Overview
| Uniprot ID | P0DMW1 |
|---|
| Protein Name | Heat shock 70 kDa protein 1B |
|---|
| Gene Name | Hspa1b |
|---|
| Organism | Rattus norvegicus |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 328 |
LRDAKLDKAQIHDLV |
| 71 |
QNTVFDAKRLIGRKF |
Function
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. 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. 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. Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling. Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation
Protein Sequence
10
MAKKTAIGID
20
LGTTYSCVGV
30
FQHGKVEIIA
40
NDQGNRTTPS
50
YVAFTDTERL
60
IGDAAKNQVA
70
LNPQNTVFDA
80
KRLIGRKFGD
90
PVVQSDMKHW
100
PFQVVNDGDK
110
PKVQVNYKGE
120
NRSFYPEEIS
130
SMVLTKMKEI
140
AEAYLGHPVT
150
NAVITVPAYF
160
NDSQRQATKD
170
AGVIAGLNVL
180
RIINEPTAAA
190
IAYGLDRTGK
200
GERNVLIFDL
210
GGGTFDVSIL
220
TIDDGIFEVK
230
ATAGDTHLGG
240
EDFDNRLVSH
250
FVEEFKRKHK
260
KDISQNKRAV
270
RRLRTACERA
280
KRTLSSSTQA
290
SLEIDSLFEG
300
IDFYTSITRA
310
RFEELCSDLF
320
RGTLEPVEKA
330
LRDAKLDKAQ
340
IHDLVLVGGS
350
TRIPKVQKLL
360
QDFFNGRDLN
370
KSINPDEAVA
380
YGAAVQAAIL
390
MGDKSENVQD
400
LLLLDVAPLS
410
LGLETAGGVM
420
TALIKRNSTI
430
PTKQTQTFTT
440
YSDNQPGVLI
450
QVYEGERAMT
460
RDNNLLGRFE
470
LSGIPPAPRG
480
VPQIEVTFDI
490
DANGILNVTA
500
TDKSTGKANK
510
ITITNDKGRL
520
SKEEIERMVQ
530
EAERYKAEDE
540
VQRERVAAKN
550
ALESYAFNMK
560
SAVEDEGLKG
570
KISEADKKKV
580
LDKCQEVISW
590
LDSNTLAEKE
600
EFVHKREELE
610
RVCNPIISGL
620
YQGAGAPGAG
630
GFGAQAPKGG
640
SGSGPTIEEV
D
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005813 |
centrosome |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0045121 |
membrane raft |
| Cellular Component |
GO:0016607 |
nuclear speck |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0048471 |
perinuclear region of cytoplasm |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0016887 |
ATP hydrolysis activity |
| Molecular Function |
GO:0031072 |
heat shock protein binding |
| Molecular Function |
GO:0051059 |
NF-kappaB binding |
| Molecular Function |
GO:0002020 |
protease binding |
| Molecular Function |
GO:0044183 |
protein folding chaperone |
| Biological Process |
GO:0006952 |
defense response |
| Biological Process |
GO:0006402 |
mRNA catabolic process |
| Biological Process |
GO:0030308 |
negative regulation of cell growth |
| Biological Process |
GO:0008285 |
negative regulation of cell population proliferation |
| Biological Process |
GO:0090201 |
negative regulation of release of cytochrome c from mitochondria |
| Biological Process |
GO:0045906 |
negative regulation of vasoconstriction |
| Biological Process |
GO:0090063 |
positive regulation of microtubule nucleation |
| Biological Process |
GO:0032436 |
positive regulation of proteasomal ubiquitin-dependent protein catabolic process |
| Biological Process |
GO:0001916 |
positive regulation of T cell mediated cytotoxicity |
| Biological Process |
GO:0042026 |
protein refolding |
| Biological Process |
GO:1901673 |
regulation of mitotic spindle assembly |
| Biological Process |
GO:0006986 |
response to unfolded protein |
Reference
[1] Sheng L, Xu H, Wang Y, Ni J, Xiang T et al.. Systematic analysis of lysine lactylation in nucleus pulposus cells.. iScience 27(11):111157. 2024 Nov 15. PMID: 39524337.