Reviewed, UniProtKB/Swiss-Prot P13667 (PDIA4_HUMAN)

Names and origin

Protein names

Recommended name:
    Protein disulfide-isomerase A4
    EC=5.3.4.1
Alternative name(s):
    Protein ERp-72
      Short name=ERp72

Gene names

Name:	PDIA4
Synonyms:	ERP70, ERP72

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	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 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.
Subcellular location	Endoplasmic reticulum lumen. Melanosome. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Ref.5 Ref.6
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	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	cell redox homeostasis Inferred from electronic annotation. Source: InterPro protein secretion Traceable author statement. Source: ProtInc
Cellular component	endoplasmic reticulum lumen Traceable author statement. Source: ProtInc melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct protein disulfide isomerase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EIF2B1	Q14232	1	EBI-1054653,EBI-491065

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.8
	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: dbSNP rs2290971.		VAR_052580

Sequences

	Sequence		Length	Mass (Da)
	P13667-1 [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: 2549034] [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: 2002068] [Abstract] Cited for: SEQUENCE REVISION.
[3]	"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: Lung and Muscle.
[4]	"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.
[5]	"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.
[6]	"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.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]	"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-366, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	J05016 mRNA. Translation: AAA58460.1. 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.
UniGene	Hs.93659
3D structure databases
HSSP	HSSP built from PDB template 1MEK based on UniProtKB P07237.
SMR	P13667. Positions 56-179, 178-284, 523-645.
ModBase	Search...
Protein-protein interaction databases
IntAct	P13667. 6 interactions.
STRING	P13667.
PTM databases
PhosphoSite	P13667.
2-D gel databases
OGP	P13667.
REPRODUCTION-2DPAGE	IPI00009904.
Proteomic databases
PeptideAtlas	P13667.
PRIDE	P13667.
Genome annotation databases
Ensembl	ENST00000286091; ENSP00000286091; ENSG00000155660; Homo sapiens. [Genome view] ENST00000413966; ENSP00000408628; ENSG00000155660; Homo sapiens. [Genome view] ENST00000414033; ENSP00000409289; ENSG00000155660; Homo sapiens. [Genome view]
GeneID	9601.
KEGG	hsa:9601.
UCSC	uc003wff.2. human.
Organism-specific databases
CTD	9601.
GeneCards	GC07M148331.
HGNC	HGNC:30167. PDIA4.
HPA	CAB017368. HPA006139. HPA006140.
PharmGKB	PA142671190.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P13667.
HOVERGEN	P13667.
OMA	RAATQFW.
Enzyme and pathway databases
BRENDA	5.3.4.1. 247.
Gene expression databases
ArrayExpress	P13667.
Bgee	P13667.
CleanEx	HS_PDIA4.
Genevestigator	P13667.
GermOnline	ENSG00000155660. Homo sapiens.
Family and domain databases
InterPro	IPR005788. Disulphide_isomerase. IPR000886. ER_target_seq_motif. IPR005792. Prot_disulphide_isomerase. IPR017068. Protein_diS-isomerase_A4. IPR017936. Thioredoxin-like. IPR006662. Thioredoxin-like_subdom. IPR017937. Thioredoxin_CS. IPR013766. Thioredoxin_domain. IPR012335. Thioredoxin_fold. [Graphical view]
Gene3D	G3DSA:3.40.30.10. Thioredoxin_fold. 3 hits.
Pfam	PF00085. Thioredoxin. 3 hits. [Graphical view]
PIRSF	PIRSF036862. Disulphide_isom_A4. 1 hit.
PRINTS	PR00421. THIOREDOXIN.
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 Resources
NextBio	36019.

Entry information

Entry name

PDIA4_HUMAN

Accession

Primary (citable) accession number: P13667

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	May 1, 1991
Last modified:	November 3, 2009
This is version 115 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.