CLPB ClpB family mitochondrial disaggregase [Homo sapiens (human)] - Gene

Summary

Official Symbol: CLPBprovided by HGNC
Official Full Name: ClpB family mitochondrial disaggregaseprovided by HGNC
Primary source: HGNC:HGNC:30664
See related: Ensembl:ENSG00000162129 MIM:616254; AllianceGenome:HGNC:30664
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: SCN9; SKD3; HSP78; MGCA7; ANKCLB; ANKCLP; MGCA7A; MEGCANN
Summary: This gene belongs to the ATP-ases associated with diverse cellular activities (AAA+) superfamily. Members of this superfamily form ring-shaped homo-hexamers and have highly conserved ATPase domains that are involved in various processes including DNA replication, protein degradation and reactivation of misfolded proteins. All members of this family hydrolyze ATP through their AAA+ domains and use the energy generated through ATP hydrolysis to exert mechanical force on their substrates. In addition to an AAA+ domain, the protein encoded by this gene contains a C-terminal D2 domain, which is characteristic of the AAA+ subfamily of Caseinolytic peptidases to which this protein belongs. It cooperates with Hsp70 in the disaggregation of protein aggregates. Allelic variants of this gene are associated with 3-methylglutaconic aciduria, which causes cataracts and neutropenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
Expression: Biased expression in testis (RPKM 59.2), brain (RPKM 5.3) and 5 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q13.4

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (72285495..72434531, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (72211988..72361006, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (71996539..72145575, complement)

Chromosome 11 - NC_000011.10 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

CLPB disaggregase dysfunction impacts the functional integrity of the proteolytic SPY complex.
Title: CLPB disaggregase dysfunction impacts the functional integrity of the proteolytic SPY complex.
Comprehensive structural characterization of the human AAA+ disaggregase CLPB in the apo- and substrate-bound states reveals a unique mode of action driven by oligomerization.
Title: Comprehensive structural characterization of the human AAA+ disaggregase CLPB in the apo- and substrate-bound states reveals a unique mode of action driven by oligomerization.
Premature Ovarian Insufficiency in CLPB Deficiency: Transcriptomic, Proteomic and Phenotypic Insights.
Title: Premature Ovarian Insufficiency in CLPB Deficiency: Transcriptomic, Proteomic and Phenotypic Insights.
Heterozygous variants of CLPB are a cause of severe congenital neutropenia.
Title: Heterozygous variants of CLPB are a cause of severe congenital neutropenia.
Neutropenia and intellectual disability are hallmarks of biallelic and de novo CLPB deficiency.
Title: Neutropenia and intellectual disability are hallmarks of biallelic and de novo CLPB deficiency.
Human CLPB forms ATP-dependent complexes in the mitochondrial intermembrane space.
Title: Human CLPB forms ATP-dependent complexes in the mitochondrial intermembrane space.
Skd3 (human ClpB) is a potent mitochondrial protein disaggregase that is inactivated by 3-methylglutaconic aciduria-linked mutations.
Title: Skd3 (human ClpB) is a potent mitochondrial protein disaggregase that is inactivated by 3-methylglutaconic aciduria-linked mutations.
It present for the first time the biochemical characteristics of the human CLPB protein with the aim of shedding light on its physiological function and the pathogenesis of MEGCANN syndrome.
Title: CLPB (caseinolytic peptidase B homolog), the first mitochondrial protein refoldase associated with human disease.
The neonatal presentation of CLPB deficiency predicts the course of disease in later life, which is extremely important for counselling.
Title: A scoring system predicting the clinical course of CLPB defect based on the foetal and neonatal presentation of 31 patients.
Case Reports: bi-allelic CLPB mutations cause cataract, renal cysts, nephrocalcinosis and 3-methylglutaconic aciduria, a novel disorder of mitochondrial protein disaggregation.
Title: Bi-allelic CLPB mutations cause cataract, renal cysts, nephrocalcinosis and 3-methylglutaconic aciduria, a novel disorder of mitochondrial protein disaggregation.

Submit: New GeneRIF Correction See all GeneRIFs (17)

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
3-methylglutaconic aciduria, type VIIA MedGen: C5676967 OMIM: 619835 GeneReviews: Not available	Compare labs
3-methylglutaconic aciduria, type VIIB MedGen: C5676893 OMIM: 616271 GeneReviews: CLPB Deficiency	Compare labs
Neutropenia, severe congenital, 9, autosomal dominant MedGen: C5676954 OMIM: 619813 GeneReviews: Not available	Compare labs

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

STS-Z40910 (e-PCR)
- UniSTS:29447

SHGC-173269 (e-PCR)
- UniSTS:185352

SHGC-80623 (e-PCR)
- UniSTS:102192

SHGC-112018 (e-PCR)
- UniSTS:182362

SHGC-111311 (e-PCR)
- UniSTS:168294

MARC_6997-6998:996689895:1 (e-PCR)
- UniSTS:269700

RH104371 (e-PCR)
- UniSTS:98696

SHGC-145253 (e-PCR)
- UniSTS:174474

SHGC-57720 (e-PCR)
- UniSTS:37277

D11S490 (e-PCR)
- UniSTS:33718

A008U48 (e-PCR)
- UniSTS:58807

D11S3830 (e-PCR)
- UniSTS:153060

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IBA Inferred from Biological aspect of Ancestor more info
enables ATP hydrolysis activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables ATP-dependent H2AZ histone chaperone activity	IEA Inferred from Electronic Annotation more info
enables ATP-dependent H3-H4 histone complex chaperone activity	IEA Inferred from Electronic Annotation more info
enables ATP-dependent protein disaggregase activity	IDA Inferred from Direct Assay more info	PubMed
enables ATP-dependent protein disaggregase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables DNA clamp loader activity	IEA Inferred from Electronic Annotation more info
enables chromatin extrusion motor activity	IEA Inferred from Electronic Annotation more info
enables cohesin loader activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in RIG-I signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in antiviral innate immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to heat	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to heat	IDA Inferred from Direct Assay more info	PubMed
involved_in chromatin looping	IEA Inferred from Electronic Annotation more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in granulocyte differentiation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrial intermembrane space	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial intermembrane space	IMP Inferred from Mutant Phenotype more info	PubMed
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: mitochondrial disaggregase

Names: ClpB caseinolytic peptidase B homolog; ClpB homolog, mitochondrial AAA ATPase chaperonin; ankyrin-repeat containing bacterial clp fusion; caseinolytic mitochondrial matrix peptidase chaperone subunit B; caseinolytic peptidase B protein homolog; suppressor of potassium transport defect 3; testicular secretory protein Li 11

NP_001245321.1

EC 3.6.1.3

NP_001245322.1

EC 3.6.1.3

NP_001245323.1

EC 3.6.1.3

NP_110440.1

EC 3.6.1.3

XP_005274377.1

EC 3.6.1.3

XP_011543591.1

EC 3.6.1.3

XP_047283611.1

EC 3.6.1.3

XP_047283612.1

EC 3.6.1.3

XP_054226051.1

EC 3.6.1.3

XP_054226052.1

EC 3.6.1.3

XP_054226053.1

EC 3.6.1.3

XP_054226054.1

EC 3.6.1.3

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

NG_042130.2 RefSeqGene

Range

5154..154190

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1338

mRNA and Protein(s)

NM_001258392.3 → NP_001245321.1 mitochondrial disaggregase isoform 2

See identical proteins and their annotated locations for NP_001245321.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the 5' coding region compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AK023214, AP000593, BU848809, DC396265

Consensus CDS

CCDS58154.1

UniProtKB/TrEMBL

A0A2U3TZY2

Related

ENSP00000441518.1, ENST00000538039.6

Conserved Domains (7) summary

smart01086
Location:545 → 630

ClpB_D2-small; C-terminal, D2-small domain, of ClpB protein

smart00382
Location:343 → 480

AAA; ATPases associated with a variety of cellular activities

cd00204
Location:137 → 285

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

pfam07724
Location:346 → 534

AAA_2; AAA domain (Cdc48 subfamily)

pfam12796
Location:138 → 266

Ank_2; Ankyrin repeats (3 copies)

sd00045
Location:137 → 164

ANK; ANK repeat [structural motif]

cl21455
Location:309 → 371

P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
NM_001258393.3 → NP_001245322.1 mitochondrial disaggregase isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two in-frame exons in the 5' coding region compared to variant 1. The encoded isoform (3) is shorter than isoform 1.

Source sequence(s)

AK302006, AP000593, BC006404, DC396265

Consensus CDS

CCDS58153.1

UniProtKB/TrEMBL

A0A2U3TZY2

Related

ENSP00000340385.5, ENST00000340729.9

Conserved Domains (7) summary

smart01086
Location:516 → 601

ClpB_D2-small; C-terminal, D2-small domain, of ClpB protein

smart00382
Location:314 → 451

AAA; ATPases associated with a variety of cellular activities

cd00204
Location:137 → 256

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

pfam07724
Location:317 → 505

AAA_2; AAA domain (Cdc48 subfamily)

pfam12796
Location:138 → 237

Ank_2; Ankyrin repeats (3 copies)

sd00045
Location:137 → 168

ANK; ANK repeat [structural motif]

cl21455
Location:280 → 342

P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
NM_001258394.3 → NP_001245323.1 mitochondrial disaggregase isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and contains an alternate exon in the 5' coding region that results in initiation of translation at an alternate start codon and a novel 5' coding region compared to variant 1. The encoded isoform (4) is shorter than and has a distinct N-terminus compared to isoform 1.

Source sequence(s)

AK302069, AP000593, BC006404, DC396265

UniProtKB/Swiss-Prot

Q9H078

Conserved Domains (7) summary

smart01086
Location:530 → 615

ClpB_D2-small; C-terminal, D2-small domain, of ClpB protein

smart00382
Location:328 → 465

AAA; ATPases associated with a variety of cellular activities

cd00204
Location:108 → 270

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

pfam07724
Location:331 → 519

AAA_2; AAA domain (Cdc48 subfamily)

pfam13857
Location:208 → 261

Ank_5; Ankyrin repeats (many copies)

sd00045
Location:121 → 152

ANK; ANK repeat [structural motif]

cl21455
Location:294 → 356

P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
NM_030813.6 → NP_110440.1 mitochondrial disaggregase isoform 1

See identical proteins and their annotated locations for NP_110440.1

Status: REVIEWED

Description

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

Source sequence(s)

AP000593, BC006404, DC396265

Consensus CDS

CCDS8215.1

UniProtKB/Swiss-Prot

B4DXJ7, B4DXP7, B4DXW4, E7EWN6, F8W7P6, Q8ND11, Q9H078, Q9H8Y0

UniProtKB/TrEMBL

A0A140VK11, A0A2U3TZY2

Related

ENSP00000294053.3, ENST00000294053.9

Conserved Domains (4) summary

COG0542
Location:339 → 655

ClpA; ATP-dependent Clp protease ATP-binding subunit ClpA [Posttranslational modification, protein turnover, chaperones]

cd00204
Location:137 → 315

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

sd00045
Location:137 → 164

ANK; ANK repeat [structural motif]

cl27362
Location:78 → 211

MCR_beta_N; Methyl-coenzyme M reductase beta subunit, N-terminal domain

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_000011.10 Reference GRCh38.p14 Primary Assembly

Range

72285495..72434531 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005274320.2 → XP_005274377.1 mitochondrial disaggregase isoform X1

UniProtKB/TrEMBL

A0A2U3TZY2

Conserved Domains (7) summary

smart01086
Location:546 → 631

ClpB_D2-small; C-terminal, D2-small domain, of ClpB protein

smart00382
Location:344 → 481

AAA; ATPases associated with a variety of cellular activities

cd00204
Location:137 → 286

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

pfam07724
Location:347 → 535

AAA_2; AAA domain (Cdc48 subfamily)

pfam13857
Location:224 → 277

Ank_5; Ankyrin repeats (many copies)

sd00045
Location:237 → 267

ANK; ANK repeat [structural motif]

cl21455
Location:310 → 372

P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
XM_047427655.1 → XP_047283611.1 mitochondrial disaggregase isoform X2
XM_047427656.1 → XP_047283612.1 mitochondrial disaggregase isoform X3
XM_011545289.3 → XP_011543591.1 mitochondrial disaggregase isoform X4

UniProtKB/TrEMBL

A0A2R8Y6R5

Conserved Domains (3) summary

cd00204
Location:137 → 315

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

pfam12796
Location:138 → 296

Ank_2; Ankyrin repeats (3 copies)

sd00045
Location:137 → 164

ANK; ANK repeat [structural motif]

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

72211988..72361006 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054370076.1 → XP_054226051.1 mitochondrial disaggregase isoform X1

UniProtKB/TrEMBL

A0A2U3TZY2
XM_054370077.1 → XP_054226052.1 mitochondrial disaggregase isoform X2
XM_054370078.1 → XP_054226053.1 mitochondrial disaggregase isoform X3
XM_054370079.1 → XP_054226054.1 mitochondrial disaggregase isoform X4

UniProtKB/TrEMBL

A0A2R8Y6R5