P13667 (PDIA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein disulfide-isomerase A4
EC=5.3.4.1

Alternative name(s):
Endoplasmic reticulum resident protein 70
Short name=ER protein 70
Short name=ERp70
Endoplasmic reticulum resident protein 72
Short name=ER protein 72
Short name=ERp-72
Short name=ERp72

Gene names

Name:	PDIA4
Synonyms:	ERP70, ERP72

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	645 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)

Catalytic activity	Catalyzes the rearrangement of -S-S- bonds in proteins.
Subunit structure	Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGT1A1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX.
Subcellular location	Endoplasmic reticulum lumen. Melanosome. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Ref.8 Ref.9
Sequence similarities	Belongs to the protein disulfide isomerase family. Contains 3 thioredoxin domains.
Caution	Was originally (Ref.1) thought to be a deoxycytidine kinase.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum
Coding sequence diversity	Polymorphism
Domain	Redox-active center Repeat Signal
Molecular function	Isomerase
PTM	Acetylation Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell redox homeostasis Inferred from electronic annotation. Source: InterPro glycerol ether metabolic process Inferred from electronic annotation. Source: InterPro protein folding Inferred from electronic annotation. Source: GOC protein secretion Traceable author statement PubMed 2295602. Source: ProtInc
Cellular_component	cell surface Inferred from direct assay PubMed 19995400. Source: MGI endoplasmic reticulum lumen Traceable author statement PubMed 2295602. Source: ProtInc melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	electron carrier activity Inferred from electronic annotation. Source: InterPro protein disulfide isomerase activity Inferred from electronic annotation. Source: EC protein disulfide oxidoreductase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	Q76353	3	EBI-1054653,EBI-6248077	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Potential

Chain

21 – 645

625

Protein disulfide-isomerase A4

PRO_0000034229

Regions

Domain

21 – 169

149

Thioredoxin 1

Domain

158 – 301

144

Thioredoxin 2

Domain

505 – 636

132

Thioredoxin 3

Motif

642 – 645

4

Prevents secretion from ER

Compositional bias

39 – 55

17

Asp/Glu-rich (acidic)

Amino acid modifications

Modified residue

366

1

N6-acetyllysine Ref.10

Disulfide bond

91 ↔ 94

Redox-active By similarity

Disulfide bond

206 ↔ 209

Redox-active By similarity

Disulfide bond

555 ↔ 558

Redox-active By similarity

Natural variations

Natural variant

173

1

T → M.
Corresponds to variant rs2290971 [ dbSNP | Ensembl ].

VAR_052580

Experimental info

Sequence conflict

102

1

E → G in BAF83660. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

645

Helix Strand Turn

Details...

Beta strand

59 – 61

3

Beta strand

64 – 66

3

Turn

69 – 71

3

Helix

72 – 76

5

Beta strand

80 – 87

8

Helix

92 – 109

18

Beta strand

111 – 113

3

Beta strand

117 – 121

5

Turn

122 – 124

3

Helix

126 – 131

6

Beta strand

136 – 144

9

Beta strand

147 – 150

4

Helix

157 – 168

12

Beta strand

178 – 181

4

Turn

184 – 186

3

Helix

187 – 193

7

Beta strand

195 – 202

8

Helix

208 – 211

4

Helix

213 – 224

12

Beta strand

226 – 228

3

Beta strand

232 – 236

5

Turn

237 – 239

3

Helix

241 – 246

6

Beta strand

251 – 259

9

Beta strand

262 – 265

4

Helix

272 – 282

11

Sequences

	Sequence		Length	Mass (Da)
	P13667 [UniParc]. Last modified May 1, 1991. Version 2. Checksum: 1919C2AE12CD2684	FASTA	645	72,932
	10 20 30 40 50 60 MRPRKAFLLL LLLGLVQLLA VAGAEGPDED SSNRENAIED EEEEEEEDDD EEEDDLEVKE 70 80 90 100 110 120 ENGVLVLNDA NFDNFVADKD TVLLEFYAPW CGHCKQFAPE YEKIANILKD KDPPIPVAKI 130 140 150 160 170 180 DATSASVLAS RFDVSGYPTI KILKKGQAVD YEGSRTQEEI VAKVREVSQP DWTPPPEVTL 190 200 210 220 230 240 VLTKENFDEV VNDADIILVE FYAPWCGHCK KLAPEYEKAA KELSKRSPPI PLAKVDATAE 250 260 270 280 290 300 TDLAKRFDVS GYPTLKIFRK GRPYDYNGPR EKYGIVDYMI EQSGPPSKEI LTLKQVQEFL 310 320 330 340 350 360 KDGDDVIIIG VFKGESDPAY QQYQDAANNL REDYKFHHTF STEIAKFLKV SQGQLVVMQP 370 380 390 400 410 420 EKFQSKYEPR SHMMDVQGST QDSAIKDFVL KYALPLVGHR KVSNDAKRYT RRPLVVVYYS 430 440 450 460 470 480 VDFSFDYRAA TQFWRSKVLE VAKDFPEYTF AIADEEDYAG EVKDLGLSES GEDVNAAILD 490 500 510 520 530 540 ESGKKFAMEP EEFDSDTLRE FVTAFKKGKL KPVIKSQPVP KNNKGPVKVV VGKTFDSIVM 550 560 570 580 590 600 DPKKDVLIEF YAPWCGHCKQ LEPVYNSLAK KYKGQKGLVI AKMDATANDV PSDRYKVEGF 610 620 630 640 PTIYFAPSGD KKNPVKFEGG DRDLEHLSKF IEEHATKLSR TKEEL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human deoxycytidine kinase. Sequence of cDNA clones and analysis of expression in cell lines with and without enzyme activity." Huang S.-H., Tomich J.M., Wu H., Jong A., Holcenberg J.S. J. Biol. Chem. 264:14762-14768(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]	Erratum Huang S.-H., Tomich J.M., Wu H., Jong A., Holcenberg J.S. J. Biol. Chem. 266:5353-5353(1991) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[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].
[4]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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].
[6]	"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]. Tissue: Lung and Muscle.
[7]	"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] [Europe PMC] [Abstract] Cited for: COMPONENT OF A CHAPERONE COMPLEX.
[8]	"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] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Melanoma.
[9]	"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] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Melanoma.
[10]	"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-366, MASS SPECTROMETRY.
[11]	"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].
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J05016 mRNA. Translation: AAA58460.1.
AK290971 mRNA. Translation: BAF83660.1.
AC093743 Genomic DNA. Translation: AAQ96863.1.
CH471146 Genomic DNA. Translation: EAW80065.1.
CH471146 Genomic DNA. Translation: EAW80066.1.
BC000425 mRNA. Translation: AAH00425.1.
BC001928 mRNA. Translation: AAH01928.1.
BC006344 mRNA. Translation: AAH06344.1.
BC011754 mRNA. Translation: AAH11754.1.

IPI

IPI00009904.

PIR

A23723.

RefSeq

NP_004902.1. NM_004911.4.

UniGene

Hs.93659.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3IDV	X-ray	1.95	A	53-284	[»]

ProteinModelPortal

P13667.

ModBase

Search...

Protein-protein interaction databases

IntAct

P13667. 6 interactions.

MINT

MINT-4999858.

STRING

9606.ENSP00000286091.

PTM databases

PhosphoSite

P13667.

Polymorphism databases

DMDM

119530.

2D gel databases

OGP

P13667.

REPRODUCTION-2DPAGE

IPI00009904.

Proteomic databases

PaxDb

P13667.

PeptideAtlas

P13667.

PRIDE

P13667.

Protocols and materials databases

DNASU

9601.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000286091; ENSP00000286091; ENSG00000155660.

GeneID

9601.

KEGG

hsa:9601.

UCSC

uc003wff.2. human.

Organism-specific databases

CTD

9601.

GeneCards

GC07M148700.

HGNC

HGNC:30167. PDIA4.

HPA

CAB017368.
HPA006139.
HPA006140.

neXtProt

NX_P13667.

PharmGKB

PA142671190.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0526.

HOGENOM

HOG000162459.

HOVERGEN

HBG005920.

InParanoid

P13667.

KO

K09582.

OMA

AKRYTRR.

OrthoDB

EOG405S0R.

PhylomeDB

P13667.

Enzyme and pathway databases

BRENDA

5.3.4.1. 2681.

Gene expression databases

ArrayExpress

P13667.

Bgee

P13667.

CleanEx

HS_PDIA4.

Genevestigator

P13667.

GermOnline

ENSG00000155660. Homo sapiens.

Family and domain databases

Gene3D

3.40.30.10. 4 hits.

InterPro

IPR005788. Disulphide_isomerase.
IPR005792. Prot_disulphide_isomerase.
IPR017068. Protein_diS-isomerase_A4.
IPR005746. Thioredoxin.
IPR012336. Thioredoxin-like_fold.
IPR017937. Thioredoxin_CS.
IPR013766. Thioredoxin_domain.
[Graphical view]

Pfam

PF00085. Thioredoxin. 3 hits.
[Graphical view]

PIRSF

PIRSF036862. Disulphide_isom_A4. 1 hit.

PRINTS

PR00421. THIOREDOXIN.

SUPFAM

SSF52833. Thiordxn-like_fd. 5 hits.

TIGRFAMs

TIGR01130. ER_PDI_fam. 1 hit.
TIGR01126. pdi_dom. 3 hits.

PROSITE

PS00014. ER_TARGET. 1 hit.
PS00194. THIOREDOXIN_1. 3 hits.
PS51352. THIOREDOXIN_2. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

PDIA4. human.

EvolutionaryTrace

P13667.

GenomeRNAi

9601.

NextBio

36019.

Entry information

Entry name

PDIA4_HUMAN

Accession

Primary (citable) accession number: P13667
Secondary accession number(s): A8K4K6, Q549T6

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	May 1, 1991
Last modified:	May 1, 2013
This is version 153 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.