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Protein

DnaJ homolog subfamily B member 2

Gene

DNAJB2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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, PARK2, 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

  • ATPase activator activity Source: UniProtKB
  • chaperone binding Source: UniProtKB
  • Hsp70 protein binding Source: UniProtKB
  • polyubiquitin binding Source: UniProtKB
  • proteasome binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
  • unfolded protein binding Source: UniProtKB

GO - Biological processi

  • chaperone-mediated protein folding Source: UniProtKB
  • ER-associated ubiquitin-dependent protein catabolic process Source: BHF-UCL
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of inclusion body assembly Source: BHF-UCL
  • negative regulation of protein binding Source: UniProtKB
  • negative regulation of protein deubiquitination Source: BHF-UCL
  • positive regulation of ATPase activity Source: UniProtKB
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: BHF-UCL
  • positive regulation of protein ubiquitination Source: BHF-UCL
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein refolding Source: UniProtKB
  • regulation of chaperone-mediated protein folding Source: UniProtKB
  • regulation of protein localization Source: ParkinsonsUK-UCL
  • regulation of protein ubiquitination Source: UniProtKB
  • response to unfolded protein Source: ProtInc

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

HGNCiHGNC:5228. DNAJB2.

Subcellular locationi

Isoform 2 :
  • Cytoplasm 2 Publications
  • Nucleus 1 Publication
Isoform 1 :
  • Endoplasmic reticulum membrane 1 Publication; Lipid-anchor 1 Publication; Cytoplasmic side 1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • inclusion body Source: BHF-UCL
  • intrinsic component of endoplasmic reticulum membrane Source: UniProtKB
  • nucleus Source: UniProtKB

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:rs730882140Ensembl.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 PARK2 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.
Orphaneti314485. 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 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, Prenylation, Ubl conjugation

Proteomic databases

EPDiP25686.
PaxDbiP25686.
PeptideAtlasiP25686.
PRIDEiP25686.

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.
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

  • chaperone binding Source: UniProtKB
  • Hsp70 protein binding Source: UniProtKB
  • polyubiquitin binding Source: UniProtKB
  • proteasome binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
  • unfolded protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109533. 44 interactors.
DIPiDIP-29051N.
IntActiP25686. 15 interactors.
MINTiMINT-1192251.
STRINGi9606.ENSP00000338019.

Structurei

Secondary structure

1324
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 7Combined sources4
Beta strandi8 – 10Combined sources3
Helixi16 – 29Combined sources14
Turni32 – 34Combined sources3
Helixi40 – 57Combined sources18
Helixi59 – 70Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LGWNMR-A1-91[»]
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 PARK2 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 PARK2 cytoplasmic aggregation (PubMed:20889486).3 Publications

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0714. Eukaryota.
COG0484. LUCA.
GeneTreeiENSGT00760000118947.
HOGENOMiHOG000111538.
HOVERGENiHBG066998.
InParanoidiP25686.
KOiK09508.
OMAiGPRHHGG.
OrthoDBiEOG093709FW.
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.
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

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

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:rs730882140Ensembl.1
Natural variantiVAR_048910270G → R. Corresponds to variant dbSNP:rs34127289Ensembl.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]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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. 44 interactors.
DIPiDIP-29051N.
IntActiP25686. 15 interactors.
MINTiMINT-1192251.
STRINGi9606.ENSP00000338019.

PTM databases

iPTMnetiP25686.
PhosphoSitePlusiP25686.

Polymorphism and mutation databases

BioMutaiDNAJB2.
DMDMi158518384.

Proteomic databases

EPDiP25686.
PaxDbiP25686.
PeptideAtlasiP25686.
PRIDEiP25686.

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]

Organism-specific databases

CTDi3300.
DisGeNETi3300.
GeneCardsiDNAJB2.
HGNCiHGNC:5228. DNAJB2.
HPAiHPA036268.
MalaCardsiDNAJB2.
MIMi604139. gene.
614881. phenotype.
neXtProtiNX_P25686.
OpenTargetsiENSG00000135924.
Orphaneti314485. Young adult-onset distal hereditary motor neuropathy.
PharmGKBiPA27415.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0714. Eukaryota.
COG0484. LUCA.
GeneTreeiENSGT00760000118947.
HOGENOMiHOG000111538.
HOVERGENiHBG066998.
InParanoidiP25686.
KOiK09508.
OMAiGPRHHGG.
OrthoDBiEOG093709FW.
PhylomeDBiP25686.
TreeFamiTF105142.

Miscellaneous databases

ChiTaRSiDNAJB2. human.
GeneWikiiDNAJB2.
GenomeRNAii3300.
PROiP25686.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135924.
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.
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: February 15, 2017
This is version 161 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.