWS7

UniProtKB/TrEMBL

A0A384NYJ4

Related

ENSP00000216027.3, ENST00000216027.8

Conserved Domains (1) summary

cl26852
Location:72 → 221

HSCB_C; HSCB C-terminal oligomerization domain

RNA

NR_134560.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses an alternate splice site in an internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

BC000004, BG696148

Related

ENST00000450178.5

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

NC_000022.11 Reference GRCh38.p14 Primary Assembly

Range

28742032..28757510

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005261359.5 → XP_005261416.1 iron-sulfur cluster co-chaperone protein HscB isoform X1

Conserved Domains (1) summary

PRK05014
Location:70 → 209

hscB; co-chaperone HscB; Provisional
XM_017028620.3 → XP_016884109.1 iron-sulfur cluster co-chaperone protein HscB isoform X2

Conserved Domains (1) summary

pfam07743
Location:1 → 73

HSCB_C; HSCB C-terminal oligomerization domain

Alternate T2T-CHM13v2.0

Genomic

NC_060946.1 Alternate T2T-CHM13v2.0

Range

29203667..29219144

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054325129.1 → XP_054181104.1 iron-sulfur cluster co-chaperone protein HscB isoform X1
XM_054325130.1 → XP_054181105.1 iron-sulfur cluster co-chaperone protein HscB isoform X2