cytochrome P450 (CYP) superfamily; Cytochrome P450 (P450, CYP) is a large 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 with > 40% sequence identity are members of the same family. There are approximately 2250 CYP families: mammals, insects, plants, fungi, bacteria, and archaea have around 18, 208, 277, 805, 591, and 14 families, respectively. 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. Their monooxygenase activity relies on the reductive scission of molecular oxygen bound to the P450 heme iron, and the delivery of two electrons to the heme iron during the catalytic cycle. CYPs use a variety of redox partners, such as the eukaryotic diflavin enzyme NADPH-cytochrome P450 oxidoreductase and the bacterial/mitochondrial NAD(P)H-ferredoxin reductase and ferredoxin partners. Some CYPs are naturally linked to their redox partners and others have evolved to bypass requirements for redox partners, and instead react directly with hydrogen peroxide or NAD(P)H to facilitate oxidative or reductive catalysis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 163 KEKVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPA 242
Cdd:cd20666  262 QEKVQAEIDTVIGPDRAPSLTDKAQMPFTEATIMEVQRMTVVVPLSIPHMASENTVLQGYTIPKGTVIVPNLWSVHRDPA 341

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 243 IWEKPEDFYPNRFLDDQGQLIKKETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFAFALPEDSKKPLLTGRFGLTLAP 322
Cdd:cd20666  342 IWEKPDDFMPSRFLDENGQLIKKEAFIPFGIGRRVCMGEQLAKMELFLMFVSLMQSFTFLLPPNAPKPSMEGRFGLTLAP 421

                 ....*
gi 530377130 323 HPFNI 327
Cdd:cd20666  422 CPFNI 426

cytochrome P450 family 2, subfamily U, polypeptide 1; CYP2U1 is a thymus- and brain-specific cytochrome P450 that catalyzes omega- and (omega-1)-hydroxylation of fatty acids such as arachidonic acid, docosahexaenoic acid, and other long chain fatty acids. Mutations in CYP2U1 are associated with hereditary spastic paraplegia (HSP), a neurological disorder, and pigmentary degenerative maculopathy associated with progressive spastic paraplegia. CYP2U1 belongs to family 2 of 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 530377130 163 KEKVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPA 242
Cdd:cd20666  262 QEKVQAEIDTVIGPDRAPSLTDKAQMPFTEATIMEVQRMTVVVPLSIPHMASENTVLQGYTIPKGTVIVPNLWSVHRDPA 341

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 243 IWEKPEDFYPNRFLDDQGQLIKKETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFAFALPEDSKKPLLTGRFGLTLAP 322
Cdd:cd20666  342 IWEKPDDFMPSRFLDENGQLIKKEAFIPFGIGRRVCMGEQLAKMELFLMFVSLMQSFTFLLPPNAPKPSMEGRFGLTLAP 421

                 ....*
gi 530377130 323 HPFNI 327
Cdd:cd20666  422 CPFNI 426

cytochrome P450; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 163 KEKVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVL-QGYTIPKGTLILPNLWSVHRDP 241
Cdd:PTZ00404 317 QEKAYNEIKSTVNGRNKVLLSDRQSTPYTVAIIKETLRYKPVSPFGLPRSTSNDIIIgGGHFIPKDAQILINYYSLGRNE 396

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 242 AIWEKPEDFYPNRFLDDQGQLikkeTFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFAFAlPEDSKKPLLTGRFGLTLA 321
Cdd:PTZ00404 397 KYFENPEQFDPSRFLNPDSND----AFMPFSIGPRNCVGQQFAQDELYLAFSNIILNFKLK-SIDGKKIDETEEYGLTLK 471

                        170
                 ....*....|.
gi 530377130 322 PHPFNITISRR 332
Cdd:PTZ00404 472 PNKFKVLLEKR 482

cytochrome P450; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130  61 PGPTPWPLVGNFGHvllppflrrrswLSSRtraagidpsvigPQVLLAHLARVYGSIFSFFIGHYLVVVLSDFHSVREAL 140
Cdd:PTZ00404  32 KGPIPIPILGNLHQ------------LGNL------------PHRDLTKMSKKYGGIFRIWFADLYTVVLSDPILIREMF 87

                         90
                 ....*....|....*.
gi 530377130 141 VQQAEVFSDRPRVPLI 156
Cdd:PTZ00404  88 VDNFDNFSDRPKIPSI 103

cytochrome P450 family 2, subfamily U, polypeptide 1; CYP2U1 is a thymus- and brain-specific cytochrome P450 that catalyzes omega- and (omega-1)-hydroxylation of fatty acids such as arachidonic acid, docosahexaenoic acid, and other long chain fatty acids. Mutations in CYP2U1 are associated with hereditary spastic paraplegia (HSP), a neurological disorder, and pigmentary degenerative maculopathy associated with progressive spastic paraplegia. CYP2U1 belongs to family 2 of 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 530377130 163 KEKVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPA 242
Cdd:cd20666  262 QEKVQAEIDTVIGPDRAPSLTDKAQMPFTEATIMEVQRMTVVVPLSIPHMASENTVLQGYTIPKGTVIVPNLWSVHRDPA 341

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 243 IWEKPEDFYPNRFLDDQGQLIKKETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFAFALPEDSKKPLLTGRFGLTLAP 322
Cdd:cd20666  342 IWEKPDDFMPSRFLDENGQLIKKEAFIPFGIGRRVCMGEQLAKMELFLMFVSLMQSFTFLLPPNAPKPSMEGRFGLTLAP 421

                 ....*
gi 530377130 323 HPFNI 327
Cdd:cd20666  422 CPFNI 426

cytochrome P450 family 15, subfamily A, polypeptide 1, and similar cytochrome P450s; This subfamily is composed of insect and crustacean cytochrome P450s including Diploptera punctata cytochrome P450 15A1 (CYP15A1 or CYP15A1), Panulirus argus CYP2L1, and CYP303A1, CYP304A1, and CYP305A1 from Drosophila melanogaster. CYP15A1, also called methyl farnesoate epoxidase, catalyzes the conversion of methyl farnesoate to juvenile hormone III acid during juvenile hormone biosynthesis. CYP303A1, CYP304A1, and CYP305A1 may be involved in the metabolism of insect hormones and in the breakdown of synthetic insecticides. The CYP15A1-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 530377130 164 EKVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPAI 243
Cdd:cd20651  260 RKVQEEIDEVVGRDRLPTLDDRSKLPYTEAVILEVLRIFTLVPIGIPHRALKDTTLGGYRIPKDTTILASLYSVHMDPEY 339

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 244 WEKPEDFYPNRFLDDQGQLIKKETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFAFALPEDSKKPLLTGRFGLTLAPH 323
Cdd:cd20651  340 WGDPEEFRPERFLDEDGKLLKDEWFLPFGAGKRRCLGESLARNELFLFFTGLLQNFTFSPPNGSLPDLEGIPGGITLSPK 419

                 ....
gi 530377130 324 PFNI 327
Cdd:cd20651  420 PFRV 423

cytochrome P450 families 1 and 2, and similar cytochrome P450s; This model includes cytochrome P450 families 1 (CYP1) and 2 (CYP2), CYP17A1, and CYP21 in vertebrates, as well as insect and crustacean CYPs similar to CYP15A1 and CYP306A1. CYP1 and CYP2 enzymes are involved in the metabolism of endogenous and exogenous compounds such as hormones, xenobiotics, and drugs. CYP17A1 catalyzes the conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products, while CYP21 catalyzes the 21-hydroxylation of steroids such as progesterone and 17-alpha-hydroxyprogesterone (17-alpha-OH-progesterone) to form 11-deoxycorticosterone and 11-deoxycortisol, respectively. Members of this 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 530377130 164 EKVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPAI 243
Cdd:cd20617  258 EKIYEEIDNVVGNDRRVTLSDRSKLPYLNAVIKEVLRLRPILPLGLPRVTTEDTEIGGYFIPKGTQIIINIYSLHRDEKY 337

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 244 WEKPEDFYPNRFLDDQGqLIKKETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFAFaLPEDSKKPLLTGRFGLTLAPH 323
Cdd:cd20617  338 FEDPEEFNPERFLENDG-NKLSEQFIPFGIGKRNCVGENLARDELFLFFANLLLNFKF-KSSDGLPIDEKEVFGLTLKPK 415

                 ....
gi 530377130 324 PFNI 327
Cdd:cd20617  416 PFKV 419

cytochrome P450 family 1; The cytochrome P450 family 1 (CYP1 or Cyp1) is composed of three functional human members: CYP1A1, CYP1A2 and CYP1B1, which are regulated by the aryl hydrocarbon receptor (AhR), ligand-activated transcriptional factor that dimerizes with AhR nuclear translocator (ARNT). CYP1 enzymes are involved in the metabolism of endogenous hormones, xenobiotics, and drugs. Included in the CYP1 family is CYP1D1 (cytochrome P450 family 1, subfamily D, polypeptide 1), which is not expressed in humans as its gene is pseudogenized due to five nonsense mutations in the putative coding region, but is functional in in other organisms including cynomolgus monkey. Zebrafish CYP1D1 expression is not regulated by AhR. The CYP1 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 530377130 164 EKVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPAI 243
Cdd:cd11028  266 EKVQAELDRVIGRERLPRLSDRPNLPYTEAFILETMRHSSFVPFTIPHATTRDTTLNGYFIPKGTVVFVNLWSVNHDEKL 345

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 244 WEKPEDFYPNRFLDDQGQLIKK--ETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFAFAlPEDSKKPLLTGRFGLTLA 321
Cdd:cd11028  346 WPDPSVFRPERFLDDNGLLDKTkvDKFLPFGAGRRRCLGEELARMELFLFFATLLQQCEFS-VKPGEKLDLTPIYGLTMK 424

                 ....*.
gi 530377130 322 PHPFNI 327
Cdd:cd11028  425 PKPFKV 430

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 530377130  164 EKVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPAI 243
Cdd:pfam00067 296 EKLREEIDEVIGDKRSPTYDDLQNMPYLDAVIKETLRLHPVVPLLLPREVTKDTVIPGYLIPKGTLVIVNLYALHRDPEV 375

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130  244 WEKPEDFYPNRFLDDQGQLIKKETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFAFALPEDSKKPLLTGRFGLTLAPH 323
Cdd:pfam00067 376 FPNPEEFDPERFLDENGKFRKSFAFLPFGAGPRNCLGERLARMEMKLFLATLLQNFEVELPPGTDPPDIDETPGLLLPPK 455

                  ..
gi 530377130  324 PF 325
Cdd:pfam00067 456 PY 457

cytochrome P450 2R1; CYP2R1, also called vitamin D 25-hydroxylase (EC 1.14.14.24), is a microsomal enzyme that is required for the activation of vitamin D; it catalyzes the initial step converting vitamin D into 25-hydroxyvitamin D (25(OH)D), the major circulating metabolite of vitamin D. The 1alpha-hydroxylation of 25(OH)D by CYP27B1 generates the fully active vitamin D metabolite, 1,25-dihydroxyvitamin D (1,25(OH)2D). Mutations in the CYP2R1 gene are associated with an atypical form of vitamin D-deficiency rickets, which has been classified as vitamin D dependent rickets type 1B. CYP2R1 belongs to family 2 of 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 530377130 163 KEKVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPA 242
Cdd:cd20661  272 QGQVQKEIDLVVGPNGMPSFEDKCKMPYTEAVLHEVLRFCNIVPLGIFHATSKDAVVRGYSIPKGTTVITNLYSVHFDEK 351

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 243 IWEKPEDFYPNRFLDDQGQLIKKETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFAFALPEDSkKPLLTGRFGLTLAP 322
Cdd:cd20661  352 YWSDPEVFHPERFLDSNGQFAKKEAFVPFSLGRRHCLGEQLARMEMFLFFTALLQRFHLHFPHGL-IPDLKPKLGMTLQP 430

                 ....*
gi 530377130 323 HPFNI 327
Cdd:cd20661  431 QPYLI 435

cytochrome P450 family 17, subfamily A, polypeptide 1; Cytochrome P450 17A1 (CYP17A1 or Cyp17a1), also called cytochrome P450c17, steroid 17-alpha-hydroxylase (EC 1.14.14.19)/17,20 lyase (EC 1.14.14.32), or 17-alpha-hydroxyprogesterone aldolase, catalyzes the conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. It is a dual enzyme that catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reactions. Severe mutations on the enzyme cause combined 17-hydroxylase/17,20-lyase deficiency (17OHD); patients with 17OHD synthesize 11-deoxycorticosterone (DOC) which causes hypertension and hypokalemia. Loss of 17,20-lyase activity precludes sex steroid synthesis and leads to sexual infantilism. Included in this group is a second 17A P450 from teleost fish, CYP17A2, that is more efficient in pregnenolone 17-alpha-hydroxylation than CYP17A1, but does not catalyze the lyase reaction. CYP17A1 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 530377130 163 KEKVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPA 242
Cdd:cd20673  266 QKKIQEEIDQNIGFSRTPTLSDRNHLPLLEATIREVLRIRPVAPLLIPHVALQDSSIGEFTIPKGTRVVINLWALHHDEK 345

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 243 IWEKPEDFYPNRFLDDQGQLIKK--ETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFAFALPEDSKKPLLTGRFGLTL 320
Cdd:cd20673  346 EWDQPDQFMPERFLDPTGSQLISpsLSYLPFGAGPRVCLGEALARQELFLFMAWLLQRFDLEVPDGGQLPSLEGKFGVVL 425

                 ....*
gi 530377130 321 APHPF 325
Cdd:cd20673  426 QIDPF 430

cytochrome P450 family 2, subfamily G; CYP2G1 is uniquely expressed in the olfactory mucosa of rats and rabbits and may have important functions for the olfactory chemosensory system. It is involved in the metabolism of sex steroids and xenobiotic compounds. In cynomolgus monkeys, CYP2G2 is a functional drug-metabolizing enzyme in nasal mucosa. In humans, two different CYP2G genes, CYP2GP1 and CYP2GP2, are pseudogenes because of loss-of-function deletions/mutations. The CYP2G 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 530377130 163 KEKVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPA 242
Cdd:cd20670  260 EAKIHEEINQVIGPHRLPSVDDRVKMPYTDAVIHEIQRLTDIVPLGVPHNVIRDTQFRGYLLPKGTDVFPLLGSVLKDPK 339

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 243 IWEKPEDFYPNRFLDDQGQLIKKETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFafalpedSKKPLLtgrfgltlap 322
Cdd:cd20670  340 YFRYPEAFYPQHFLDEQGRFKKNEAFVPFSSGKRVCLGEAMARMELFLYFTSILQNF-------SLRSLV---------- 402

                        170
                 ....*....|
gi 530377130 323 HPFNITISRR 332
Cdd:cd20670  403 PPADIDITPK 412

cytochrome P450 family 2, subfamily C, and similar cytochrome P450s; This CYP2C-like group includes CYP2C, and similar CYPs including mammalian CYP2E1, also called 4-nitrophenol 2-hydroxylase, as well as chicken CYP2H1 and CYP2H2. The CYP2C subfamily is composed of four human members (CYP2C8, CYP2C9, CYP2C18, CYP2C19) that metabolize approximately 20% of clinically used drugs, and all four exhibit genetic polymorphisms that results in toxicity or altered efficacy of some drugs in affected individuals. CYP2E1 participates in the metabolism of endogenous substrates, including acetone and fatty acids, and exogenous compounds such as anesthetics, ethanol, nicotine, acetaminophen, aspartame, and chlorzoxazone, among others. The CYP2C-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 530377130 164 EKVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPAI 243
Cdd:cd20665  261 AKVQEEIDRVIGRHRSPCMQDRSHMPYTDAVIHEIQRYIDLVPNNLPHAVTCDTKFRNYLIPKGTTVITSLTSVLHDDKE 340

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 530377130 244 WEKPEDFYPNRFLDDQGQLIKKETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSF 299
Cdd:cd20665  341 FPNPEKFDPGHFLDENGNFKKSDYFMPFSAGKRICAGEGLARMELFLFLTTILQNF 396

cytochrome P450 family 2, subfamily B; The human cytochrome P450 family 2, subfamily B (CYP2B) consists of only one functional member CYP2B6, which shows broad substrate specificity and plays a key role in the metabolism of many clinical drugs, environmental toxins, and endogenous compounds. Rodents have multiple functional CYP2B proteins; mouse subfamily members include CYP2B9, 2B10, 2B13, 2B19, and 2B23. CYP2B enzymes are highly inducible by chemicals that interact with the constitutive androstane receptor (CAR) and/or pregnane X receptor (PXR), such as rifampicin and phenobarbital. The CYP2B 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 530377130 164 EKVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPAI 243
Cdd:cd20672  261 EKVQKEIDQVIGSHRLPTLDDRAKMPYTDAVIHEIQRFSDLIPIGVPHRVTKDTLFRGYLLPKNTEVYPILSSALHDPQY 340

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 244 WEKPEDFYPNRFLDDQGQLIKKETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFAFALPEDSKKPLLTGR-FGLTLAP 322
Cdd:cd20672  341 FEQPDTFNPDHFLDANGALKKSEAFMPFSTGKRICLGEGIARNELFLFFTTILQNFSVASPVAPEDIDLTPKeSGVGKIP 420

                 ....*
gi 530377130 323 HPFNI 327
Cdd:cd20672  421 PTYQI 425

cytochrome P450 family 1, subfamily A; Cytochrome P450 family 1, subfamily A (CYP1A) consists of two human members, CYP1A1 and CYP1A2, which overlap in their activities. CYP1A2 is the highly expressed cytochrome enzyme in the human liver, while CYP1A1 is mostly found in extrahepatic tissues. Known common substrates include aromatic compounds such as polycyclic aromatic hydrocarbons, arachidonic acid and eicosapentoic acid, as well as melatonin and 6-hydroxylate melatonin. In addition, CYP1A1 activates procarcinogens into carcinogens via epoxides, and metabolizes heterocyclic aromatic amines of industrial origin. CYP1A2 metabolizes numerous natural products that result in toxic products, such as the transformation of methyleugenol to 1'-hydroxymethyleugenol, estragole to reactive metabolites, and oxidation of nephrotoxins. It also plays an important role in the metabolism of several clinical drugs including analgesics, antipyretics, antipsychotics, antidepressants, anti-inflammatory, and cardiovascular drugs. The CYP1A 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 530377130 163 KEKVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPA 242
Cdd:cd20676  271 QKKIQEELDEVIGRERRPRLSDRPQLPYLEAFILETFRHSSFVPFTIPHCTTRDTSLNGYYIPKDTCVFINQWQVNHDEK 350

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 243 IWEKPEDFYPNRFLDDQGQLIKK---ETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFAFALPeDSKKPLLTGRFGLT 319
Cdd:cd20676  351 LWKDPSSFRPERFLTADGTEINKtesEKVMLFGLGKRRCIGESIARWEVFLFLAILLQQLEFSVP-PGVKVDMTPEYGLT 429

                 ...
gi 530377130 320 LAP 322
Cdd:cd20676  430 MKH 432

cytochrome P450 family 1, subfamily B, polypeptide 1 and similar cytochrome P450s; Cytochrome P450 1B1 (CYP1B1) is expressed in liver and extrahepatic tissues where it carries out the metabolism of numerous xenobiotics, including metabolic activation of polycyclic aromatic hydrocarbons. It is also important in regulating endogenous metabolic pathways, including the metabolism of steroid hormones, fatty acids, melatonin, and vitamins. CYP1B1 is overexpressed in a wide variety of tumors and is associated with angiogenesis. It is also associated with adipogenesis, obesity, hypertension, and atherosclerosis. It is therefore a target for the treatment of metabolic diseases and cancer. Also included in this subfamily are CYP1C proteins from fish, birds and amphibians. The CYP1B1-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 530377130 161 KEKEKVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRD 240
Cdd:cd20675  267 DVQARLQEELDRVVGRDRLPCIEDQPNLPYVMAFLYEAMRFSSFVPVTIPHATTADTSILGYHIPKDTVVFVNQWSVNHD 346

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 241 PAIWEKPEDFYPNRFLDDQGQLIKKETF--IPFGIGKRVCMGEQLAKMELFLmFVSLM--QSFAFALPEDSkkPLLTGRF 316
Cdd:cd20675  347 PQKWPNPEVFDPTRFLDENGFLNKDLASsvMIFSVGKRRCIGEELSKMQLFL-FTSILahQCNFTANPNEP--LTMDFSY 423

                        170
                 ....*....|.
gi 530377130 317 GLTLAPHPFNI 327
Cdd:cd20675  424 GLTLKPKPFTI 434

cytochrome P450 family 64-like fungal cytochrome P450s; This group includes Aspergillus flavus cytochrome P450 64 (CYP64), also called O-methylsterigmatocystin (OMST) oxidoreductase or aflatoxin B synthase or aflatoxin biosynthesis protein Q, and similar fungal cytochrome P450s. CYP64 converts OMST to aflatoxin B1 and converts dihydro-O-methylsterigmatocystin (DHOMST) to aflatoxin B2 in the aflatoxin biosynthesis pathway. The CYP64-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 530377130 165 KVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPAIW 244
Cdd:cd11065  259 KAQEELDRVVGPDRLPTFEDRPNLPYVNAIVKEVLRWRPVAPLGIPHALTEDDEYEGYFIPKGTTVIPNAWAIHHDPEVY 338

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 245 EKPEDFYPNRFLDDqGQLIKKET---FIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFAFALPEDSKK--PLLTGRF--G 317
Cdd:cd11065  339 PDPEEFDPERYLDD-PKGTPDPPdppHFAFGFGRRICPGRHLAENSLFIAIARLLWAFDIKKPKDEGGkeIPDEPEFtdG 417

                 ....*...
gi 530377130 318 LTLAPHPF 325
Cdd:cd11065  418 LVSHPLPF 425

cytochrome P450 family 76 and similar cytochrome P450s; Characterized members of the plant cytochrome P450 family 76 (CYP76 or Cyp76) include: Catharanthus roseus CYP76B6, a multifunctional enzyme catalyzing two sequential oxidation steps leading to the formation of 8-oxogeraniol from geraniol; the Brassicaceae-specific CYP76C subfamily of enzymes that are involved in the metabolism of monoterpenols and phenylurea herbicides; and two P450s from Lamiaceae, CYP76AH and CYP76AK, that are involved in the oxidation of abietane diterpenes. CYP76AH produces ferruginol and 11-hydroxyferruginol, while CYP76AK catalyzes oxidations at the C20 position. Also included in this group is Berberis stolonifera Cyp80, also called berbamunine synthase or (S)-N-methylcoclaurine oxidase [C-O phenol-coupling], that catalyzes the phenol oxidation of N-methylcoclaurine to form the bisbenzylisoquinoline alkaloid berbamunine. The CYP76-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 530377130 164 EKVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPAI 243
Cdd:cd11073  266 AKARAELDEVIGKDKIVEESDISKLPYLQAVVKETLRLHPPAPLLLPRKAEEDVEVMGYTIPKGTQVLVNVWAIGRDPSV 345

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 244 WEKPEDFYPNRFLDDQGQLIKKE-TFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFAFALPE--DSKKPLLTGRFGLTL 320
Cdd:cd11073  346 WEDPLEFKPERFLGSEIDFKGRDfELIPFGSGRRICPGLPLAERMVHLVLASLLHSFDWKLPDgmKPEDLDMEEKFGLTL 425

                 .
gi 530377130 321 A 321
Cdd:cd11073  426 Q 426

cytochrome P450 family 71 and similar cytochrome P450s; The group includes plant cytochrome P450 family 71 (CYP71) proteins, as well as some CYPs designated as belonging to a different family including CYP99A1, CYP83B1, and CYP84A1, among others. Characterized CYP71 enzymes include: parsnip (Pastinaca sativa) CYP71AJ4, also called angelicin synthase, that converts (+)-columbianetin to angelicin, an angular furanocumarin; periwinkle (Catharanthus roseus) CYP71D351, also called tabersonine 16-hydroxylase 2, that is involved in the foliar biosynthesis of vindoline; sorghum CYP71E1, also called 4-hydroxyphenylacetaldehyde oxime monooxygenase, that catalyzes the conversion of p-hydroxyphenylacetaldoxime to p-hydroxymandelonitrile; as well as maize CYP71C1, CYP71C2, and CYP71C4, which are monooxygenases catalyzing the oxidation of 3-hydroxyindolin-2-one, indolin-2-one, and indole, respectively. CYPs within a single CYP71 subfamily, such as the C subfamily, usually metabolize similar/related compounds. The CYP71-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 530377130 164 EKVHEEIERVIGANRAPSLTDKAQMPYTEATIMEVQRLTVVVPLAIPHMTSENTVLQGYTIPKGTLILPNLWSVHRDPAI 243
Cdd:cd11072  263 KKAQEEVREVVGGKGKVTEEDLEKLKYLKAVIKETLRLHPPAPLLLPRECREDCKINGYDIPAKTRVIVNAWAIGRDPKY 342

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530377130 244 WEKPEDFYPNRFLDD----QGQLIKketFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFAFALPEDSK--KPLLTGRFG 317
Cdd:cd11072  343 WEDPEEFRPERFLDSsidfKGQDFE---LIPFGAGRRICPGITFGLANVELALANLLYHFDWKLPDGMKpeDLDMEEAFG 419