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Protein

Heat shock cognate 71 kDa protein

Gene

Hspa8

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Chaperone. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex (By similarity). Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion. Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase CHIP (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei71 – 711ATPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi12 – 154ATPBy similarity
Nucleotide bindingi202 – 2043ATPBy similarity
Nucleotide bindingi268 – 2758ATPBy similarity
Nucleotide bindingi339 – 3424ATPBy similarity

GO - Molecular functioni

  • A1 adenosine receptor binding Source: RGD
  • ADP binding Source: RGD
  • ATPase activity Source: MGI
  • ATPase activity, coupled Source: RGD
  • ATP binding Source: RGD
  • clathrin-uncoating ATPase activity Source: RGD
  • enzyme binding Source: RGD
  • peptide binding Source: RGD
  • prostaglandin binding Source: RGD
  • receptor binding Source: RGD
  • RNA binding Source: RGD
  • transcription factor binding Source: RGD
  • unfolded protein binding Source: RGD

GO - Biological processi

  • aging Source: RGD
  • axo-dendritic transport Source: RGD
  • cellular protein complex disassembly Source: MGI
  • cellular response to cadmium ion Source: RGD
  • cellular response to heat Source: RGD
  • cerebellum development Source: RGD
  • chaperone-mediated autophagy Source: ParkinsonsUK-UCL
  • chaperone-mediated autophagy translocation complex disassembly Source: ParkinsonsUK-UCL
  • chaperone-mediated protein folding Source: RGD
  • chaperone mediated protein folding requiring cofactor Source: RGD
  • chaperone-mediated protein transport involved in chaperone-mediated autophagy Source: MGI
  • clathrin coat disassembly Source: RGD
  • estrous cycle Source: RGD
  • forebrain development Source: RGD
  • G1/S transition of mitotic cell cycle Source: RGD
  • intracellular protein transmembrane import Source: RGD
  • kidney development Source: RGD
  • mRNA processing Source: UniProtKB-KW
  • negative regulation of cardiac muscle cell apoptotic process Source: RGD
  • negative regulation of hydrogen peroxide-induced cell death Source: RGD
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of catalytic activity Source: RGD
  • positive regulation of gene expression Source: RGD
  • positive regulation of lysosomal membrane permeability Source: RGD
  • positive regulation of phagocytosis Source: RGD
  • positive regulation of protein refolding Source: RGD
  • positive regulation of proteolysis Source: RGD
  • positive regulation of T cell mediated cytotoxicity Source: RGD
  • protein autophosphorylation Source: RGD
  • protein import into nucleus Source: RGD
  • protein refolding Source: ParkinsonsUK-UCL
  • regulation of protein complex stability Source: ParkinsonsUK-UCL
  • response to activity Source: RGD
  • response to drug Source: RGD
  • response to estradiol Source: RGD
  • response to ethanol Source: RGD
  • response to heat Source: RGD
  • response to nickel cation Source: RGD
  • response to odorant Source: RGD
  • response to progesterone Source: RGD
  • response to starvation Source: RGD
  • RNA splicing Source: UniProtKB-KW
  • sensory perception of smell Source: RGD
  • skeletal muscle tissue development Source: RGD
  • slow axonal transport Source: RGD
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chaperone, Repressor

Keywords - Biological processi

mRNA processing, mRNA splicing, Stress response, Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Heat shock cognate 71 kDa protein
Alternative name(s):
Heat shock 70 kDa protein 8
Gene namesi
Name:Hspa8
Synonyms:Hsc70, Hsc73
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621725. Hspa8.

Subcellular locationi

  • Cytoplasm By similarity
  • Melanosome By similarity
  • Nucleusnucleolus By similarity
  • Cell membrane By similarity

  • Note: Localized in cytoplasmic mRNP granules containing untranslated mRNAs. Translocates rapidly from the cytoplasm to the nuclei, and especially to the nucleoli, upon heat shock (By similarity).By similarity

GO - Cellular componenti

  • asymmetric synapse Source: RGD
  • autophagosome Source: RGD
  • axon Source: RGD
  • cell surface Source: RGD
  • cytoplasm Source: RGD
  • cytosol Source: RGD
  • dendrite Source: RGD
  • dendritic shaft Source: RGD
  • dendritic spine Source: RGD
  • extracellular exosome Source: RGD
  • intermediate filament Source: RGD
  • intracellular ribonucleoprotein complex Source: UniProtKB
  • lysosomal matrix Source: MGI
  • lysosomal membrane Source: ParkinsonsUK-UCL
  • lysosome Source: RGD
  • melanosome Source: UniProtKB-SubCell
  • membrane raft Source: RGD
  • messenger ribonucleoprotein complex Source: RGD
  • microtubule Source: RGD
  • neuronal cell body Source: RGD
  • neuron projection Source: RGD
  • nucleolus Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
  • perikaryon Source: RGD
  • perinuclear region of cytoplasm Source: RGD
  • photoreceptor inner segment Source: RGD
  • plasma membrane Source: UniProtKB-SubCell
  • postsynaptic density Source: RGD
  • protein complex Source: RGD
  • Prp19 complex Source: UniProtKB
  • spliceosomal complex Source: UniProtKB-KW
  • synaptic vesicle Source: RGD
  • terminal bouton Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus, Spliceosome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 646645Heat shock cognate 71 kDa proteinPRO_0000078273Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Modified residuei108 – 1081N6-acetyllysineBy similarity
Modified residuei153 – 1531PhosphoserineBy similarity
Modified residuei246 – 2461N6-acetyllysineBy similarity
Modified residuei319 – 3191N6-acetyllysine; alternateBy similarity
Modified residuei319 – 3191N6-succinyllysine; alternateBy similarity
Modified residuei328 – 3281N6-acetyllysineBy similarity
Modified residuei329 – 3291PhosphoserineBy similarity
Modified residuei362 – 3621PhosphoserineBy similarity
Modified residuei512 – 5121N6-acetyllysine; alternateBy similarity
Modified residuei512 – 5121N6-succinyllysine; alternateBy similarity
Cross-linki512 – 512Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateBy similarity
Cross-linki512 – 512Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei524 – 5241N6-acetyllysineBy similarity
Modified residuei541 – 5411PhosphoserineBy similarity
Modified residuei561 – 5611N6,N6,N6-trimethyllysine; by METTL21ABy similarity
Modified residuei589 – 5891N6-acetyllysineBy similarity
Modified residuei597 – 5971N6-acetyllysineBy similarity
Modified residuei601 – 6011N6-acetyllysineBy similarity

Post-translational modificationi

Acetylated.By similarity
ISGylated.By similarity
Trimethylation at Lys-561 reduces fibrillar SNCA binding.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP63018.
PRIDEiP63018.

2D gel databases

World-2DPAGE0004:P63018.

PTM databases

iPTMnetiP63018.
PhosphoSiteiP63018.

Expressioni

Inductioni

Constitutively synthesized.

Interactioni

Subunit structurei

Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with PACRG. Interacts with HSPH1/HSP105. Interacts with IRAK1BP1 and BAG1. Interacts with DNAJC7 and DNAJB14 (via J domain) (PubMed:10567422). Interacts (via C-terminus) with the E3 ligase CHIP forming a 210 kDa complex of one CHIP and two HSPA8 molecules. Interacts with CITED1 (via N-terminus); the interaction suppresses the association of CITED1 to p300/CBP and Smad-mediated transcription transactivation. Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts with TRIM5. Part of a complex composed at least of ASCL2, EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may have a histone H3-specific methyltransferase activity. Following LPS binding, may form a complex with CXCR4, GDF5 and HSP90AA1. Interacts with PARK2. Interacts with FOXP3. Interacts with DNAJC9 (via J domain) (By similarity). Interacts with MLLT11. Interacts with RNF207 (By similarity).By similarity1 Publication

GO - Molecular functioni

  • A1 adenosine receptor binding Source: RGD
  • enzyme binding Source: RGD
  • receptor binding Source: RGD
  • transcription factor binding Source: RGD
  • unfolded protein binding Source: RGD

Protein-protein interaction databases

BioGridi246629. 16 interactions.
DIPiDIP-33262N.
IntActiP63018. 8 interactions.
MINTiMINT-2514077.
STRINGi10116.ENSRNOP00000058593.

Structurei

Secondary structure

1
646
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi6 – 105Combined sources
Beta strandi13 – 2210Combined sources
Beta strandi25 – 284Combined sources
Beta strandi32 – 343Combined sources
Beta strandi41 – 444Combined sources
Beta strandi49 – 524Combined sources
Helixi53 – 586Combined sources
Turni59 – 613Combined sources
Beta strandi66 – 683Combined sources
Turni71 – 755Combined sources
Helixi81 – 866Combined sources
Beta strandi91 – 977Combined sources
Beta strandi100 – 1056Combined sources
Beta strandi112 – 1143Combined sources
Helixi116 – 13520Combined sources
Beta strandi141 – 1466Combined sources
Helixi152 – 16514Combined sources
Beta strandi168 – 1747Combined sources
Helixi175 – 1828Combined sources
Turni183 – 1864Combined sources
Beta strandi193 – 2008Combined sources
Beta strandi205 – 2139Combined sources
Beta strandi216 – 2238Combined sources
Helixi230 – 24920Combined sources
Helixi257 – 27620Combined sources
Beta strandi278 – 28811Combined sources
Beta strandi291 – 2988Combined sources
Helixi299 – 3057Combined sources
Helixi307 – 3126Combined sources
Helixi314 – 32310Combined sources
Helixi328 – 3303Combined sources
Beta strandi332 – 3387Combined sources
Helixi339 – 3424Combined sources
Helixi344 – 35310Combined sources
Turni354 – 3563Combined sources
Turni365 – 3673Combined sources
Helixi368 – 38013Combined sources
Beta strandi388 – 3914Combined sources
Beta strandi396 – 3994Combined sources
Beta strandi401 – 4055Combined sources
Turni406 – 4083Combined sources
Beta strandi409 – 4113Combined sources
Beta strandi418 – 42912Combined sources
Beta strandi431 – 4344Combined sources
Beta strandi438 – 4458Combined sources
Beta strandi447 – 4504Combined sources
Beta strandi452 – 46110Combined sources
Beta strandi468 – 4703Combined sources
Beta strandi472 – 48110Combined sources
Turni482 – 4843Combined sources
Beta strandi485 – 4928Combined sources
Turni493 – 4964Combined sources
Beta strandi497 – 5037Combined sources
Helixi511 – 5188Combined sources
Turni519 – 5213Combined sources
Helixi522 – 5276Combined sources
Turni532 – 5343Combined sources
Beta strandi537 – 5415Combined sources
Helixi542 – 55312Combined sources
Helixi556 – 5583Combined sources
Turni559 – 5613Combined sources
Helixi564 – 59532Combined sources
Helixi597 – 61014Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CKRNMR-A385-543[»]
1Q2Gmodel-C385-543[»]
1UD0X-ray3.45A/B/C/D542-646[»]
2V7ZX-ray3.50A/B1-543[»]
7HSCNMR-A385-543[»]
ProteinModelPortaliP63018.
SMRiP63018. Positions 1-646.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP63018.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni186 – 377192Interaction with BAG1By similarityAdd
BLAST

Domaini

The N-terminal 1-386 residues constitute the ATPase domain, while residues 387-646 form the peptide-binding domain.By similarity

Sequence similaritiesi

Belongs to the heat shock protein 70 family.Curated

Phylogenomic databases

eggNOGiKOG0101. Eukaryota.
COG0443. LUCA.
HOVERGENiHBG051845.
InParanoidiP63018.
KOiK03283.
PhylomeDBiP63018.

Family and domain databases

Gene3Di1.20.1270.10. 1 hit.
2.60.34.10. 1 hit.
InterProiIPR018181. Heat_shock_70_CS.
IPR029048. HSP70_C.
IPR029047. HSP70_peptide-bd.
IPR013126. Hsp_70_fam.
[Graphical view]
PfamiPF00012. HSP70. 1 hit.
[Graphical view]
PRINTSiPR00301. HEATSHOCK70.
SUPFAMiSSF100920. SSF100920. 1 hit.
SSF100934. SSF100934. 1 hit.
PROSITEiPS00297. HSP70_1. 1 hit.
PS00329. HSP70_2. 1 hit.
PS01036. HSP70_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P63018-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSKGPAVGID LGTTYSCVGV FQHGKVEIIA NDQGNRTTPS YVAFTDTERL
60 70 80 90 100
IGDAAKNQVA MNPTNTVFDA KRLIGRRFDD AVVQSDMKHW PFMVVNDAGR
110 120 130 140 150
PKVQVEYKGE TKSFYPEEVS SMVLTKMKEI AEAYLGKTVT NAVVTVPAYF
160 170 180 190 200
NDSQRQATKD AGTIAGLNVL RIINEPTAAA IAYGLDKKVG AERNVLIFDL
210 220 230 240 250
GGGTFDVSIL TIEDGIFEVK STAGDTHLGG EDFDNRMVNH FIAEFKRKHK
260 270 280 290 300
KDISENKRAV RRLRTACERA KRTLSSSTQA SIEIDSLYEG IDFYTSITRA
310 320 330 340 350
RFEELNADLF RGTLDPVEKA LRDAKLDKSQ IHDIVLVGGS TRIPKIQKLL
360 370 380 390 400
QDFFNGKELN KSINPDEAVA YGAAVQAAIL SGDKSENVQD LLLLDVTPLS
410 420 430 440 450
LGIETAGGVM TVLIKRNTTI PTKQTQTFTT YSDNQPGVLI QVYEGERAMT
460 470 480 490 500
KDNNLLGKFE LTGIPPAPRG VPQIEVTFDI DANGILNVSA VDKSTGKENK
510 520 530 540 550
ITITNDKGRL SKEDIERMVQ EAEKYKAEDE KQRDKVSSKN SLESYAFNMK
560 570 580 590 600
ATVEDEKLQG KINDEDKQKI LDKCNEIISW LDKNQTAEKE EFEHQQKELE
610 620 630 640
KVCNPIITKL YQSAGGMPGG MPGGFPGGGA PPSGGASSGP TIEEVD
Length:646
Mass (Da):70,871
Last modified:August 1, 1988 - v1
Checksum:i03A27B30E6C076ED
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00054 Genomic DNA. Translation: CAA68265.1.
M11942 mRNA. Translation: AAA41354.1.
BC061547 mRNA. Translation: AAH61547.1.
BC098914 mRNA. Translation: AAH98914.1.
PIRiS07197.
RefSeqiNP_077327.1. NM_024351.2.
UniGeneiRn.120392.
Rn.129299.
Rn.201298.

Genome annotation databases

GeneIDi24468.
KEGGirno:24468.
UCSCiRGD:621725. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00054 Genomic DNA. Translation: CAA68265.1.
M11942 mRNA. Translation: AAA41354.1.
BC061547 mRNA. Translation: AAH61547.1.
BC098914 mRNA. Translation: AAH98914.1.
PIRiS07197.
RefSeqiNP_077327.1. NM_024351.2.
UniGeneiRn.120392.
Rn.129299.
Rn.201298.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CKRNMR-A385-543[»]
1Q2Gmodel-C385-543[»]
1UD0X-ray3.45A/B/C/D542-646[»]
2V7ZX-ray3.50A/B1-543[»]
7HSCNMR-A385-543[»]
ProteinModelPortaliP63018.
SMRiP63018. Positions 1-646.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246629. 16 interactions.
DIPiDIP-33262N.
IntActiP63018. 8 interactions.
MINTiMINT-2514077.
STRINGi10116.ENSRNOP00000058593.

PTM databases

iPTMnetiP63018.
PhosphoSiteiP63018.

2D gel databases

World-2DPAGE0004:P63018.

Proteomic databases

PaxDbiP63018.
PRIDEiP63018.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi24468.
KEGGirno:24468.
UCSCiRGD:621725. rat.

Organism-specific databases

CTDi3312.
RGDi621725. Hspa8.

Phylogenomic databases

eggNOGiKOG0101. Eukaryota.
COG0443. LUCA.
HOVERGENiHBG051845.
InParanoidiP63018.
KOiK03283.
PhylomeDBiP63018.

Miscellaneous databases

EvolutionaryTraceiP63018.
PROiP63018.

Family and domain databases

Gene3Di1.20.1270.10. 1 hit.
2.60.34.10. 1 hit.
InterProiIPR018181. Heat_shock_70_CS.
IPR029048. HSP70_C.
IPR029047. HSP70_peptide-bd.
IPR013126. Hsp_70_fam.
[Graphical view]
PfamiPF00012. HSP70. 1 hit.
[Graphical view]
PRINTSiPR00301. HEATSHOCK70.
SUPFAMiSSF100920. SSF100920. 1 hit.
SSF100934. SSF100934. 1 hit.
PROSITEiPS00297. HSP70_1. 1 hit.
PS00329. HSP70_2. 1 hit.
PS01036. HSP70_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHSP7C_RAT
AccessioniPrimary (citable) accession number: P63018
Secondary accession number(s): P08109
, P12225, Q4FZY7, Q62373, Q62374, Q62375
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: July 6, 2016
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

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.