Reviewed, UniProtKB/Swiss-Prot Q9NZL4 (HPBP1_HUMAN)

Names and origin

Protein names

Recommended name:
    Hsp70-binding protein 1
      Short name=HspBP1
Alternative name(s):
    Heat shock protein-binding protein 1
    Hsp70-interacting protein 1
    Hsp70-binding protein 2
      Short name=HspBP2
    Hsp70-interacting protein 2

Gene names

Name:	HSPBP1
Synonyms:	HSPBP
ORF Names:	PP1845

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	362 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Inhibits HSPA1A chaperone activity by changing the conformation of the ATP-binding domain of HSPA1A and interfering with ATP binding. Interferes with ubiquitination mediated by STUB1 and inhibits chaperone-assisted degradation of immature CFTR. Ref.1 Ref.2 Ref.9 Ref.10
Subunit structure	Interacts with the ATP-binding domain of HSPA1A. Detected in a ternary complex containing STUB1, HSPA1A and HSPBP1. Ref.1 Ref.9 Ref.10
Tissue specificity	Ubiquitous. Ref.1
Sequence similarities	Contains 4 ARM repeats.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from direct assay. Source: UniProtKB positive regulation of protein ubiquitination Inferred from direct assay. Source: UniProtKB protein folding Ref.1 Traceable author statement. Source: ProtInc
Molecular function	enzyme inhibitor activity Ref.1 Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HSPA8	P11142	2	EBI-356763,EBI-351896

Alternative products

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

Isoform 1 (identifier: Q9NZL4-1)

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: Q9NZL4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     207-309: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 362

362

Hsp70-binding protein 1

PRO_0000084035

Regions

Repeat

135 – 177

43

ARM 1

Repeat

180 – 220

41

ARM 2

Repeat

223 – 262

40

ARM 3

Repeat

265 – 304

40

ARM 4

Compositional bias

21 – 40

20

Gly-rich

Amino acid modifications

Modified residue

354

1

Phosphoserine Ref.11

Modified residue

359

1

Phosphoserine Ref.11

Natural variations

Alternative sequence

207 – 309

103

Missing in isoform 2.

VSP_015945

Natural variant

25 – 27

3

Missing

VAR_023645

Secondary structure

1

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362

Helix Strand Turn

Details...

Helix

90 – 104

15

Helix

113 – 134

22

Helix

137 – 145

9

Helix

148 – 154

7

Turn

155 – 158

4

Helix

162 – 176

15

Helix

180 – 188

9

Helix

191 – 201

11

Helix

205 – 219

15

Helix

223 – 231

9

Helix

234 – 243

10

Helix

247 – 263

17

Helix

265 – 267

3

Helix

268 – 273

6

Helix

276 – 284

9

Helix

291 – 303

13

Helix

307 – 314

8

Helix

316 – 318

3

Helix

320 – 331

12

Helix

335 – 337

3

Helix

338 – 351

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 2B6AAB4161D5A326	FASTA	362	39,474
	10 20 30 40 50 60 MSDEGSRGSR LPLALPPASQ GCSSGGGGGG GGGSSAGGSG NSRPPRNLQG LLQMAITAGS 70 80 90 100 110 120 EEPDPPPEPM SEERRQWLQE AMSAAFRGQR EEVEQMKSCL RVLSQPMPPT AGEAEQAADQ 130 140 150 160 170 180 QEREGALELL ADLCENMDNA ADFCQLSGMH LLVGRYLEAG AAGLRWRAAQ LIGTCSQNVA 190 200 210 220 230 240 AIQEQVLGLG ALRKLLRLLD RDACDTVRVK ALFAISCLVR EQEAGLLQFL RLDGFSVLMR 250 260 270 280 290 300 AMQQQVQKLK VKSAFLLQNL LVGHPEHKGT LCSMGMVQQL VALVRTEHSP FHEHVLGALC 310 320 330 340 350 360 SLVTDFPQGV RECREPELGL EELLRHRCQL LQQHEEYQEE LEFCEKLLQT CFSSPADDSM DR
	Isoform 2. Checksum: 50A959E12693AF09	FASTA	259	28,024
	10 20 30 40 50 60 MSDEGSRGSR LPLALPPASQ GCSSGGGGGG GGGSSAGGSG NSRPPRNLQG LLQMAITAGS 70 80 90 100 110 120 EEPDPPPEPM SEERRQWLQE AMSAAFRGQR EEVEQMKSCL RVLSQPMPPT AGEAEQAADQ 130 140 150 160 170 180 QEREGALELL ADLCENMDNA ADFCQLSGMH LLVGRYLEAG AAGLRWRAAQ LIGTCSQNVA 190 200 210 220 230 240 AIQEQVLGLG ALRKLLRLLD RDACDTVREC REPELGLEEL LRHRCQLLQQ HEEYQEELEF 250 CEKLLQTCFS SPADDSMDR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Inhibition of Hsp70 ATPase activity and protein renaturation by a novel Hsp70-binding protein." Raynes D.A., Guerriero V. Jr. J. Biol. Chem. 273:32883-32888(1998) [PubMed: 9830037] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT 25-GLY--GLY-27 DEL, FUNCTION, INTERACTION WITH HSPA1A, TISSUE SPECIFICITY. Tissue: Heart.
[2]	"Isolation and characterization of isoforms of HspBP1, inhibitors of Hsp70." Guerriero V. Jr., Raynes D.A. Biochim. Biophys. Acta 1490:203-207(2000) [PubMed: 10786638] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, POLYMORPHISM OF POLY-GLY REGION. Tissue: Heart.
[3]	Tanimura S., Tsujimoto M., Kohno M. Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT 25-GLY--GLY-27 DEL.
[4]	"Large-scale cDNA transfection screening for genes related to cancer development and progression." Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J. Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed: 15498874] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Spleen.
[6]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT 25-GLY--GLY-27 DEL.
[7]	"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries." Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T. DNA Res. 12:117-126(2005) [PubMed: 16303743] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[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] (ISOFORM 1), VARIANT 25-GLY--GLY-27 DEL. Tissue: Lung and Placenta.
[9]	"HspBP1, an Hsp70 cochaperone, has two structural domains and is capable of altering the conformation of the Hsp70 ATPase domain." McLellan C.A., Raynes D.A., Guerriero V. Jr. J. Biol. Chem. 278:19017-19022(2003) [PubMed: 12651857] [Abstract] Cited for: FUNCTION, INTERACTION WITH HSPA1A.
[10]	"The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator." Alberti S., Boehse K., Arndt V., Schmitz A., Hoehfeld J. Mol. Biol. Cell 15:4003-4010(2004) [PubMed: 15215316] [Abstract] Cited for: FUNCTION, INTERACTION WITH HSPA1A AND STUB1.
[11]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-354 AND SER-359, MASS SPECTROMETRY.
[12]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[13]	"Regulation of Hsp70 function by HspBP1: structural analysis reveals an alternate mechanism for Hsp70 nucleotide exchange." Shomura Y., Dragovic Z., Chang H.-C., Tzvetkov N., Young J.C., Brodsky J.L., Guerriero V. Jr., Hartl F.U., Bracher A. Mol. Cell 17:367-379(2005) [PubMed: 15694338] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 87-362 IN COMPLEX WITH HSPA1A.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF093420 mRNA. Translation: AAC79703.1.
AF187859 mRNA. Translation: AAF35833.1.
AB020592 mRNA. Translation: BAB18742.1.
AF217996 mRNA. Translation: AAG17238.1.
AK130636 mRNA. Translation: BAC85399.1.
CR457118 mRNA. Translation: CAG33399.1.
AK075293 mRNA. Translation: BAG52102.1.
BC001236 mRNA. Translation: AAH01236.1.
BC002373 mRNA. Translation: AAH02373.1.

IPI

IPI00100748.
IPI00442503.

RefSeq

NP_001123578.1.
NP_036399.3.

UniGene

Hs.53066

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XQR	X-ray	2.10	A/B	87-362	[»]
1XQS	X-ray	2.90	A/B	87-362	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NZL4. 7 interactions.

STRING

Q9NZL4.

PTM databases

PhosphoSite

Q9NZL4.

Proteomic databases

PRIDE

Q9NZL4.

Genome annotation databases

Ensembl

ENST00000255631; ENSP00000255631; ENSG00000133265; Homo sapiens. [Genome view]
ENST00000433386; ENSP00000398244; ENSG00000133265; Homo sapiens. [Genome view]

GeneID

23640.

KEGG

hsa:23640.

UCSC

uc002qjx.1. human.

Organism-specific databases

CTD

23640.

GeneCards

GC19M060465.

H-InvDB

HIX0015460.

HGNC

HGNC:24989. HSPBP1.

HPA

CAB005865.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG18691.

HOVERGEN

Q9NZL4.

InParanoid

Q9NZL4.

Gene expression databases

ArrayExpress

Q9NZL4.

Bgee

Q9NZL4.

Genevestigator

Q9NZL4.

GermOnline

ENSG00000133265. Homo sapiens.

Family and domain databases

InterPro

IPR011989. ARM-like.
IPR016024. ARM-type_fold.
[Graphical view]

Gene3D

G3DSA:1.25.10.10. ARM-like. 1 hit.

PROSITE

PS50176. ARM_REPEAT. False negative.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

46437.

Entry information

Entry name

HPBP1_HUMAN

Accession

Primary (citable) accession number: Q9NZL4
Secondary accession number(s): B3KQP0, O95351, Q6ZNU5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 25, 2005
Last sequence update:	October 1, 2000
Last modified:	February 9, 2010
This is version 66 of the entry and version 1 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.