ID PDIA2_HUMAN Reviewed; 525 AA. AC Q13087; A6ZJ64; B4DI27; Q2WGM4; Q4TT67; Q6B010; Q96KJ6; Q9BW95; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 27-MAY-2002, sequence version 2. DT 13-JUL-2010, entry version 105. DE RecName: Full=Protein disulfide-isomerase A2; DE EC=5.3.4.1; DE AltName: Full=Pancreas-specific protein disulfide isomerase; DE Short=PDIp; DE Flags: Precursor; GN Name=PDIA2; Synonyms=PDIP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-502. RA Hayashi A., Tabata Y., Sato S., Mitsuyama M., Kanai S., Furuya T., RA Saito T.; RT "A human polycistronic mRNA composed of ARHGDIG and PDIP."; RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX MEDLINE=21096910; PubMed=11157797; DOI=10.1093/hmg/10.4.339; RA Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., RA Tufarelli C., Kearney L., Buckle V.J., Doggett N.A., Flint J., RA Higgs D.R.; RT "Sequence, structure and pathology of the fully annotated terminal 2 RT Mb of the short arm of human chromosome 16."; RL Hum. Mol. Genet. 10:339-352(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., RA Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-525 (ISOFORM 1), AND RP VARIANT SER-502. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 16-525 (ISOFORM 1), TISSUE SPECIFICITY, RP AND VARIANT SER-502. RC TISSUE=Pancreas; RX MEDLINE=96152236; PubMed=8561901; DOI=10.1089/dna.1996.15.9; RA Desilva M.G., Lu J., Donadel G., Modi W.S., Xie H., Notkins A.L., RA Lan M.S.; RT "Characterization and chromosomal localization of a new protein RT disulfide isomerase, PDIp, highly expressed in human pancreas."; RL DNA Cell Biol. 15:9-16(1996). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 20-525 (ISOFORM 1). RC TISSUE=Corpus callosum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP TISSUE SPECIFICITY, AND GLYCOSYLATION. RX PubMed=9115635; RA Desilva M.G., Notkins A.L., Lan M.S.; RT "Molecular characterization of a pancreas-specific protein disulfide RT isomerase, PDIp."; RL DNA Cell Biol. 16:269-274(1997). RN [9] RP COMPONENT OF A CHAPERONE COMPLEX. RX PubMed=12475965; DOI=10.1091/mbc.E02-05-0311; RA Meunier L., Usherwood Y.-K., Chung K.T., Hendershot L.M.; RT "A subset of chaperones and folding enzymes form multiprotein RT complexes in endoplasmic reticulum to bind nascent proteins."; RL Mol. Biol. Cell 13:4456-4469(2002). RN [10] RP FUNCTION, SUBUNIT, DISULFIDE BOND, AND MUTAGENESIS OF CYS-18 AND RP CYS-364. RX PubMed=19150607; DOI=10.1016/j.abb.2008.12.021; RA Fu X., Zhu B.T.; RT "Human pancreas-specific protein disulfide isomerase homolog (PDIp) is RT redox-regulated through formation of an inter-subunit disulfide RT bond."; RL Arch. Biochem. Biophys. 485:1-9(2009). RN [11] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=19429457; DOI=10.1016/j.jsbmb.2009.02.008; RA Fu X.M., Zhu B.T.; RT "Human pancreas-specific protein disulfide isomerase homolog (PDIp) is RT an intracellular estrogen-binding protein that modulates estrogen RT levels and actions in target cells."; RL J. Steroid Biochem. Mol. Biol. 115:20-29(2009). CC -!- FUNCTION: Acts as an intracellular estrogen-binding protein. May CC be involved in modulating cellular levels and biological functions CC of estrogens in the pancreas. May act as a chaperone that inhibits CC aggregation of misfolded proteins. CC -!- CATALYTIC ACTIVITY: Catalyzes the rearrangement of -S-S- bonds in CC proteins. CC -!- SUBUNIT: Monomer; predominantly as monomer under reducing CC conditions. Homodimer; disulfide-linked. Part a large chaperone CC multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, CC PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGT1A1 and very small amounts CC of ERP29, but not, or at very low levels, CALR nor CANX. CC -!- INTERACTION: CC P00519:ABL1; NbExp=1; IntAct=EBI-1752525, EBI-375543; CC P46108:CRK; NbExp=1; IntAct=EBI-1752525, EBI-886; CC P06241:FYN; NbExp=1; IntAct=EBI-1752525, EBI-515315; CC P62993:GRB2; NbExp=1; IntAct=EBI-1752525, EBI-401755; CC P16333:NCK1; NbExp=1; IntAct=EBI-1752525, EBI-389883; CC P27986:PIK3R1; NbExp=1; IntAct=EBI-1752525, EBI-79464; CC P19174:PLCG1; NbExp=1; IntAct=EBI-1752525, EBI-79387; CC P12931:SRC; NbExp=1; IntAct=EBI-1752525, EBI-621482; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen (By similarity). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q13087-1; Sequence=Displayed; CC Name=2; CC IsoId=Q13087-2; Sequence=VSP_039292; CC -!- TISSUE SPECIFICITY: Highly expressed in pancreas (at protein CC level). CC -!- PTM: The disulfide-linked homodimer exhibits an enhanced chaperone CC activity. CC -!- PTM: Glycosylated. CC -!- SIMILARITY: Belongs to the protein disulfide isomerase family. CC -!- SIMILARITY: Contains 2 thioredoxin domains. CC -!- SEQUENCE CAUTION: CC Sequence=AAC50401.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part; CC Sequence=AAH75029.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part; CC Sequence=BAG58339.1; Type=Erroneous initiation; Note=Translation N-terminally extended; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB127078; BAE48734.1; -; mRNA. DR EMBL; AE006463; AAK61223.1; -; Genomic_DNA. DR EMBL; Z69667; CAI95586.1; -; Genomic_DNA. DR EMBL; Z69667; CAO78188.1; -; Genomic_DNA. DR EMBL; CH471112; EAW85838.1; -; Genomic_DNA. DR EMBL; BC000537; AAH00537.2; -; mRNA. DR EMBL; BC075029; AAH75029.1; ALT_SEQ; mRNA. DR EMBL; U19948; AAC50401.1; ALT_SEQ; mRNA. DR EMBL; AK295383; BAG58339.1; ALT_INIT; mRNA. DR IPI; IPI00011571; -. DR RefSeq; NP_006840.2; -. DR UniGene; Hs.66581; -. DR SMR; Q13087; 37-499. DR IntAct; Q13087; 8. DR MINT; MINT-1513985; -. DR STRING; Q13087; -. DR PRIDE; Q13087; -. DR Ensembl; ENST00000219406; ENSP00000219406; ENSG00000185615; Homo sapiens. DR Ensembl; ENST00000404312; ENSP00000384410; ENSG00000185615; Homo sapiens. DR GeneID; 64714; -. DR KEGG; hsa:64714; -. DR UCSC; uc002cgn.1; human. DR CTD; 64714; -. DR GeneCards; GC16P000276; -. DR HGNC; HGNC:14180; PDIA2. DR MIM; 608012; gene. DR PharmGKB; PA33153; -. DR eggNOG; prNOG08977; -. DR HOVERGEN; HBG005920; -. DR InParanoid; Q13087; -. DR PhylomeDB; Q13087; -. DR BRENDA; 5.3.4.1; 247. DR NextBio; 66651; -. DR ArrayExpress; Q13087; -. DR Bgee; Q13087; -. DR CleanEx; HS_PDIA2; -. DR Genevestigator; Q13087; -. DR GermOnline; ENSG00000185615; Homo sapiens. DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell. DR GO; GO:0005515; F:protein binding; IPI:IntAct. DR GO; GO:0003756; F:protein disulfide isomerase activity; TAS:ProtInc. DR GO; GO:0006915; P:apoptosis; IMP:HGNC. DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro. DR GO; GO:0006457; P:protein folding; TAS:ProtInc. DR GO; GO:0006621; P:protein retention in ER lumen; TAS:ProtInc. DR GO; GO:0001666; P:response to hypoxia; IMP:HGNC. DR InterPro; IPR005788; Disulphide_isomerase. DR InterPro; IPR005792; Prot_disulphide_isomerase. DR InterPro; IPR017936; Thioredoxin-like. DR InterPro; IPR012336; Thioredoxin-like_fold. DR InterPro; IPR006662; Thioredoxin-like_subdom. DR InterPro; IPR017937; Thioredoxin_CS. DR InterPro; IPR013766; Thioredoxin_domain. DR InterPro; IPR012335; Thioredoxin_fold. DR Gene3D; G3DSA:3.40.30.10; Thioredoxin_fold; 2. DR Pfam; PF00085; Thioredoxin; 2. DR PRINTS; PR00421; THIOREDOXIN. DR SUPFAM; SSF52833; Thiordxn-like_fd; 4. DR TIGRFAMs; TIGR01130; ER_PDI_fam; 1. DR TIGRFAMs; TIGR01126; pdi_dom; 2. DR PROSITE; PS00014; ER_TARGET; 1. DR PROSITE; PS00194; THIOREDOXIN_1; 2. DR PROSITE; PS51352; THIOREDOXIN_2; 2. PE 1: Evidence at protein level; KW Alternative splicing; Chaperone; Complete proteome; Disulfide bond; KW Endoplasmic reticulum; Glycoprotein; Isomerase; Lipid-binding; KW Polymorphism; Redox-active center; Repeat; Signal; Steroid-binding. FT SIGNAL 1 21 Potential. FT CHAIN 22 525 Protein disulfide-isomerase A2. FT /FTId=PRO_0000034222. FT DOMAIN 27 152 Thioredoxin 1. FT DOMAIN 367 496 Thioredoxin 2. FT MOTIF 522 525 Prevents secretion from ER (Potential). FT ACT_SITE 71 71 Nucleophile (By similarity). FT ACT_SITE 74 74 Nucleophile (By similarity). FT ACT_SITE 418 418 Nucleophile (By similarity). FT ACT_SITE 421 421 Nucleophile (By similarity). FT SITE 72 72 Contributes to redox potential value (By FT similarity). FT SITE 73 73 Contributes to redox potential value (By FT similarity). FT SITE 138 138 Lowers pKa of C-terminal Cys of first FT active site (By similarity). FT SITE 419 419 Contributes to redox potential value (By FT similarity). FT SITE 420 420 Contributes to redox potential value (By FT similarity). FT SITE 482 482 Lowers pKa of C-terminal Cys of second FT active site (By similarity). FT CARBOHYD 127 127 N-linked (GlcNAc...) (Potential). FT CARBOHYD 284 284 N-linked (GlcNAc...) (Potential). FT CARBOHYD 516 516 N-linked (GlcNAc...) (Potential). FT DISULFID 18 18 Interchain. FT DISULFID 71 74 Redox-active (By similarity). FT DISULFID 418 421 Redox-active (By similarity). FT VAR_SEQ 181 183 Missing (in isoform 2). FT /FTId=VSP_039292. FT VARIANT 39 39 P -> S (in dbSNP:rs45455191). FT /FTId=VAR_048087. FT VARIANT 119 119 T -> R (in dbSNP:rs45614840). FT /FTId=VAR_048088. FT VARIANT 185 185 E -> K (in dbSNP:rs419949). FT /FTId=VAR_048089. FT VARIANT 286 286 T -> M (in dbSNP:rs2685127). FT /FTId=VAR_048090. FT VARIANT 382 382 P -> A (in dbSNP:rs45529833). FT /FTId=VAR_048091. FT VARIANT 388 388 R -> Q (in dbSNP:rs400037). FT /FTId=VAR_048092. FT VARIANT 502 502 P -> S (in dbSNP:rs1048786). FT /FTId=VAR_048093. FT MUTAGEN 18 18 C->A: Impairs interchain disulfide bridge FT formation. FT MUTAGEN 364 364 C->A: No effect on interchain disulfide FT bridge formation. FT CONFLICT 96 96 T -> M (in Ref. 7; BAG58339). FT CONFLICT 484 484 L -> Q (in Ref. 7; BAG58339). SQ SEQUENCE 525 AA; 58206 MW; B741851AA2C40540 CRC64; MSRQLLPVLL LLLLRASCPW GQEQGARSPS EEPPEEEIPK EDGILVLSRH TLGLALREHP ALLVEFYAPW CGHCQALAPE YSKAAAVLAA ESMVVTLAKV DGPAQRELAE EFGVTEYPTL KFFRNGNRTH PEEYTGPRDA EGIAEWLRRR VGPSAMRLED EAAAQALIGG RDLVVIGFFQ DLQDEDVATF LALAQDALDM TFGLTDRPRL FQQFGLTKDT VVLFKKFDEG RADFPVDEEL GLDLGDLSRF LVTHSMRLVT EFNSQTSAKI FAARILNHLL LFVNQTLAAH RELLAGFGEA APRFRGQVLF VVVDVAADNE HVLQYFGLKA EAAPTLRLVN LETTKKYAPV DGGPVTAASI TAFCHAVLNG QVKPYLLSQE IPPDWDQRPV KTLVGKNFEQ VAFDETKNVF VKFYAPWCTH CKEMAPAWEA LAEKYQDHED IIIAELDATA NELDAFAVHG FPTLKYFPAG PGRKVIEYKS TRDLETFSKF LDNGGVLPTE EPPEEPAAPF PEPPANSTMG SKEEL //