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Protein

Heat shock 70 kDa protein 1B

Gene

HSPA1B

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

  • ATPase activity Source: BHF-UCL
  • ATPase activity, coupled Source: UniProtKB
  • ATP binding Source: BHF-UCL
  • C3HC4-type RING finger domain binding Source: BHF-UCL
  • enzyme binding Source: BHF-UCL
  • G-protein coupled receptor binding Source: ParkinsonsUK-UCL
  • heat shock protein binding Source: UniProtKB
  • histone deacetylase binding Source: BHF-UCL
  • protein binding involved in protein folding Source: BHF-UCL
  • protein N-terminus binding Source: UniProtKB
  • receptor binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
  • unfolded protein binding Source: UniProtKB
  • virus receptor activity Source: UniProtKB-KW

GO - Biological processi

  • ATP metabolic process Source: BHF-UCL
  • cellular heat acclimation Source: UniProtKB
  • cellular response to heat Source: UniProtKB
  • cellular response to oxidative stress Source: ParkinsonsUK-UCL
  • mRNA catabolic process Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cell death Source: ParkinsonsUK-UCL
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
  • negative regulation of inclusion body assembly Source: UniProtKB
  • negative regulation of protein ubiquitination Source: ParkinsonsUK-UCL
  • neutrophil degranulation Source: Reactome
  • positive regulation of gene expression Source: BHF-UCL
  • positive regulation of interleukin-8 production Source: UniProtKB
  • positive regulation of microtubule nucleation Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway Source: UniProtKB
  • positive regulation of tumor necrosis factor-mediated signaling pathway Source: UniProtKB
  • protein refolding Source: UniProtKB
  • protein stabilization Source: UniProtKB
  • regulation of cellular response to heat Source: Reactome
  • regulation of mitotic spindle assembly Source: UniProtKB
  • regulation of protein ubiquitination Source: BHF-UCL

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.

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.

Polymorphism and mutation databases

DMDMi147744565.

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

MaxQBiP0DMV9.
PRIDEiP0DMV9.

2D gel databases

REPRODUCTION-2DPAGEiIPI00304925.

PTM databases

iPTMnetiP0DMV9.

Expressioni

Tissue specificityi

HSPA1B is testis-specific.

Inductioni

By heat shock.

Gene expression databases

BgeeiENSG00000204388.
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

  • C3HC4-type RING finger domain binding Source: BHF-UCL
  • enzyme binding Source: BHF-UCL
  • G-protein coupled receptor binding Source: ParkinsonsUK-UCL
  • heat shock protein binding Source: UniProtKB
  • histone deacetylase binding Source: BHF-UCL
  • protein binding involved in protein folding Source: BHF-UCL
  • protein N-terminus binding Source: UniProtKB
  • receptor binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
  • unfolded protein binding Source: UniProtKB

Protein-protein interaction databases

CORUMiP0DMV9.
IntActiP0DMV9. 2 interactors.
MINTiMINT-96699.

Chemistry databases

BindingDBiP0DMV9.

Structurei

Secondary structure

1641
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi7 – 11Combined sources5
Beta strandi13 – 22Combined sources10
Beta strandi25 – 28Combined sources4
Beta strandi36 – 39Combined sources4
Beta strandi42 – 44Combined sources3
Beta strandi49 – 51Combined sources3
Helixi53 – 57Combined sources5
Helixi59 – 61Combined sources3
Helixi63 – 65Combined sources3
Helixi70 – 73Combined sources4
Helixi81 – 87Combined sources7
Beta strandi91 – 99Combined sources9
Beta strandi101 – 107Combined sources7
Beta strandi110 – 114Combined sources5
Helixi116 – 135Combined sources20
Beta strandi141 – 146Combined sources6
Helixi152 – 164Combined sources13
Beta strandi168 – 174Combined sources7
Helixi175 – 182Combined sources8
Turni183 – 187Combined sources5
Beta strandi193 – 200Combined sources8
Beta strandi205 – 213Combined sources9
Beta strandi216 – 225Combined sources10
Helixi230 – 249Combined sources20
Helixi257 – 276Combined sources20
Beta strandi278 – 288Combined sources11
Beta strandi291 – 298Combined sources8
Helixi299 – 305Combined sources7
Helixi307 – 311Combined sources5
Helixi315 – 324Combined sources10
Helixi328 – 330Combined sources3
Beta strandi333 – 338Combined sources6
Helixi339 – 342Combined sources4
Helixi344 – 353Combined sources10
Turni354 – 356Combined sources3
Turni365 – 367Combined sources3
Helixi368 – 382Combined sources15
Helixi384 – 386Combined sources3
Helixi426 – 444Combined sources19
Helixi449 – 457Combined sources9
Helixi462 – 466Combined sources5
Helixi475 – 487Combined sources13
Helixi491 – 504Combined sources14
Helixi523 – 534Combined sources12
Helixi538 – 551Combined sources14
Helixi563 – 578Combined sources16
Helixi587 – 597Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4J8FX-ray2.70A1-382[»]
A384-600[»]
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

GeneTreeiENSGT00900000140908.
HOGENOMiHOG000228135.
HOVERGENiHBG051845.
KOiK03283.
OrthoDBiEOG093705LK.
PhylomeDBiP0DMV9.
TreeFamiTF105042.

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.
IPR029047. HSP70_peptide-bd.
IPR013126. Hsp_70_fam.
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.

Sequencei

Sequence statusi: Complete.

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

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

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

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: October 25, 2017
This is version 23 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. Human chromosome 6
    Human chromosome 6: 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
  6. SIMILARITY comments
    Index of protein domains and families