Peroxiredoxin (PRX) family, PRX5-like subfamily; members are similar to the human protein, PRX5, a homodimeric TRX peroxidase, widely expressed in tissues and found cellularly in mitochondria, peroxisomes and the cytosol. The cellular location of PRX5 suggests that it may have an important antioxidant role in organelles that are major sources of reactive oxygen species (ROS), as well as a role in the control of signal transduction. PRX5 has been shown to reduce hydrogen peroxide, alkyl hydroperoxides and peroxynitrite. As with all other PRXs, the N-terminal peroxidatic cysteine of PRX5 is oxidized into a sulfenic acid intermediate upon reaction with peroxides. Human PRX5 is able to resolve this intermediate by forming an intramolecular disulfide bond with its C-terminal cysteine (the resolving cysteine), which can then be reduced by TRX, just like an atypical 2-cys PRX. This resolving cysteine, however, is not conserved in other members of the subfamily. In such cases, it is assumed that the oxidized cysteine is directly resolved by an external small-molecule or protein reductant, typical of a 1-cys PRX. In the case of the H. influenza PRX5 hybrid, the resolving glutaredoxin domain is on the same protein chain as PRX. PRX5 homodimers show an A-type interface, similar to atypical 2-cys PRXs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218878   6 VGDFVPDGSIsFFDDDDQLQTVSVHSLAAGKKVILFGVPGAFPPTCSMNHVNGFIEKAEELKSNGVDEIICLSGDDPFMI 85
Cdd:cd03013   1 VGDKLPNVTL-FEYVPGPPNPVNLSELFKGKKVVIFGVPGAFTPTCSAQHLPGYVENADELKAKGVDEVICVSVNDPFVM 79

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 15218878  86 TACSE----NKHVKFVEDGSGEYIQLLGLELEVKDKGLGVRSRGFALLLDNLKVIVVNV 140
Cdd:cd03013  80 KAWGKalgaKDKIRFLADGNGEFTKALGLTLDLSAAGGGIRSKRYALIVDDGKVKYLFV 138

Peroxiredoxin (PRX) family, PRX5-like subfamily; members are similar to the human protein, PRX5, a homodimeric TRX peroxidase, widely expressed in tissues and found cellularly in mitochondria, peroxisomes and the cytosol. The cellular location of PRX5 suggests that it may have an important antioxidant role in organelles that are major sources of reactive oxygen species (ROS), as well as a role in the control of signal transduction. PRX5 has been shown to reduce hydrogen peroxide, alkyl hydroperoxides and peroxynitrite. As with all other PRXs, the N-terminal peroxidatic cysteine of PRX5 is oxidized into a sulfenic acid intermediate upon reaction with peroxides. Human PRX5 is able to resolve this intermediate by forming an intramolecular disulfide bond with its C-terminal cysteine (the resolving cysteine), which can then be reduced by TRX, just like an atypical 2-cys PRX. This resolving cysteine, however, is not conserved in other members of the subfamily. In such cases, it is assumed that the oxidized cysteine is directly resolved by an external small-molecule or protein reductant, typical of a 1-cys PRX. In the case of the H. influenza PRX5 hybrid, the resolving glutaredoxin domain is on the same protein chain as PRX. PRX5 homodimers show an A-type interface, similar to atypical 2-cys PRXs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218878   6 VGDFVPDGSIsFFDDDDQLQTVSVHSLAAGKKVILFGVPGAFPPTCSMNHVNGFIEKAEELKSNGVDEIICLSGDDPFMI 85
Cdd:cd03013   1 VGDKLPNVTL-FEYVPGPPNPVNLSELFKGKKVVIFGVPGAFTPTCSAQHLPGYVENADELKAKGVDEVICVSVNDPFVM 79

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 15218878  86 TACSE----NKHVKFVEDGSGEYIQLLGLELEVKDKGLGVRSRGFALLLDNLKVIVVNV 140
Cdd:cd03013  80 KAWGKalgaKDKIRFLADGNGEFTKALGLTLDLSAAGGGIRSKRYALIVDDGKVKYLFV 138

F-box protein interaction domain; This model describes a large family of plant domains, with several hundred members in Arabidopsis thaliana. Most examples are found C-terminal to an F-box (pfam00646), a 60 amino acid motif involved in ubiquitination of target proteins to mark them for degradation. Two-hybid experiments support the idea that most members are interchangeable F-box subunits of SCF E3 complexes. Some members have two copies of this domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218878   259 VFCCEGLLlCILKDDdtKIVVWNPYLGQTRWIQTR-LICCVSGWKKYALGYgNNSENrscrSPKILRVTD-NFNIFSENi 336
Cdd:TIGR01640   1 VVPCDGLI-CFSYGK--RLVVWNPSTGQSRWLPTPkSRRSNKESDTYFLGY-DPIEK----QYKVLCFSDrSGNRNQSE- 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218878   337 plqYEIYDFDSDVWTTLDVSPHWFIMSERGLSLKGNTYWGAKERHAYgSIDHIICFDFTRERFGPLLPLPFSAWGAQFAS 416
Cdd:TIGR01640  72 ---HQVYTLGSNSWRTIECSPPHHPLKSRGVCINGVLYYLAYTLKTN-PDYFIVSFDVSSERFKEFIPLPCGNSDSVDYL 147

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15218878   417 LSSVREDKITALFQNCRAYKLELWITTkiDVNNATWSKFFTMDTPYLHEILSLK--TFFIDeENKIVVVSNKERD 489
Cdd:TIGR01640 148 SLINYKGKLAVLKQKKDTNNFDLWVLN--DAGKQEWSKLFTVPIPPLPDLVDDNflSGFTD-KGEIVLCCEDENP 219

F-box domain found in Arabidopsis thaliana F-box/WD-40 repeat-containing protein 1 (AtFBW1) and similar proteins; AtFBW1, also called WD-40-associated F-box protein 1, is an F-box protein that contains four WD-40 repeats, which are separated from each other by a spacer region. Like other F-box proteins, AtFBW1 may be a component of SCF (Skp1 Cdc53 F-box protein) E3 ubiquitin ligase complexes, which may mediate the ubiquitination and subsequent proteasomal degradation of target proteins. This subfamily also contains many F-box only proteins that do not have any WD repeat. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 15218878 160 SNLPTDLLEEIISRVPRKYMRAVRLTCKRWNGMFKSQSF 198
Cdd:cd22157   1 SSLPDDLVEEILSRLPAKSLLRFRCVCKQWNSLISSPSF 39

A Receptor for Ubiquitination Targets;

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 15218878    162 LPTDLLEEIISRVPRKYMRAVRLTCKRWNGMFKSQSFTK 200
Cdd:smart00256   1 LPDEILEEILSKLDPKDLLRLRKVSRKWRSLIDSHDFWF 39

Peroxiredoxin (PRX) family, PRX5-like subfamily; members are similar to the human protein, PRX5, a homodimeric TRX peroxidase, widely expressed in tissues and found cellularly in mitochondria, peroxisomes and the cytosol. The cellular location of PRX5 suggests that it may have an important antioxidant role in organelles that are major sources of reactive oxygen species (ROS), as well as a role in the control of signal transduction. PRX5 has been shown to reduce hydrogen peroxide, alkyl hydroperoxides and peroxynitrite. As with all other PRXs, the N-terminal peroxidatic cysteine of PRX5 is oxidized into a sulfenic acid intermediate upon reaction with peroxides. Human PRX5 is able to resolve this intermediate by forming an intramolecular disulfide bond with its C-terminal cysteine (the resolving cysteine), which can then be reduced by TRX, just like an atypical 2-cys PRX. This resolving cysteine, however, is not conserved in other members of the subfamily. In such cases, it is assumed that the oxidized cysteine is directly resolved by an external small-molecule or protein reductant, typical of a 1-cys PRX. In the case of the H. influenza PRX5 hybrid, the resolving glutaredoxin domain is on the same protein chain as PRX. PRX5 homodimers show an A-type interface, similar to atypical 2-cys PRXs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218878   6 VGDFVPDGSIsFFDDDDQLQTVSVHSLAAGKKVILFGVPGAFPPTCSMNHVNGFIEKAEELKSNGVDEIICLSGDDPFMI 85
Cdd:cd03013   1 VGDKLPNVTL-FEYVPGPPNPVNLSELFKGKKVVIFGVPGAFTPTCSAQHLPGYVENADELKAKGVDEVICVSVNDPFVM 79

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 15218878  86 TACSE----NKHVKFVEDGSGEYIQLLGLELEVKDKGLGVRSRGFALLLDNLKVIVVNV 140
Cdd:cd03013  80 KAWGKalgaKDKIRFLADGNGEFTKALGLTLDLSAAGGGIRSKRYALIVDDGKVKYLFV 138

F-box protein interaction domain; This model describes a large family of plant domains, with several hundred members in Arabidopsis thaliana. Most examples are found C-terminal to an F-box (pfam00646), a 60 amino acid motif involved in ubiquitination of target proteins to mark them for degradation. Two-hybid experiments support the idea that most members are interchangeable F-box subunits of SCF E3 complexes. Some members have two copies of this domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218878   259 VFCCEGLLlCILKDDdtKIVVWNPYLGQTRWIQTR-LICCVSGWKKYALGYgNNSENrscrSPKILRVTD-NFNIFSENi 336
Cdd:TIGR01640   1 VVPCDGLI-CFSYGK--RLVVWNPSTGQSRWLPTPkSRRSNKESDTYFLGY-DPIEK----QYKVLCFSDrSGNRNQSE- 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218878   337 plqYEIYDFDSDVWTTLDVSPHWFIMSERGLSLKGNTYWGAKERHAYgSIDHIICFDFTRERFGPLLPLPFSAWGAQFAS 416
Cdd:TIGR01640  72 ---HQVYTLGSNSWRTIECSPPHHPLKSRGVCINGVLYYLAYTLKTN-PDYFIVSFDVSSERFKEFIPLPCGNSDSVDYL 147

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15218878   417 LSSVREDKITALFQNCRAYKLELWITTkiDVNNATWSKFFTMDTPYLHEILSLK--TFFIDeENKIVVVSNKERD 489
Cdd:TIGR01640 148 SLINYKGKLAVLKQKKDTNNFDLWVLN--DAGKQEWSKLFTVPIPPLPDLVDDNflSGFTD-KGEIVLCCEDENP 219

Peroxiredoxin (PRX) family; composed of the different classes of PRXs including many proteins originally known as bacterioferritin comigratory proteins (BCP), based on their electrophoretic mobility before their function was identified. PRXs are thiol-specific antioxidant (TSA) proteins also known as TRX peroxidases and alkyl hydroperoxide reductase C22 (AhpC) proteins. They confer a protective antioxidant role in cells through their peroxidase activity in which hydrogen peroxide, peroxynitrate, and organic hydroperoxides are reduced and detoxified using reducing equivalents derived from either TRX, glutathione, trypanothione and AhpF. They are distinct from other peroxidases in that they have no cofactors such as metals or prosthetic groups. The first step of catalysis, common to all PRXs, is the nucleophilic attack by the catalytic cysteine (also known as the peroxidatic cysteine) on the peroxide leading to cleavage of the oxygen-oxygen bond and the formation of a cysteine sulfenic acid intermediate. The second step of the reaction, the resolution of the intermediate, distinguishes the different types of PRXs. The presence or absence of a second cysteine (the resolving cysteine) classifies PRXs as either belonging to the 2-cys or 1-cys type. The resolving cysteine of 2-cys PRXs is either on the same chain (atypical) or on the second chain (typical) of a functional homodimer. Structural and motif analysis of this growing family supports the need for a new classification system. The peroxidase activity of PRXs is regulated in vivo by irreversible cysteine over-oxidation into a sulfinic acid, phosphorylation and limited proteolysis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218878  20 DDDQLQTVSVHSLAaGKKVILFGVPGAFPPTCSMNhVNGFIEKAEELKsNGVDEIICLSGDDPF-MITACSENKHVKF-- 96
Cdd:cd02971   8 PATDGGEVSLSDFK-GKWVVLFFYPKDFTPVCTTE-LCAFRDLAEEFA-KGGAEVLGVSVDSPFsHKAWAEKEGGLNFpl 84

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 15218878  97 VEDGSGEYIQLLGLELEvKDKGLGVRSRGfALLLDNLKVIV 137
Cdd:cd02971  85 LSDPDGEFAKAYGVLIE-KSAGGGLAARA-TFIIDPDGKIR 123

F-box domain; This domain is approximately 50 amino acids long, and is usually found in the N-terminal half of a variety of proteins. Two motifs that are commonly found associated with the F-box domain are the leucine rich repeats (LRRs; pfam00560 and pfam07723) and the WD repeat (pfam00400). The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 15218878   159 MSNLPTDLLEEIISRVPRKYMRAVRLTCKRWNGMFKSQSFTK 200
Cdd:pfam00646   1 LLDLPDDLLLEILSRLDPKDLLRLSLVSKRWRSLVDSLKLWK 42

Peroxiredoxin (PRX) family, AhpE-like subfamily; composed of proteins similar to Mycobacterium tuberculosis AhpE. AhpE is described as a 1-cys PRX because of the absence of a resolving cysteine. The structure and sequence of AhpE, however, show greater similarity to 2-cys PRXs than 1-cys PRXs. PRXs are thiol-specific antioxidant (TSA) proteins that confer a protective role in cells through their peroxidase activity in which hydrogen peroxide, peroxynitrate, and organic hydroperoxides are reduced and detoxified using reducing equivalents derived from either thioredoxin, glutathione, trypanothione and AhpF. The first step of catalysis is the nucleophilic attack by the peroxidatic cysteine on the peroxide leading to the formation of a cysteine sulfenic acid intermediate. The absence of a resolving cysteine suggests that functional AhpE is regenerated by an external reductant. The solution behavior and crystal structure of AhpE show that it forms dimers and octamers.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218878   4 IDVGDFVPDgsisfFDDDDQ-LQTVSVHSLAAGKKVILFGVPGAFPPTCSmNHVNGFIEKAEELKSNGVdEIICLSGDDP 82
Cdd:cd03018   1 LEVGDKAPD-----FELPDQnGQEVRLSEFRGRKPVVLVFFPLAFTPVCT-KELCALRDSLELFEAAGA-EVLGISVDSP 73

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 15218878  83 FMITACSENKHVKF--VED--GSGEYIQLLGLELEvkDKGLGVRS 123
Cdd:cd03018  74 FSLRAWAEENGLTFplLSDfwPHGEVAKAYGVFDE--DLGVAERA 116

Peroxiredoxin (PRX) family, Bacterioferritin comigratory protein (BCP) subfamily; composed of thioredoxin-dependent thiol peroxidases, widely expressed in pathogenic bacteria, that protect cells against toxicity from reactive oxygen species by reducing and detoxifying hydroperoxides. The protein was named BCP based on its electrophoretic mobility before its function was known. BCP shows substrate selectivity toward fatty acid hydroperoxides rather than hydrogen peroxide or alkyl hydroperoxides. BCP contains the peroxidatic cysteine but appears not to possess a resolving cysteine (some sequences, not all, contain a second cysteine but its role is still unknown). Unlike other PRXs, BCP exists as a monomer. The plant homolog of BCP is PRX Q, which is expressed only in leaves and is cellularly localized in the chloroplasts and the guard cells of stomata. Also included in this subfamily is the fungal nuclear protein, Dot5p (for disrupter of telomere silencing protein 5), which functions as an alkyl-hydroperoxide reductase during post-diauxic growth.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15218878   8 DFVPDgsISFFDDDDQlqTVSVhSLAAGKKVILFGVPGAFPPTCSmNHVNGFIEKAEELKSNGVdEIICLSGDDPfmita 87
Cdd:cd03017   1 DKAPD--FTLPDQDGE--TVSL-SDLRGKPVVLYFYPKDDTPGCT-KEACDFRDLYEEFKALGA-VVIGVSPDSV----- 68

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15218878  88 cseNKHVKFVE----------DGSGEYIQLLGLELEVKDKGLGV-RSrgfALLLDNLKVIV 137
Cdd:cd03017  69 ---ESHAKFAEkyglpfpllsDPDGKLAKAYGVWGEKKKKYMGIeRS---TFLIDPDGKIV 123

F-box domain found in F-box only proteins FBXO6, FBXO44 and similar proteins; This subfamily includes FBXO6 and FBXO44. FBXO6, also called FBX6, F-box protein that recognizes sugar chains 2 (FBS2), or F-box/G-domain protein 2 (FBG2), is a substrate-recognition component of SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complexes. It is involved in the endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal proteins, by recognizing and binding sugar chains on unfolded glycoproteins that are retro-translocated into the cytosol and promoting their ubiquitination and subsequent degradation. FBXO6 can recognize and bind denatured glycoproteins, which are modified with not only high-mannose but also complex-type oligosaccharides. It also recognizes sulfated glycans. FBXO6 is involved in DNA damage response by specifically recognizing activated CHEK1 (phosphorylated on 'Ser-345'), promoting its ubiquitination and degradation. FBXO44, also called FBXO6A, FBX44, or F-box/G-domain protein 3 (FBG3), is a substrate-recognition component of an SCF-type E3 ubiquitin ligase complex. It interacts with SKP1 and CUL1. FBXO44 mediates BRCA1 ubiquitination and degradation. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                        10        20        30
                ....*....|....*....|....*....|....
gi 15218878 157 TTMSNLPTDLLEEIISRVPRKYM-RAVRLTCKRW 189
Cdd:cd22168   2 LTISDLPEDVLLEILSLVPARDLiLSCRLVCSRW 35

F-box domain found in Arabidopsis thaliana transport inhibitor response 1 protein (TIR1), coronatine-insensitive protein 1 (COI1) and similar proteins; TIR1, also called F-box/LRR-repeat protein 1 (FBL1), is part of an SCF (SKP1-cullin-F-box) protein ligase complex that promotes the ubiquitin-dependent proteolysis of a family of transcriptional regulators known as Aux/IAAs in an auxin-dependent manner. TIR1 is an auxin receptor that plays a potential role in plant hormone signaling. COI1, also called F-box/LRR-repeat protein 2 (FBL2), is the substrate-recruiting module of an SCF ubiquitin E3 ligase complex. It mediates jasmonate signalling by promoting hormone-dependent ubiquitylation and degradation of transcriptional repressor JASMONATE ZIM-domain (JAZ) family proteins. This subfamily also includes Arabidopsis thaliana EIN3-binding F-box protein 1 (EBF1). EBF1, also called F-box/LRR-repeat protein 6 (FBL6), is a component of the SCF(EBF1) E3 ubiquitin ligase complex, which may mediate the ubiquitination and subsequent proteasomal degradation of target proteins (probably including EIN3 and EIL1). The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                        10        20        30
                ....*....|....*....|....*....|...
gi 15218878 159 MSNLPTDLLEEIISRVPRKYMR-AVRLTCKRWN 190
Cdd:cd22159   1 IDLLPDEILELIFSYLSDPWDRnSCSLVCKRWY 33

F-box-like; This is an F-box-like family.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 15218878   159 MSNLPTDLLEEIISRVPRKYMRAVRLTCKRWN 190
Cdd:pfam12937   1 LSSLPDEILLQIFSYLDPKDLLRLALVCRRWR 32