P38646 (GRP75_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Stress-70 protein, mitochondrial

Alternative name(s):
75 kDa glucose-regulated protein
Short name=GRP-75
Heat shock 70 kDa protein 9
Mortalin
Short name=MOT
Peptide-binding protein 74
Short name=PBP74

Gene names

Name:	HSPA9
Synonyms:	GRP75, HSPA9B

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	679 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	Implicated in the control of cell proliferation and cellular aging. May also act as a chaperone.
Subunit structure	Interacts with FXN. Interacts with HSCB. Component of the MINOS/MitOS complex, that includes IMMT, HSPA9 and CHCHD3 and associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2. Ref.13 Ref.15 Ref.18
Subcellular location	Mitochondrion. Nucleus › nucleolus Ref.19.
Sequence similarities	Belongs to the heat shock protein 70 family.

Ontologies

Keywords
Cellular component	Mitochondrion Nucleus
Coding sequence diversity	Polymorphism
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Chaperone
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular protein metabolic process Traceable author statement. Source: Reactome negative regulation of apoptotic process Traceable author statement PubMed 16130169. Source: UniProtKB protein export from nucleus Inferred from electronic annotation. Source: Compara protein folding Inferred from electronic annotation. Source: InterPro protein targeting to mitochondrion Traceable author statement. Source: Reactome
Cellular_component	cell surface Inferred from direct assay PubMed 12493773. Source: UniProtKB mitochondrial nucleoid Inferred from direct assay PubMed 18063578. Source: BHF-UCL nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW unfolded protein binding Traceable author statement PubMed 16130169. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
COBRA1	Q8WX92	2	EBI-354932,EBI-347721
TP53	P04637	2	EBI-354932,EBI-366083
TP73	O15350	11	EBI-354932,EBI-389606

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 46

46

Mitochondrion Ref.8 Ref.9 Ref.10

Chain

47 – 679

633

Stress-70 protein, mitochondrial

PRO_0000013563

Amino acid modifications

Modified residue

135

1

N6-acetyllysine Ref.14

Modified residue

138

1

N6-acetyllysine Ref.14

Modified residue

143

1

N6-acetyllysine Ref.14

Modified residue

206

1

N6-malonyllysine Ref.17

Modified residue

234

1

N6-acetyllysine Ref.14

Modified residue

288

1

N6-acetyllysine Ref.14

Modified residue

300

1

N6-acetyllysine Ref.14

Modified residue

567

1

N6-acetyllysine Ref.14

Modified residue

646

1

N6-acetyllysine Ref.14

Natural variations

Natural variant

74

1

Q → R. Ref.7
Corresponds to variant rs17856004 [ dbSNP | Ensembl ].

VAR_046482

Natural variant

127

1

R → G.
Corresponds to variant rs35091799 [ dbSNP | Ensembl ].

VAR_049622

Natural variant

184

1

H → Y. Ref.5

VAR_046483

Natural variant

225

1

A → G.
Corresponds to variant rs34558740 [ dbSNP | Ensembl ].

VAR_049623

Experimental info

Sequence conflict

48

1

S → P AA sequence Ref.9

Sequence conflict

66

1

C → S AA sequence Ref.9

Sequence conflict

176

1

E → V in BAG37618. Ref.3

Sequence conflict

184

1

H → R in AAH00478. Ref.7

Sequence conflict

184

1

H → R in AAH24034. Ref.7

Sequence conflict

249

1

T → A in BAD96478. Ref.4

Sequence conflict

385

1

L → P in BAD96478. Ref.4

Sequence conflict

540

1

G → R in AAA67526. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

679

Helix Strand Turn

Details...

Beta strand

445 – 448

4

Beta strand

452 – 458

7

Beta strand

463 – 472

10

Beta strand

482 – 490

9

Helix

494 – 496

3

Beta strand

497 – 505

9

Beta strand

518 – 524

7

Beta strand

530 – 536

7

Turn

537 – 539

3

Beta strand

542 – 548

7

Helix

555 – 567

13

Helix

569 – 590

22

Sequences

	Sequence		Length	Mass (Da)
	P38646 [UniParc]. Last modified May 27, 2002. Version 2. Checksum: 90969A8D06757753	FASTA	679	73,680
	10 20 30 40 50 60 MISASRAAAA RLVGAAASRG PTAARHQDSW NGLSHEAFRL VSRRDYASEA IKGAVVGIDL 70 80 90 100 110 120 GTTNSCVAVM EGKQAKVLEN AEGARTTPSV VAFTADGERL VGMPAKRQAV TNPNNTFYAT 130 140 150 160 170 180 KRLIGRRYDD PEVQKDIKNV PFKIVRASNG DAWVEAHGKL YSPSQIGAFV LMKMKETAEN 190 200 210 220 230 240 YLGHTAKNAV ITVPAYFNDS QRQATKDAGQ ISGLNVLRVI NEPTAAALAY GLDKSEDKVI 250 260 270 280 290 300 AVYDLGGGTF DISILEIQKG VFEVKSTNGD TFLGGEDFDQ ALLRHIVKEF KRETGVDLTK 310 320 330 340 350 360 DNMALQRVRE AAEKAKCELS SSVQTDINLP YLTMDSSGPK HLNMKLTRAQ FEGIVTDLIR 370 380 390 400 410 420 RTIAPCQKAM QDAEVSKSDI GEVILVGGMT RMPKVQQTVQ DLFGRAPSKA VNPDEAVAIG 430 440 450 460 470 480 AAIQGGVLAG DVTDVLLLDV TPLSLGIETL GGVFTKLINR NTTIPTKKSQ VFSTAADGQT 490 500 510 520 530 540 QVEIKVCQGE REMAGDNKLL GQFTLIGIPP APRGVPQIEV TFDIDANGIV HVSAKDKGTG 550 560 570 580 590 600 REQQIVIQSS GGLSKDDIEN MVKNAEKYAE EDRRKKERVE AVNMAEGIIH DTETKMEEFK 610 620 630 640 650 660 DQLPADECNK LKEEISKMRE LLARKDSETG ENIRQAASSL QQASLKLFEM AYKKMASERE 670 GSGSSGTGEQ KEDQKEEKQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the gene encoding peptide-binding protein 74 shows that it is a new member of the heat shock protein 70 family." Domanico S.Z., Denagel D.C., Dahlseid J.N., Green J.M., Pierce S.K. Mol. Cell. Biol. 13:3598-3610(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: B-cell.
[2]	"Cloning and subcellular localization of human mitochondrial hsp70." Bhattacharyya T., Karnezis A.N., Murphy S.P., Hoang T., Freeman B.C., Phillips B., Morimoto R.I. J. Biol. Chem. 270:1705-1710(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Teratocarcinoma.
[4]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[5]	NIEHS SNPs program Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT TYR-184.
[6]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-74. Tissue: Muscle.
[8]	"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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 47-68. Tissue: Colon carcinoma.
[9]	"Analysis of proteins from human breast epithelial cells using two-dimensional gel electrophoresis." Giometti C.S., Tollaksen S.L., Chubb C., Williams C., Huberman E. Electrophoresis 16:1215-1224(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 47-66. Tissue: Mammary gland.
[10]	"Human liver protein map: a reference database established by microsequencing and gel comparison." Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F., Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R., Appel R.D., Hughes G.J. Electrophoresis 13:992-1001(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 47-56. Tissue: Liver.
[11]	"Human liver protein map: update 1993." Hughes G.J., Frutiger S., Paquet N., Pasquali C., Sanchez J.-C., Tissot J.-D., Bairoch A., Appel R.D., Hochstrasser D.F. Electrophoresis 14:1216-1222(1993) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION. Tissue: Liver.
[12]	Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 86-99; 108-121; 160-173; 188-202; 207-234; 349-360; 378-391; 395-405; 469-485; 499-513 AND 542-555, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[13]	"Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones." Shan Y., Napoli E., Cortopassi G. Hum. Mol. Genet. 16:929-941(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FXN.
[14]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-135; LYS-138; LYS-143; LYS-234; LYS-288; LYS-300; LYS-567 AND LYS-646, MASS SPECTROMETRY.
[15]	"Characterization of the human HSC20, an unusual DnaJ type III protein, involved in iron-sulfur cluster biogenesis." Uhrigshardt H., Singh A., Kovtunovych G., Ghosh M., Rouault T.A. Hum. Mol. Genet. 19:3816-3834(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HSCB.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"The first identification of lysine malonylation substrates and its regulatory enzyme." Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y., He W., Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C., Dai J., Verdin E., Ye Y., Zhao Y. Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011) [PubMed] [Europe PMC] [Abstract] Cited for: MALONYLATION AT LYS-206.
[18]	"MINOS1 is a conserved component of mitofilin complexes and required for mitochondrial function and cristae organization." Alkhaja A.K., Jans D.C., Nikolov M., Vukotic M., Lytovchenko O., Ludewig F., Schliebs W., Riedel D., Urlaub H., Jakobs S., Deckers M. Mol. Biol. Cell 23:247-257(2012) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE MINOS/MITOS COMPLEX.
[19]	"Systematic analysis of protein pools, isoforms, and modifications affecting turnover and subcellular localization." Ahmad Y., Boisvert F.M., Lundberg E., Uhlen M., Lamond A.I. Mol. Cell. Proteomics 11:M111.013680.01-M111.013680.15(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L11066 mRNA. No translation available.
L15189 mRNA. Translation: AAA67526.1.
AK315177 mRNA. Translation: BAG37618.1.
AK222758 mRNA. Translation: BAD96478.1.
DQ531046 Genomic DNA. Translation: ABF50973.1.
CH471062 Genomic DNA. Translation: EAW62129.1.
BC000478 mRNA. Translation: AAH00478.1.
BC024034 mRNA. Translation: AAH24034.1.

IPI

IPI00007765.

PIR

B48127.

RefSeq

NP_004125.3. NM_004134.6.

UniGene

Hs.184233.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3N8E	X-ray	2.80	A/B	439-597	[»]

ProteinModelPortal

P38646.

ModBase

Search...

Protein-protein interaction databases

IntAct

P38646. 32 interactions.

MINT

MINT-1143092.

PTM databases

PhosphoSite

P38646.

Polymorphism databases

DMDM

21264428.

2D gel databases

DOSAC-COBS-2DPAGE

P38646.

OGP

P38646.

REPRODUCTION-2DPAGE

IPI00007765.

SWISS-2DPAGE

P38646.

UCD-2DPAGE

P38646.

Proteomic databases

PaxDb

P38646.

PRIDE

P38646.

Protocols and materials databases

DNASU

3313.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000297185; ENSP00000297185; ENSG00000113013.

GeneID

3313.

KEGG

hsa:3313.

UCSC

uc003ldf.3. human.

Organism-specific databases

CTD

3313.

GeneCards

GC05M137890.

HGNC

HGNC:5244. HSPA9.

HPA

CAB005219.
HPA000898.

MIM

600548. gene.

neXtProt

NX_P38646.

PharmGKB

PA162391712.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0443.

HOVERGEN

HBG051845.

InParanoid

P38646.

KO

K04043.

OMA

PYKNINP.

OrthoDB

EOG49KFQ6.

PhylomeDB

P38646.

Enzyme and pathway databases

Reactome

REACT_17015. Metabolism of proteins.

Gene expression databases

ArrayExpress

P38646.

Bgee

P38646.

Genevestigator

P38646.

GermOnline

ENSG00000113013. Homo sapiens.

Family and domain databases

InterPro

IPR012725. Chaperone_DnaK.
IPR018181. Heat_shock_70_CS.
IPR013126. Hsp_70_fam.
[Graphical view]

Pfam

PF00012. HSP70. 1 hit.
[Graphical view]

PRINTS

PR00301. HEATSHOCK70.

TIGRFAMs

TIGR02350. prok_dnaK. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

ChiTaRS

HSPA9. human.

EvolutionaryTrace

P38646.

GenomeRNAi

3313.

NextBio

13142.

SOURCE

Search...

Entry information

Entry name

GRP75_HUMAN

Accession

Primary (citable) accession number: P38646
Secondary accession number(s): B2RCM1 , P30036, P31932, Q1HB43, Q53H23, Q6GU03, Q9BWB7, Q9UC56

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	May 27, 2002
Last modified:	May 1, 2013
This is version 144 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.