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Q13087 (PDIA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length525 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 Ref.12

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 componentEndoplasmic reticulum
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRedox-active center
Repeat
Signal
   LigandLipid-binding
Steroid-binding
   Molecular functionChaperone
Isomerase
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell redox homeostasis

Inferred from electronic annotation. Source: InterPro

glycerol ether metabolic process

Inferred from electronic annotation. Source: InterPro

peptidyl-proline hydroxylation

Inferred from Biological aspect of Ancestor. Source: GOC

protein folding

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein retention in ER lumen

Traceable author statement Ref.6. Source: ProtInc

regulation of intrinsic apoptotic signaling pathway in response to oxidative stress

Inferred from Biological aspect of Ancestor. Source: RefGenome

response to endoplasmic reticulum stress

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentendoplasmic reticulum

Inferred from Biological aspect of Ancestor. Source: RefGenome

endoplasmic reticulum lumen

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 17474147. Source: IntAct

protein disulfide isomerase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

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

NCK1P163333EBI-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 525504Protein disulfide-isomerase A2
PRO_0000034222

Regions

Domain27 – 152126Thioredoxin 1
Domain367 – 496130Thioredoxin 2
Motif522 – 5254Prevents secretion from ER Potential

Sites

Active site711Nucleophile By similarity
Active site741Nucleophile By similarity
Active site4181Nucleophile By similarity
Active site4211Nucleophile By similarity
Site721Contributes to redox potential value By similarity
Site731Contributes to redox potential value By similarity
Site1381Lowers pKa of C-terminal Cys of first active site By similarity
Site4191Contributes to redox potential value By similarity
Site4201Contributes to redox potential value By similarity
Site4821Lowers pKa of C-terminal Cys of second active site By similarity

Amino acid modifications

Glycosylation1271N-linked (GlcNAc...) Ref.12
Glycosylation2841N-linked (GlcNAc...) Ref.12
Glycosylation5161N-linked (GlcNAc...) Ref.12
Disulfide bond18Interchain Ref.10
Disulfide bond71 ↔ 74Redox-active By similarity
Disulfide bond418 ↔ 421Redox-active By similarity

Natural variations

Alternative sequence181 – 1833Missing in isoform 2.
VSP_039292
Natural variant391P → S.
Corresponds to variant rs45455191 [ dbSNP | Ensembl ].
VAR_048087
Natural variant1191T → R.
Corresponds to variant rs45614840 [ dbSNP | Ensembl ].
VAR_048088
Natural variant1851E → K.
Corresponds to variant rs419949 [ dbSNP | Ensembl ].
VAR_048089
Natural variant2861T → M.
Corresponds to variant rs2685127 [ dbSNP | Ensembl ].
VAR_048090
Natural variant3821P → A.
Corresponds to variant rs45529833 [ dbSNP | Ensembl ].
VAR_048091
Natural variant3881R → Q.
Corresponds to variant rs400037 [ dbSNP | Ensembl ].
VAR_048092
Natural variant5021P → S. Ref.1 Ref.5 Ref.6
Corresponds to variant rs1048786 [ dbSNP | Ensembl ].
VAR_048093

Experimental info

Mutagenesis181C → A: Impairs interchain disulfide bridge formation. Ref.10
Mutagenesis2841N → Q: Increases formation of a highly stable disulfide-bonded PDIA2 dimer. Ref.12
Mutagenesis3641C → A: No effect on interchain disulfide bridge formation. Ref.10
Sequence conflict961T → M in BAG58339. Ref.7
Sequence conflict4841L → Q in BAG58339. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 27, 2002. Version 2.
Checksum: B741851AA2C40540

FASTA52558,206
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 815CD5F3060B5747
Show »

FASTA52257,850

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.
[12]"N-linked glycosylation modulates dimerization of protein disulfide isomerase family A member 2 (PDIA2)."
Walker A.K., Soo K.Y., Levina V., Talbo G.H., Atkin J.D.
FEBS J. 280:233-243(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-127; ASN-284 AND ASN-516, MUTAGENESIS OF ASN-284.
+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.
CCDSCCDS42089.1. [Q13087-1]
RefSeqNP_006840.2. NM_006849.2. [Q13087-1]
UniGeneHs.66581.

3D structure databases

ProteinModelPortalQ13087.
SMRQ13087. Positions 32-495.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122240. 16 interactions.
IntActQ13087. 10 interactions.
MINTMINT-1513985.
STRING9606.ENSP00000219406.

PTM databases

PhosphoSiteQ13087.

Polymorphism databases

DMDM21264492.

Proteomic databases

MaxQBQ13087.
PaxDbQ13087.
PRIDEQ13087.

Protocols and materials databases

DNASU64714.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000219406; ENSP00000219406; ENSG00000185615. [Q13087-1]
ENST00000404312; ENSP00000384410; ENSG00000185615. [Q13087-2]
GeneID64714.
KEGGhsa:64714.
UCSCuc002cgn.1. human. [Q13087-1]

Organism-specific databases

CTD64714.
GeneCardsGC16P000336.
H-InvDBHIX0202311.
HGNCHGNC:14180. PDIA2.
HPAHPA051692.
HPA053492.
MIM608012. gene.
neXtProtNX_Q13087.
PharmGKBPA33153.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0526.
HOVERGENHBG005920.
InParanoidQ13087.
KOK09581.
OMAQEVPPDW.
OrthoDBEOG7VHSX1.
PhylomeDBQ13087.
TreeFamTF106381.

Enzyme and pathway databases

BRENDA5.3.4.1. 2681.

Gene expression databases

ArrayExpressQ13087.
BgeeQ13087.
CleanExHS_PDIA2.
GenevestigatorQ13087.

Family and domain databases

Gene3D3.40.30.10. 4 hits.
InterProIPR005792. Prot_disulphide_isomerase.
IPR012336. Thioredoxin-like_fold.
IPR017937. Thioredoxin_CS.
IPR013766. Thioredoxin_domain.
[Graphical view]
PfamPF00085. Thioredoxin. 2 hits.
[Graphical view]
SUPFAMSSF52833. SSF52833. 4 hits.
TIGRFAMsTIGR01130. ER_PDI_fam. 1 hit.
PROSITEPS00014. ER_TARGET. 1 hit.
PS00194. THIOREDOXIN_1. 2 hits.
PS51352. THIOREDOXIN_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPDIA2. human.
GenomeRNAi64714.
NextBio66651.
PROQ13087.
SOURCESearch...

Entry information

Entry namePDIA2_HUMAN
AccessionPrimary (citable) accession number: Q13087
Secondary accession number(s): A6ZJ64 expand/collapse secondary AC list , B4DI27, Q2WGM4, Q4TT67, Q6B010, Q96KJ6, Q9BW95
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 27, 2002
Last modified: July 9, 2014
This is version 143 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM