Full text data of PRDX2
PRDX2
(NKEFB, TDPX1)
[Confidence: high (present in two of the MS resources)]
Peroxiredoxin-2; 1.11.1.15 (Natural killer cell-enhancing factor B; NKEF-B; PRP; Thiol-specific antioxidant protein; TSA; Thioredoxin peroxidase 1; Thioredoxin-dependent peroxide reductase 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Peroxiredoxin-2; 1.11.1.15 (Natural killer cell-enhancing factor B; NKEF-B; PRP; Thiol-specific antioxidant protein; TSA; Thioredoxin peroxidase 1; Thioredoxin-dependent peroxide reductase 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00027350
IPI00027350 Peroxiredoxin 2 Peroxiredoxin 2 membrane n/a n/a n/a n/a n/a n/a n/a n/a 6 n/a 5 4 n/a 3 n/a n/a n/a 1 2 n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00027350 Peroxiredoxin 2 Peroxiredoxin 2 membrane n/a n/a n/a n/a n/a n/a n/a n/a 6 n/a 5 4 n/a 3 n/a n/a n/a 1 2 n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P32119
ID PRDX2_HUMAN Reviewed; 198 AA.
AC P32119; A8K0C0; P31945; P32118; P35701; Q6FHG4; Q92763; Q9UC23;
read moreDT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 5.
DT 22-JAN-2014, entry version 163.
DE RecName: Full=Peroxiredoxin-2;
DE EC=1.11.1.15;
DE AltName: Full=Natural killer cell-enhancing factor B;
DE Short=NKEF-B;
DE AltName: Full=PRP;
DE AltName: Full=Thiol-specific antioxidant protein;
DE Short=TSA;
DE AltName: Full=Thioredoxin peroxidase 1;
DE AltName: Full=Thioredoxin-dependent peroxide reductase 1;
GN Name=PRDX2; Synonyms=NKEFB, TDPX1;
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).
RC TISSUE=Brain;
RX PubMed=8144038; DOI=10.1016/0378-1119(94)90558-4;
RA Lim Y.-S., Cha M.-K., Kim H.-K., Kim I.-H.;
RT "The thiol-specific antioxidant protein from human brain: gene cloning
RT and analysis of conserved cysteine regions.";
RL Gene 140:279-284(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8026862; DOI=10.1007/BF00188176;
RA Shau H., Butterfield L.H., Chiu R., Kim A.;
RT "Cloning and sequence analysis of candidate human natural killer-
RT enhancing factor genes.";
RL Immunogenetics 40:129-134(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-153.
RG NIEHS SNPs program;
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hypothalamus, and Lung;
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 [9]
RP PROTEIN SEQUENCE OF 8-26; 67-135 AND 140-150, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [10]
RP PROTEIN SEQUENCE OF 8-24, AND CATALYTIC ACTIVITY.
RC TISSUE=Erythrocyte;
RX PubMed=8554614; DOI=10.1006/bbrc.1995.2856;
RA Cha M.-K., Kim I.-H.;
RT "Thioredoxin-linked peroxidase from human red blood cell: evidence for
RT the existence of thioredoxin and thioredoxin reductase in human red
RT blood cell.";
RL Biochem. Biophys. Res. Commun. 217:900-907(1995).
RN [11]
RP PROTEIN SEQUENCE OF 17-26; 93-103 AND 120-129.
RC TISSUE=Erythrocyte;
RX PubMed=8313871; DOI=10.1002/elps.11501401183;
RA Golaz O., Hughes G.J., Frutiger S., Paquet N., Bairoch A.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Appel R.D., Walzer C.,
RA Balant L., Hochstrasser D.F.;
RT "Plasma and red blood cell protein maps: update 1993.";
RL Electrophoresis 14:1223-1231(1993).
RN [12]
RP PROTEIN SEQUENCE OF 17-26; 111-135 AND 140-157.
RC TISSUE=Colon carcinoma;
RX PubMed=9150948; DOI=10.1002/elps.1150180344;
RA Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J.;
RT "A two-dimensional gel database of human colon carcinoma proteins.";
RL Electrophoresis 18:605-613(1997).
RN [13]
RP PROTEIN SEQUENCE OF 17-25; 140-150 AND 163-185.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [14]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 35-198 (ISOFORM 1).
RA Oberbaeumer I.;
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN [15]
RP OVEROXIDATION AT CYS-51.
RX PubMed=11904290; DOI=10.1074/jbc.M106585200;
RA Rabilloud T., Heller M., Gasnier F., Luche S., Rey C., Aebersold R.,
RA Benahmed M., Louisot P., Lunardi J.;
RT "Proteomics analysis of cellular response to oxidative stress.
RT Evidence for in vivo overoxidation of peroxiredoxins at their active
RT site.";
RL J. Biol. Chem. 277:19396-19401(2002).
RN [16]
RP RETROREDUCTION OF CYS-51, AND MASS SPECTROMETRY.
RX PubMed=12853451; DOI=10.1074/jbc.M305161200;
RA Chevallet M., Wagner E., Luche S., van Dorsselaer A., Leize-Wagner E.,
RA Rabilloud T.;
RT "Regeneration of peroxiredoxins during recovery after oxidative
RT stress: only some overoxidized peroxiredoxins can be reduced during
RT recovery after oxidative stress.";
RL J. Biol. Chem. 278:37146-37153(2003).
RN [17]
RP INTERACTION WITH TIPIN.
RX PubMed=17141802; DOI=10.1016/j.jmb.2006.10.097;
RA Gotter A.L., Suppa C., Emanuel B.S.;
RT "Mammalian TIMELESS and Tipin are evolutionarily conserved replication
RT fork-associated factors.";
RL J. Mol. Biol. 366:36-52(2007).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-198.
RX PubMed=10873855; DOI=10.1016/S0969-2126(00)00147-7;
RA Schroeder E., Littlechild J.A., Lebedev A.A., Errington N.,
RA Vagin A.A., Isupov M.N.;
RT "Crystal structure of decameric 2-Cys peroxiredoxin from human
RT erythrocytes at 1.7 A resolution.";
RL Structure 8:605-615(2000).
CC -!- FUNCTION: Involved in redox regulation of the cell. Reduces
CC peroxides with reducing equivalents provided through the
CC thioredoxin system. It is not able to receive electrons from
CC glutaredoxin. May play an important role in eliminating peroxides
CC generated during metabolism. Might participate in the signaling
CC cascades of growth factors and tumor necrosis factor-alpha by
CC regulating the intracellular concentrations of H(2)O(2).
CC -!- CATALYTIC ACTIVITY: 2 R'-SH + ROOH = R'-S-S-R' + H(2)O + ROH.
CC -!- SUBUNIT: Homodimer; disulfide-linked, upon oxidation. May be found
CC as a toroid-shaped decamer composed of 5 dimers, depending on pH
CC and calcium concentration. Interacts with TIPIN.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P32119-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P32119-2; Sequence=VSP_042924;
CC Note=No experimental confirmation available. Due to intron
CC retention. May be produced at very low levels due to a premature
CC stop codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC -!- MISCELLANEOUS: The active site is the redox-active Cys-51 oxidized
CC to Cys-SOH. Cys-SOH rapidly reacts with Cys-172-SH of the other
CC subunit to form an intermolecular disulfide with a concomitant
CC homodimer formation. The enzyme may be subsequently regenerated by
CC reduction of the disulfide by thioredoxin.
CC -!- MISCELLANEOUS: Inactivated upon oxidative stress by overoxidation
CC of Cys-51 to Cys-SO(2)H and Cys-SO(3)H. Cys-SO(2)H is retroreduced
CC to Cys-SOH after removal of H(2)O(2), while Cys-SO(3)H may be
CC irreversibly oxidized.
CC -!- SIMILARITY: Belongs to the AhpC/TSA family.
CC -!- SIMILARITY: Contains 1 thioredoxin domain.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/prdx2/";
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DR EMBL; Z22548; CAA80269.1; -; mRNA.
DR EMBL; L19185; AAA50465.1; -; mRNA.
DR EMBL; CR450356; CAG29352.1; -; mRNA.
DR EMBL; CR541789; CAG46588.1; -; mRNA.
DR EMBL; AK289485; BAF82174.1; -; mRNA.
DR EMBL; DQ231563; ABB02182.1; -; Genomic_DNA.
DR EMBL; AC018761; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84311.1; -; Genomic_DNA.
DR EMBL; BC000452; AAH00452.1; -; mRNA.
DR EMBL; BC003022; AAH03022.1; -; mRNA.
DR EMBL; BC039428; AAH39428.1; -; mRNA.
DR EMBL; X82321; CAA57764.1; -; mRNA.
DR PIR; I68897; I68897.
DR RefSeq; NP_005800.3; NM_005809.5.
DR UniGene; Hs.432121; -.
DR PDB; 1QMV; X-ray; 1.70 A; A/B/C/D/E/F/G/H/I/J=2-198.
DR PDBsum; 1QMV; -.
DR ProteinModelPortal; P32119; -.
DR SMR; P32119; 3-198.
DR IntAct; P32119; 27.
DR MINT; MINT-3012817; -.
DR STRING; 9606.ENSP00000301522; -.
DR PeroxiBase; 4475; Hs2CysPrx02.
DR PhosphoSite; P32119; -.
DR DMDM; 2507169; -.
DR DOSAC-COBS-2DPAGE; P32119; -.
DR OGP; P32119; -.
DR REPRODUCTION-2DPAGE; IPI00027350; -.
DR SWISS-2DPAGE; P32119; -.
DR UCD-2DPAGE; P32119; -.
DR PaxDb; P32119; -.
DR PRIDE; P32119; -.
DR DNASU; 7001; -.
DR Ensembl; ENST00000301522; ENSP00000301522; ENSG00000167815.
DR Ensembl; ENST00000435703; ENSP00000408905; ENSG00000167815.
DR GeneID; 7001; -.
DR KEGG; hsa:7001; -.
DR UCSC; uc002mvd.4; human.
DR CTD; 7001; -.
DR GeneCards; GC19M012907; -.
DR HGNC; HGNC:9353; PRDX2.
DR HPA; CAB008713; -.
DR MIM; 600538; gene.
DR neXtProt; NX_P32119; -.
DR PharmGKB; PA33723; -.
DR eggNOG; COG0450; -.
DR HOGENOM; HOG000022343; -.
DR HOVERGEN; HBG000286; -.
DR InParanoid; P32119; -.
DR KO; K03386; -.
DR OMA; LQFTEEF; -.
DR PhylomeDB; P32119; -.
DR ChiTaRS; PRDX2; human.
DR EvolutionaryTrace; P32119; -.
DR GeneWiki; Peroxiredoxin_2; -.
DR GenomeRNAi; 7001; -.
DR NextBio; 27342; -.
DR PRO; PR:P32119; -.
DR ArrayExpress; P32119; -.
DR Bgee; P32119; -.
DR CleanEx; HS_PRDX2; -.
DR Genevestigator; P32119; -.
DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0008379; F:thioredoxin peroxidase activity; IDA:UniProtKB.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; TAS:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0019430; P:removal of superoxide radicals; IDA:BHF-UCL.
DR Gene3D; 3.40.30.10; -; 1.
DR InterPro; IPR000866; AhpC/TSA.
DR InterPro; IPR024706; Peroxiredoxin_AhpC-typ.
DR InterPro; IPR019479; Peroxiredoxin_C.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR Pfam; PF10417; 1-cysPrx_C; 1.
DR Pfam; PF00578; AhpC-TSA; 1.
DR PIRSF; PIRSF000239; AHPC; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Antioxidant;
KW Complete proteome; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; Oxidoreductase; Peroxidase; Polymorphism;
KW Redox-active center; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 198 Peroxiredoxin-2.
FT /FTId=PRO_0000135080.
FT DOMAIN 6 164 Thioredoxin.
FT ACT_SITE 51 51 Cysteine sulfenic acid (-SOH)
FT intermediate.
FT MOD_RES 2 2 N-acetylalanine.
FT DISULFID 51 51 Interchain (with C-172); in linked form
FT (By similarity).
FT DISULFID 172 172 Interchain (with C-51); in linked form
FT (By similarity).
FT VAR_SEQ 87 198 INTPRKEGGLGPLNIPLLADVTRRLSEDYGVLKTDEGIAYR
FT GLFIIDGKGVLRQITVNDLPVGRSVDEALRLVQAFQYTDEH
FT GEVCPAGWKPGSDTIKPNVDDSKEYFSKHN -> YEQGPKR
FT EVAAKLTPSGPSSVASWPLLNLWNLRFPIVKIMETLPPKSL
FT RMMTVISI (in isoform 2).
FT /FTId=VSP_042924.
FT VARIANT 153 153 D -> E (in dbSNP:rs34012472).
FT /FTId=VAR_025051.
FT CONFLICT 59 66 SNRAEDFR -> TTVKRTSA (in Ref. 1;
FT CAA80269).
FT CONFLICT 82 82 T -> N (in Ref. 2; AAA50465).
FT CONFLICT 105 105 A -> G (in Ref. 2; AAA50465).
FT CONFLICT 120 120 T -> N (in Ref. 1; CAA80269).
FT CONFLICT 126 127 YR -> TT (in Ref. 11; AA sequence).
FT CONFLICT 175 175 G -> A (in Ref. 1; CAA80269).
FT CONFLICT 180 180 S -> R (in Ref. 1; CAA80269).
FT STRAND 16 21
FT STRAND 24 29
FT HELIX 30 33
FT STRAND 36 42
FT HELIX 50 60
FT HELIX 62 66
FT TURN 67 69
FT STRAND 70 78
FT HELIX 80 87
FT HELIX 91 93
FT STRAND 103 105
FT HELIX 110 114
FT TURN 120 122
FT STRAND 127 132
FT STRAND 136 144
FT HELIX 152 168
FT HELIX 187 197
SQ SEQUENCE 198 AA; 21892 MW; 1AC781D908B32B46 CRC64;
MASGNARIGK PAPDFKATAV VDGAFKEVKL SDYKGKYVVL FFYPLDFTFV CPTEIIAFSN
RAEDFRKLGC EVLGVSVDSQ FTHLAWINTP RKEGGLGPLN IPLLADVTRR LSEDYGVLKT
DEGIAYRGLF IIDGKGVLRQ ITVNDLPVGR SVDEALRLVQ AFQYTDEHGE VCPAGWKPGS
DTIKPNVDDS KEYFSKHN
//
ID PRDX2_HUMAN Reviewed; 198 AA.
AC P32119; A8K0C0; P31945; P32118; P35701; Q6FHG4; Q92763; Q9UC23;
read moreDT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 5.
DT 22-JAN-2014, entry version 163.
DE RecName: Full=Peroxiredoxin-2;
DE EC=1.11.1.15;
DE AltName: Full=Natural killer cell-enhancing factor B;
DE Short=NKEF-B;
DE AltName: Full=PRP;
DE AltName: Full=Thiol-specific antioxidant protein;
DE Short=TSA;
DE AltName: Full=Thioredoxin peroxidase 1;
DE AltName: Full=Thioredoxin-dependent peroxide reductase 1;
GN Name=PRDX2; Synonyms=NKEFB, TDPX1;
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).
RC TISSUE=Brain;
RX PubMed=8144038; DOI=10.1016/0378-1119(94)90558-4;
RA Lim Y.-S., Cha M.-K., Kim H.-K., Kim I.-H.;
RT "The thiol-specific antioxidant protein from human brain: gene cloning
RT and analysis of conserved cysteine regions.";
RL Gene 140:279-284(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8026862; DOI=10.1007/BF00188176;
RA Shau H., Butterfield L.H., Chiu R., Kim A.;
RT "Cloning and sequence analysis of candidate human natural killer-
RT enhancing factor genes.";
RL Immunogenetics 40:129-134(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-153.
RG NIEHS SNPs program;
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hypothalamus, and Lung;
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 [9]
RP PROTEIN SEQUENCE OF 8-26; 67-135 AND 140-150, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [10]
RP PROTEIN SEQUENCE OF 8-24, AND CATALYTIC ACTIVITY.
RC TISSUE=Erythrocyte;
RX PubMed=8554614; DOI=10.1006/bbrc.1995.2856;
RA Cha M.-K., Kim I.-H.;
RT "Thioredoxin-linked peroxidase from human red blood cell: evidence for
RT the existence of thioredoxin and thioredoxin reductase in human red
RT blood cell.";
RL Biochem. Biophys. Res. Commun. 217:900-907(1995).
RN [11]
RP PROTEIN SEQUENCE OF 17-26; 93-103 AND 120-129.
RC TISSUE=Erythrocyte;
RX PubMed=8313871; DOI=10.1002/elps.11501401183;
RA Golaz O., Hughes G.J., Frutiger S., Paquet N., Bairoch A.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Appel R.D., Walzer C.,
RA Balant L., Hochstrasser D.F.;
RT "Plasma and red blood cell protein maps: update 1993.";
RL Electrophoresis 14:1223-1231(1993).
RN [12]
RP PROTEIN SEQUENCE OF 17-26; 111-135 AND 140-157.
RC TISSUE=Colon carcinoma;
RX PubMed=9150948; DOI=10.1002/elps.1150180344;
RA Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J.;
RT "A two-dimensional gel database of human colon carcinoma proteins.";
RL Electrophoresis 18:605-613(1997).
RN [13]
RP PROTEIN SEQUENCE OF 17-25; 140-150 AND 163-185.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [14]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 35-198 (ISOFORM 1).
RA Oberbaeumer I.;
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN [15]
RP OVEROXIDATION AT CYS-51.
RX PubMed=11904290; DOI=10.1074/jbc.M106585200;
RA Rabilloud T., Heller M., Gasnier F., Luche S., Rey C., Aebersold R.,
RA Benahmed M., Louisot P., Lunardi J.;
RT "Proteomics analysis of cellular response to oxidative stress.
RT Evidence for in vivo overoxidation of peroxiredoxins at their active
RT site.";
RL J. Biol. Chem. 277:19396-19401(2002).
RN [16]
RP RETROREDUCTION OF CYS-51, AND MASS SPECTROMETRY.
RX PubMed=12853451; DOI=10.1074/jbc.M305161200;
RA Chevallet M., Wagner E., Luche S., van Dorsselaer A., Leize-Wagner E.,
RA Rabilloud T.;
RT "Regeneration of peroxiredoxins during recovery after oxidative
RT stress: only some overoxidized peroxiredoxins can be reduced during
RT recovery after oxidative stress.";
RL J. Biol. Chem. 278:37146-37153(2003).
RN [17]
RP INTERACTION WITH TIPIN.
RX PubMed=17141802; DOI=10.1016/j.jmb.2006.10.097;
RA Gotter A.L., Suppa C., Emanuel B.S.;
RT "Mammalian TIMELESS and Tipin are evolutionarily conserved replication
RT fork-associated factors.";
RL J. Mol. Biol. 366:36-52(2007).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-198.
RX PubMed=10873855; DOI=10.1016/S0969-2126(00)00147-7;
RA Schroeder E., Littlechild J.A., Lebedev A.A., Errington N.,
RA Vagin A.A., Isupov M.N.;
RT "Crystal structure of decameric 2-Cys peroxiredoxin from human
RT erythrocytes at 1.7 A resolution.";
RL Structure 8:605-615(2000).
CC -!- FUNCTION: Involved in redox regulation of the cell. Reduces
CC peroxides with reducing equivalents provided through the
CC thioredoxin system. It is not able to receive electrons from
CC glutaredoxin. May play an important role in eliminating peroxides
CC generated during metabolism. Might participate in the signaling
CC cascades of growth factors and tumor necrosis factor-alpha by
CC regulating the intracellular concentrations of H(2)O(2).
CC -!- CATALYTIC ACTIVITY: 2 R'-SH + ROOH = R'-S-S-R' + H(2)O + ROH.
CC -!- SUBUNIT: Homodimer; disulfide-linked, upon oxidation. May be found
CC as a toroid-shaped decamer composed of 5 dimers, depending on pH
CC and calcium concentration. Interacts with TIPIN.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P32119-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P32119-2; Sequence=VSP_042924;
CC Note=No experimental confirmation available. Due to intron
CC retention. May be produced at very low levels due to a premature
CC stop codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC -!- MISCELLANEOUS: The active site is the redox-active Cys-51 oxidized
CC to Cys-SOH. Cys-SOH rapidly reacts with Cys-172-SH of the other
CC subunit to form an intermolecular disulfide with a concomitant
CC homodimer formation. The enzyme may be subsequently regenerated by
CC reduction of the disulfide by thioredoxin.
CC -!- MISCELLANEOUS: Inactivated upon oxidative stress by overoxidation
CC of Cys-51 to Cys-SO(2)H and Cys-SO(3)H. Cys-SO(2)H is retroreduced
CC to Cys-SOH after removal of H(2)O(2), while Cys-SO(3)H may be
CC irreversibly oxidized.
CC -!- SIMILARITY: Belongs to the AhpC/TSA family.
CC -!- SIMILARITY: Contains 1 thioredoxin domain.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/prdx2/";
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DR EMBL; Z22548; CAA80269.1; -; mRNA.
DR EMBL; L19185; AAA50465.1; -; mRNA.
DR EMBL; CR450356; CAG29352.1; -; mRNA.
DR EMBL; CR541789; CAG46588.1; -; mRNA.
DR EMBL; AK289485; BAF82174.1; -; mRNA.
DR EMBL; DQ231563; ABB02182.1; -; Genomic_DNA.
DR EMBL; AC018761; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84311.1; -; Genomic_DNA.
DR EMBL; BC000452; AAH00452.1; -; mRNA.
DR EMBL; BC003022; AAH03022.1; -; mRNA.
DR EMBL; BC039428; AAH39428.1; -; mRNA.
DR EMBL; X82321; CAA57764.1; -; mRNA.
DR PIR; I68897; I68897.
DR RefSeq; NP_005800.3; NM_005809.5.
DR UniGene; Hs.432121; -.
DR PDB; 1QMV; X-ray; 1.70 A; A/B/C/D/E/F/G/H/I/J=2-198.
DR PDBsum; 1QMV; -.
DR ProteinModelPortal; P32119; -.
DR SMR; P32119; 3-198.
DR IntAct; P32119; 27.
DR MINT; MINT-3012817; -.
DR STRING; 9606.ENSP00000301522; -.
DR PeroxiBase; 4475; Hs2CysPrx02.
DR PhosphoSite; P32119; -.
DR DMDM; 2507169; -.
DR DOSAC-COBS-2DPAGE; P32119; -.
DR OGP; P32119; -.
DR REPRODUCTION-2DPAGE; IPI00027350; -.
DR SWISS-2DPAGE; P32119; -.
DR UCD-2DPAGE; P32119; -.
DR PaxDb; P32119; -.
DR PRIDE; P32119; -.
DR DNASU; 7001; -.
DR Ensembl; ENST00000301522; ENSP00000301522; ENSG00000167815.
DR Ensembl; ENST00000435703; ENSP00000408905; ENSG00000167815.
DR GeneID; 7001; -.
DR KEGG; hsa:7001; -.
DR UCSC; uc002mvd.4; human.
DR CTD; 7001; -.
DR GeneCards; GC19M012907; -.
DR HGNC; HGNC:9353; PRDX2.
DR HPA; CAB008713; -.
DR MIM; 600538; gene.
DR neXtProt; NX_P32119; -.
DR PharmGKB; PA33723; -.
DR eggNOG; COG0450; -.
DR HOGENOM; HOG000022343; -.
DR HOVERGEN; HBG000286; -.
DR InParanoid; P32119; -.
DR KO; K03386; -.
DR OMA; LQFTEEF; -.
DR PhylomeDB; P32119; -.
DR ChiTaRS; PRDX2; human.
DR EvolutionaryTrace; P32119; -.
DR GeneWiki; Peroxiredoxin_2; -.
DR GenomeRNAi; 7001; -.
DR NextBio; 27342; -.
DR PRO; PR:P32119; -.
DR ArrayExpress; P32119; -.
DR Bgee; P32119; -.
DR CleanEx; HS_PRDX2; -.
DR Genevestigator; P32119; -.
DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0008379; F:thioredoxin peroxidase activity; IDA:UniProtKB.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; TAS:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0019430; P:removal of superoxide radicals; IDA:BHF-UCL.
DR Gene3D; 3.40.30.10; -; 1.
DR InterPro; IPR000866; AhpC/TSA.
DR InterPro; IPR024706; Peroxiredoxin_AhpC-typ.
DR InterPro; IPR019479; Peroxiredoxin_C.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR Pfam; PF10417; 1-cysPrx_C; 1.
DR Pfam; PF00578; AhpC-TSA; 1.
DR PIRSF; PIRSF000239; AHPC; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Antioxidant;
KW Complete proteome; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; Oxidoreductase; Peroxidase; Polymorphism;
KW Redox-active center; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 198 Peroxiredoxin-2.
FT /FTId=PRO_0000135080.
FT DOMAIN 6 164 Thioredoxin.
FT ACT_SITE 51 51 Cysteine sulfenic acid (-SOH)
FT intermediate.
FT MOD_RES 2 2 N-acetylalanine.
FT DISULFID 51 51 Interchain (with C-172); in linked form
FT (By similarity).
FT DISULFID 172 172 Interchain (with C-51); in linked form
FT (By similarity).
FT VAR_SEQ 87 198 INTPRKEGGLGPLNIPLLADVTRRLSEDYGVLKTDEGIAYR
FT GLFIIDGKGVLRQITVNDLPVGRSVDEALRLVQAFQYTDEH
FT GEVCPAGWKPGSDTIKPNVDDSKEYFSKHN -> YEQGPKR
FT EVAAKLTPSGPSSVASWPLLNLWNLRFPIVKIMETLPPKSL
FT RMMTVISI (in isoform 2).
FT /FTId=VSP_042924.
FT VARIANT 153 153 D -> E (in dbSNP:rs34012472).
FT /FTId=VAR_025051.
FT CONFLICT 59 66 SNRAEDFR -> TTVKRTSA (in Ref. 1;
FT CAA80269).
FT CONFLICT 82 82 T -> N (in Ref. 2; AAA50465).
FT CONFLICT 105 105 A -> G (in Ref. 2; AAA50465).
FT CONFLICT 120 120 T -> N (in Ref. 1; CAA80269).
FT CONFLICT 126 127 YR -> TT (in Ref. 11; AA sequence).
FT CONFLICT 175 175 G -> A (in Ref. 1; CAA80269).
FT CONFLICT 180 180 S -> R (in Ref. 1; CAA80269).
FT STRAND 16 21
FT STRAND 24 29
FT HELIX 30 33
FT STRAND 36 42
FT HELIX 50 60
FT HELIX 62 66
FT TURN 67 69
FT STRAND 70 78
FT HELIX 80 87
FT HELIX 91 93
FT STRAND 103 105
FT HELIX 110 114
FT TURN 120 122
FT STRAND 127 132
FT STRAND 136 144
FT HELIX 152 168
FT HELIX 187 197
SQ SEQUENCE 198 AA; 21892 MW; 1AC781D908B32B46 CRC64;
MASGNARIGK PAPDFKATAV VDGAFKEVKL SDYKGKYVVL FFYPLDFTFV CPTEIIAFSN
RAEDFRKLGC EVLGVSVDSQ FTHLAWINTP RKEGGLGPLN IPLLADVTRR LSEDYGVLKT
DEGIAYRGLF IIDGKGVLRQ ITVNDLPVGR SVDEALRLVQ AFQYTDEHGE VCPAGWKPGS
DTIKPNVDDS KEYFSKHN
//
MIM
600538
*RECORD*
*FIELD* NO
600538
*FIELD* TI
*600538 PEROXIREDOXIN 2; PRDX2
;;PRX2;;
PEROXIDE REDUCTASE, THIOREDOXIN-DEPENDENT; TDPX1; TPX1;;
read moreNATURAL KILLER-ENHANCING FACTOR B; NKEFB
*FIELD* TX
CLONING
Shau et al. (1994) identified a red blood cell factor, NKEF, that
enhances natural killer (NK) cell activity. By immunoscreening an
erythroleukemia cDNA library, they isolated cDNAs encoding NKEFA (PRDX1;
176763) and NKEFB. The NKEFA and NKEFB proteins contain 199 and 198
amino acids, respectively, and are 75% identical. The authors noted that
proteins related to NKEFA and NKEFB appear to be induced by oxidative
stress. Shau et al. (1994) concluded that in addition to
immunoregulation of NK activity, the NKEFs may be important for cells in
coping with oxidative insults.
Reactive oxygen species (ROS) and free radicals that are produced during
normal metabolism have the potential of damaging cellular
macromolecules. Defenses against such damage include a number of
antioxidant enzymes that specifically target the removal or dismutation
of the reactive agent. Pahl et al. (1995) isolated a human gene,
symbolized TDPX1 (for thioredoxin-dependent peroxide reductase-1), that
encodes an enzyme homologous to the yeast thioredoxin peroxidase (TPX).
The human coding sequence was determined from the product of a PCR
amplification of human cDNA using primers based on the rat sequence
(Chae et al., 1994). The 198-amino acid rat protein was, in turn,
isolated as a cDNA from a brain expression library with antibodies to
bovine thiol-specific antioxidant (TSA) enzyme. The rat and yeast TSA
proteins show significant similarity to Salmonella typhimurium alkyl
hydroperoxide reductase.
MAPPING
Based on PCR analysis of DNAs from a human/rodent somatic cell hybrid
panel, Pahl et al. (1995) assigned the TDPX1 locus to chromosome 13.
Further localization to 13q12 was achieved by fluorescence in situ
hybridization, using as a probe DNA from a YAC that contained the TDPX1
gene. However, Gross (2012) mapped the PRDX2 gene to chromosome 19p13.2
based on an alignment of the PRDX2 sequence (GenBank GENBANK BC003022)
with the genomic sequence (GRCh37).
GENE FUNCTION
To clarify the physiologic relevance of peroxiredoxins, Lee et al.
(2003) generated a mouse model deficient in PRDX2, which is abundantly
expressed in all types of cells. The Prdx2 -/- mice were healthy in
appearance and fertile. However, they had splenomegaly caused by the
congestion of red pulp with hemosiderin accumulation. Heinz bodies were
detected in their peripheral blood, and morphologically abnormal cells
were increased in the dense red blood cell (RBC) fractions, which
contained markedly higher levels of ROS. The null mice had significantly
decreased hematocrit levels, but increased reticulocyte counts and
erythropoietin levels, indicative of a compensatory action to maintain
hematologic homeostasis. A labeling experiment in null mice showed that
a variety of RBC proteins were highly oxidized. The results suggested
that Prdx -/- mice have hemolytic anemia and that peroxiredoxin II plays
a major role in protecting RBCs from oxidative stress in mice.
Choi et al. (2005) demonstrated that PRDX2 is a negative regulator of
PDGF (see 190040) signaling. Prx II deficiency results in increased
production of peroxide, enhanced activation of PDGF receptor (PDGFR; see
173490) and phospholipase C-gamma-1 (172420), and subsequently increased
cell proliferation and migration in response to PDGF. These responses
are suppressed by expression of wildtype Prx II, but not an inactive
mutant. Notably, Prx II is recruited to PDGFR upon PDGF stimulation, and
suppresses protein tyrosine phosphatase inactivation. Prx II also leads
to the suppression of PDGFR activation in primary culture and in a
murine restenosis model, including PDGF-dependent neointimal thickening
of vascular smooth muscle cells. Choi et al. (2005) concluded that their
results demonstrate a localized role for endogenous peroxide in PDGF
signaling, and indicate a biologic function for Prx II in cardiovascular
disease.
By immunoblot, liquid chromatographic mass spectrometric,
immunoelectron, and confocal microscopic analyses, Koncarevic et al.
(2009) showed that human PRX2 was enriched in the malaria parasite,
Plasmodium falciparum. Importation of PRX2 into the parasite cytosol
compensated for the lack of catalase and glutathione peroxidase and
helped to maintain an adequate antioxidant defense. Pull-down
experiments demonstrated that PRX2 interacted with and was active with
parasite Trx1. PRX2 accounted for about half of the thioredoxin activity
in parasite extracts, and PRX2 expression was increased in the presence
of chloroquine, regardless of P. falciparum strain susceptibility to the
drug. Koncarevic et al. (2009) concluded that P. falciparum has adapted
to adopt PRX2, using the host protein for its own purposes.
O'Neill and Reddy (2011) studied circadian clocks in human red blood
cells in order to avoid the transcription-translation feedloop that is
presumed to be essential for clock formation. Human red blood cells have
no nucleus and therefore cannot perform transcription. O'Neill and Reddy
(2011) found that transcription is not required for circadian
oscillations in humans, and that nontranscriptional events seem to be
sufficient to sustain cellular circadian rhythms. Using red blood cells,
they found that peroxiredoxins, highly conserved antioxidant proteins,
undergo approximately 24-hour redox cycles, which persist for many days
under constant conditions (i.e., in the absence of external cues).
Moreover, these rhythms are entrainable (i.e., tunable by environmental
stimuli) and temperature-compensated, both key features of circadian
rhythms. O'Neill and Reddy (2011) anticipated that their findings would
facilitate more sophisticated cellular clock models, highlighting the
interdependency of transcriptional and nontranscriptional oscillations
in potentially all eukaryotic cells.
O'Neill et al. (2011) showed that nontranscriptional mechanisms are
sufficient to sustain circadian timekeeping in the eukaryotic lineage,
although they normally function in conjunction with transcriptional
components. They identified oxidation of peroxiredoxin proteins as a
transcription-independent rhythmic biomarker, which is also rhythmic in
mammals. Moreover, O'Neill et al. (2011) showed that pharmacologic
modulators of the mammalian clock mechanism have the same effects on
rhythms in Ostreococcus tauri, a unicellular pico-eukaryotic alga that
possesses a naturally minimized clock. Posttranslational mechanisms, and
at least 1 rhythmic marker, seem to be better conserved than
transcriptional clock regulators. O'Neill et al. (2011) postulated that
it is plausible that the oldest oscillator components are
nontranscriptional in nature, as in cyanobacteria, and are conserved
across kingdoms.
*FIELD* RF
1. Chae, H. Z.; Robinson, K.; Poole, L. B.; Church, G.; Storz, G.;
Rhee, S. G.: Cloning and sequencing of thiol-specific antioxidant
from mammalian brain: alkyl hydroperoxide reductase and thiol-specific
antioxidant define a large family of antioxidant genes. Proc. nat.
Acad. Sci. 91: 7017-7021, 1994.
2. Choi, M. H.; Lee, I. K.; Kim, G. W.; Kim, B. U.; Han, Y.-H.; Yu,
D.-Y.; Park, H. S.; Kim, K. Y.; Lee, J. S.; Choi, C.; Bae, Y. S.;
Lee, B. I.; Rhee, S. G.; Kang, S. W.: Regulation of PDGF signalling
and vascular remodelling by peroxiredoxin II. Nature 435: 347-353,
2005.
3. Gross, M. B.: Personal Communication. Baltimore, Md. 10/2/2012.
4. Koncarevic, S.; Rohrbach, P.; Deponte, M.; Krohne, G.; Prieto,
J. H.; Yates, J., III; Rahlfs, S.; Becker, K.: The malarial parasite
Plasmodium falciparum imports the human protein peroxiredoxin 2 for
peroxide detoxification. Proc. Nat. Acad. Sci. 106: 13323-13328,
2009.
5. Lee, T.-H.; Kim, S.-U.; Yu, S.-L.; Kim, S. H.; Park, D. S.; Moon,
H.-B.; Dho, S. H.; Kwon, K.-S.; Kwon, H. J.; Han, Y.-H.; Jeong, S.;
Kang, S. W.; Shin, H.-S.; Lee, K.-K.; Rhee, S. G.; Yu, D.-Y.: Peroxiredoxin
II is essential for sustaining life span of erythrocytes in mice. Blood 101:
5033-5038, 2003.
6. O'Neill, J. S.; Reddy, A. B.: Circadian clocks in human red blood
cells. Nature 469: 498-503, 2011.
7. O'Neill, J. S.; van Ooijen, G.; Dixon, L. E.; Troein, C.; Corellou,
F.; Bouget, F.-Y.; Reddy, A. B.; Millar, A. J.: Circadian rhythms
persist without transcription in a eukaryote. Nature 469: 554-558,
2011.
8. Pahl, P.; Berger, R.; Hart, I.; Chae, H. Z.; Rhee, S. G.; Patterson,
D.: Localization of TDPX1, a human homologue of the yeast thioredoxin-dependent
peroxide reductase gene (TPX), to chromosome 13q12. Genomics 26:
602-606, 1995.
9. Shau, H.; Butterfield, L. H.; Chiu, R.; Kim, A.: Cloning and sequence
analysis of candidate human natural killer-enhancing factor genes. Immunogenetics 40:
129-134, 1994.
*FIELD* CN
Matthew B. Gross - updated: 10/02/2012
Ada Hamosh - updated: 5/6/2011
Paul J. Converse - updated: 7/29/2010
Ada Hamosh - updated: 6/2/2005
Victor A. McKusick - updated: 9/4/2003
Paul J. Converse - updated: 8/13/2001
Alan F. Scott - updated: 3/10/1996
*FIELD* CD
Victor A. McKusick: 5/17/1995
*FIELD* ED
mgross: 10/02/2012
alopez: 5/9/2011
terry: 5/6/2011
mgross: 8/19/2010
terry: 7/29/2010
wwang: 6/7/2005
wwang: 6/3/2005
terry: 6/2/2005
ckniffin: 9/10/2004
cwells: 9/8/2003
terry: 9/4/2003
mgross: 8/13/2001
alopez: 8/1/2000
terry: 4/17/1996
mark: 3/10/1996
mark: 5/17/1995
*RECORD*
*FIELD* NO
600538
*FIELD* TI
*600538 PEROXIREDOXIN 2; PRDX2
;;PRX2;;
PEROXIDE REDUCTASE, THIOREDOXIN-DEPENDENT; TDPX1; TPX1;;
read moreNATURAL KILLER-ENHANCING FACTOR B; NKEFB
*FIELD* TX
CLONING
Shau et al. (1994) identified a red blood cell factor, NKEF, that
enhances natural killer (NK) cell activity. By immunoscreening an
erythroleukemia cDNA library, they isolated cDNAs encoding NKEFA (PRDX1;
176763) and NKEFB. The NKEFA and NKEFB proteins contain 199 and 198
amino acids, respectively, and are 75% identical. The authors noted that
proteins related to NKEFA and NKEFB appear to be induced by oxidative
stress. Shau et al. (1994) concluded that in addition to
immunoregulation of NK activity, the NKEFs may be important for cells in
coping with oxidative insults.
Reactive oxygen species (ROS) and free radicals that are produced during
normal metabolism have the potential of damaging cellular
macromolecules. Defenses against such damage include a number of
antioxidant enzymes that specifically target the removal or dismutation
of the reactive agent. Pahl et al. (1995) isolated a human gene,
symbolized TDPX1 (for thioredoxin-dependent peroxide reductase-1), that
encodes an enzyme homologous to the yeast thioredoxin peroxidase (TPX).
The human coding sequence was determined from the product of a PCR
amplification of human cDNA using primers based on the rat sequence
(Chae et al., 1994). The 198-amino acid rat protein was, in turn,
isolated as a cDNA from a brain expression library with antibodies to
bovine thiol-specific antioxidant (TSA) enzyme. The rat and yeast TSA
proteins show significant similarity to Salmonella typhimurium alkyl
hydroperoxide reductase.
MAPPING
Based on PCR analysis of DNAs from a human/rodent somatic cell hybrid
panel, Pahl et al. (1995) assigned the TDPX1 locus to chromosome 13.
Further localization to 13q12 was achieved by fluorescence in situ
hybridization, using as a probe DNA from a YAC that contained the TDPX1
gene. However, Gross (2012) mapped the PRDX2 gene to chromosome 19p13.2
based on an alignment of the PRDX2 sequence (GenBank GENBANK BC003022)
with the genomic sequence (GRCh37).
GENE FUNCTION
To clarify the physiologic relevance of peroxiredoxins, Lee et al.
(2003) generated a mouse model deficient in PRDX2, which is abundantly
expressed in all types of cells. The Prdx2 -/- mice were healthy in
appearance and fertile. However, they had splenomegaly caused by the
congestion of red pulp with hemosiderin accumulation. Heinz bodies were
detected in their peripheral blood, and morphologically abnormal cells
were increased in the dense red blood cell (RBC) fractions, which
contained markedly higher levels of ROS. The null mice had significantly
decreased hematocrit levels, but increased reticulocyte counts and
erythropoietin levels, indicative of a compensatory action to maintain
hematologic homeostasis. A labeling experiment in null mice showed that
a variety of RBC proteins were highly oxidized. The results suggested
that Prdx -/- mice have hemolytic anemia and that peroxiredoxin II plays
a major role in protecting RBCs from oxidative stress in mice.
Choi et al. (2005) demonstrated that PRDX2 is a negative regulator of
PDGF (see 190040) signaling. Prx II deficiency results in increased
production of peroxide, enhanced activation of PDGF receptor (PDGFR; see
173490) and phospholipase C-gamma-1 (172420), and subsequently increased
cell proliferation and migration in response to PDGF. These responses
are suppressed by expression of wildtype Prx II, but not an inactive
mutant. Notably, Prx II is recruited to PDGFR upon PDGF stimulation, and
suppresses protein tyrosine phosphatase inactivation. Prx II also leads
to the suppression of PDGFR activation in primary culture and in a
murine restenosis model, including PDGF-dependent neointimal thickening
of vascular smooth muscle cells. Choi et al. (2005) concluded that their
results demonstrate a localized role for endogenous peroxide in PDGF
signaling, and indicate a biologic function for Prx II in cardiovascular
disease.
By immunoblot, liquid chromatographic mass spectrometric,
immunoelectron, and confocal microscopic analyses, Koncarevic et al.
(2009) showed that human PRX2 was enriched in the malaria parasite,
Plasmodium falciparum. Importation of PRX2 into the parasite cytosol
compensated for the lack of catalase and glutathione peroxidase and
helped to maintain an adequate antioxidant defense. Pull-down
experiments demonstrated that PRX2 interacted with and was active with
parasite Trx1. PRX2 accounted for about half of the thioredoxin activity
in parasite extracts, and PRX2 expression was increased in the presence
of chloroquine, regardless of P. falciparum strain susceptibility to the
drug. Koncarevic et al. (2009) concluded that P. falciparum has adapted
to adopt PRX2, using the host protein for its own purposes.
O'Neill and Reddy (2011) studied circadian clocks in human red blood
cells in order to avoid the transcription-translation feedloop that is
presumed to be essential for clock formation. Human red blood cells have
no nucleus and therefore cannot perform transcription. O'Neill and Reddy
(2011) found that transcription is not required for circadian
oscillations in humans, and that nontranscriptional events seem to be
sufficient to sustain cellular circadian rhythms. Using red blood cells,
they found that peroxiredoxins, highly conserved antioxidant proteins,
undergo approximately 24-hour redox cycles, which persist for many days
under constant conditions (i.e., in the absence of external cues).
Moreover, these rhythms are entrainable (i.e., tunable by environmental
stimuli) and temperature-compensated, both key features of circadian
rhythms. O'Neill and Reddy (2011) anticipated that their findings would
facilitate more sophisticated cellular clock models, highlighting the
interdependency of transcriptional and nontranscriptional oscillations
in potentially all eukaryotic cells.
O'Neill et al. (2011) showed that nontranscriptional mechanisms are
sufficient to sustain circadian timekeeping in the eukaryotic lineage,
although they normally function in conjunction with transcriptional
components. They identified oxidation of peroxiredoxin proteins as a
transcription-independent rhythmic biomarker, which is also rhythmic in
mammals. Moreover, O'Neill et al. (2011) showed that pharmacologic
modulators of the mammalian clock mechanism have the same effects on
rhythms in Ostreococcus tauri, a unicellular pico-eukaryotic alga that
possesses a naturally minimized clock. Posttranslational mechanisms, and
at least 1 rhythmic marker, seem to be better conserved than
transcriptional clock regulators. O'Neill et al. (2011) postulated that
it is plausible that the oldest oscillator components are
nontranscriptional in nature, as in cyanobacteria, and are conserved
across kingdoms.
*FIELD* RF
1. Chae, H. Z.; Robinson, K.; Poole, L. B.; Church, G.; Storz, G.;
Rhee, S. G.: Cloning and sequencing of thiol-specific antioxidant
from mammalian brain: alkyl hydroperoxide reductase and thiol-specific
antioxidant define a large family of antioxidant genes. Proc. nat.
Acad. Sci. 91: 7017-7021, 1994.
2. Choi, M. H.; Lee, I. K.; Kim, G. W.; Kim, B. U.; Han, Y.-H.; Yu,
D.-Y.; Park, H. S.; Kim, K. Y.; Lee, J. S.; Choi, C.; Bae, Y. S.;
Lee, B. I.; Rhee, S. G.; Kang, S. W.: Regulation of PDGF signalling
and vascular remodelling by peroxiredoxin II. Nature 435: 347-353,
2005.
3. Gross, M. B.: Personal Communication. Baltimore, Md. 10/2/2012.
4. Koncarevic, S.; Rohrbach, P.; Deponte, M.; Krohne, G.; Prieto,
J. H.; Yates, J., III; Rahlfs, S.; Becker, K.: The malarial parasite
Plasmodium falciparum imports the human protein peroxiredoxin 2 for
peroxide detoxification. Proc. Nat. Acad. Sci. 106: 13323-13328,
2009.
5. Lee, T.-H.; Kim, S.-U.; Yu, S.-L.; Kim, S. H.; Park, D. S.; Moon,
H.-B.; Dho, S. H.; Kwon, K.-S.; Kwon, H. J.; Han, Y.-H.; Jeong, S.;
Kang, S. W.; Shin, H.-S.; Lee, K.-K.; Rhee, S. G.; Yu, D.-Y.: Peroxiredoxin
II is essential for sustaining life span of erythrocytes in mice. Blood 101:
5033-5038, 2003.
6. O'Neill, J. S.; Reddy, A. B.: Circadian clocks in human red blood
cells. Nature 469: 498-503, 2011.
7. O'Neill, J. S.; van Ooijen, G.; Dixon, L. E.; Troein, C.; Corellou,
F.; Bouget, F.-Y.; Reddy, A. B.; Millar, A. J.: Circadian rhythms
persist without transcription in a eukaryote. Nature 469: 554-558,
2011.
8. Pahl, P.; Berger, R.; Hart, I.; Chae, H. Z.; Rhee, S. G.; Patterson,
D.: Localization of TDPX1, a human homologue of the yeast thioredoxin-dependent
peroxide reductase gene (TPX), to chromosome 13q12. Genomics 26:
602-606, 1995.
9. Shau, H.; Butterfield, L. H.; Chiu, R.; Kim, A.: Cloning and sequence
analysis of candidate human natural killer-enhancing factor genes. Immunogenetics 40:
129-134, 1994.
*FIELD* CN
Matthew B. Gross - updated: 10/02/2012
Ada Hamosh - updated: 5/6/2011
Paul J. Converse - updated: 7/29/2010
Ada Hamosh - updated: 6/2/2005
Victor A. McKusick - updated: 9/4/2003
Paul J. Converse - updated: 8/13/2001
Alan F. Scott - updated: 3/10/1996
*FIELD* CD
Victor A. McKusick: 5/17/1995
*FIELD* ED
mgross: 10/02/2012
alopez: 5/9/2011
terry: 5/6/2011
mgross: 8/19/2010
terry: 7/29/2010
wwang: 6/7/2005
wwang: 6/3/2005
terry: 6/2/2005
ckniffin: 9/10/2004
cwells: 9/8/2003
terry: 9/4/2003
mgross: 8/13/2001
alopez: 8/1/2000
terry: 4/17/1996
mark: 3/10/1996
mark: 5/17/1995