Reviewed, UniProtKB/Swiss-Prot P11021 (GRP78_HUMAN)

Names and origin

Protein names

Recommended name:
    78 kDa glucose-regulated protein
      Short name=GRP-78
Alternative name(s):
    Heat shock 70 kDa protein 5
    Immunoglobulin heavy chain-binding protein
      Short name=BiP
    Endoplasmic reticulum lumenal Ca(2+)-binding protein grp78

Gene names

Name:	HSPA5
Synonyms:	GRP78

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	654 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Probably plays a role in facilitating the assembly of multimeric protein complexes inside the ER. Ref.12
Subunit structure	Interacts with DNAJC1 (via J domain) By similarity. Component of an EIF2 complex at least composed of CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5. Part a large chaperone multiprotein complex comprising CABP1, DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PPIB, SDF2L1, UGT1A1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX. Interacts with TMEM132A. May form a complex with ERLEC1, OS9, SEL1L and SYVN1. Ref.20 Ref.21
Subcellular location	Endoplasmic reticulum lumen. Melanosome. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Ref.16 Ref.17
Involvement in disease	Autoantigen in rheumatoid arthritis [MIM:180300]. Ref.10
Sequence similarities	Belongs to the heat shock protein 70 family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	ATP-binding Nucleotide-binding
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	anti-apoptosis Inferred from mutant phenotype. Source: UniProtKB cellular response to glucose starvation Inferred from direct assay. Source: UniProtKB negative regulation of caspase activity Inferred from direct assay. Source: UniProtKB
Cellular component	ER-Golgi intermediate compartment Inferred from direct assay. Source: UniProtKB cell surface Inferred from direct assay. Source: UniProtKB endoplasmic reticulum lumen Traceable author statement. Source: UniProtKB integral to endoplasmic reticulum membrane Inferred from direct assay. Source: UniProtKB melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Non-traceable author statement. Source: UniProtKB calcium ion binding Traceable author statement. Source: UniProtKB caspase inhibitor activity Inferred from direct assay. Source: UniProtKB protein binding, bridging Non-traceable author statement. Source: UniProtKB unfolded protein binding Traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EIF2AK3	Q9NZJ5	1	EBI-354921,EBI-766076
NDRG1	Q92597	1	EBI-354921,EBI-716486
PAWR	Q96IZ0	4	EBI-354921,EBI-595869
Pawr	Q62627	2	EBI-354921,EBI-1187240	From a different organism.
PTEN	P60484	1	EBI-354921,EBI-696162
RAF1	P04049	3	EBI-354921,EBI-365996

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Ref.12 Ref.13
	Chain	19 – 654	636	78 kDa glucose-regulated protein		PRO_0000013566
Regions
	Motif	651 – 654	4	Prevents secretion from ER
Amino acid modifications
	Modified residue	166	1	Phosphothreonine By similarity
	Modified residue	268	1	N6-acetyllysine Ref.22
	Modified residue	466	1	Phosphotyrosine Ref.18
	Modified residue	571	1	Phosphoserine By similarity
Natural variations
	Natural variant	543	1	N → H: dbSNP rs35356639. Ref.5		VAR_025815
Experimental info
	Sequence conflict	297	1	Missing Ref.1
	Sequence conflict	297	1	Missing Ref.2
	Sequence conflict	418	1	D → H Ref.1
	Sequence conflict	418	1	D → H Ref.2
	Sequence conflict	439	1	R → S Ref.1
	Sequence conflict	439	1	R → S Ref.2
	Sequence conflict	447	1	K → N Ref.1
	Sequence conflict	447	1	K → N Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P11021-1 [UniParc]. Last modified July 11, 2001. Version 2. Checksum: 59B7D8D85BC32A00	FASTA	654	72,333
	10 20 30 40 50 60 MKLSLVAAML LLLSAARAEE EDKKEDVGTV VGIDLGTTYS CVGVFKNGRV EIIANDQGNR 70 80 90 100 110 120 ITPSYVAFTP EGERLIGDAA KNQLTSNPEN TVFDAKRLIG RTWNDPSVQQ DIKFLPFKVV 130 140 150 160 170 180 EKKTKPYIQV DIGGGQTKTF APEEISAMVL TKMKETAEAY LGKKVTHAVV TVPAYFNDAQ 190 200 210 220 230 240 RQATKDAGTI AGLNVMRIIN EPTAAAIAYG LDKREGEKNI LVFDLGGGTF DVSLLTIDNG 250 260 270 280 290 300 VFEVVATNGD THLGGEDFDQ RVMEHFIKLY KKKTGKDVRK DNRAVQKLRR EVEKAKRALS 310 320 330 340 350 360 SQHQARIEIE SFYEGEDFSE TLTRAKFEEL NMDLFRSTMK PVQKVLEDSD LKKSDIDEIV 370 380 390 400 410 420 LVGGSTRIPK IQQLVKEFFN GKEPSRGINP DEAVAYGAAV QAGVLSGDQD TGDLVLLDVC 430 440 450 460 470 480 PLTLGIETVG GVMTKLIPRN TVVPTKKSQI FSTASDNQPT VTIKVYEGER PLTKDNHLLG 490 500 510 520 530 540 TFDLTGIPPA PRGVPQIEVT FEIDVNGILR VTAEDKGTGN KNKITITNDQ NRLTPEEIER 550 560 570 580 590 600 MVNDAEKFAE EDKKLKERID TRNELESYAY SLKNQIGDKE KLGGKLSSED KETMEKAVEE 610 620 630 640 650 KIEWLESHQD ADIEDFKAKK KELEEIVQPI ISKLYGSAGP PPTGEEDTAE KDEL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human gene encoding the 78,000-dalton glucose-regulated protein and its pseudogene: structure, conservation, and regulation." Ting J., Lee A.S. DNA 7:275-286(1988) [PubMed: 2840249] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	Chao C.C.K. Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Cervix carcinoma.
[3]	"Grp78 is involved in the quality control of the LDL-receptor." Hansen J.J., Nielsen M.N., Jorgensen M.M., Gregersen N., Bolund L. Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fibroblast.
[4]	"Sequence differences between human grp78/BiP isolated from HeLa cells and previously reported human sequences." Bermudez-Fajardo A., Llewellyn D.H., Campbell A.K., Errington R.R. Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	NIEHS SNPs program Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HIS-543.
[6]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Muscle.
[9]	"A direct-repeat sequence of the human BiP gene is required for A23187-mediated inducibility and an inducible nuclear factor binding." Chao C.C.K., Lin-Chao S. Nucleic Acids Res. 20:6481-6485(1992) [PubMed: 1480470] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-25.
[10]	"The human endoplasmic reticulum molecular chaperone BiP is an autoantigen for rheumatoid arthritis and prevents the induction of experimental arthritis." Corrigall V.M., Bodman-Smith M.D., Fife M.S., Canas B., Myers L.K., Wooley P., Soh C., Staines N.A., Pappin D.J.C., Berlo S.E., van Eden W., van Der Zee R., Lanchbury J.S., Panayi G.S. J. Immunol. 166:1492-1498(2001) [PubMed: 11160188] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 20-650, DISEASE. Tissue: Articular cartilage.
[11]	"Two-dimensional electrophoretic analysis of human breast carcinoma proteins: mapping of proteins that bind to the SH3 domain of mixed lineage kinase MLK2." Rasmussen R.K., Ji H., Eddes J.S., Moritz R.L., Reid G.E., Simpson R.J., Dorow D.S. Electrophoresis 18:588-598(1997) [PubMed: 9150946] [Abstract] Cited for: PROTEIN SEQUENCE OF 22-38. Tissue: Mammary carcinoma.
[12]	"Heat shock proteins bind calcitonin." Dana R.C., Welch W.J., Deftos L.J. Endocrinology 126:672-674(1990) [PubMed: 2294010] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-39, FUNCTION.
[13]	"A two-dimensional gel database of human colon carcinoma proteins." Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J. Electrophoresis 18:605-613(1997) [PubMed: 9150948] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-40. Tissue: Colon carcinoma.
[14]	Lubec G., Vishwanath V., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 61-74; 82-96; 102-113; 124-152; 164-181; 186-214; 307-336; 353-367; 448-464; 475-492; 563-573; 602-617 AND 622-654, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[15]	"A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins." Meunier L., Usherwood Y.-K., Chung K.T., Hendershot L.M. Mol. Biol. Cell 13:4456-4469(2002) [PubMed: 12475965] [Abstract] Cited for: COMPONENT OF A CHAPERONE COMPLEX.
[16]	"Proteomic analysis of early melanosomes: identification of novel melanosomal proteins." Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., Appella E. J. Proteome Res. 2:69-79(2003) [PubMed: 12643545] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[17]	"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes." Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F. J. Proteome Res. 5:3135-3144(2006) [PubMed: 17081065] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[18]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-466, MASS SPECTROMETRY.
[19]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[20]	"Human XTP3-B forms an endoplasmic reticulum quality control scaffold with the HRD1-SEL1L ubiquitin ligase complex and BiP." Hosokawa N., Wada I., Nagasawa K., Moriyama T., Okawa K., Nagata K. J. Biol. Chem. 283:20914-20924(2008) [PubMed: 18502753] [Abstract] Cited for: INTERACTION WITH ERLEC1; OS9; SEL1L AND SYVN1.
[21]	"OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD." Christianson J.C., Shaler T.A., Tyler R.E., Kopito R.R. Nat. Cell Biol. 10:272-282(2008) [PubMed: 18264092] [Abstract] Cited for: INTERACTION WITH ERLEC1; OS9; SEL1L AND SYVN1.
[22]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-268, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M19645 Genomic DNA. Translation: AAA52614.1.
X87949 mRNA. Translation: CAA61201.1.
AJ271729 mRNA. Translation: CAB71335.1.
AF216292 mRNA. Translation: AAF42836.1.
DQ385847 Genomic DNA. Translation: ABD04090.1.
AL354710 Genomic DNA. Translation: CAQ08732.1.
CH471090 Genomic DNA. Translation: EAW87620.1.
BC020235 mRNA. Translation: AAH20235.1.
X59969 Genomic DNA. Translation: CAA42595.1.
AF188611 mRNA. Translation: AAF13605.1. Sequence problems.

IPI

IPI00003362.

PIR

A29821.

RefSeq

NP_005338.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3IUC	X-ray	2.40	A/C	26-410	[»]

SMR

P11021. Positions 28-570, 417-641.

ModBase

Search...

Protein-protein interaction databases

IntAct

P11021. 56 interactions.

STRING

P11021.

PTM databases

PhosphoSite

P11021.

2-D gel databases

SWISS-2DPAGE

P11021.

DOSAC-COBS-2DPAGE

P11021.

OGP

P11021.

PHCI-2DPAGE

P11021.

PMMA-2DPAGE

P11021.

REPRODUCTION-2DPAGE

P11021.

Siena-2DPAGE

P11021.

Proteomic databases

PRIDE

P11021.

Genome annotation databases

Ensembl

ENST00000324460; ENSP00000324173; ENSG00000044574; Homo sapiens. [Genome view]

GeneID

3309.

KEGG

hsa:3309.

UCSC

uc004bpn.1. human.

Organism-specific databases

CTD

3309.

GeneCards

GC09M127036.

H-InvDB

HIX0008382.

HGNC

HGNC:5238. HSPA5.

HPA

CAB005221.
CAB019420.

MIM

138120. gene.
180300. phenotype.

PharmGKB

PA29504.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG14855.

HOVERGEN

P11021.

InParanoid

P11021.

OMA

KNSKPHI.

OrthoDB

EOG9X6FTN.

PhylomeDB

P11021.

Enzyme and pathway databases

Reactome

REACT_15380. Diabetes pathways.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P11021.

Bgee

P11021.

CleanEx

HS_HSPA5.

Genevestigator

P11021.

GermOnline

ENSG00000044574. Homo sapiens.

Family and domain databases

InterPro

IPR018181. Heat_shock_70_CS.
IPR001023. Hsp70.
IPR013126. Hsp_70.
[Graphical view]

PANTHER

PTHR19375. Hsp70. 1 hit.

Pfam

PF00012. HSP70. 1 hit.
[Graphical view]

PRINTS

PR00301. HEATSHOCK70.

PROSITE

PS00014. ER_TARGET. 1 hit.
PS00297. HSP70_1. 1 hit.
PS00329. HSP70_2. 1 hit.
PS01036. HSP70_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00025. Antihemophilic Factor.

NextBio

13123.

SOURCE

Search...

Entry information

Entry name

GRP78_HUMAN

Accession

Primary (citable) accession number: P11021
Secondary accession number(s): B0QZ61 , Q2EF78, Q9NPF1, Q9UK02

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 11, 2001
Last modified:	February 9, 2010
This is version 122 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.