Reviewed, UniProtKB/Swiss-Prot Q99933 (BAG1_HUMAN)

Names and origin

Protein names

Recommended name:
    BAG family molecular chaperone regulator 1
      Short name=BAG-1
Alternative name(s):
    Bcl-2-associated athanogene 1
    Glucocorticoid receptor-associated protein RAP46

Gene names

Name:	BAG1
Synonyms:	HAP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	345 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Inhibits the chaperone activity of HSP70/HSC70 by promoting substrate release. Inhibits the pro-apoptotic function of PPP1R15A, and has anti-apoptotic activity. Markedly increases the anti-cell death function of BCL2 induced by various stimuli. Ref.7 Ref.9
Subunit structure	Binds to the ATPase domain of HSP70/HSC chaperones. Binds to BCL2 and NR3C1. Interacts with N-terminal region of STK19. Interacts with PPP1R15A. Isoform 2 doesn't interact with HSP70/HSC or BCL2. Ref.9 Ref.4 Ref.6 Ref.8
Subcellular location	Isoform 2: Cytoplasm. Nucleus. Note: Isoform2 localizes to the cytoplasm and shuttles into the nucleus in response to heat shock. Ref.4
Post-translational modification	Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its subsequent proteasomal degradation Probable.
Involvement in disease	May be linked to the cryptophthalmos syndrome (Fraser syndrome), an autosomal recessive disorder characterized by the failure of eyes fissures to form during embryogenesis, webbed fingers, and atresia of ear canals, anus, vagina, alimentary tract, or larynx. All these developmental processes require cell death.
Sequence similarities	Contains 1 BAG domain. Contains 1 ubiquitin-like domain.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat
Molecular function	Chaperone
PTM	Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	anti-apoptosis Traceable author statement. Source: ProtInc apoptosis Inferred from electronic annotation. Source: UniProtKB-KW cell surface receptor linked signal transduction Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Traceable author statement. Source: ProtInc nucleus Inferred from direct assay. Source: LIFEdb
Molecular function	protein binding Ref.10 Inferred from physical interaction. Source: IntAct receptor signaling protein activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HSPA8	P19120	1	EBI-1030678,EBI-907802	From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q99933-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q99933-2)

Also known as: BAG1V; HAPV;

The sequence of this isoform differs from the canonical sequence as follows:
     302-345: KDSRLKRKGLVKKVQAFLAECDTVEQNICQETERLQSTNFALAE → PTLTLVLNEK

Note: Isoform2 localizes to the cytoplasm and shuttles into the nucleus in response to heat shock. Ref.4

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 345

345

BAG family molecular chaperone regulator 1

PRO_0000088865

Regions

Repeat

96 – 101

6

1

Repeat

102 – 107

6

2

Repeat

108 – 113

6

3

Repeat

114 – 119

6

4

Repeat

120 – 125

6

5

Repeat

126 – 131

6

6

Repeat

132 – 137

6

7

Domain

144 – 224

81

Ubiquitin-like

Domain

246 – 326

81

BAG

Region

96 – 137

42

7 X 6 AA tandem repeat of E-E-X(4)

Region

216 – 345

130

Interaction with PPP1R15A

Compositional bias

4 – 82

79

Arg-rich

Natural variations

Alternative sequence

302 – 345

44

KDSRL…FALAE → PTLTLVLNEK in isoform 2.

VSP_000453

Experimental info

Sequence conflict

79

1

R → F in AAD11467. Ref.2

Sequence conflict

84

1

E → K in AAD11467. Ref.2

Sequence conflict

90

1

E → K in AAD11467. Ref.2

Sequence conflict

245

1

D → N in AAD11467. Ref.2

Sequence conflict

293

1

D → H in AAD11467. Ref.2

Secondary structure

1

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345

Helix Strand Turn

Details...

Beta strand

72 – 78

7

Beta strand

80 – 88

9

Beta strand

92 – 96

5

Helix

99 – 109

11

Turn

114 – 116

3

Beta strand

118 – 121

4

Beta strand

124 – 126

3

Beta strand

129 – 132

4

Helix

133 – 136

4

Beta strand

140 – 148

9

Helix

224 – 259

36

Helix

264 – 272

9

Helix

275 – 292

18

Helix

302 – 326

25

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 28, 2006. Version 3. Checksum: 9895EF082D73335B	FASTA	345	38,878
	10 20 30 40 50 60 MAQRGGARRP RGDRERLGSR LRALRPGREP RQSEPPAQRG PPPSRRPPAR STASGHDRPT 70 80 90 100 110 120 RGAAAGARRP RMKKKTRRRS TRSEELTRSE ELTLSEEATW SEEATQSEEA TQGEEMNRSQ 130 140 150 160 170 180 EVTRDEESTR SEEVTREEMA AAGLTVTVTH SNEKHDLHVT SQQGSSEPVV QDLAQVVEEV 190 200 210 220 230 240 IGVPQSFQKL IFKGKSLKEM ETPLSALGIQ DGCRVMLIGK KNSPQEEVEL KKLKHLEKSV 250 260 270 280 290 300 EKIADQLEEL NKELTGIQQG FLPKDLQAEA LCKLDRRVKA TIEQFMKILE EIDTLILPEN 310 320 330 340 FKDSRLKRKG LVKKVQAFLA ECDTVEQNIC QETERLQSTN FALAE
	Isoform 2 (BAG1V) (HAPV). Checksum: EA94BE05A7169FD3	FASTA	311	34,965
	10 20 30 40 50 60 MAQRGGARRP RGDRERLGSR LRALRPGREP RQSEPPAQRG PPPSRRPPAR STASGHDRPT 70 80 90 100 110 120 RGAAAGARRP RMKKKTRRRS TRSEELTRSE ELTLSEEATW SEEATQSEEA TQGEEMNRSQ 130 140 150 160 170 180 EVTRDEESTR SEEVTREEMA AAGLTVTVTH SNEKHDLHVT SQQGSSEPVV QDLAQVVEEV 190 200 210 220 230 240 IGVPQSFQKL IFKGKSLKEM ETPLSALGIQ DGCRVMLIGK KNSPQEEVEL KKLKHLEKSV 250 260 270 280 290 300 EKIADQLEEL NKELTGIQQG FLPKDLQAEA LCKLDRRVKA TIEQFMKILE EIDTLILPEN 310 FPTLTLVLNE K

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A protein that interacts with members of the nuclear hormone receptor family: identification and cDNA cloning." Zeiner M., Gehring U. Proc. Natl. Acad. Sci. U.S.A. 92:11465-11469(1995) [PubMed: 8524784] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[2]	"Cloning of cDNAs encoding the human BAG1 protein and localization of the human BAG1 gene to chromosome 9p12." Takayama S., Kochel K., Irie S., Inazawa J., Abe T., Sato T., Druck T., Huebner K., Reed J.C. Genomics 35:494-498(1996) [PubMed: 8812483] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Mammary gland.
[3]	Takayama S. Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO N-TERMINUS; 79; 84; 90; 245 AND 293.
[4]	"Characterization of Hap/BAG-1 variants as RP1 binding proteins with antiapoptotic activity." Wadle A., Mischo A., Henrich P.P., Stenner-Lieven F., Scherer C., Imig J., Petersen G., Pfreundschuh M., Renner C. Int. J. Cancer 117:896-904(2005) [PubMed: 15986447] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ANTI-APOPTOTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH STK19. Tissue: T-cell.
[5]	"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] (ISOFORM 1). Tissue: Cervix and Lung.
[6]	"p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1." Matsuzawa S., Takayama S., Froesch B.A., Zapata J.M., Reed J.C. EMBO J. 17:2736-2747(1998) [PubMed: 9582267] [Abstract] Cited for: INTERACTION WITH SIAH1.
[7]	"An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators." Takayama S., Xie Z., Reed J.C. J. Biol. Chem. 274:781-786(1999) [PubMed: 9873016] [Abstract] Cited for: FUNCTION.
[8]	"A nuclear action of the eukaryotic cochaperone RAP46 in downregulation of glucocorticoid receptor activity." Schneikert J., Huebner S., Martin E., Cato A.B.C. J. Cell Biol. 146:929-940(1999) [PubMed: 10477749] [Abstract] Cited for: INTERACTION WITH NR3C1.
[9]	"Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions." Hung W.J., Roberson R.S., Taft J., Wu D.Y. Mol. Cell. Biol. 23:3477-3486(2003) [PubMed: 12724406] [Abstract] Cited for: INTERACTION WITH PPP1R15A, FUNCTION.
[10]	"Structure of a Bag/Hsc70 complex: convergent functional evolution of Hsp70 nucleotide exchange factors." Sondermann H., Scheufler C., Schneider C., Hohfeld J., Hartl F.U., Moarefi I. Science 291:1553-1557(2001) [PubMed: 11222862] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 222-334 IN COMPLEX WITH HSC70.
[11]	"Solution structure of the ubiquitin domain of Bcl-2 binding athanogene-1." RIKEN structural genomics initiative (RSGI) Submitted (AUG-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 72-152.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

Z35491 mRNA. Translation: CAA84624.1. Different initiation.
U46917 mRNA. Translation: AAD11467.1. Different initiation.
AF022224 mRNA. Translation: AAC34258.1.
AF116273 mRNA. Translation: AAD25045.1. Different initiation.
BC001936 mRNA. Translation: AAH01936.2.
BC014774 mRNA. Translation: AAH14774.2.

IPI

IPI00218546.
IPI00300531.

UniGene

Hs.377484

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HX1	X-ray	1.90	B	222-334	[»]
1WXV	NMR	-	A	143-223	[»]
3FZF	X-ray	2.20	B	222-334	[»]
3FZH	X-ray	2.00	B	222-334	[»]
3FZK	X-ray	2.10	B	222-334	[»]
3FZL	X-ray	2.20	B	222-334	[»]
3FZM	X-ray	2.30	B	222-334	[»]

SMR

Q99933. Positions 216-345.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:3341N.

IntAct

Q99933. 1 interaction.

Proteomic databases

PRIDE

Q99933.

Genome annotation databases

Ensembl

ENSG00000107262. Homo sapiens. [Contig view]

Organism-specific databases

GeneCards

GC09M033245.

H-InvDB

HIX0007978.
HIX0080318.

HGNC

HGNC:937. BAG1.

HPA

CAB002486.
HPA018121.

MIM

601497. gene.

PharmGKB

PA25237.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q99933.

Enzyme and pathway databases

Pathway_Interaction_DB

met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).

Gene expression databases

ArrayExpress

Q99933.

Bgee

Q99933.

CleanEx

HS_BAG1.

GermOnline

ENSG00000107262. Homo sapiens.

Family and domain databases

InterPro

IPR003103. Apoptosis_reg_Bcl-2_prot_BAG.
IPR017093. Molecular_chp_reg_BAG_1.
IPR000626. Ubiquitin.
IPR019954. Ubiquitin_CS.
IPR019955. Ubiquitin_supergroup.
[Graphical view]

Pfam

PF02179. BAG. 1 hit.
PF00240. ubiquitin. 1 hit.
[Graphical view]

PIRSF

PIRSF037029. BAG_1. 1 hit.

SMART

SM00264. BAG. 1 hit.
SM00213. UBQ. 1 hit.
[Graphical view]

PROSITE

PS51035. BAG. 1 hit.
PS00299. UBIQUITIN_1. False negative.
PS50053. UBIQUITIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

SOURCE

Search...

Entry information

Entry name

BAG1_HUMAN

Accession

Primary (citable) accession number: Q99933
Secondary accession number(s): O75315 , Q14414, Q96TG2, Q9Y2V4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 28, 2006
Last modified:	June 16, 2009
This is version 96 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)