Seroatlas · Human Serome Atlas

HSPA5

Endoplasmic reticulum chaperone BiP

Also known as: BiP, BIP_HUMAN, GRP78

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P11021
Gene
HSPA5
Ensembl
ENSG00000044574
Chromosome
9
Canonical length
654 aa
Protein class
Disease related genes, Enzymes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Transporters
Subcellular location
Cytosol,Mid piece,Principal piece,End piece,Annulus
Secretome location
Intracellular and membrane
Quaternary structure
Homooligomer

OverviewNCBI Gene

The protein encoded by this gene is a member of the heat shock protein 70 (HSP70) family. This protein localizes to the lumen of the endoplasmic reticulum (ER) where it operates as a typical HSP70 chaperone involved in the folding and assembly of proteins in the ER and is a master regulator of ER homeostasis. During cellular stress, as during viral infection or tumorogenesis, this protein interacts with the transmembrane stress sensor proteins PERK (protein kinase R-like endoplasmic reticulum kinase), IRE1 (inositol-requiring kinase 1), and ATF6 (activating transcription factor 6) where it acts as a repressor of the unfolded protein response (UPR) and also plays a role in cellular apoptosis and senescence. Elevated expression and atypical translocation of this protein to the cell surface has been reported in viral infections and some types of cancer cells. At the cell surface this protein may facilitate viral attachment and entry to host cells. This gene is a therapeutic target for the treatment of coronavirus diseases and chemoresistant cancers. [provided by RefSeq, Jul 2020]

Canonical amino-acid sequenceUniProt

654 residues, UniProt reviewed canonical sequence.

>P11021|HSPA5
     1  MKLSLVAAML LLLSAARAEE EDKKEDVGTV VGIDLGTTYS CVGVFKNGRV EIIANDQGNR
    61  ITPSYVAFTP EGERLIGDAA KNQLTSNPEN TVFDAKRLIG RTWNDPSVQQ DIKFLPFKVV
   121  EKKTKPYIQV DIGGGQTKTF APEEISAMVL TKMKETAEAY LGKKVTHAVV TVPAYFNDAQ
   181  RQATKDAGTI AGLNVMRIIN EPTAAAIAYG LDKREGEKNI LVFDLGGGTF DVSLLTIDNG
   241  VFEVVATNGD THLGGEDFDQ RVMEHFIKLY KKKTGKDVRK DNRAVQKLRR EVEKAKRALS
   301  SQHQARIEIE SFYEGEDFSE TLTRAKFEEL NMDLFRSTMK PVQKVLEDSD LKKSDIDEIV
   361  LVGGSTRIPK IQQLVKEFFN GKEPSRGINP DEAVAYGAAV QAGVLSGDQD TGDLVLLDVC
   421  PLTLGIETVG GVMTKLIPRN TVVPTKKSQI FSTASDNQPT VTIKVYEGER PLTKDNHLLG
   481  TFDLTGIPPA PRGVPQIEVT FEIDVNGILR VTAEDKGTGN KNKITITNDQ NRLTPEEIER
   541  MVNDAEKFAE EDKKLKERID TRNELESYAY SLKNQIGDKE KLGGKLSSED KETMEKAVEE
   601  KIEWLESHQD ADIEDFKAKK KELEEIVQPI ISKLYGSAGP PPTGEEDTAE KDEL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HSPA5 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Cell surface
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.26
Highest tissue expression
809 nTPM

Expression across tissuesHPA

Tissue

  • bone marrow: 809 nTPM
  • thyroid gland: 648 nTPM
  • epididymis: 358 nTPM
  • liver: 314 nTPM
  • placenta: 293 nTPM
  • heart muscle: 277 nTPM

Single-cell type

  • epididymal basal cells: 2,675 nCPM
  • epididymal principal cells: 2,136 nCPM
  • syncytiotrophoblasts: 1,847 nCPM
  • plasma cells: 1,403 nCPM
  • extravillous trophoblasts: 1,248 nCPM
  • pancreatic duct cells: 902 nCPM

Immune cell

  • total PBMC: 758 nTPM
  • basophil: 457 nTPM
  • MAIT T-cell: 391 nTPM
  • gdT-cell: 386 nTPM
  • classical monocyte: 367 nTPM
  • NK-cell: 364 nTPM

Brain region

  • white matter: 260 nTPM
  • hypothalamus: 184 nTPM
  • medulla oblongata: 172 nTPM
  • pons: 156 nTPM
  • choroid plexus: 153 nTPM
  • spinal cord: 151 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HSPA5.

Disease | ImmuneIEDB

Conditions an epitope on HSPA5 was assayed in.

Disease | AutoantibodyPubMed

Conditions in which antibodies against HSPA5 are reported. Each links to that disease's full target list.

Showing 3 of 5 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for HSPA5 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Reference: AutoantibodyPubMed

37 publications

Show 20 more of 37 total

Reference: B cellIEDB

4 publications

Reference: T cellIEDB

6 publications

Show 1 more

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.41
gnomAD pLI
0.77
gnomAD missense Z
4.03
DepMap mean gene effect
-1.25
DepMap dependency class
common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of HSPA5 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads HSPA5 as an antibody target. Whether an autoantibody or antibody against HSPA5 could matter depends on whether native HSPA5 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

HSPA5 is annotated at the cell surface, where native HSPA5 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label HSPA5 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/HSPA5. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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