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Protein

Heat shock 70 kDa protein 1-like

Gene

HSPA1L

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 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 (PubMed:26865365). Positive regulator of PRKN translocation to damaged mitochondria (PubMed:24270810).1 Publication1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei73ATP1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi14 – 17ATP4
Nucleotide bindingi204 – 206ATP3
Nucleotide bindingi270 – 277ATP8
Nucleotide bindingi341 – 344ATP4

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • heat shock protein binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
  • unfolded protein binding Source: UniProtKB

GO - Biological processi

  • binding of sperm to zona pellucida Source: Ensembl
  • positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
  • protein refolding Source: UniProtKB
  • regulation of cellular response to heat Source: Reactome
  • response to unfolded protein Source: ProtInc

Keywordsi

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.

Names & Taxonomyi

Protein namesi
Recommended name:
Heat shock 70 kDa protein 1-like
Short name:
Heat shock 70 kDa protein 1L
Alternative name(s):
Heat shock 70 kDa protein 1-Hom
Short name:
HSP70-Hom
Gene namesi
Name:HSPA1L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000204390.9.
HGNCiHGNC:5234. HSPA1L.

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi73K → E: No rescue of PRKN translocation deficit in knockout cells. 1 Publication1
Mutagenesisi396L → D: No rescue of PRKN translocation deficit in knockout cells. 1 Publication1
Mutagenesisi638 – 641Missing : No rescue of PRKN translocation deficit in knockout cells. 1 Publication4

Organism-specific databases

DisGeNETi3305.
OpenTargetsiENSG00000204390.
PharmGKBiPA29500.

Polymorphism and mutation databases

BioMutaiHSPA1L.
DMDMi23831140.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000782551 – 641Heat shock 70 kDa protein 1-likeAdd BLAST641

Proteomic databases

EPDiP34931.
MaxQBiP34931.
PaxDbiP34931.
PeptideAtlasiP34931.
PRIDEiP34931.
TopDownProteomicsiP34931.

2D gel databases

UCD-2DPAGEiP34931.

PTM databases

iPTMnetiP34931.
PhosphoSitePlusiP34931.
SwissPalmiP34931.

Expressioni

Tissue specificityi

Expressed in spermatids.1 Publication

Inductioni

Not induced by heat shock.1 Publication

Gene expression databases

BgeeiENSG00000204390.
CleanExiHS_HSPA1L.
GenevisibleiP34931. HS.

Organism-specific databases

HPAiHPA043285.
HPA052504.

Interactioni

Subunit structurei

Interacts with PRKN.2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • heat shock protein binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
  • unfolded protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109537. 162 interactors.
ELMiP34931.
IntActiP34931. 79 interactors.
MINTiMINT-1136903.
STRINGi9606.ENSP00000364805.

Structurei

Secondary structure

1641
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi9 – 12Combined sources4
Beta strandi15 – 24Combined sources10
Beta strandi27 – 30Combined sources4
Beta strandi38 – 41Combined sources4
Beta strandi44 – 46Combined sources3
Beta strandi51 – 53Combined sources3
Helixi55 – 59Combined sources5
Helixi60 – 63Combined sources4
Helixi65 – 67Combined sources3
Helixi72 – 75Combined sources4
Helixi83 – 89Combined sources7
Beta strandi93 – 99Combined sources7
Beta strandi102 – 109Combined sources8
Beta strandi112 – 116Combined sources5
Helixi118 – 137Combined sources20
Beta strandi143 – 148Combined sources6
Helixi154 – 166Combined sources13
Beta strandi170 – 176Combined sources7
Helixi177 – 184Combined sources8
Turni185 – 188Combined sources4
Beta strandi195 – 202Combined sources8
Beta strandi207 – 215Combined sources9
Beta strandi218 – 227Combined sources10
Helixi232 – 251Combined sources20
Helixi255 – 257Combined sources3
Helixi259 – 275Combined sources17
Turni276 – 278Combined sources3
Beta strandi279 – 290Combined sources12
Beta strandi293 – 300Combined sources8
Helixi301 – 307Combined sources7
Helixi309 – 314Combined sources6
Helixi316 – 325Combined sources10
Helixi330 – 332Combined sources3
Beta strandi335 – 340Combined sources6
Helixi341 – 344Combined sources4
Helixi346 – 355Combined sources10
Turni356 – 358Combined sources3
Turni367 – 369Combined sources3
Helixi370 – 383Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3GDQX-ray1.80A1-386[»]
ProteinModelPortaliP34931.
SMRiP34931.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP34931.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni3 – 388Nucleotide-binding domain (NBD)By similarityAdd BLAST386
Regioni396 – 511Substrate-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.1 Publication

Sequence similaritiesi

Belongs to the heat shock protein 70 family.Curated

Phylogenomic databases

eggNOGiKOG0101. Eukaryota.
COG0443. LUCA.
GeneTreeiENSGT00890000139483.
HOVERGENiHBG051845.
InParanoidiP34931.
KOiK03283.
OMAiGEKKAFY.
OrthoDBiEOG091G03SF.
PhylomeDBiP34931.
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.

P34931-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATAKGIAIG IDLGTTYSCV GVFQHGKVEI IANDQGNRTT PSYVAFTDTE
60 70 80 90 100
RLIGDAAKNQ VAMNPQNTVF DAKRLIGRKF NDPVVQADMK LWPFQVINEG
110 120 130 140 150
GKPKVLVSYK GENKAFYPEE ISSMVLTKLK ETAEAFLGHP VTNAVITVPA
160 170 180 190 200
YFNDSQRQAT KDAGVIAGLN VLRIINEPTA AAIAYGLDKG GQGERHVLIF
210 220 230 240 250
DLGGGTFDVS ILTIDDGIFE VKATAGDTHL GGEDFDNRLV SHFVEEFKRK
260 270 280 290 300
HKKDISQNKR AVRRLRTACE RAKRTLSSST QANLEIDSLY EGIDFYTSIT
310 320 330 340 350
RARFEELCAD LFRGTLEPVE KALRDAKMDK AKIHDIVLVG GSTRIPKVQR
360 370 380 390 400
LLQDYFNGRD LNKSINPDEA VAYGAAVQAA ILMGDKSEKV QDLLLLDVAP
410 420 430 440 450
LSLGLETAGG VMTALIKRNS TIPTKQTQIF TTYSDNQPGV LIQVYEGERA
460 470 480 490 500
MTKDNNLLGR FDLTGIPPAP RGVPQIEVTF DIDANGILNV TATDKSTGKV
510 520 530 540 550
NKITITNDKG RLSKEEIERM VLDAEKYKAE DEVQREKIAA KNALESYAFN
560 570 580 590 600
MKSVVSDEGL KGKISESDKN KILDKCNELL SWLEVNQLAE KDEFDHKRKE
610 620 630 640
LEQMCNPIIT KLYQGGCTGP ACGTGYVPGR PATGPTIEEV D
Length:641
Mass (Da):70,375
Last modified:October 10, 2002 - v2
Checksum:iA9339D7657166FF7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti408A → V in AAA63228 (PubMed:1700760).Curated1
Sequence conflicti416I → M in AAH34483 (PubMed:15489334).Curated1
Sequence conflicti424T → P in AAA63228 (PubMed:1700760).Curated1
Sequence conflicti506T → A in AAH34483 (PubMed:15489334).Curated1
Sequence conflicti627V → M in BAA32521 (PubMed:9685725).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0258418A → P1 PublicationCorresponds to variant dbSNP:rs9469057Ensembl.1
Natural variantiVAR_025842268A → T1 PublicationCorresponds to variant dbSNP:rs34620296Ensembl.1
Natural variantiVAR_025843294D → G1 PublicationCorresponds to variant dbSNP:rs34360259Ensembl.1
Natural variantiVAR_025844479T → M1 PublicationCorresponds to variant dbSNP:rs482145Ensembl.1
Natural variantiVAR_003820493T → M4 PublicationsCorresponds to variant dbSNP:rs2227956Ensembl.1
Natural variantiVAR_025845558E → A1 PublicationCorresponds to variant dbSNP:rs2227955Ensembl.1
Natural variantiVAR_025846602E → K1 PublicationCorresponds to variant dbSNP:rs2075800Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M59829 Genomic DNA. Translation: AAA63228.1.
D85730 mRNA. Translation: BAA32521.1.
AF134726 Genomic DNA. Translation: AAD21817.1.
BA000025 Genomic DNA. Translation: BAB63301.1.
DQ383515 Genomic DNA. Translation: ABC88476.1.
AL662834 Genomic DNA. No translation available.
AL671762 Genomic DNA. No translation available.
AL929592 Genomic DNA. No translation available.
CR388202 Genomic DNA. No translation available.
BC034483 mRNA. Translation: AAH34483.1.
CCDSiCCDS34413.1.
PIRiB45871.
RefSeqiNP_005518.3. NM_005527.3.
UniGeneiHs.690634.

Genome annotation databases

EnsembliENST00000375654; ENSP00000364805; ENSG00000204390.
ENST00000383390; ENSP00000372881; ENSG00000206383.
ENST00000417601; ENSP00000396486; ENSG00000234258.
ENST00000456772; ENSP00000408347; ENSG00000236251.
GeneIDi3305.
KEGGihsa:3305.
UCSCiuc003nxh.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHS71L_HUMAN
AccessioniPrimary (citable) accession number: P34931
Secondary accession number(s): A6NNB0
, B0UXW8, O75634, Q2HXR3, Q8NE72, Q96QC9, Q9UQM1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: October 10, 2002
Last modified: September 27, 2017
This is version 166 of the entry and version 2 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 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