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 1958751028 149 KEKVHEEIERVIGRDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRDPV 228
Cdd:cd20666   262 QEKVQAEIDTVIGPDRAPSLTDKAQMPFTEATIMEVQRMTVVVPLSIPHMASENTVLQGYTIPKGTVIVPNLWSVHRDPA 341

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958751028 229 IWEKPDDFCPHRFLDDQGQLLKRETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFTFALPEGSEKPIMTGRFGLTLAP 308
Cdd:cd20666   342 IWEKPDDFMPSRFLDENGQLIKKEAFIPFGIGRRVCMGEQLAKMELFLMFVSLMQSFTFLLPPNAPKPSMEGRFGLTLAP 421

                  ....*
gi 1958751028 309 HPFNV 313
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 1958751028 149 KEKVHEEIERVIGRDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRDPV 228
Cdd:cd20666   262 QEKVQAEIDTVIGPDRAPSLTDKAQMPFTEATIMEVQRMTVVVPLSIPHMASENTVLQGYTIPKGTVIVPNLWSVHRDPA 341

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958751028 229 IWEKPDDFCPHRFLDDQGQLLKRETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFTFALPEGSEKPIMTGRFGLTLAP 308
Cdd:cd20666   342 IWEKPDDFMPSRFLDENGQLIKKEAFIPFGIGRRVCMGEQLAKMELFLMFVSLMQSFTFLLPPNAPKPSMEGRFGLTLAP 421

                  ....*
gi 1958751028 309 HPFNV 313
Cdd:cd20666   422 CPFNI 426

flavonoid 3'-monooxygenase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958751028 151 KVHEEIERVIGRDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRDPVIW 230
Cdd:PLN02687  333 KAQEELDAVVGRDRLVSESDLPQLTYLQAVIKETFRLHPSTPLSLPRMAAEECEINGYHIPKGATLLVNVWAIARDPEQW 412

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958751028 231 EKPDDFCPHRFL---DDQGQLLKRETF--IPFGIGKRVCMGEQLAKMELFLMFVSLMQSFTFALPEG--SEKPIMTGRFG 303
Cdd:PLN02687  413 PDPLEFRPDRFLpggEHAGVDVKGSDFelIPFGAGRRICAGLSWGLRMVTLLTATLVHAFDWELADGqtPDKLNMEEAYG 492

                  ...
gi 1958751028 304 LTL 306
Cdd:PLN02687  493 LTL 495

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958751028  90 HVYLARLARVYGNIFSFFIGHRLVVVLSDFQSVREALVQQAEVFSDRPRMPLISILTK 147
Cdd:cd20661     2 HVYMKKQSQIHGQIFSLDLGGISTVVLNGYDAVKECLVHQSEIFADRPSLPLFMKLTN 59

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 1958751028 149 KEKVHEEIERVIGRDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRDPV 228
Cdd:cd20666   262 QEKVQAEIDTVIGPDRAPSLTDKAQMPFTEATIMEVQRMTVVVPLSIPHMASENTVLQGYTIPKGTVIVPNLWSVHRDPA 341

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958751028 229 IWEKPDDFCPHRFLDDQGQLLKRETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFTFALPEGSEKPIMTGRFGLTLAP 308
Cdd:cd20666   342 IWEKPDDFMPSRFLDENGQLIKKEAFIPFGIGRRVCMGEQLAKMELFLMFVSLMQSFTFLLPPNAPKPSMEGRFGLTLAP 421

                  ....*
gi 1958751028 309 HPFNV 313
Cdd:cd20666   422 CPFNI 426

cytochrome P450 family 17, subfamily A, polypeptide 1, and similar cytochrome P450s; This subfamily contains cytochrome P450 17A1 (CYP17A1 or Cyp17a1), cytochrome P450 21 (CYP21 or Cyp21) and similar proteins. 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 catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. This subfamily also contains CYP21, also called steroid 21-hydroxylase (EC 1.14.14.16) or cytochrome P-450c21 or CYP21A2, catalyzes the 21-hydroxylation of steroids and is required for the adrenal synthesis of mineralocorticoids and glucocorticoids. The CYP17A1-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 1958751028 149 KEKVHEEIERVIGRDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRDPV 228
Cdd:cd11027   263 QAKLHAELDDVIGRDRLPTLSDRKRLPYLEATIAEVLRLSSVVPLALPHKTTCDTTLRGYTIPKGTTVLVNLWALHHDPK 342

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958751028 229 IWEKPDDFCPHRFLDDQGQLL-KRETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFTFALPEGSEKPIMTGRFGLTLA 307
Cdd:cd11027   343 EWDDPDEFRPERFLDENGKLVpKPESFLPFSAGRRVCLGESLAKAELFLFLARLLQKFRFSPPEGEPPPELEGIPGLVLY 422

                  ....*.
gi 1958751028 308 PHPFNV 313
Cdd:cd11027   423 PLPYKV 428

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 1958751028 150 EKVHEEIERVIGRDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRDPVI 229
Cdd:cd20617   258 EKIYEEIDNVVGNDRRVTLSDRSKLPYLNAVIKEVLRLRPILPLGLPRVTTEDTEIGGYFIPKGTQIIINIYSLHRDEKY 337

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958751028 230 WEKPDDFCPHRFLDDQGqLLKRETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFTFALPEGseKPIMTGR-FGLTLAP 308
Cdd:cd20617   338 FEDPEEFNPERFLENDG-NKLSEQFIPFGIGKRNCVGENLARDELFLFFANLLLNFKFKSSDG--LPIDEKEvFGLTLKP 414

                  ....*
gi 1958751028 309 HPFNV 313
Cdd:cd20617   415 KPFKV 419

cytochrome P450 family 2, subfamily D; Members of CYP2D are present in mammals, birds, reptiles, and amphibians. The hominin CYP2D subfamily consists of a functional CYP2D6 and two paralogs, CYP2D7 and CYP2D8, that are often not functional in some species. Human CYP2D6 has a high affinity for alkaloids and can detoxify them. It is also responsible for metabolizing about 25% of commonly used drugs, such as antidepressants, beta-blockers, and antiarrhythmics. The CYP2D 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 1958751028 151 KVHEEIERVIGRDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRDPVIW 230
Cdd:cd20663   266 RVQQEIDEVIGQVRRPEMADQARMPYTNAVIHEVQRFGDIVPLGVPHMTSRDIEVQGFLIPKGTTLITNLSSVLKDETVW 345

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958751028 231 EKPDDFCPHRFLDDQGQLLKRETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFTFALPEGSEKPIMTGRFGLTLAPHP 310
Cdd:cd20663   346 EKPLRFHPEHFLDAQGHFVKPEAFMPFSAGRRACLGEPLARMELFLFFTCLLQRFSFSVPAGQPRPSDHGVFAFLVSPSP 425

                  .
gi 1958751028 311 F 311
Cdd:cd20663   426 Y 426

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 1958751028 150 EKVHEEIERVIGRDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRDPVI 229
Cdd:pfam00067 296 EKLREEIDEVIGDKRSPTYDDLQNMPYLDAVIKETLRLHPVVPLLLPREVTKDTVIPGYLIPKGTLVIVNLYALHRDPEV 375

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958751028 230 WEKPDDFCPHRFLDDQGQLLKRETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFTFALPEGSEKPIMTGRFGLTLAPH 309
Cdd:pfam00067 376 FPNPEEFDPERFLDENGKFRKSFAFLPFGAGPRNCLGERLARMEMKLFLATLLQNFEVELPPGTDPPDIDETPGLLLPPK 455

                  ....*.
gi 1958751028 310 PFNVTV 315
Cdd:pfam00067 456 PYKLKF 461

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 1958751028 149 KEKVHEEIERVIGRDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRDPV 228
Cdd:cd20673   266 QKKIQEEIDQNIGFSRTPTLSDRNHLPLLEATIREVLRIRPVAPLLIPHVALQDSSIGEFTIPKGTRVVINLWALHHDEK 345

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958751028 229 IWEKPDDFCPHRFLDDQGQLLK--RETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFTFALPEGSEKPIMTGRFGLTL 306
Cdd:cd20673   346 EWDQPDQFMPERFLDPTGSQLIspSLSYLPFGAGPRVCLGEALARQELFLFMAWLLQRFDLEVPDGGQLPSLEGKFGVVL 425

                  ....*..
gi 1958751028 307 APHPFNV 313
Cdd:cd20673   426 QIDPFKV 432

cytochrome P450 family 2, subfamily K; Members of CYP2K are present in fish, birds, and amphibians. CYP2K6 from zebrafish has been shown to catalyze the conversion of aflatoxin B1 (AFB1) to its cytotoxic derivative AFB1 exo-8,9-epoxide, while its ortholog in rainbow trout CYP2K1 is also capable of oxidizing lauric acid. In birds, CYP2K is one of the largest CYP2 subfamilies. The CYP2K 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 1958751028 149 KEKVHEEIERVIGrDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRDPV 228
Cdd:cd20664   259 QKKVQEEIDRVIG-SRQPQVEHRKNMPYTDAVIHEIQRFANIVPMNLPHATTRDVTFRGYFIPKGTYVIPLLTSVLQDKT 337

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958751028 229 IWEKPDDFCPHRFLDDQGQLLKRETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFTFALPEG-SEKPIMTGR-FGLTL 306
Cdd:cd20664   338 EWEKPEEFNPEHFLDSQGKFVKRDAFMPFSAGRRVCIGETLAKMELFLFFTSLLQRFRFQPPPGvSEDDLDLTPgLGFTL 417

                  ....
gi 1958751028 307 APHP 310
Cdd:cd20664   418 NPLP 421

cytochrome P450 family 2, subfamily F; Cytochrome P450 family 2, subfamily F (CYP2F) members are selectively expressed in lung tissues. They are responsible for the bioactivation of several pneumotoxic and carcinogenic chemicals such as benzene, styrene, naphthalene, and 1,1-dichloroethylene. CYP2F1 and CYP2F3 selectively catalyzes the 3-methyl dehydrogenation of 3-methylindole, forming toxic reactive intermediates that can form adducts with proteins and DNA. The CYP2F 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 1958751028 150 EKVHEEIERVIGRDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRDPVI 229
Cdd:cd20669   261 ARVQEEIDRVVGRNRLPTLEDRARMPYTDAVIHEIQRFADIIPMSLPHAVTRDTNFRGFLIPKGTDVIPLLNSVHYDPTQ 340

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958751028 230 WEKPDDFCPHRFLDDQGQLLKRETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFTFaLPEGSEKPI 297
Cdd:cd20669   341 FKDPQEFNPEHFLDDNGSFKKNDAFMPFSAGKRICLGESLARMELFLYLTAILQNFSL-QPLGAPEDI 407

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 1958751028 147 KEKEKVHEEIERVIGRDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRD 226
Cdd:cd20675   267 DVQARLQEELDRVVGRDRLPCIEDQPNLPYVMAFLYEAMRFSSFVPVTIPHATTADTSILGYHIPKDTVVFVNQWSVNHD 346

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958751028 227 PVIWEKPDDFCPHRFLDDQGQLLKRETF--IPFGIGKRVCMGEQLAKMELFLMFVSLMQSFTF-ALPegSEKPIMTGRFG 303
Cdd:cd20675   347 PQKWPNPEVFDPTRFLDENGFLNKDLASsvMIFSVGKRRCIGEELSKMQLFLFTSILAHQCNFtANP--NEPLTMDFSYG 424

                         170
                  ....*....|
gi 1958751028 304 LTLAPHPFNV 313
Cdd:cd20675   425 LTLKPKPFTI 434

cytochrome P450 21, also called steroid 21-hydroxylase; Cytochrome P450 21 (CYP21 or Cyp21), also called steroid 21-hydroxylase (EC 1.14.14.16) or cytochrome P-450c21 or CYP21A2 (in humans), 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. It is required for the adrenal synthesis of mineralocorticoids and glucocorticoids. Deficiency of this CYP is involved in ~95% of cases of human congenital adrenal hyperplasia, a disorder of adrenal steroidogenesis. There are two CYP21 genes in the human genome, CYP21A1 (a pseudogene) and CYP21A2 (the functional gene). Deficiencies in steroid 21-hydroxylase activity lead to a type of congenital adrenal hyperplasia, which has three clinical forms: a severe form with concurrent defects in both cortisol and aldosterone biosynthesis; a form with adequate aldosterone biosynthesis; and a mild, non-classic form that can be asymptomatic or associated with signs of postpubertal androgen excess without cortisol deficiency. CYP21A2 is also the major autoantigen in autoimmune Addison disease. Cyp21 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 1958751028 149 KEKVHEEIERVIGRDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRDPV 228
Cdd:cd20674   260 QDRLQEELDRVLGPGASPSYKDRARLPLLNATIAEVLRLRPVVPLALPHRTTRDSSIAGYDIPKGTVVIPNLQGAHLDET 339

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958751028 229 IWEKPDDFCPHRFLDDQGqllKRETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFTFALPEGSEKPIMTGRFGLTLAP 308
Cdd:cd20674   340 VWEQPHEFRPERFLEPGA---ANRALLPFGCGARVCLGEPLARLELFVFLARLLQAFTLLPPSDGALPSLQPVAGINLKV 416

                  ....*...
gi 1958751028 309 HPFNVTVS 316
Cdd:cd20674   417 QPFQVRLQ 424

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 1958751028 150 EKVHEEIERVIGRDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRDPVI 229
Cdd:cd20672   261 EKVQKEIDQVIGSHRLPTLDDRAKMPYTDAVIHEIQRFSDLIPIGVPHRVTKDTLFRGYLLPKNTEVYPILSSALHDPQY 340

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958751028 230 WEKPDDFCPHRFLDDQGQLLKRETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFTFALPEGSE 294
Cdd:cd20672   341 FEQPDTFNPDHFLDANGALKKSEAFMPFSTGKRICLGEGIARNELFLFFTTILQNFSVASPVAPE 405

cytochrome P450, family 2, subfamily AB, polypeptide 1 and similar cytochrome P450s; The function of CYP2AB1 is unknown. CYP2AB1 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 1958751028 149 KEKVHEEIERVIGRDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRDPV 228
Cdd:cd20667   259 QEKVQQELDEVLGASQLICYEDRKRLPYTNAVIHEVQRLSNVVSVGAVRQCVTSTTMHGYYVEKGTIILPNLASVLYDPE 338

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958751028 229 IWEKPDDFCPHRFLDDQGQLLKRETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFTFALPEGSEKPIMTGRFGLTLAP 308
Cdd:cd20667   339 CWETPHKFNPGHFLDKDGNFVMNEAFLPFSAGHRVCLGEQLARMELFIFFTTLLRTFNFQLPEGVQELNLEYVFGGTLQP 418

                  ....*
gi 1958751028 309 HPFNV 313
Cdd:cd20667   419 QPYKI 423

cytochrome P450 family 1, subfamily D, polypeptide 1; The cytochrome P450 1D1 (CYP1D1) gene is pseudogenized in humans because of five nonsense mutations in the putative coding region. However, in other organisms including cynomolgus monkey, CYP1D1 is a functional drug-metabolizing enzyme that is highly expressed in the liver. CYP1D1 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 1958751028 151 KVHEEIERVIGRDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRDPVIW 230
Cdd:cd20677   272 KIQEEIDEKIGLSRLPRFEDRKSLHYTEAFINEVFRHSSFVPFTIPHCTTADTTLNGYFIPKDTCVFINMYQVNHDETLW 351

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958751028 231 EKPDDFCPHRFLDDQGQLLKR--ETFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFTFALPEGsEKPIMTGRFGLTLAP 308
Cdd:cd20677   352 KDPDLFMPERFLDENGQLNKSlvEKVLIFGMGVRKCLGEDVARNEIFVFLTTILQQLKLEKPPG-QKLDLTPVYGLTMKP 430

                  ....*
gi 1958751028 309 HPFNV 313
Cdd:cd20677   431 KPYRL 435

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 1958751028 150 EKVHEEIERVIGRDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRDPVI 229
Cdd:cd11073   266 AKARAELDEVIGKDKIVEESDISKLPYLQAVVKETLRLHPPAPLLLPRKAEEDVEVMGYTIPKGTQVLVNVWAIGRDPSV 345

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958751028 230 WEKPDDFCPHRFLDDQGQLLKRE-TFIPFGIGKRVCMGEQLAKMELFLMFVSLMQSFTFALPEG--SEKPIMTGRFGLTL 306
Cdd:cd11073   346 WEDPLEFKPERFLGSEIDFKGRDfELIPFGSGRRICPGLPLAERMVHLVLASLLHSFDWKLPDGmkPEDLDMEEKFGLTL 425

                  .
gi 1958751028 307 A 307
Cdd:cd11073   426 Q 426

cytochrome P450 family 75; The cytochrome P450 family 75 (CYP75) play important roles in the biosynthesis of colored class of flavonoids, anthocyanins, which confer a diverse range of colors to flowers from orange to red to violet and blue. The number of hydroxyl groups on the B-ring of anthocyanidins, the chromophores and precursors of anthocyanins, impact the anthocyanin color - the more the bluer. The hydroxylation pattern is determined by CYP75 proteins: flavonoid 3'-hydroxylase (F3'H, EC 1.14.14.82) and and flavonoid 3',5'-hydroxylase (F3'5'H, EC 1.14.14.81), which belong to CYP75B and CYP75A subfamilies, respectively. Both enzymes have broad substrate specificity and catalyze the hydroxylation of flavanones, dihydroflavonols, flavonols and flavones. F3'H catalyzes the 3'-hydroxylation of the flavonoid B-ring to the 3',4'-hydroxylated state. F3'5'H catalysis leads to trihydroxylated delphinidin-based anthocyanins that tend to have violet/blue colours. CYP75 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 1958751028 151 KVHEEIERVIGRDRAPSLTDKAQMPYTEATIMEVQRLSMVVPLAIPHMTSEKTVLQGYSIPKGTVVLPNLWSIHRDPVIW 230
Cdd:cd20657   264 KAQEEMDQVIGRDRRLLESDIPNLPYLQAICKETFRLHPSTPLNLPRIASEACEVDGYYIPKGTRLLVNIWAIGRDPDVW 343