cytochrome P450 family 74; The cytochrome P450 74 (CYP74) family controls several enzymatic conversions of fatty acid hydroperoxides to bioactive oxylipins in plants, some invertebrates, and bacteria. It includes two dehydrases, namely allene oxide synthase (AOS) and divinyl ether synthase (DES), and two isomerases, hydroperoxide lyase (HPL) and epoxyalcohol synthase (EAS). AOS (EC 4.2.1.92, also called hydroperoxide dehydratase), such as Arabidopsis thaliana CYP74A acts on a number of unsaturated fatty-acid hydroperoxides, forming the corresponding allene oxides. DES (EC 4.2.1.121), also called colneleate synthase or CYP74D, catalyzes the selective removal of pro-R hydrogen at C-8 in the biosynthesis of colneleic acid. The linolenate HPL, Arabidopsis thaliana CYP74B2, is required for the synthesis of the green leaf volatiles (GLVs) hexanal and trans-2-hexenal. The fatty acid HPL, Solanum lycopersicum CYP74B, is involved in the biosynthesis of traumatin and C6 aldehydes. The epoxyalcohol synthase Ranunculus japonicus CYP74A88 (also known as RjEAS) specifically converts linoleic acid 9- and 13-hydroperoxides to oxiranyl carbinols 9,10-epoxy-11-hydroxy-12-octadecenoic acid and 11-hydroxy-12,13-epoxy-9-octadecenoic acid, respectively. The CYP74 family belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600  49 KTRMQKYHSTVFRANMPPGPFISSDSKVVVLLDTVSFPVLFDSSKVEKRNVFVGTFMPSTDLTGGYRVLPYLDPSEPKHD 128
Cdd:cd11071    1 KSRMEKYKSTVFRVNMPPGPPISSDPRVVALLDAKSFPVLFDNSKVEKEDVFGGTYMPSTSFTGGYRVLPYLDTSEPKHA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 129 LLKRFSFSLLASRHRDFIPVFRSGLPDLFSTIEDDVSRKGKANFNDIADDMYFNFVFRLICGKDPSDAKIRSEGPNIFLK 208
Cdd:cd11071   81 KLKAFLFELLKSRSSRFIPEFRSALSELFDKWEAELAKKGKASFNDDLEKLAFDFLFRLLFGADPSETKLGSDGPDALDK 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 209 WLFLQLSPLLTLGLsilPNFIDDLLLHTFPFPPFLVKSDYNKLYKAFYESASSVLDEGERMGIKRDEACHNLVFLAGFNS 288
Cdd:cd11071  161 WLALQLAPTLSLGL---PKILEELLLHTFPLPFFLVKPDYQKLYKFFANAGLEVLDEAEKLGLSREEAVHNLLFMLGFNA 237

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 289 FGGMKVFFPALIKWVGLAGEKLHRELADEIRTVIKAEGGVTFAALDKMALTKSMVYEALRIEPPVPFQYGKAREDMVIHS 368
Cdd:cd11071  238 FGGFSALLPSLLARLGLAGEELHARLAEEIRSALGSEGGLTLAALEKMPLLKSVVYETLRLHPPVPLQYGRARKDFVIES 317

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 369 HDAAFEIKKGEMIFGYQPFATKDPKVFENPEEFVAHRFMGEGEKLLKYVYWSNGRETDNPTAENKQCSGKDLVVLISRLM 448
Cdd:cd11071  318 HDASYKIKKGELLVGYQPLATRDPKVFDNPDEFVPDRFMGEEGKLLKHLIWSNGPETEEPTPDNKQCPGKDLVVLLARLF 397

                        410       420
                 ....*....|....*....|....*..
gi 225428600 449 LVEIFLRYDTFEVESGTMLLGSSLLFK 475
Cdd:cd11071  398 VAELFLRYDTFTIEPGWTGKKLSVTVT 424

Cytochrome P450 [Secondary metabolites biosynthesis, transport and catabolism, Defense mechanisms]; Cytochrome P450 is part of the Pathway/BioSystem: Biotin biosynthesis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 337 ALTKSMVYEALRIEPPVPFQYGKAREDMVIHSHdaafEIKKGEMIFGYQPFATKDPKVFENPEEFVAHRFMGEgekllkY 416
Cdd:COG2124  268 ELLPAAVEETLRLYPPVPLLPRTATEDVELGGV----TIPAGDRVLLSLAAANRDPRVFPDPDRFDPDRPPNA------H 337

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 225428600 417 VYWSNGretdnptaeNKQCSGKDLVVLISRLMLVEIFLRYDTFEVESG 464
Cdd:COG2124  338 LPFGGG---------PHRCLGAALARLEARIALATLLRRFPDLRLAPP 376

cytochrome P450 family 74; The cytochrome P450 74 (CYP74) family controls several enzymatic conversions of fatty acid hydroperoxides to bioactive oxylipins in plants, some invertebrates, and bacteria. It includes two dehydrases, namely allene oxide synthase (AOS) and divinyl ether synthase (DES), and two isomerases, hydroperoxide lyase (HPL) and epoxyalcohol synthase (EAS). AOS (EC 4.2.1.92, also called hydroperoxide dehydratase), such as Arabidopsis thaliana CYP74A acts on a number of unsaturated fatty-acid hydroperoxides, forming the corresponding allene oxides. DES (EC 4.2.1.121), also called colneleate synthase or CYP74D, catalyzes the selective removal of pro-R hydrogen at C-8 in the biosynthesis of colneleic acid. The linolenate HPL, Arabidopsis thaliana CYP74B2, is required for the synthesis of the green leaf volatiles (GLVs) hexanal and trans-2-hexenal. The fatty acid HPL, Solanum lycopersicum CYP74B, is involved in the biosynthesis of traumatin and C6 aldehydes. The epoxyalcohol synthase Ranunculus japonicus CYP74A88 (also known as RjEAS) specifically converts linoleic acid 9- and 13-hydroperoxides to oxiranyl carbinols 9,10-epoxy-11-hydroxy-12-octadecenoic acid and 11-hydroxy-12,13-epoxy-9-octadecenoic acid, respectively. The CYP74 family belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600  49 KTRMQKYHSTVFRANMPPGPFISSDSKVVVLLDTVSFPVLFDSSKVEKRNVFVGTFMPSTDLTGGYRVLPYLDPSEPKHD 128
Cdd:cd11071    1 KSRMEKYKSTVFRVNMPPGPPISSDPRVVALLDAKSFPVLFDNSKVEKEDVFGGTYMPSTSFTGGYRVLPYLDTSEPKHA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 129 LLKRFSFSLLASRHRDFIPVFRSGLPDLFSTIEDDVSRKGKANFNDIADDMYFNFVFRLICGKDPSDAKIRSEGPNIFLK 208
Cdd:cd11071   81 KLKAFLFELLKSRSSRFIPEFRSALSELFDKWEAELAKKGKASFNDDLEKLAFDFLFRLLFGADPSETKLGSDGPDALDK 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 209 WLFLQLSPLLTLGLsilPNFIDDLLLHTFPFPPFLVKSDYNKLYKAFYESASSVLDEGERMGIKRDEACHNLVFLAGFNS 288
Cdd:cd11071  161 WLALQLAPTLSLGL---PKILEELLLHTFPLPFFLVKPDYQKLYKFFANAGLEVLDEAEKLGLSREEAVHNLLFMLGFNA 237

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 289 FGGMKVFFPALIKWVGLAGEKLHRELADEIRTVIKAEGGVTFAALDKMALTKSMVYEALRIEPPVPFQYGKAREDMVIHS 368
Cdd:cd11071  238 FGGFSALLPSLLARLGLAGEELHARLAEEIRSALGSEGGLTLAALEKMPLLKSVVYETLRLHPPVPLQYGRARKDFVIES 317

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 369 HDAAFEIKKGEMIFGYQPFATKDPKVFENPEEFVAHRFMGEGEKLLKYVYWSNGRETDNPTAENKQCSGKDLVVLISRLM 448
Cdd:cd11071  318 HDASYKIKKGELLVGYQPLATRDPKVFDNPDEFVPDRFMGEEGKLLKHLIWSNGPETEEPTPDNKQCPGKDLVVLLARLF 397

                        410       420
                 ....*....|....*....|....*..
gi 225428600 449 LVEIFLRYDTFEVESGTMLLGSSLLFK 475
Cdd:cd11071  398 VAELFLRYDTFTIEPGWTGKKLSVTVT 424

Cytochrome P450; Cytochrome P450s are haem-thiolate proteins involved in the oxidative degradation of various compounds. They are particularly well known for their role in the degradation of environmental toxins and mutagens. They can be divided into 4 classes, according to the method by which electrons from NAD(P)H are delivered to the catalytic site. Sequence conservation is relatively low within the family - there are only 3 absolutely conserved residues - but their general topography and structural fold are highly conserved. The conserved core is composed of a coil termed the 'meander', a four-helix bundle, helices J and K, and two sets of beta-sheets. These constitute the haem-binding loop (with an absolutely conserved cysteine that serves as the 5th ligand for the haem iron), the proton-transfer groove and the absolutely conserved EXXR motif in helix K. While prokaryotic P450s are soluble proteins, most eukaryotic P450s are associated with microsomal membranes. their general enzymatic function is to catalyze regiospecific and stereospecific oxidation of non-activated hydrocarbons at physiological temperatures.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600  308 EKLHREladeIRTVIKAEGGVTFAALDKMALTKSMVYEALRIEPPVPFQYG-KAREDMVIHSHDaafeIKKGEMIFGYqP 386
Cdd:pfam00067 296 EKLREE----IDEVIGDKRSPTYDDLQNMPYLDAVIKETLRLHPVVPLLLPrEVTKDTVIPGYL----IPKGTLVIVN-L 366

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600  387 FAT-KDPKVFENPEEFVAHRFMGEGEKLLKYVYW---SNGRetdnptaenKQCSGKDLVVLISRLMLVEIFLRYDtFEVE 462
Cdd:pfam00067 367 YALhRDPEVFPNPEEFDPERFLDENGKFRKSFAFlpfGAGP---------RNCLGERLARMEMKLFLATLLQNFE-VELP 436

                  ....
gi 225428600  463 SGTM 466
Cdd:pfam00067 437 PGTD 440

cytochrome P450 families 77 and 89, and similar cytochrome P450s; This group includes cytochrome P450 families 73 (CYP77) and 89 (CYP89), which are sister families that share a common ancestor. CYP89, present only in angiosperms, is younger than CYP77, which is already found in lycopods; thus, CYP89 may have evolved from CYP77 after duplication and divergence. Also included in this group is ent-kaurene oxidase, called CYP701A3 in Arabidopsis thaliana and CYP701B1 in Physcomitrella patens, that catalyzes the oxidation of ent-kaurene to form ent-kaurenoic acid. CYP701A3 is sensitive to inhibitor uniconazole-P while CYP701B1 is not. This CYP77/89 group belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 308 EKLHREladeIRTVIKAEGGVTFAALDKMALTKSMVYEALRIEPPVPFQ-YGKAREDMVIHSHDaafeIKKGEMIFGYQP 386
Cdd:cd11075  266 EKLYEE----IKEVVGDEAVVTEEDLPKMPYLKAVVLETLRRHPPGHFLlPHAVTEDTVLGGYD----IPAGAEVNFNVA 337

                         90       100
                 ....*....|....*....|....*
gi 225428600 387 FATKDPKVFENPEEFVAHRFMGEGE 411
Cdd:cd11075  338 AIGRDPKVWEDPEEFKPERFLAGGE 362

C-terminal cytochrome P450 domain of linoleate diol synthase and similar cytochrome P450s; This family contains Gaeumannomyces graminis linoleate diol synthase (LDS) and similar proteins including Ssp1 from the phytopathogenic basidiomycete Ustilago maydis. LDS, also called linoleate (8R)-dioxygenase, catalyzes the dioxygenation of linoleic acid to (8R)-hydroperoxylinoleate and the isomerization of the resulting hydroperoxide to (7S,8S)-dihydroxylinoleate. Ssp1 is expressed in mature teliospores, which are produced by U. maydis only after infection of its host plant, maize. Ssp1 is localized on lipid bodies in germinating teliospores, suggesting a role in the mobilization of storage lipids. LDS and Ssp1 contain an N-terminal dioxygenase domain related to animal heme peroxidases, and a C-terminal cytochrome P450 domain. The LDS-like subfamily belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 343 VYEALRIEPPVPFQYGKAREDMVIHS-HDAAFEIKKGEMIFGYQPFATKDPKVFENPEEFVAHRfmgegeKLLKYVYWSN 421
Cdd:cd20612  244 VLEALRLNPIAPGLYRRATTDTTVADgGGRTVSIKAGDRVFVSLASAMRDPRAFPDPERFRLDR------PLESYIHFGH 317

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 225428600 422 GretdnPTaenkQCSGKDLVVLISRLMLVEIFLRY 456
Cdd:cd20612  318 G-----PH----QCLGEEIARAALTEMLRVVLRLP 343

plant cytochrome P450s similar to cytochrome P450 family 90, subfamily A, polypeptide 1, cytochrome P450 family 90, subfamily B, polypeptide 1, and cytochrome P450 family 90, subfamily D, polypeptide 2; This family is composed of plant cytochrome P450s including: Arabidopsis thaliana cytochrome P450s 85A1 (CYP85A1 or brassinosteroid-6-oxidase 1), 90A1 (CYP90A1), 88A3 (CYP88A3 or ent-kaurenoic acid oxidase 1), 90B1 (CYP90B1 or Dwarf4 or steroid 22-alpha-hydroxylase), and 90C1 (CYP90C1 or 3-epi-6-deoxocathasterone 23-monooxygenase); Oryza sativa cytochrome P450s 90D2 (CYP90D2 or C6-oxidase), 87A3 (CYP87A3), and 724B1 (CYP724B1 or dwarf protein 11); and Taxus cuspidata cytochrome P450 725A2 (CYP725A2 or taxane 13-alpha-hydroxylase). These enzymes are monooxygenases that catalyze oxidation reactions involved in steroid or hormone biosynthesis. CYP85A1, CYP90D2, and CYP90C1 are involved in brassinosteroids biosynthesis, while CYP88A3 catalyzes three successive oxidations of ent-kaurenoic acid, which is a key step in the synthesis of gibberellins. This family belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 308 EKLHRElADEIRTVIKAEGGVTFAALDKMALTKSMVYEALRIEPPVPFQYGKAREDMVIhshdAAFEIKKGEMIFGYqPF 387
Cdd:cd11043  245 QELLEE-HEEIAKRKEEGEGLTWEDYKSMKYTWQVINETLRLAPIVPGVFRKALQDVEY----KGYTIPKGWKVLWS-AR 318

                         90       100
                 ....*....|....*....|....*
gi 225428600 388 AT-KDPKVFENPEEFVAHRFMGEGE 411
Cdd:cd11043  319 AThLDPEYFPDPLKFNPWRWEGKGK 343

cytochrome P450 family 24 subfamily A, polypeptide 1 and similar cytochrome P450s; This family is composed of vertebrate cytochrome P450 24A1 (CYP24A1) and similar proteins including several Drosophila proteins such as CYP315A1 (also called protein shadow) and CYP314A1 (also called ecdysone 20-monooxygenase), and vertebrate CYP11 and CYP27 subfamilies. Both CYP314A1 and CYP315A1, which has ecdysteroid C2-hydroxylase activity, are involved in the metabolism of insect hormones. CYP24A1 and CYP27B1 have roles in calcium homeostasis and metabolism, and the regulation of vitamin D. CYP24A1 catabolizes calcitriol (1,25(OH)2D), the physiologically active vitamin D hormone, by catalyzing its hydroxylation, while CYP27B1 is a calcidiol 1-monooxygenase that coverts 25-hydroxyvitamin D3 to calcitriol. The CYP24A1-like family belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 308 EKLHrelaDEIRTVIKAEGGVTFAALDKMALTKSMVYEALRIEPPVPFQYGKAREDMVIhshdAAFEIKKGEMIFGYQPF 387
Cdd:cd11054  266 EKLY----EEIRSVLPDGEPITAEDLKKMPYLKACIKESLRLYPVAPGNGRILPKDIVL----SGYHIPKGTLVVLSNYV 337

                         90       100
                 ....*....|....*....|....*
gi 225428600 388 ATKDPKVFENPEEFVAHRFMGEGEK 412
Cdd:cd11054  338 MGRDEEYFPDPEEFIPERWLRDDSE 362

cytochrome P450 monooxygenase CYP5011A1 and similar cytochrome P450s; This subfamily is composed of CYPs from unicellular ciliates similar to Tetrahymena thermophila CYP5011A1, whose function is still unknown. It belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 313 ELADEIRTVIKAEGGVTFAALDKMALTKSMVYEALRIEPPVPF-QYGKAREDMVIHShdaaFEIKKGEMIFGYQPFATKD 391
Cdd:cd20621  265 KLRQEIKSVVGNDDDITFEDLQKLNYLNAFIKEVLRLYNPAPFlFPRVATQDHQIGD----LKIKKGWIVNVGYIYNHFN 340

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 225428600 392 PKVFENPEEFVAHRFMGEGEKLLK-YVY--WSNGRetdnptaenKQCSGKDLVVLISRLMLVEIFLRYD 457
Cdd:cd20621  341 PKYFENPDEFNPERWLNQNNIEDNpFVFipFSAGP---------RNCIGQHLALMEAKIILIYILKNFE 400

cytochrome P450 family 51 and similar cytochrome P450s; This family is composed of cytochrome P450 51 (CYP51 or sterol 14alpha-demethylase) and related cytochrome P450s. CYP51 is the only cytochrome P450 enzyme with a conserved function across animals, fungi, and plants, in the synthesis of essential sterols. In mammals, it is expressed in many different tissues, with highest expression in testis, ovary, adrenal gland, prostate, liver, kidney, and lung. In fungi, CYP51 is a significant drug target for treatment of human protozoan infections. In plants, it functions within a specialized defense-related metabolic pathway. CYP51 is also found in several bacterial species. This family belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 312 RELADEIRTVI-KAEGGVTFAALDKMALTKSMVYEALRIEPPVPFQYGKAREDMviHSHDAAFEIKKGEMIFGYQPFATK 390
Cdd:cd11042  247 EALREEQKEVLgDGDDPLTYDVLKEMPLLHACIKETLRLHPPIHSLMRKARKPF--EVEGGGYVIPKGHIVLASPAVSHR 324

                         90       100
                 ....*....|....*....|.
gi 225428600 391 DPKVFENPEEFVAHRFMGEGE 411
Cdd:cd11042  325 DPEIFKNPDEFDPERFLKGRA 345

cytochrome P450 306A1 and similar cytochrome P450s; This subfamily is composed of insect and crustacean cytochrome P450s including insect cytochrome P450 306A1 (CYP306A1 or Cyp306a1) and CYP18A1. CYP306A1 functions as a carbon 25-hydroxylase and has an essential role in ecdysteroid biosynthesis during insect development. CYP18A1 is a 26-hydroxylase and plays a key role in steroid hormone inactivation. The CYP306A1-like subfamily belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 309 KLHRELADEIRTVIKAEGGVTFAALDKMALTKSMVYEALRIEPPVPF--QYGkAREDMVIhshdAAFEIKKGEMIFGYQP 386
Cdd:cd20652  266 KEQRRIQRELDEVVGRPDLVTLEDLSSLPYLQACISESQRIRSVVPLgiPHG-CTEDAVL----AGYRIPKGSMIIPLLW 340

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 387 FATKDPKVFENPEEFVAHRFMGEGEKLLK---YVYWSNGRetdnptaenKQCSGKDLVVLISRLMLVEIFLRYDtFEVES 463
Cdd:cd20652  341 AVHMDPNLWEEPEEFRPERFLDTDGKYLKpeaFIPFQTGK---------RMCLGDELARMILFLFTARILRKFR-IALPD 410

                 ..
gi 225428600 464 GT 465
Cdd:cd20652  411 GQ 412

cytochrome P450 family 7, subfamily A, polypeptide 1; Cytochrome P450 7A1 (CYP7A1) is also called cholesterol 7-alpha-monooxygenase (EC 1.14.14.23) or cholesterol 7-alpha-hydroxylase. It catalyzes the hydroxylation at position 7 of cholesterol, a rate-limiting step in the classic (or neutral) pathway of cholesterol catabolism and bile acid biosynthesis. It is important for cholesterol homeostasis. CYP7A1 belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 333 LDKMALTKSMVYEALRIEPpVPFQYGKAREDMVIH-SHDAAFEIKKGEMIFGYQPFATKDPKVFENPEEFVAHRFMGEGE 411
Cdd:cd20631  293 LDDMPVLGSIIKEALRLSS-ASLNIRVAKEDFTLHlDSGESYAIRKDDIIALYPQLLHLDPEIYEDPLTFKYDRYLDENG 371

                         90
                 ....*....|..
gi 225428600 412 KlLKYVYWSNGR 423
Cdd:cd20631  372 K-EKTTFYKNGR 382

cytochrome P450 family 4; Cytochrome P450 family 4 (CYP4) proteins catalyze the omega-hydroxylation of the terminal carbon of fatty acids, including essential signaling molecules such as eicosanoids, prostaglandins and leukotrienes, and they are important for chemical defense. There are seven vertebrate family 4 subfamilies: CYP4A, CYP4B, CYP4F, CYP4T, CYP4V, CYP4X, and CYP4Z; three (CYP4X, CYP4A, CYP4Z) are specific to mammals. CYP4 enzymes metabolize fatty acids off various length, level of saturation, and branching. Specific subfamilies show preferences for the length of fatty acids; CYP4B, CYP4A and CYP4V, and CYP4F preferentially metabolize short (C7-C10), medium (C10-C16), and long to very long (C18-C26) fatty acid chains, respectively. CYP4 belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 308 EKLHrelaDEIRTVI-KAEGGVTFAALDKMALTKSMVYEALRIEPPVPFQYGKAREDMVIHSHdaafEIKKGEMIFgYQP 386
Cdd:cd20628  264 EKVY----EELDEIFgDDDRRPTLEDLNKMKYLERVIKETLRLYPSVPFIGRRLTEDIKLDGY----TIPKGTTVV-ISI 334

                         90       100
                 ....*....|....*....|....
gi 225428600 387 FAT-KDPKVFENPEEFVAHRFMGE 409
Cdd:cd20628  335 YALhRNPEYFPDPEKFDPDRFLPE 358

cytochrome P450 family 27, subfamily B, polypeptide 1, also called calcidiol 1-monooxygenase; Cytochrome p450 27B1 (CYP27B1) is also called calcidiol 1-monooxygenase (EC 1.14.15.18), 25-hydroxyvitamin D(3) 1-alpha-hydroxylase (VD3 1A hydroxylase), 25-hydroxyvitamin D-1 alpha hydroxylase, 25-OHD-1 alpha-hydroxylase, 25-hydroxycholecalciferol 1-hydroxylase, or 25-hydroxycholecalciferol 1-monooxygenase. It catalyzes the conversion of 25-hydroxyvitamin D3 (25(OH)D3) to 1-alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3 or calcitriol), and of 24,25-dihydroxyvitamin D3 (24,25(OH)(2)D3) to 1-alpha,24,25-trihydroxyvitamin D3 (1alpha,24,25(OH)(3)D3). It is also active with 25-hydroxy-24-oxo-vitamin D3, and has an important role in normal bone growth, calcium metabolism, and tissue differentiation. CYP27B1 belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 314 LADEIRTVIKAEGGVTFAALDKMALTKSMVYEALRIEPPVPfqyGKARedmVIHSHDaafeIKKGEMIFGYQPFAT---- 389
Cdd:cd20648  271 LHREITAALKDNSVPSAADVARMPLLKAVVKEVLRLYPVIP---GNAR---VIPDRD----IQVGEYIIPKKTLITlchy 340

                         90       100
                 ....*....|....*....|....*
gi 225428600 390 ---KDPKVFENPEEFVAHRFMGEGE 411
Cdd:cd20648  341 atsRDENQFPDPNSFRPERWLGKGD 365

cytochrome P450 family 7, subfamily B, polypeptide 1; Cytochrome P450 7B1 (CYP7B1) is also called 25-hydroxycholesterol 7-alpha-hydroxylase (EC 1.14.14.29) or oxysterol 7-alpha-hydroxylase. It catalyzes the 7alpha-hydroxylation of both steroids and oxysterols, and is thus implicated in the metabolism of neurosteroids and bile acid synthesis, respectively. It participates in the alternative (or acidic) pathway of cholesterol catabolism and bile acid biosynthesis. It also mediates the formation of 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC) from 25-hydroxycholesterol; 7-alpha,25-OHC acts as a ligand for the G protein-coupled receptor GPR183/EBI2, a chemotactic receptor in lymphoid cells. CYP7B1 belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 333 LDKMALTKSMVYEALRIEP---PVPFqygkAREDMVIHSHDA-AFEIKKGEMIFGYQPFATKDPKVFENPEEFVAHRFMG 408
Cdd:cd20632  280 LDSLVYLESAINESLRLSSasmNIRV----VQEDFTLKLESDgSVNLRKGDIVALYPQSLHMDPEIYEDPEVFKFDRFVE 355

                         90
                 ....*....|....*.
gi 225428600 409 EGEKllKYVYWSNGRE 424
Cdd:cd20632  356 DGKK--KTTFYKRGQK 369

Fusarium verticillioides cytochrome P450 monooxygenase FUM15, and similar cytochrome P450s; Fusarium verticillioides cytochrome P450 monooxygenase FUM15, is also called fumonisin biosynthesis cluster protein 15. The FUM15 gene is part of the gene cluster that mediates the biosynthesis of fumonisins B1, B2, B3, and B4, which are carcinogenic mycotoxins. This FUM15-like subfamily belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 314 LADEIRTVIKAEGGVTFAA--LDKMALTKSMVYEALRIEPPVPFQYGKAREDMVIHSHdaafEIKKGEMIFgYQPFAT-K 390
Cdd:cd11069  272 LREEIRAALPDPPDGDLSYddLDRLPYLNAVCRETLRLYPPVPLTSREATKDTVIKGV----PIPKGTVVL-IPPAAInR 346

                         90       100
                 ....*....|....*....|...
gi 225428600 391 DPKVF-ENPEEFVAHRFMGEGEK 412
Cdd:cd11069  347 SPEIWgPDAEEFNPERWLEPDGA 369

putative cytochrome P450 family 136 and similar cytochrome P450s; This group is composed of Mycobacterium tuberculosis putative cytochrome P450 136 (CYP136) and similar proteins. It belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 326 GGVTFAALDKMALTKSMVYEALRIEPPVPFQYGKAREDMVIHSHDaafeIKKGEMIFGYQPFATKDPKVFENPEEFVAHR 405
Cdd:cd11045  258 GTLDYEDLGQLEVTDWVFKEALRLVPPVPTLPRRAVKDTEVLGYR----IPAGTLVAVSPGVTHYMPEYWPNPERFDPER 333

                 ....
gi 225428600 406 FMGE 409
Cdd:cd11045  334 FSPE 337

cytochrome P450 family 3, subfamily A and similar cytochrome P450s; This family includes vertebrate CYP3A subfamily enzymes and CYP5a1, and similar proteins. CYP5A1, also called thromboxane-A synthase, converts prostaglandin H2 into thromboxane A2, a biologically active metabolite of arachidonic acid. CYP3A enzymes are drug-metabolizing enzymes embedded in the endoplasmic reticulum, where they can catalyze a wide variety of biochemical reactions including hydroxylation, N-demethylation, O-dealkylation, S-oxidation, deamination, or epoxidation of substrates. The CYP3A-like family belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 308 EKLHrelaDEIRTVIKAEGGVTFAALDKMALTKSMVYEALRIEPPVPFQYGKAREDMVIhshdAAFEIKKGEMIFgyqpF 387
Cdd:cd11055  261 EKLI----EEIDEVLPDDGSPTYDTVSKLKYLDMVINETLRLYPPAFFISRECKEDCTI----NGVFIPKGVDVV----I 328

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 388 ATK----DPKVFENPEEFVAHRFMGEGE-KLLKYVYWSNGretdnptAENKQCSGKDLVVLISRLMLVEIFLRYdTFEVE 462
Cdd:cd11055  329 PVYaihhDPEFWPDPEKFDPERFSPENKaKRHPYAYLPFG-------AGPRNCIGMRFALLEVKLALVKILQKF-RFVPC 400

                 ...
gi 225428600 463 SGT 465
Cdd:cd11055  401 KET 403

cytochrome P450 family 86, subfamily A; This subfamily includes several Arabidopsis thaliana cytochrome P450s (CYP86A1, CYP86A2, CYP86A4, among others), Petunia x hybrida CYP86A22, and Vicia sativa CYP94A1 and CYP94A2. They are P450-dependent fatty acid omega-hydroxylases that catalyze the omega-hydroxylation of various fatty acids. CYP86A2 acts on saturated and unsaturated fatty acids with chain lengths from C12 to C18; CYP86A22 prefers substrates with chain lengths of C16 and C18; and CYP94A1 acts on various fatty acids from 10 to 18 carbons. They play roles in the biosynthesis of extracellular lipids, cutin synthesis, and plant defense. The CYP86A subfamily belongs to the large cytochrome P450 (P450, CYP) superfamily of heme-containing proteins that catalyze a variety of oxidative reactions of a large number of structurally different endogenous and exogenous compounds in organisms from all major domains of life. CYPs bind their diverse ligands in a buried, hydrophobic active site, which is accessed through a substrate access channel formed by two flexible helices and their connecting loop.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 308 EKLHRELADEIRTVIKAEGGV-TFAALDKMALTKSMVYEALRIEPPVPFQYGKAREDMVIHShdaAFEIKKGEMIFgYQP 386
Cdd:cd11064  265 EKIREELKSKLPKLTTDESRVpTYEELKKLVYLHAALSESLRLYPPVPFDSKEAVNDDVLPD---GTFVKKGTRIV-YSI 340

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225428600 387 FAT-KDPKVF-ENPEEFVAHRFMGEGEKLL-----KYVYWSNGretdnPtaenKQCSGKDLVVLISRLMLVEIFLRYDtF 459
Cdd:cd11064  341 YAMgRMESIWgEDALEFKPERWLDEDGGLRpespyKFPAFNAG-----P----RICLGKDLAYLQMKIVAAAILRRFD-F 410

                 ....*
gi 225428600 460 EVESG 464
Cdd:cd11064  411 KVVPG 415