ID PRDX4_HUMAN Reviewed; 271 AA. AC Q13162; Q6FHT3; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 04-NOV-2008, entry version 82. DE RecName: Full=Peroxiredoxin-4; DE EC=1.11.1.15; DE AltName: Full=Prx-IV; DE AltName: Full=Thioredoxin peroxidase AO372; DE AltName: Full=Thioredoxin-dependent peroxide reductase A0372; DE AltName: Full=Antioxidant enzyme AOE372; DE Short=AOE37-2; GN Name=PRDX4; 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]. RX MEDLINE=98049564; PubMed=9388242; DOI=10.1074/jbc.272.49.30952; RA Jin D.-Y., Chae H.Z., Rhee S.G., Jeang K.-T.; RT "Regulatory role for a novel human thioredoxin peroxidase in NF-kappaB RT activation."; RL J. Biol. Chem. 272:30952-30961(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [4] RP PROTEIN SEQUENCE OF 48-66 AND 174-200, AND MASS SPECTROMETRY. RC TISSUE=Brain, and Cajal-Retzius cell; RA Lubec G., Afjehi-Sadat L.; RL Submitted (MAR-2007) to UniProtKB. RN [5] RP OVEROXIDATION AT CYS-124. RX MEDLINE=22201787; PubMed=12059788; DOI=10.1042/BJ20020525; RA Wagner E., Luche S., Penna L., Chevallet M., van Dorsselaer A., RA Leize-Wagner E., Rabilloud T.; RT "A method for detection of overoxidation of cysteines: peroxiredoxins RT are oxidized in vivo at the active-site cysteine during oxidative RT stress."; RL Biochem. J. 366:777-785(2002). CC -!- FUNCTION: Probably involved in redox regulation of the cell. CC Regulates the activation of NF-kappa-B in the cytosol by a CC modulation of I-kappa-B-alpha phosphorylation. CC -!- CATALYTIC ACTIVITY: 2 R'-SH + ROOH = R'-S-S-R' + H(2)O + ROH. CC -!- SUBUNIT: Homodimer or heterodimer with PRDX1; disulfide-linked, CC upon oxidation (By similarity). CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- MISCELLANEOUS: The active site is the redox-active Cys-124 CC oxidized to Cys-SOH. Cys-SOH rapidly reacts with Cys-245-SH of the CC other subunit to form an intermolecular disulfide with a CC concomitant homodimer formation. The enzyme may be subsequently CC regenerated by reduction of the disulfide by thioredoxin. CC -!- MISCELLANEOUS: Irreversibly inactivated by overoxidation of Cys- CC 124 (to Cys-SO(3)H) upon oxidative stress. CC -!- SIMILARITY: Belongs to the ahpC/TSA family. CC -!- SIMILARITY: Contains 1 thioredoxin domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; U25182; AAB95175.1; -; mRNA. DR EMBL; CR541668; CAG46469.1; -; mRNA. DR EMBL; CR541705; CAG46506.1; -; mRNA. DR EMBL; BC003609; AAH03609.1; -; mRNA. DR EMBL; BC007107; AAH07107.1; -; mRNA. DR EMBL; BC016770; AAH16770.1; -; mRNA. DR PIR; G01790; G01790. DR RefSeq; NP_006397.1; -. DR UniGene; Hs.83383; -. DR PDB; 2PN8; X-ray; 1.80 A; A/B/C/D/E/F/G/H/I/J=82-271. DR PDBsum; 2PN8; -. DR PeroxiBase; 4530; Hs2CysPrx04. DR OGP; Q13162; -. DR REPRODUCTION-2DPAGE; IPI00011937; -. DR PeptideAtlas; Q13162; -. DR Ensembl; ENSG00000123131; Homo sapiens. DR GeneID; 10549; -. DR KEGG; hsa:10549; -. DR NMPDR; fig|9606.3.peg.32551; -. DR H-InvDB; HIX0016701; -. DR HGNC; HGNC:17169; PRDX4. DR HPA; CAB008659; -. DR MIM; 606506; gene. DR PharmGKB; PA33725; -. DR HOGENOM; Q13162; -. DR HOVERGEN; Q13162; -. DR LinkHub; Q13162; -. DR NextBio; 40013; -. DR ArrayExpress; Q13162; -. DR CleanEx; HS_PRDX4; -. DR GermOnline; ENSG00000123131; Homo sapiens. DR GO; GO:0008379; F:thioredoxin peroxidase activity; TAS:ProtInc. DR GO; GO:0007252; P:I-kappaB phosphorylation; TAS:ProtInc. DR InterPro; IPR000866; AhpC-TSA. DR InterPro; IPR012335; Thioredoxin_fold. DR Gene3D; G3DSA:3.40.30.10; Thioredoxin_fold; 1. DR Pfam; PF00578; AhpC-TSA; 1. DR PROSITE; PS51352; THIOREDOXIN_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Antioxidant; Cytoplasm; Direct protein sequencing; KW Oxidoreductase; Peroxidase; Redox-active center. FT CHAIN 1 271 Peroxiredoxin-4. FT /FTId=PRO_0000135098. FT DOMAIN 79 237 Thioredoxin. FT COMPBIAS 20 30 Poly-Leu. FT ACT_SITE 124 124 Cysteine sulfenic acid (-SOH) FT intermediate (By similarity). FT DISULFID 124 124 Interchain (with C-245); in linked form FT (By similarity). FT DISULFID 245 245 Interchain (with C-124); in linked form FT (By similarity). FT CONFLICT 12 12 P -> S (in Ref. 3; CAG46469). FT CONFLICT 51 51 C -> Y (in Ref. 3; CAG46469). FT STRAND 89 94 FT STRAND 97 102 FT HELIX 103 106 FT STRAND 109 115 FT HELIX 123 133 FT HELIX 135 139 FT TURN 140 142 FT STRAND 143 151 FT HELIX 153 160 FT HELIX 164 166 FT STRAND 176 178 FT HELIX 183 187 FT TURN 193 195 FT STRAND 196 198 FT STRAND 200 205 FT STRAND 209 217 FT HELIX 225 241 FT TURN 260 262 FT HELIX 263 267 SQ SEQUENCE 271 AA; 30540 MW; 7E56B580049FC60F CRC64; MEALPLLAAT TPDHGRHRRL LLLPLLLFLL PAGAVQGWET EERPRTREEE CHFYAGGQVY PGEASRVSVA DHSLHLSKAK ISKPAPYWEG TAVIDGEFKE LKLTDYRGKY LVFFFYPLDF TFVCPTEIIA FGDRLEEFRS INTEVVACSV DSQFTHLAWI NTPRRQGGLG PIRIPLLSDL THQISKDYGV YLEDSGHTLR GLFIIDDKGI LRQITLNDLP VGRSVDETLR LVQAFQYTDK HGEVCPAGWK PGSETIIPDP AGKLKYFDKL N //