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Protein

DnaJ homolog subfamily B member 6

Gene

DNAJB6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Plays an indispensable role in the organization of KRT8/KRT18 filaments. Acts as an endogenous molecular chaperone for neuronal proteins including huntingtin. Suppresses aggregation and toxicity of polyglutamine-containing, aggregation-prone proteins. Isoform B but not isoform A inhibits huntingtin aggregation. Has a stimulatory effect on the ATPase activity of HSP70 in a dose-dependent and time-dependent manner and hence acts as a co-chaperone of HSP70. Also reduces cellular toxicity and caspase-3 activity.5 Publications

GO - Molecular functioni

  • ATPase activator activity Source: UniProtKB
  • chaperone binding Source: UniProtKB
  • DNA binding Source: Ensembl
  • heat shock protein binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • unfolded protein binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionChaperone

Enzyme and pathway databases

ReactomeiR-HSA-3371453 Regulation of HSF1-mediated heat shock response

Names & Taxonomyi

Protein namesi
Recommended name:
DnaJ homolog subfamily B member 6
Alternative name(s):
HHDJ1
Heat shock protein J2
Short name:
HSJ-2
MRJ
MSJ-1
Gene namesi
Name:DNAJB6
Synonyms:HSJ2, MRJ, MSJ1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000105993.14
HGNCiHGNC:14888 DNAJB6
MIMi611332 gene
neXtProtiNX_O75190

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Limb-girdle muscular dystrophy 1E (LGMD1E)2 Publications
The disease is caused by mutations affecting the gene represented in this entry. There is evidence that LGMD1E is caused by dysfunction of isoform B (PubMed:22366786).1 Publication
Disease descriptionAn autosomal dominant myopathy characterized by adult onset of proximal muscle weakness, beginning in the hip girdle region and later progressing to the shoulder girdle region.
See also OMIM:603511
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06783389F → I in LGMD1E; the mutation results in inefficient inhibition of protein aggregation by isoform B. 1 PublicationCorresponds to variant dbSNP:rs387907150EnsemblClinVar.1
Natural variantiVAR_06783493F → L in LGMD1E; the mutation results in inefficient inhibition of protein aggregation by isoform B. 2 PublicationsCorresponds to variant dbSNP:rs387907046EnsemblClinVar.1
Natural variantiVAR_06783596P → R in LGMD1E. 1 PublicationCorresponds to variant dbSNP:rs387907047EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Limb-girdle muscular dystrophy

Organism-specific databases

DisGeNETi10049
GeneReviewsiDNAJB6
MalaCardsiDNAJB6
MIMi603511 phenotype
OpenTargetsiENSG00000105993
Orphaneti34516 Autosomal dominant limb-girdle muscular dystrophy type 1D
PharmGKBiPA27418

Polymorphism and mutation databases

BioMutaiDNAJB6

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000710252 – 326DnaJ homolog subfamily B member 6Add BLAST325

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei135Omega-N-methylarginineBy similarity1
Modified residuei277PhosphoserineCombined sources1

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiO75190
MaxQBiO75190
PaxDbiO75190
PeptideAtlasiO75190
PRIDEiO75190
ProteomicsDBi49860
49861 [O75190-2]
49862 [O75190-3]
TopDownProteomicsiO75190-1 [O75190-1]

PTM databases

iPTMnetiO75190
PhosphoSitePlusiO75190
SwissPalmiO75190

Expressioni

Tissue specificityi

Widely expressed. Highest levels in testis and brain, and lower levels in heart, spleen, intestine, ovary, placenta, lung, kidney, pancreas, thymus, prostate, skeletal muscle, liver and leukocytes. In testis, expressed in germ cells in the earlier stages of differentiation pathway as well as in spermatids. In brain, expressed at a higher level in hippocampus and thalamus and a lower level in amygdala, substantia nigra, corpus callosum and caudate nucleus.4 Publications

Gene expression databases

BgeeiENSG00000105993 Expressed in 218 organ(s), highest expression level in cerebellar hemisphere
CleanExiHS_DNAJB6
ExpressionAtlasiO75190 baseline and differential
GenevisibleiO75190 HS

Organism-specific databases

HPAiCAB004670
HPA024258
HPA058593

Interactioni

Subunit structurei

Homooligomer. Interacts with BAG3, HSPB8 and STUB1. Interacts with ALKBH1 (By similarity). Interacts with HSP70, KRT18 and PTTG. Isoform B interacts with histone deacetylases HDAC4, HDAC6, and SIRT2, HDAC activity is required for antiaggregation.By similarity3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115360, 59 interactors
IntActiO75190, 68 interactors
MINTiO75190
STRINGi9606.ENSP00000262177

Structurei

3D structure databases

ProteinModelPortaliO75190
SMRiO75190
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 69JPROSITE-ProRule annotationAdd BLAST68

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 146Interaction with HSP701 PublicationAdd BLAST145
Regioni119 – 242Interaction with KRT181 PublicationAdd BLAST124

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi83 – 172Gly/Phe-richAdd BLAST90
Compositional biasi155 – 194Ser-richAdd BLAST40

Domaini

The antiaggregation activity of isoform B resides in the serine-rich region and the C-terminus.

Phylogenomic databases

eggNOGiKOG0714 Eukaryota
COG0484 LUCA
GeneTreeiENSGT00760000118947
HOVERGENiHBG066998
InParanoidiO75190
KOiK09512
OrthoDBiEOG091G152F
PhylomeDBiO75190
TreeFamiTF105142

Family and domain databases

CDDicd06257 DnaJ, 1 hit
Gene3Di1.10.287.110, 1 hit
InterProiView protein in InterPro
IPR001623 DnaJ_domain
IPR018253 DnaJ_domain_CS
IPR036869 J_dom_sf
PfamiView protein in Pfam
PF00226 DnaJ, 1 hit
PRINTSiPR00625 JDOMAIN
SMARTiView protein in SMART
SM00271 DnaJ, 1 hit
SUPFAMiSSF46565 SSF46565, 1 hit
PROSITEiView protein in PROSITE
PS00636 DNAJ_1, 1 hit
PS50076 DNAJ_2, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 9 potential isoforms that are computationally mapped.iShow all

Isoform A (identifier: O75190-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MVDYYEVLGV QRHASPEDIK KAYRKLALKW HPDKNPENKE EAERKFKQVA
60 70 80 90 100
EAYEVLSDAK KRDIYDKYGK EGLNGGGGGG SHFDSPFEFG FTFRNPDDVF
110 120 130 140 150
REFFGGRDPF SFDFFEDPFE DFFGNRRGPR GSRSRGTGSF FSAFSGFPSF
160 170 180 190 200
GSGFSSFDTG FTSFGSLGHG GLTSFSSTSF GGSGMGNFKS ISTSTKMVNG
210 220 230 240 250
RKITTKRIVE NGQERVEVEE DGQLKSLTIN GVADDDALAE ERMRRGQNAL
260 270 280 290 300
PAQPAGLRPP KPPRPASLLR HAPHCLSEEE GEQDRPRAPG PWDPLASAAG
310 320
LKEGGKRKKQ KQREESKKKK STKGNH
Length:326
Mass (Da):36,087
Last modified:October 18, 2001 - v2
Checksum:iECF1628BF7A524F3
GO
Isoform B (identifier: O75190-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     232-241: VADDDALAEE → KEQLLRLDNK
     242-326: Missing.

Show »
Length:241
Mass (Da):26,900
Checksum:iCD5A49CAB66C2E16
GO
Isoform C (identifier: O75190-3) [UniParc]FASTAAdd to basket
Also known as: a

The sequence of this isoform differs from the canonical sequence as follows:
     301-326: LKEGGKRKKQKQREESKKKKSTKGNH → VQREAAVEQAQSETSLGARGQRGHK

Note: No experimental confirmation available.
Show »
Length:325
Mass (Da):35,714
Checksum:i01F47DA9A87EBC74
GO
Isoform D (identifier: O75190-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: MVDYYEVLGVQRHASPEDIKKAYRKLALKWHPDKNPENKEEAERKFKQVAEAYEVLSDA → MPHPRILKRP

Note: No experimental confirmation available.
Show »
Length:277
Mass (Da):30,369
Checksum:i97C70A8C1DF2CACC
GO

Computationally mapped potential isoform sequencesi

There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PH18E9PH18_HUMAN
DnaJ homolog subfamily B member 6
DNAJB6
211Annotation score:
A0A0J9YX62A0A0J9YX62_HUMAN
DnaJ homolog subfamily B member 6
DNAJB6
334Annotation score:
C9J2C4C9J2C4_HUMAN
DnaJ homolog subfamily B member 6
DNAJB6
228Annotation score:
C9JDR7C9JDR7_HUMAN
DnaJ homolog subfamily B member 6
DNAJB6
98Annotation score:
C9JDX6C9JDX6_HUMAN
DnaJ homolog subfamily B member 6
DNAJB6
125Annotation score:
C9J2P2C9J2P2_HUMAN
DnaJ homolog subfamily B member 6
DNAJB6
145Annotation score:
C9JB42C9JB42_HUMAN
DnaJ homolog subfamily B member 6
DNAJB6
66Annotation score:
F8WCZ4F8WCZ4_HUMAN
DnaJ homolog subfamily B member 6
DNAJB6
129Annotation score:
C9JN01C9JN01_HUMAN
DnaJ homolog subfamily B member 6
DNAJB6
45Annotation score:

Sequence cautioni

The sequence AAD16010 differs from that shown. Reason: Frameshift at position 197.Curated
The sequence BAD93096 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti128G → S in BAD97321 (Ref. 9) Curated1
Sequence conflicti303E → G in BAF85714 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06783389F → I in LGMD1E; the mutation results in inefficient inhibition of protein aggregation by isoform B. 1 PublicationCorresponds to variant dbSNP:rs387907150EnsemblClinVar.1
Natural variantiVAR_06783493F → L in LGMD1E; the mutation results in inefficient inhibition of protein aggregation by isoform B. 2 PublicationsCorresponds to variant dbSNP:rs387907046EnsemblClinVar.1
Natural variantiVAR_07942896P → L Found in a family with autosomal-dominantly inherited distal-onset myopathy; significant loss of its ability to suppress aggregation of polyglutamine-containing proteins. 1 Publication1
Natural variantiVAR_06783596P → R in LGMD1E. 1 PublicationCorresponds to variant dbSNP:rs387907047EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0538941 – 59MVDYY…VLSDA → MPHPRILKRP in isoform D. CuratedAdd BLAST59
Alternative sequenceiVSP_001289232 – 241VADDDALAEE → KEQLLRLDNK in isoform B. 10 Publications10
Alternative sequenceiVSP_001290242 – 326Missing in isoform B. 10 PublicationsAdd BLAST85
Alternative sequenceiVSP_026180301 – 326LKEGG…TKGNH → VQREAAVEQAQSETSLGARG QRGHK in isoform C. 4 PublicationsAdd BLAST26

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF080569 mRNA Translation: AAD16010.1 Frameshift.
AB015798 mRNA Translation: BAA88769.1
AB015799 mRNA Translation: BAA88770.1
AF060703 mRNA Translation: AAF21257.1
AB014888 mRNA Translation: BAA32209.1
AF075601 mRNA Translation: AAD43194.1
CR533498 mRNA Translation: CAG38529.1
AB209859 mRNA Translation: BAD93096.1 Different initiation.
AK223601 mRNA Translation: BAD97321.1
AK291953 mRNA Translation: BAF84642.1
AK293025 mRNA Translation: BAF85714.1
AK297796 mRNA Translation: BAG60135.1
AL136707 mRNA Translation: CAB66642.1
AC006372 Genomic DNA No translation available.
AC079306 Genomic DNA Translation: AAS07392.1
AC079306 Genomic DNA Translation: AAS07393.1
CH236954 Genomic DNA Translation: EAL23923.1
CH236954 Genomic DNA Translation: EAL23924.1
CH471149 Genomic DNA Translation: EAX04570.1
BC000177 mRNA Translation: AAH00177.1
BC002446 mRNA Translation: AAH02446.1
CCDSiCCDS47755.1 [O75190-2]
CCDS5946.1 [O75190-1]
RefSeqiNP_005485.1, NM_005494.2 [O75190-2]
NP_490647.1, NM_058246.3 [O75190-1]
UniGeneiHs.188591
Hs.490745

Genome annotation databases

EnsembliENST00000262177; ENSP00000262177; ENSG00000105993 [O75190-1]
ENST00000429029; ENSP00000397556; ENSG00000105993 [O75190-2]
GeneIDi10049
KEGGihsa:10049
UCSCiuc003wnj.4 human [O75190-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiDNJB6_HUMAN
AccessioniPrimary (citable) accession number: O75190
Secondary accession number(s): A4D232
, A8K7D8, A8KAG0, B4DN73, E9PCZ2, O95806, Q53EN8, Q59EF2, Q6FIC8, Q75MA2, Q9UIK6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: October 18, 2001
Last modified: September 12, 2018
This is version 182 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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