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Protein

DnaJ homolog subfamily B member 2

Gene

DNAJB2

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

Functioni

Functions as a co-chaperone, regulating the substrate binding and activating the ATPase activity of chaperones of the HSP70/heat shock protein 70 family (PubMed:7957263, PubMed:22219199). In parallel, also contributes to the ubiquitin-dependent proteasomal degradation of misfolded proteins (PubMed:15936278, PubMed:21625540). Thereby, may regulate the aggregation and promote the functional recovery of misfolded proteins like HTT, MC4R, PRKN, RHO and SOD1 and be crucial for many biological processes (PubMed:12754272, PubMed:20889486, PubMed:21719532, PubMed:22396390, PubMed:24023695). Isoform 1 which is localized to the endoplasmic reticulum membranes may specifically function in ER-associated protein degradation of misfolded proteins (PubMed:15936278).9 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChaperone

Names & Taxonomyi

Protein namesi
Recommended name:
DnaJ homolog subfamily B member 2Curated
Alternative name(s):
Heat shock 40 kDa protein 3Imported
Heat shock protein J11 Publication
Short name:
HSJ-11 Publication
Gene namesi
Name:DNAJB2Imported
Synonyms:HSJ11 Publication, HSPF3Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000135924.15
HGNCiHGNC:5228 DNAJB2
MIMi604139 gene
neXtProtiNX_P25686

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, Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Distal spinal muscular atrophy, autosomal recessive, 5 (DSMA5)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive neurologic disorder characterized by young adult onset of slowly progressive distal muscle weakness and atrophy resulting in gait impairment and loss of reflexes due to impaired function of motor nerves. Sensation and cognition are not impaired.
See also OMIM:614881
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0732865Y → C in DSMA5. 2 PublicationsCorresponds to variant dbSNP:rs730882140EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi31 – 33HPD → QPN: Loss of interaction with HSP70 and loss of the ability to promote ATXN3 proteasomal degradation. 1 Publication3
Mutagenesisi31H → Q: Probable loss of interaction with HSP70 and loss of the ability to reduce PRKN aggregation. 2 Publications1
Mutagenesisi219S → A: Loss of interaction with polyubiquitin chains, loss of interaction with PSMA3, and loss of the ability to protect ATXN3 from proteasomal degradation; when associated with A-222; A-262 and A-265. 2 Publications1
Mutagenesisi222E → A: Loss of interaction with polyubiquitin chains, loss of interaction with PSMA3, and loss of the ability to protect ATXN3 from proteasomal degradation; when associated with A-219; A-262 and A-265. 2 Publications1
Mutagenesisi262S → A: Loss of interaction with polyubiquitin chains, loss of interaction with PSMA3, and loss of the ability to protect ATXN3 from proteasomal degradation; when associated with A-219; A-222 and A-265. 2 Publications1
Mutagenesisi265E → A: Loss of interaction with polyubiquitin chains, loss of interaction with PSMA3, and loss of the ability to protect ATXN3 from proteasomal degradation; when associated with A-219; A-222 and A-262. 2 Publications1
Mutagenesisi321C → S: Loss of localization to the endoplasmic reticulum and relocalization to cytoplasm and nucleus. 1 Publication1
Mutagenesisi324L → M: No effect on localization to the endoplasmic reticulum membrane. 1 Publication1

Keywords - Diseasei

Neurodegeneration

Organism-specific databases

DisGeNETi3300
MalaCardsiDNAJB2
MIMi614881 phenotype
OpenTargetsiENSG00000135924
Orphaneti443950 DNAJB2-related Charcot-Marie-Tooth disease type 2
314485 Young adult-onset distal hereditary motor neuropathy
PharmGKBiPA27415

Polymorphism and mutation databases

BioMutaiDNAJB2
DMDMi158518384

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000710182 – 321DnaJ homolog subfamily B member 2Add BLAST320
PropeptideiPRO_0000438687322 – 324Removed in mature form1 Publication3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei311PhosphoserineBy similarity1
Modified residuei321Cysteine methyl ester1 Publication1
Lipidationi321S-geranylgeranyl cysteine1 Publication1

Post-translational modificationi

Ubiquitinated by STUB1; does not lead to proteasomal degradation.1 Publication

Keywords - PTMi

Acetylation, Lipoprotein, Methylation, Phosphoprotein, Prenylation, Ubl conjugation

Proteomic databases

EPDiP25686
PaxDbiP25686
PeptideAtlasiP25686
PRIDEiP25686
ProteomicsDBi54281
54282 [P25686-2]

PTM databases

iPTMnetiP25686
PhosphoSitePlusiP25686

Expressioni

Tissue specificityi

More abundantly expressed in neocortex, cerebellum, spinal cord and retina where it is expressed by neuronal cells (at protein level) (PubMed:1599432, PubMed:12754272). Detected at much lower level in non-neuronal tissues including kidney, lung, heart, skeletal muscle, spleen and testis (at protein level) (PubMed:12754272, PubMed:1599432). Isoform 1 is more abundant in neocortex and cerebellum compared to isoform 2 (at protein level) (PubMed:12754272).2 Publications

Gene expression databases

BgeeiENSG00000135924 Expressed in 224 organ(s), highest expression level in C1 segment of cervical spinal cord
CleanExiHS_DNAJB2
ExpressionAtlasiP25686 baseline and differential
GenevisibleiP25686 HS

Organism-specific databases

HPAiHPA036268

Interactioni

Subunit structurei

Interacts with HSP70 (HSPA1A or HSPA1B) (PubMed:21625540, PubMed:22219199). Interacts with HSPA8/Hsc70 (PubMed:15936278). Interacts with PSMA3 and most probably with the whole proteasomal complex (PubMed:15936278).3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109533, 49 interactors
CORUMiP25686
DIPiDIP-29051N
IntActiP25686, 18 interactors
MINTiP25686
STRINGi9606.ENSP00000338019

Structurei

Secondary structure

1324
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP25686
SMRiP25686
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 71JPROSITE-ProRule annotationAdd BLAST70
Domaini210 – 226UIM 1PROSITE-ProRule annotationAdd BLAST17
Domaini250 – 269UIM 2PROSITE-ProRule annotationAdd BLAST20

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi321 – 324CAAX motif1 Publication4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi141 – 170Ser-richPROSITE-ProRule annotationAdd BLAST30

Domaini

The J domain is sufficient to interact with HSP70 (HSPA1A or HSPA1B) and activate its ATPase activity (PubMed:22219199). The J domain is also required for the HSP70-mediated and ubiquitin-dependent proteasomal degradation of proteins like ATXN3 (PubMed:21625540). The J domain is required to reduce PRKN cytoplasmic aggregation (PubMed:20889486).3 Publications
The UIM domains mediate interaction with ubiquitinated chaperone clients and with the proteasome (PubMed:15936278). The UIM domains may have an opposite activity to the J domain, binding ubiquitinated proteins and protecting them from HSP70-mediated proteasomal degradation (PubMed:21625540). The UIM domains are not required to reduce PRKN cytoplasmic aggregation (PubMed:20889486).3 Publications

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0714 Eukaryota
COG0484 LUCA
GeneTreeiENSGT00760000118947
HOGENOMiHOG000111538
HOVERGENiHBG066998
InParanoidiP25686
KOiK09508
OMAiTFTFRNP
OrthoDBiEOG091G152F
PhylomeDBiP25686
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
IPR003903 UIM_dom
PfamiView protein in Pfam
PF00226 DnaJ, 1 hit
PF02809 UIM, 2 hits
PRINTSiPR00625 JDOMAIN
SMARTiView protein in SMART
SM00271 DnaJ, 1 hit
SM00726 UIM, 2 hits
SUPFAMiSSF46565 SSF46565, 1 hit
PROSITEiView protein in PROSITE
PS00636 DNAJ_1, 1 hit
PS50076 DNAJ_2, 1 hit
PS50330 UIM, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P25686-3) [UniParc]FASTAAdd to basket
Also known as: HSJ1b1 Publication

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
MASYYEILDV PRSASADDIK KAYRRKALQW HPDKNPDNKE FAEKKFKEVA
60 70 80 90 100
EAYEVLSDKH KREIYDRYGR EGLTGTGTGP SRAEAGSGGP GFTFTFRSPE
110 120 130 140 150
EVFREFFGSG DPFAELFDDL GPFSELQNRG SRHSGPFFTF SSSFPGHSDF
160 170 180 190 200
SSSSFSFSPG AGAFRSVSTS TTFVQGRRIT TRRIMENGQE RVEVEEDGQL
210 220 230 240 250
KSVTINGVPD DLALGLELSR REQQPSVTSR SGGTQVQQTP ASCPLDSDLS
260 270 280 290 300
EDEDLQLAMA YSLSEMEAAG KKPAGGREAQ HRRQGRPKAQ HQDPGLGGTQ
310 320
EGARGEATKR SPSPEEKASR CLIL
Length:324
Mass (Da):35,580
Last modified:September 11, 2007 - v3
Checksum:i0154ED3E29F34B4A
GO
Isoform 2 (identifier: P25686-2) [UniParc]FASTAAdd to basket
Also known as: HSJ1a1 Publication, DNAJB2a1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     275-277: GGR → DVF
     278-324: Missing.

Show »
Length:277
Mass (Da):30,569
Checksum:i1C843287D7856CFB
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JRD2C9JRD2_HUMAN
DnaJ homolog subfamily B member 2
DNAJB2
228Annotation score:
C9J1G2C9J1G2_HUMAN
DnaJ homolog subfamily B member 2
DNAJB2
122Annotation score:
C9JX00C9JX00_HUMAN
DnaJ homolog subfamily B member 2
DNAJB2
148Annotation score:
C9JXB9C9JXB9_HUMAN
DnaJ homolog subfamily B member 2
DNAJB2
244Annotation score:
E7ETU0E7ETU0_HUMAN
DnaJ homolog subfamily B member 2
DNAJB2
132Annotation score:

Sequence cautioni

The sequence AAA09035 differs from that shown. Reason: Frameshift at position 288.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti214L → R in AAA09034 (PubMed:1599432).Curated1
Sequence conflicti214L → R in AAA09035 (PubMed:1599432).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0732865Y → C in DSMA5. 2 PublicationsCorresponds to variant dbSNP:rs730882140EnsemblClinVar.1
Natural variantiVAR_048910270G → R. Corresponds to variant dbSNP:rs34127289EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001286275 – 277GGR → DVF in isoform 2. 2 Publications3
Alternative sequenceiVSP_001287278 – 324Missing in isoform 2. 2 PublicationsAdd BLAST47

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S37375 mRNA Translation: AAA09034.1
S37374 mRNA Translation: AAA09035.1 Frameshift.
X63368 Genomic DNA Translation: CAA44968.2
X63368 Genomic DNA Translation: CAA44969.2
BT007088 mRNA Translation: AAP35751.1
AK292761 mRNA Translation: BAF85450.1
AK312723 mRNA Translation: BAG35597.1
AC114803 Genomic DNA Translation: AAY24037.1
CH471063 Genomic DNA Translation: EAW70722.1
BC011609 mRNA Translation: AAH11609.1
BC047056 mRNA Translation: AAH47056.1
CCDSiCCDS2439.1 [P25686-3]
CCDS46519.1 [P25686-2]
PIRiS23508
RefSeqiNP_001034639.1, NM_001039550.1 [P25686-2]
NP_006727.2, NM_006736.5 [P25686-3]
UniGeneiHs.77768

Genome annotation databases

EnsembliENST00000336576; ENSP00000338019; ENSG00000135924 [P25686-3]
ENST00000392086; ENSP00000375936; ENSG00000135924 [P25686-2]
GeneIDi3300
KEGGihsa:3300
UCSCiuc002vkw.2 human [P25686-3]
uc002vkx.2 human

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S37375 mRNA Translation: AAA09034.1
S37374 mRNA Translation: AAA09035.1 Frameshift.
X63368 Genomic DNA Translation: CAA44968.2
X63368 Genomic DNA Translation: CAA44969.2
BT007088 mRNA Translation: AAP35751.1
AK292761 mRNA Translation: BAF85450.1
AK312723 mRNA Translation: BAG35597.1
AC114803 Genomic DNA Translation: AAY24037.1
CH471063 Genomic DNA Translation: EAW70722.1
BC011609 mRNA Translation: AAH11609.1
BC047056 mRNA Translation: AAH47056.1
CCDSiCCDS2439.1 [P25686-3]
CCDS46519.1 [P25686-2]
PIRiS23508
RefSeqiNP_001034639.1, NM_001039550.1 [P25686-2]
NP_006727.2, NM_006736.5 [P25686-3]
UniGeneiHs.77768

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LGWNMR-A1-91[»]
ProteinModelPortaliP25686
SMRiP25686
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109533, 49 interactors
CORUMiP25686
DIPiDIP-29051N
IntActiP25686, 18 interactors
MINTiP25686
STRINGi9606.ENSP00000338019

PTM databases

iPTMnetiP25686
PhosphoSitePlusiP25686

Polymorphism and mutation databases

BioMutaiDNAJB2
DMDMi158518384

Proteomic databases

EPDiP25686
PaxDbiP25686
PeptideAtlasiP25686
PRIDEiP25686
ProteomicsDBi54281
54282 [P25686-2]

Protocols and materials databases

DNASUi3300
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000336576; ENSP00000338019; ENSG00000135924 [P25686-3]
ENST00000392086; ENSP00000375936; ENSG00000135924 [P25686-2]
GeneIDi3300
KEGGihsa:3300
UCSCiuc002vkw.2 human [P25686-3]
uc002vkx.2 human

Organism-specific databases

CTDi3300
DisGeNETi3300
EuPathDBiHostDB:ENSG00000135924.15
GeneCardsiDNAJB2
HGNCiHGNC:5228 DNAJB2
HPAiHPA036268
MalaCardsiDNAJB2
MIMi604139 gene
614881 phenotype
neXtProtiNX_P25686
OpenTargetsiENSG00000135924
Orphaneti443950 DNAJB2-related Charcot-Marie-Tooth disease type 2
314485 Young adult-onset distal hereditary motor neuropathy
PharmGKBiPA27415
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0714 Eukaryota
COG0484 LUCA
GeneTreeiENSGT00760000118947
HOGENOMiHOG000111538
HOVERGENiHBG066998
InParanoidiP25686
KOiK09508
OMAiTFTFRNP
OrthoDBiEOG091G152F
PhylomeDBiP25686
TreeFamiTF105142

Miscellaneous databases

ChiTaRSiDNAJB2 human
GeneWikiiDNAJB2
GenomeRNAii3300
PROiPR:P25686
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135924 Expressed in 224 organ(s), highest expression level in C1 segment of cervical spinal cord
CleanExiHS_DNAJB2
ExpressionAtlasiP25686 baseline and differential
GenevisibleiP25686 HS

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
IPR003903 UIM_dom
PfamiView protein in Pfam
PF00226 DnaJ, 1 hit
PF02809 UIM, 2 hits
PRINTSiPR00625 JDOMAIN
SMARTiView protein in SMART
SM00271 DnaJ, 1 hit
SM00726 UIM, 2 hits
SUPFAMiSSF46565 SSF46565, 1 hit
PROSITEiView protein in PROSITE
PS00636 DNAJ_1, 1 hit
PS50076 DNAJ_2, 1 hit
PS50330 UIM, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDNJB2_HUMAN
AccessioniPrimary (citable) accession number: P25686
Secondary accession number(s): A8K9P6
, Q53QD7, Q8IUK1, Q8IUK2, Q96F52
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: September 11, 2007
Last modified: November 7, 2018
This is version 176 of the entry and version 3 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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