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Protein

Heat shock 70 kDa protein 1B

Gene

HSPA1B

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

Functioni

Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The co-chaperones are of three types: J-domain co-chaperones such as HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24012426, PubMed:26865365, PubMed:24318877). Maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines whether it functions in protein refolding or protein degradation by controlling the competitive binding of co-chaperones HOPX and STUB1. During the early stress response, the acetylated form binds to HOPX which assists in chaperone-mediated protein refolding, thereafter, it is deacetylated and binds to ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein degradation (PubMed:27708256). Regulates centrosome integrity during mitosis, and is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle (PubMed:27137183). Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling (PubMed:24613385). Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223).2 Publications6 Publications
(Microbial infection) In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei71ATP1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi12 – 15ATP4
Nucleotide bindingi202 – 204ATP3
Nucleotide bindingi268 – 275ATP8
Nucleotide bindingi339 – 342ATP4

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChaperone, Host cell receptor for virus entry, Receptor
Biological processStress response
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-3371453 Regulation of HSF1-mediated heat shock response
R-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR)
R-HSA-3371568 Attenuation phase
R-HSA-3371571 HSF1-dependent transactivation
R-HSA-6798695 Neutrophil degranulation
SIGNORiP0DMV9

Names & Taxonomyi

Protein namesi
Recommended name:
Heat shock 70 kDa protein 1BImported
Alternative name(s):
Heat shock 70 kDa protein 2
Short name:
HSP70-22 Publications
Short name:
HSP70.2
Gene namesi
Name:HSPA1BImported
Synonyms:HSP721 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000204388.6
HGNCiHGNC:5233 HSPA1B
MIMi140550 gene
603012 gene
neXtProtiNX_P0DMV9

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, Cytoskeleton

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi10D → A: Reduces affinity for ADP. 1 Publication1
Mutagenesisi77K → Q: No loss of acetylation and ATPase activity. Exhibits normal protein refolding activity during the early phase but exhibits defects in ubiquitin-mediated protein degradation during the later phase. 1 Publication1
Mutagenesisi77K → R: Significant loss of acetylation and ATPase activity. Decreased binding to HOPX and HSP90 and increased binding to STUB1 and NAA10. Impaired capacity for protein refolding during the early phase after stress but shows normal protein degradation activity in the late phase. 1 Publication1
Mutagenesisi199D → A: Reduces affinity for ADP. 1 Publication1
Mutagenesisi561K → R: Complete loss of in vitro methylation by METTL21A. 2 Publications1

Organism-specific databases

DisGeNETi3303
3304
OpenTargetsiENSG00000204388
ENSG00000204389

Chemistry databases

ChEMBLiCHEMBL3885585

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00004331152 – 641Heat shock 70 kDa protein 1BAdd BLAST640

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei77N6-acetyllysine1 Publication1
Modified residuei108N6-acetyllysineCombined sources1
Modified residuei246N6-acetyllysineCombined sources1
Modified residuei348N6-acetyllysineCombined sources1
Modified residuei469Omega-N-methylarginineCombined sources1
Modified residuei561N6,N6,N6-trimethyllysine; by METTL21A; alternateCombined sources2 Publications1
Modified residuei561N6,N6-dimethyllysine; alternateCombined sources1
Modified residuei631PhosphoserineCombined sources1
Modified residuei633PhosphoserineCombined sources1
Modified residuei636PhosphothreonineCombined sources1

Post-translational modificationi

In response to cellular stress, acetylated at Lys-77 by NA110 and then gradually deacetylated by HDAC4 at later stages. Acetylation enhances its chaperone activity and also determines whether it will function as a chaperone for protein refolding or degradation by controlling its binding to co-chaperones HOPX and STUB1. The acetylated form and the non-acetylated form bind to HOPX and STUB1 respectively. Acetylation also protects cells against various types of cellular stress.1 Publication

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiP0DMV9
MaxQBiP0DMV9
PRIDEiP0DMV9

2D gel databases

REPRODUCTION-2DPAGEiIPI00304925

PTM databases

GlyConnecti1296
iPTMnetiP0DMV9

Expressioni

Tissue specificityi

HSPA1B is testis-specific.

Inductioni

By heat shock.

Gene expression databases

BgeeiENSG00000204388 Expressed in 238 organ(s), highest expression level in adenohypophysis
CleanExiHS_HSPA1A
ExpressionAtlasiP0DMV9 baseline and differential

Organism-specific databases

HPAiCAB008640
HPA052504

Interactioni

Subunit structurei

Component of the CatSper complex. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661). Interacts with CHCHD3, DNAJC7, IRAK1BP1, PPP5C and TSC2 (PubMed:21081504, PubMed:12853476, PubMed:18620420, PubMed:17233114, PubMed:15383005, PubMed:15963462). Interacts with TERT; the interaction occurs in the absence of the RNA component, TERC, and dissociates once the TERT complex has formed (PubMed:11274138). Interacts with TRIM5 (via B30.2/SPRY domain) (PubMed:20053985). Interacts with METTL21A (PubMed:23921388). Interacts with PRKN (PubMed:24270810). Interacts with FOXP3 (PubMed:23973223). Interacts with NOD2; the interaction enhances NOD2 stability (PubMed:24790089). Interacts with DNAJC9 (via J domain) (PubMed:17182002). Interacts with ATF5; the interaction protects ATF5 from degradation via proteasome-dependent and caspase-dependent processes (PubMed:22528486). Interacts with NAA10, HSP40, HSP90 and HDAC4. The acetylated form and the non-acetylated form interact with HOPX and STUB1 respectively (PubMed:27708256). Interacts with NEDD1 (PubMed:27137183). Interacts (via NBD) with BAG1, BAG2, BAG3 and HSPH1/HSP105 (PubMed:24318877). Interacts with SMAD3 (PubMed:24613385). Interacts with DNAJC8 (PubMed:27133716).24 Publications

GO - Molecular functioni

Protein-protein interaction databases

CORUMiP0DMV9
IntActiP0DMV9, 5 interactors
MINTiP0DMV9

Chemistry databases

BindingDBiP0DMV9

Structurei

Secondary structure

1641
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP0DMV9
SMRiP0DMV9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 386Nucleotide-binding domain (NBD)By similarityAdd BLAST385
Regioni394 – 509Substrate-binding domain (SBD)By similarityAdd BLAST116

Domaini

The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide-binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins.2 Publications

Sequence similaritiesi

Belongs to the heat shock protein 70 family.Curated

Phylogenomic databases

GeneTreeiENSGT00930000150862
KOiK03283
OrthoDBiEOG093705LK
PhylomeDBiP0DMV9

Family and domain databases

Gene3Di1.20.1270.10, 1 hit
2.60.34.10, 1 hit
InterProiView protein in InterPro
IPR018181 Heat_shock_70_CS
IPR029048 HSP70_C_sf
IPR029047 HSP70_peptide-bd_sf
IPR013126 Hsp_70_fam
PANTHERiPTHR19375 PTHR19375, 1 hit
PfamiView protein in Pfam
PF00012 HSP70, 1 hit
PRINTSiPR00301 HEATSHOCK70
SUPFAMiSSF100920 SSF100920, 1 hit
SSF100934 SSF100934, 1 hit
PROSITEiView protein in PROSITE
PS00297 HSP70_1, 1 hit
PS00329 HSP70_2, 1 hit
PS01036 HSP70_3, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

P0DMV9-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAKAAAIGID LGTTYSCVGV FQHGKVEIIA NDQGNRTTPS YVAFTDTERL
60 70 80 90 100
IGDAAKNQVA LNPQNTVFDA KRLIGRKFGD PVVQSDMKHW PFQVINDGDK
110 120 130 140 150
PKVQVSYKGE TKAFYPEEIS SMVLTKMKEI AEAYLGYPVT NAVITVPAYF
160 170 180 190 200
NDSQRQATKD AGVIAGLNVL RIINEPTAAA IAYGLDRTGK GERNVLIFDL
210 220 230 240 250
GGGTFDVSIL TIDDGIFEVK ATAGDTHLGG EDFDNRLVNH FVEEFKRKHK
260 270 280 290 300
KDISQNKRAV RRLRTACERA KRTLSSSTQA SLEIDSLFEG IDFYTSITRA
310 320 330 340 350
RFEELCSDLF RSTLEPVEKA LRDAKLDKAQ IHDLVLVGGS TRIPKVQKLL
360 370 380 390 400
QDFFNGRDLN KSINPDEAVA YGAAVQAAIL MGDKSENVQD LLLLDVAPLS
410 420 430 440 450
LGLETAGGVM TALIKRNSTI PTKQTQIFTT YSDNQPGVLI QVYEGERAMT
460 470 480 490 500
KDNNLLGRFE LSGIPPAPRG VPQIEVTFDI DANGILNVTA TDKSTGKANK
510 520 530 540 550
ITITNDKGRL SKEEIERMVQ EAEKYKAEDE VQRERVSAKN ALESYAFNMK
560 570 580 590 600
SAVEDEGLKG KISEADKKKV LDKCQEVISW LDANTLAEKD EFEHKRKELE
610 620 630 640
QVCNPIISGL YQGAGGPGPG GFGAQGPKGG SGSGPTIEEV D
Length:641
Mass (Da):70,052
Last modified:May 27, 2015 - v1
Checksum:i78F513118C96DE66
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0G2JIW1A0A0G2JIW1_HUMAN
Heat shock 70 kDa protein 1B
HSPA1B
642Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03215295I → V1 Publication1
Natural variantiVAR_032153467A → V1 PublicationCorresponds to variant dbSNP:rs538280104Ensembl.1
Natural variantiVAR_029054499N → S2 PublicationsCorresponds to variant dbSNP:rs483638Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M59830 Genomic DNA Translation: AAA63227.1
BA000025 Genomic DNA Translation: BAB63299.1
AF134726 Genomic DNA Translation: AAD21815.1
DQ388429 Genomic DNA Translation: ABD48956.1
AL671762 Genomic DNA No translation available.
BC009322 mRNA Translation: AAH09322.1
BC018740 mRNA Translation: AAH18740.1
BC057397 mRNA Translation: AAH57397.1
BC063507 mRNA Translation: AAH63507.1
M24744 Genomic DNA Translation: AAA59845.1
CCDSiCCDS34415.1
PIRiA29160
A45871
I59139
I79540
RefSeqiNP_005336.3, NM_005345.5
NP_005337.2, NM_005346.4
UniGeneiHs.274402
Hs.702139
Hs.719966
Hs.743411

Genome annotation databases

EnsembliENST00000375650; ENSP00000364801; ENSG00000204388
ENST00000391548; ENSP00000375391; ENSG00000224501
ENST00000391555; ENSP00000375399; ENSG00000212866
ENST00000445736; ENSP00000403530; ENSG00000231555
ENST00000450744; ENSP00000393087; ENSG00000232804
GeneIDi3303
3304
KEGGihsa:3303
hsa:3304

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M59830 Genomic DNA Translation: AAA63227.1
BA000025 Genomic DNA Translation: BAB63299.1
AF134726 Genomic DNA Translation: AAD21815.1
DQ388429 Genomic DNA Translation: ABD48956.1
AL671762 Genomic DNA No translation available.
BC009322 mRNA Translation: AAH09322.1
BC018740 mRNA Translation: AAH18740.1
BC057397 mRNA Translation: AAH57397.1
BC063507 mRNA Translation: AAH63507.1
M24744 Genomic DNA Translation: AAA59845.1
CCDSiCCDS34415.1
PIRiA29160
A45871
I59139
I79540
RefSeqiNP_005336.3, NM_005345.5
NP_005337.2, NM_005346.4
UniGeneiHs.274402
Hs.702139
Hs.719966
Hs.743411

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4J8FX-ray2.70A1-382[»]
A384-600[»]
6FDTNMR-B633-641[»]
ProteinModelPortaliP0DMV9
SMRiP0DMV9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

CORUMiP0DMV9
IntActiP0DMV9, 5 interactors
MINTiP0DMV9

Chemistry databases

BindingDBiP0DMV9
ChEMBLiCHEMBL3885585

PTM databases

GlyConnecti1296
iPTMnetiP0DMV9

2D gel databases

REPRODUCTION-2DPAGEiIPI00304925

Proteomic databases

EPDiP0DMV9
MaxQBiP0DMV9
PRIDEiP0DMV9

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000375650; ENSP00000364801; ENSG00000204388
ENST00000391548; ENSP00000375391; ENSG00000224501
ENST00000391555; ENSP00000375399; ENSG00000212866
ENST00000445736; ENSP00000403530; ENSG00000231555
ENST00000450744; ENSP00000393087; ENSG00000232804
GeneIDi3303
3304
KEGGihsa:3303
hsa:3304

Organism-specific databases

CTDi3303
3304
DisGeNETi3303
3304
EuPathDBiHostDB:ENSG00000204388.6
GeneCardsiHSPA1B
HGNCiHGNC:5233 HSPA1B
HPAiCAB008640
HPA052504
MIMi140550 gene
603012 gene
neXtProtiNX_P0DMV9
OpenTargetsiENSG00000204388
ENSG00000204389
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00930000150862
KOiK03283
OrthoDBiEOG093705LK
PhylomeDBiP0DMV9

Enzyme and pathway databases

ReactomeiR-HSA-3371453 Regulation of HSF1-mediated heat shock response
R-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR)
R-HSA-3371568 Attenuation phase
R-HSA-3371571 HSF1-dependent transactivation
R-HSA-6798695 Neutrophil degranulation
SIGNORiP0DMV9

Miscellaneous databases

ChiTaRSiHSPA1B human
PROiPR:P0DMV9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000204388 Expressed in 238 organ(s), highest expression level in adenohypophysis
CleanExiHS_HSPA1A
ExpressionAtlasiP0DMV9 baseline and differential

Family and domain databases

Gene3Di1.20.1270.10, 1 hit
2.60.34.10, 1 hit
InterProiView protein in InterPro
IPR018181 Heat_shock_70_CS
IPR029048 HSP70_C_sf
IPR029047 HSP70_peptide-bd_sf
IPR013126 Hsp_70_fam
PANTHERiPTHR19375 PTHR19375, 1 hit
PfamiView protein in Pfam
PF00012 HSP70, 1 hit
PRINTSiPR00301 HEATSHOCK70
SUPFAMiSSF100920 SSF100920, 1 hit
SSF100934 SSF100934, 1 hit
PROSITEiView protein in PROSITE
PS00297 HSP70_1, 1 hit
PS00329 HSP70_2, 1 hit
PS01036 HSP70_3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHS71B_HUMAN
AccessioniPrimary (citable) accession number: P0DMV9
Secondary accession number(s): B4E3B6
, P08107, P19790, Q5JQI4, Q5SP17, Q9UQL9, Q9UQM0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 27, 2015
Last sequence update: May 27, 2015
Last modified: November 7, 2018
This is version 33 of the entry and version 1 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, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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
  6. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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