CLPB

Protein identityUniProt · HPA

UniProt accession

Q9H078

Gene

CLPB

Ensembl

ENSG00000162129

Chromosome

11

Canonical length

707 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

Quaternary structure

Homohexamer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

707 residues, UniProt reviewed canonical sequence.

>Q9H078|CLPB
     1  MLGSLVLRRK ALAPRLLLRL LRSPTLRGHG GASGRNVTTG SLGEPQWLRV ATGGRPGTSP
    61  ALFSGRGAAT GGRQGGRFDT KCLAAATWGR LPGPEETLPG QDSWNGVPSR AGLGMCALAA
   121  ALVVHCYSKS PSNKDAALLE AARANNMQEV SRLLSEGADV NAKHRLGWTA LMVAAINRNN
   181  SVVQVLLAAG ADPNLGDDFS SVYKTAKEQG IHSLEDGGQD GASRHITNQW TSALEFRRWL
   241  GLPAGVLITR EDDFNNRLNN RASFKGCTAL HYAVLADDYR TVKELLDGGA NPLQRNEMGH
   301  TPLDYAREGE VMKLLRTSEA KYQEKQRKRE AEERRRFPLE QRLKEHIIGQ ESAIATVGAA
   361  IRRKENGWYD EEHPLVFLFL GSSGIGKTEL AKQTAKYMHK DAKKGFIRLD MSEFQERHEV
   421  AKFIGSPPGY VGHEEGGQLT KKLKQCPNAV VLFDEVDKAH PDVLTIMLQL FDEGRLTDGK
   481  GKTIDCKDAI FIMTSNVASD EIAQHALQLR QEALEMSRNR IAENLGDVQI SDKITISKNF
   541  KENVIRPILK AHFRRDEFLG RINEIVYFLP FCHSELIQLV NKELNFWAKR AKQRHNITLL
   601  WDREVADVLV DGYNVHYGAR SIKHEVERRV VNQLAAAYEQ DLLPGGCTLR ITVEDSDKQL
   661  LKSPELPSPQ AEKRLPKLRL EIIDKDSKTR RLDIRAPLHP EKVCNTI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CLPB can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.4

Highest tissue expression

120 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CLPB.

Disease | AllUniProt

Conditions CLPB is implicated in, by any mechanism.

• 3-methylglutaconic aciduria 7B (MGCA7B) MIM:616271
• 3-methylglutaconic aciduria 7A (MGCA7A) MIM:619835
• Neutropenia, severe congenital 9, autosomal dominant (SCN9) MIM:619813

Disease | GeneticClinVar

51 pathogenic / likely-pathogenic of 892 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• 3-methylglutaconic aciduria, type VIIB
• Neutropenia, severe congenital, 9, autosomal dominant
• Inborn genetic diseases
• 3-methylglutaconic aciduria, type VIIA
• Decreased total neutrophil count

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.54

gnomAD pLI

0

gnomAD missense Z

1.05

DepMap mean gene effect

-0.2

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• antiviral innate immune response
• cellular response to heat
• granulocyte differentiation
• RIG-I signaling pathway

Molecular functions

• ATP binding
• ATP hydrolysis activity
• ATP-dependent protein disaggregase activity

Cellular components

• cytoplasm
• mitochondrial intermembrane space
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• ClpA/B family
• Ankyrin repeat
• AAA+ ATPase domain
• ATPase, AAA-type, core
• Clp ATPase, C-terminal
• P-loop containing nucleoside triphosphate hydrolase
• Ankyrin repeat-containing domain superfamily
• AAA domain (Cdc48 subfamily)
• C-terminal, D2-small domain, of ClpB protein
• Ankyrin repeats (3 copies)
• ATP-dependent Clp protease/Chaperone ClpA/ClpB

KeywordsUniProt

• Acetylation
• ANK repeat
• ATP-binding
• Cataract
• Epilepsy
• Hydrolase
• Intellectual disability
• Mitochondrion
• Nucleotide-binding
• Repeat
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of CLPB in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MAVS
• PHB
• PHB2
• PHB1
• AKAP1
• ATAD3A
• TTF2
• UCHL3