Q13087 (PDIA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein disulfide-isomerase A2
EC=5.3.4.1

Alternative name(s):
Pancreas-specific protein disulfide isomerase
Short name=PDIp

Gene names

Name:	PDIA2
Synonyms:	PDIP

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	525 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	Acts as an intracellular estrogen-binding protein. May be involved in modulating cellular levels and biological functions of estrogens in the pancreas. May act as a chaperone that inhibits aggregation of misfolded proteins. Ref.10 Ref.11
Catalytic activity	Catalyzes the rearrangement of -S-S- bonds in proteins.
Subunit structure	Monomer; predominantly as monomer under reducing conditions. Homodimer; disulfide-linked. 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. Ref.10
Subcellular location	Endoplasmic reticulum lumen By similarity.
Tissue specificity	Highly expressed in pancreas (at protein level). Ref.6 Ref.8 Ref.11
Post-translational modification	The disulfide-linked homodimer exhibits an enhanced chaperone activity. Glycosylated. Ref.8
Sequence similarities	Belongs to the protein disulfide isomerase family. Contains 2 thioredoxin domains.
Sequence caution	The sequence AAC50401.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part. The sequence AAH75029.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part. The sequence BAG58339.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Redox-active center Repeat Signal
Ligand	Lipid-binding Steroid-binding
Molecular function	Chaperone Isomerase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from mutant phenotype PubMed 12095988. Source: HGNC cell redox homeostasis Inferred from electronic annotation. Source: InterPro glycerol ether metabolic process Inferred from electronic annotation. Source: InterPro protein retention in ER lumen Traceable author statement Ref.6. Source: ProtInc response to hypoxia Inferred from mutant phenotype PubMed 12095988. Source: HGNC
Cellular_component	endoplasmic reticulum Inferred from direct assay PubMed 12095988. Source: HGNC endoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	electron carrier activity Inferred from electronic annotation. Source: InterPro protein disulfide isomerase activity Traceable author statement Ref.6. Source: ProtInc protein disulfide oxidoreductase activity Inferred from electronic annotation. Source: InterPro steroid binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCK1	P16333	3	EBI-1752525,EBI-389883

Alternative products

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

Isoform 1 (identifier: Q13087-1)

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: Q13087-2)

The sequence of this isoform differs from the canonical sequence as follows:
     181-183: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 525	504	Protein disulfide-isomerase A2		PRO_0000034222
Regions
	Domain	27 – 152	126	Thioredoxin 1
	Domain	367 – 496	130	Thioredoxin 2
	Motif	522 – 525	4	Prevents secretion from ER Potential
Sites
	Active site	71	1	Nucleophile By similarity
	Active site	74	1	Nucleophile By similarity
	Active site	418	1	Nucleophile By similarity
	Active site	421	1	Nucleophile By similarity
	Site	72	1	Contributes to redox potential value By similarity
	Site	73	1	Contributes to redox potential value By similarity
	Site	138	1	Lowers pKa of C-terminal Cys of first active site By similarity
	Site	419	1	Contributes to redox potential value By similarity
	Site	420	1	Contributes to redox potential value By similarity
	Site	482	1	Lowers pKa of C-terminal Cys of second active site By similarity
Amino acid modifications
	Glycosylation	127	1	N-linked (GlcNAc...) Potential
	Glycosylation	284	1	N-linked (GlcNAc...) Potential
	Glycosylation	516	1	N-linked (GlcNAc...) Potential
	Disulfide bond	18		Interchain Ref.10
	Disulfide bond	71 ↔ 74		Redox-active By similarity
	Disulfide bond	418 ↔ 421		Redox-active By similarity
Natural variations
	Alternative sequence	181 – 183	3	Missing in isoform 2.		VSP_039292
	Natural variant	39	1	P → S. Corresponds to variant rs45455191 [ dbSNP | Ensembl ].		VAR_048087
	Natural variant	119	1	T → R. Corresponds to variant rs45614840 [ dbSNP | Ensembl ].		VAR_048088
	Natural variant	185	1	E → K. Corresponds to variant rs419949 [ dbSNP | Ensembl ].		VAR_048089
	Natural variant	286	1	T → M. Corresponds to variant rs2685127 [ dbSNP | Ensembl ].		VAR_048090
	Natural variant	382	1	P → A. Corresponds to variant rs45529833 [ dbSNP | Ensembl ].		VAR_048091
	Natural variant	388	1	R → Q. Corresponds to variant rs400037 [ dbSNP | Ensembl ].		VAR_048092
	Natural variant	502	1	P → S. Ref.1 Ref.5 Ref.6 Corresponds to variant rs1048786 [ dbSNP | Ensembl ].		VAR_048093
Experimental info
	Mutagenesis	18	1	C → A: Impairs interchain disulfide bridge formation. Ref.10
	Mutagenesis	364	1	C → A: No effect on interchain disulfide bridge formation. Ref.10
	Sequence conflict	96	1	T → M in BAG58339. Ref.7
	Sequence conflict	484	1	L → Q in BAG58339. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 27, 2002. Version 2. Checksum: B741851AA2C40540	FASTA	525	58,206
	10 20 30 40 50 60 MSRQLLPVLL LLLLRASCPW GQEQGARSPS EEPPEEEIPK EDGILVLSRH TLGLALREHP 70 80 90 100 110 120 ALLVEFYAPW CGHCQALAPE YSKAAAVLAA ESMVVTLAKV DGPAQRELAE EFGVTEYPTL 130 140 150 160 170 180 KFFRNGNRTH PEEYTGPRDA EGIAEWLRRR VGPSAMRLED EAAAQALIGG RDLVVIGFFQ 190 200 210 220 230 240 DLQDEDVATF LALAQDALDM TFGLTDRPRL FQQFGLTKDT VVLFKKFDEG RADFPVDEEL 250 260 270 280 290 300 GLDLGDLSRF LVTHSMRLVT EFNSQTSAKI FAARILNHLL LFVNQTLAAH RELLAGFGEA 310 320 330 340 350 360 APRFRGQVLF VVVDVAADNE HVLQYFGLKA EAAPTLRLVN LETTKKYAPV DGGPVTAASI 370 380 390 400 410 420 TAFCHAVLNG QVKPYLLSQE IPPDWDQRPV KTLVGKNFEQ VAFDETKNVF VKFYAPWCTH 430 440 450 460 470 480 CKEMAPAWEA LAEKYQDHED IIIAELDATA NELDAFAVHG FPTLKYFPAG PGRKVIEYKS 490 500 510 520 TRDLETFSKF LDNGGVLPTE EPPEEPAAPF PEPPANSTMG SKEEL
	Isoform 2 [UniParc]. Checksum: 815CD5F3060B5747	FASTA	522	57,850
	10 20 30 40 50 60 MSRQLLPVLL LLLLRASCPW GQEQGARSPS EEPPEEEIPK EDGILVLSRH TLGLALREHP 70 80 90 100 110 120 ALLVEFYAPW CGHCQALAPE YSKAAAVLAA ESMVVTLAKV DGPAQRELAE EFGVTEYPTL 130 140 150 160 170 180 KFFRNGNRTH PEEYTGPRDA EGIAEWLRRR VGPSAMRLED EAAAQALIGG RDLVVIGFFQ 190 200 210 220 230 240 DEDVATFLAL AQDALDMTFG LTDRPRLFQQ FGLTKDTVVL FKKFDEGRAD FPVDEELGLD 250 260 270 280 290 300 LGDLSRFLVT HSMRLVTEFN SQTSAKIFAA RILNHLLLFV NQTLAAHREL LAGFGEAAPR 310 320 330 340 350 360 FRGQVLFVVV DVAADNEHVL QYFGLKAEAA PTLRLVNLET TKKYAPVDGG PVTAASITAF 370 380 390 400 410 420 CHAVLNGQVK PYLLSQEIPP DWDQRPVKTL VGKNFEQVAF DETKNVFVKF YAPWCTHCKE 430 440 450 460 470 480 MAPAWEALAE KYQDHEDIII AELDATANEL DAFAVHGFPT LKYFPAGPGR KVIEYKSTRD 490 500 510 520 LETFSKFLDN GGVLPTEEPP EEPAAPFPEP PANSTMGSKE EL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A human polycistronic mRNA composed of ARHGDIG and PDIP." Hayashi A., Tabata Y., Sato S., Mitsuyama M., Kanai S., Furuya T., Saito T. Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-502.
[2]	"Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16." Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C., Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R. Hum. Mol. Genet. 10:339-352(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-525 (ISOFORM 1), VARIANT SER-502. Tissue: Brain.
[6]	"Characterization and chromosomal localization of a new protein disulfide isomerase, PDIp, highly expressed in human pancreas." Desilva M.G., Lu J., Donadel G., Modi W.S., Xie H., Notkins A.L., Lan M.S. DNA Cell Biol. 15:9-16(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 16-525 (ISOFORM 1), TISSUE SPECIFICITY, VARIANT SER-502. Tissue: Pancreas.
[7]	"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] OF 20-525 (ISOFORM 1). Tissue: Corpus callosum.
[8]	"Molecular characterization of a pancreas-specific protein disulfide isomerase, PDIp." Desilva M.G., Notkins A.L., Lan M.S. DNA Cell Biol. 16:269-274(1997) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, GLYCOSYLATION.
[9]	"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.
[10]	"Human pancreas-specific protein disulfide isomerase homolog (PDIp) is redox-regulated through formation of an inter-subunit disulfide bond." Fu X., Zhu B.T. Arch. Biochem. Biophys. 485:1-9(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, DISULFIDE BOND, MUTAGENESIS OF CYS-18 AND CYS-364.
[11]	"Human pancreas-specific protein disulfide isomerase homolog (PDIp) is an intracellular estrogen-binding protein that modulates estrogen levels and actions in target cells." Fu X.M., Zhu B.T. J. Steroid Biochem. Mol. Biol. 115:20-29(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB127078 mRNA. Translation: BAE48734.1. AE006463 Genomic DNA. Translation: AAK61223.1. Z69667 Genomic DNA. Translation: CAI95586.1. Z69667 Genomic DNA. Translation: CAO78188.1. CH471112 Genomic DNA. Translation: EAW85838.1. BC000537 mRNA. Translation: AAH00537.2. BC075029 mRNA. Translation: AAH75029.1. Sequence problems. U19948 mRNA. Translation: AAC50401.1. Sequence problems. AK295383 mRNA. Translation: BAG58339.1. Different initiation.
IPI	IPI00011571. IPI00878546.
RefSeq	NP_006840.2. NM_006849.2.
UniGene	Hs.66581.
3D structure databases
ProteinModelPortal	Q13087.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13087. 8 interactions.
MINT	MINT-1513985.
STRING	9606.ENSP00000219406.
PTM databases
PhosphoSite	Q13087.
Polymorphism databases
DMDM	21264492.
Proteomic databases
PaxDb	Q13087.
PRIDE	Q13087.
Protocols and materials databases
DNASU	64714.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000219406; ENSP00000219406; ENSG00000185615. ENST00000404312; ENSP00000384410; ENSG00000185615.
GeneID	64714.
KEGG	hsa:64714.
UCSC	uc002cgn.1. human.
Organism-specific databases
CTD	64714.
GeneCards	GC16P000336.
H-InvDB	HIX0202311.
HGNC	HGNC:14180. PDIA2.
HPA	HPA051692. HPA053492.
MIM	608012. gene.
neXtProt	NX_Q13087.
PharmGKB	PA33153.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0526.
HOVERGEN	HBG005920.
InParanoid	Q13087.
KO	K09581.
OMA	TEFNSQT.
PhylomeDB	Q13087.
Enzyme and pathway databases
BRENDA	5.3.4.1. 2681.
Gene expression databases
ArrayExpress	Q13087.
Bgee	Q13087.
CleanEx	HS_PDIA2.
Genevestigator	Q13087.
GermOnline	ENSG00000185615. Homo sapiens.
Family and domain databases
Gene3D	3.40.30.10. 4 hits.
InterPro	IPR005792. Prot_disulphide_isomerase. IPR005746. Thioredoxin. IPR012336. Thioredoxin-like_fold. IPR017937. Thioredoxin_CS. IPR013766. Thioredoxin_domain. [Graphical view]
Pfam	PF00085. Thioredoxin. 2 hits. [Graphical view]
PRINTS	PR00421. THIOREDOXIN.
SUPFAM	SSF52833. Thiordxn-like_fd. 4 hits.
TIGRFAMs	TIGR01130. ER_PDI_fam. 1 hit.
PROSITE	PS00014. ER_TARGET. 1 hit. PS00194. THIOREDOXIN_1. 2 hits. PS51352. THIOREDOXIN_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PDIA2. human.
GenomeRNAi	64714.
NextBio	66651.
SOURCE	Search...

Entry information

Entry name

PDIA2_HUMAN

Accession

Primary (citable) accession number: Q13087
Secondary accession number(s): A6ZJ64 , B4DI27, Q2WGM4, Q4TT67, Q6B010, Q96KJ6, Q9BW95

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	May 27, 2002
Last modified:	May 1, 2013
This is version 130 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.