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PR00463

Identifier
EP450I  [View Relations]  [View Alignment]  
Accession
PR00463
No. of Motifs
9
Creation Date
05-MAR-1996  (UPDATE 08-JUL-1999)
Title
E-class P450 group I signature
Database References
PRINTS; PR00385 P450; PR01683 EP450ICYP1A; PR01684 EP450ICYP2A
PRINTS; PR01685 EP450ICYP2B; PR01686 EP450ICYP2D; PR01687 EP450ICYP2E
PRINTS; PR01957 EP450ICYP2F; PR01688 EP450ICYP2J
INTERPRO; IPR002401
PDB; 2HPD
SCOP; 2HPD
CATH; 2HPD
Literature References
1. NOMENCLATURE COMMITTEE OF THE INTERNATIONAL UNION OF BIOCHEMISTRY (NC-IUB).
Nomenclature of electron-transfer proteins. Recommendations 1989.
EUR.J.BIOCHEMISTRY 200 599-611 (1991).
 
2. NEBERT, D.W. AND GONZALEZ, F.J.
P450 genes: structure, evolution, and regulation.
ANNU.REV.BIOCHEMISTRY 56 945-993 (1987).
 
3. NELSON, D.R., KAMATAKI, T., WAXMAN, D.J., GUENGERICH, F.P.,
ESTABROOK, R.W., FEYEREISEN, R., GONZALEZ, F.J., COON, M.J.,
GUNSALUS, I.C., GOTOH, O., OKUDA, K. AND NEBERT, D.W.
The P450 superfamily: update on new sequences, gene mapping, accession
numbers, early trivial names of enzymes, and nomenclature.
DNA CELL BIOL. 12 1-51 (1993).
 
4. GOTOH, O.
Evolution and differentiation of P-450 genes.
IN BIOCHEMISTRY T., ISHIMURA, Y. AND FUJII-KURIYAMA, Y., EDS. 
2ND ED., PP.255-272 (1993). KODANSHA, TOKYO.
 
5. SZKLARZ, G.D., HE, Y.A. AND HALPERT, J.R.
Site-directed mutagenesis as a tool for molecular modeling of cytochrome 
P450 2B1.
BIOCHEMISTRY 34 14312-14322 (1995).

Documentation
P450 enzymes constitute a superfamily of haem-thiolate proteins [1],
widely distributed in bacteria, fungi, plants and animals. The enzymes
are involved in metabolism of a plethora of both exogenous and endogenous
compounds [2]. Usually, they act as terminal oxidases in multi-component
electron transfer chains, called P450-containing monooxygenase systems.
 
Current P450 nomenclature, based on divergent evolution of the P450
superfamily, was proposed and developed by Nebert et al. [3]. On the basis
of sequence similarity, all P450s can be categorised into 2 main classes,
the so-called B- and E-classes: P450 proteins of prokaryotic 3-component
systems and fungal P450nor (CYP55) belong to the B-class; all other known
P450s from distinct systems are of the E-class [4]. E-class P450s may be
further divided into 5 subclasses (groups) according to protein sequence
similarities. The data suggest that divergence of the P450 superfamily 
into B- and E-classes, and further divergence into stable P450 groups 
within the E-class, must be very ancient and had occured before the 
appearance of eukaryotes. 
 
Group I is richest in members, consisting of P450 families CYP1, CYP2,
CYP17, CYP21 and CYP71 [4]. The members of the first 4 families are of
vertebrate origin, while those from CYP71 derive from plants. CYP1 and CYP2
enzymes mainly metabolise exogenous substrates, whereas CYP17 and CYP21 are
involved in metabolism of endogenous physiologically-active compounds.
 
EP450I is a 9-element fingerprint that provides a signature for group I
E-class P450s. The fingerprint was derived from an initial alignment of 19
sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length. Since no 3D structure is available for a group I
E-class P450 representative, the assignment of secondary structure elements
given below has been adopted from the modelling study of Szklarz et al. [5].
Motifs 1 and 2 span the first beta-strand and helix B; motif 3 includes
helix E; motif 4 corresponds to the N-terminus of helix I, which is thought
to be central to the catalytic function of P450s; motif 5 spans the helix I
C-terminus and the neighbouring J helix (cf. motifs 1 and 2 of signature
P450); motif 6 corresponds to helix K (cf. motif 3 of signature P450);
motif 7 spans the K' helix N-terminus and the "aromatic region" typical of
E-class P450s [4]; and motifs 8 and 9 are adjacent, spanning the L helix and
including the invariant Cys residue that provides the haem iron thiolate
ligand (cf. PROSITE pattern CYTOCHROME_P450 (PS00086) and motifs 4 and 5 of
signature P450). Three iterations on OWL27.0 were required to reach
convergence, at which point a true set comprising 194 sequences was
identified. In addition to the aforementioned families, several C.elegans 
sequences comprising subfamilies CYP14A (CEK09A111, CEK09A112, CEK09A113),
CYP22A (CELT13C53) and CYP23A (CELB0304) were found to match all 9 motifs.
Numerous partial matches were also found. Those matching 8 motifs should
also be classified as group I E-class P450s: CYP2E1 (CPE1_MACFA), CYP71A
(C712_SOLME, S45039) and CYP71B (THLCYP450A) fail to make a significant
match with motif 2; CYP71A (C771_SOLME, C772_SOLME), CYP71C4 (ZMCYP71C4),
CYP75 (CP75_SOLME, S33515, S33521), CYP76A1 (C761_SOLME) and CYP13A
(CEZK13203) lack motif 3; CYP73A (TCMO_MEDSA, TCMO_HELTU, S44169, ZEU19922,
PSU29243, PUMC4H) lack motif 4; and CYP1A2 (S16875) and CYP71A4 (C714_SOLME)
lack motif 5. The sequences matching 7 motifs include both group I E-class 
P450s and other E-class P450s. Most of the sequences matching only 2 motifs
are noise.
 
An update on SPTR37_9f identified a true set of 242 sequences, and 486
partial matches.
Summary Information
 241 codes involving  9 elements
48 codes involving 8 elements
50 codes involving 7 elements
66 codes involving 6 elements
111 codes involving 5 elements
85 codes involving 4 elements
57 codes involving 3 elements
39 codes involving 2 elements
Composite Feature Index
9241241241241241241241241241
8482228464848484848
744206385046465050
651146395752516363
5195858998867108103
41144216646537659
3811202515283934
2111152518728
123456789
True Positives
C2F1_HUMAN    C2F2_MOUSE    C2F3_CAPHI    C2F4_RAT      
C719_SOYBN C751_PETHY C752_SOLME C753_PETHY
C756_CAMME C7B1_THLAR C7B2_ARATH C7B3_ARATH
C7B4_ARATH C7B5_ARATH C7B6_ARATH C7B7_ARATH
C7C1_ARATH C7C2_ARATH C7C3_ARATH C7C4_ARATH
C7E1_SORBI C823_SOYBN C824_SOYBN C981_SORBI
C982_SOYBN C983_ARATH CP11_CANFA CP11_CAVPO
CP11_HUMAN CP11_MACFA CP11_MESAU CP11_MICTO
CP11_MOUSE CP11_ONCMY CP11_OPSTA CP11_PLEPL
CP11_RABIT CP11_RAT CP11_SHEEP CP11_SPAAU
CP11_STECH CP12_CANFA CP12_CAVPO CP12_HUMAN
CP12_MESAU CP12_MOUSE CP12_RABIT CP12_RAT
CP14_CHICK CP15_CHICK CP1B_HUMAN CP1B_MOUSE
CP1B_RAT CP71_PERAE CP83_ARATH CPA1_RAT
CPA2_RAT CPA3_RAT CPA4_MOUSE CPA5_MOUSE
CPA6_HUMAN CPA7_HUMAN CPA8_MESAU CPA9_MESAU
CPAA_RABIT CPAB_RABIT CPAC_MOUSE CPAD_HUMAN
CPB1_RAT CPB2_RAT CPB3_RAT CPB4_RABIT
CPB5_RABIT CPB6_HUMAN CPB9_MOUSE CPBA_MOUSE
CPBB_CANFA CPBC_RAT CPBJ_MOUSE CPC2_RABIT
CPC3_RABIT CPC4_RABIT CPC5_RABIT CPC6_RAT
CPC7_RAT CPC8_HUMAN CPC9_HUMAN CPCA_HUMAN
CPCB_RAT CPCC_RAT CPCD_RAT CPCE_RABIT
CPCG_RABIT CPCH_HUMAN CPCI_HUMAN CPCJ_HUMAN
CPCK_MACFA CPCM_RAT CPCN_RAT CPCP_MESAU
CPCQ_MESAU CPCT_MOUSE CPCU_RABIT CPD1_RAT
CPD2_RAT CPD3_RAT CPD4_RAT CPD5_RAT
CPD6_HUMAN CPD9_MOUSE CPDA_MOUSE CPDB_MOUSE
CPDF_CANFA CPDG_CAVPO CPDH_MACFA CPDI_RAT
CPDJ_CALJA CPDP_PIG CPE1_BOVIN CPE1_HUMAN
CPE1_MESAU CPE1_MOUSE CPE1_PIG CPE1_RABIT
CPE1_RAT CPG1_RABIT CPG1_RAT CPH1_CHICK
CPH2_CHICK CPJ1_RABIT CPJ2_HUMAN CPJ3_RAT
CPJ5_MOUSE CPJ6_MOUSE CPK1_ONCMY CPS1_BOVIN
CPS1_HUMAN CPS1_MOUSE CPS1_PIG CPS3_PIG
CPT7_BOVIN CPT7_CAVPO CPT7_CHICK CPT7_HORSE
CPT7_HUMAN CPT7_ICTPU CPT7_MESAU CPT7_MOUSE
CPT7_ONCMY CPT7_ORYLA CPT7_PIG CPT7_RANDY
CPT7_RAT CPT7_SHEEP CPT7_SQUAC CPZ6_CANFA
O17655 O22185 O22188 O23155
O23156 O24315 O42195 O42231
O42430 O44649 O44650 O44651
O44652 O44655 O44657 O44658
O44659 O45364 O45659 O48532
O54797 O61204 O61935 O62377
O62378 O64901 O65782 O65814
O65815 O77809 O77810 O88304
O93297 O93299 O93304 P79716
P79829 P79830 Q08078 Q13120
Q16741 Q16742 Q16749 Q16753
Q16872 Q16874 Q27465 Q27482
Q27499 Q27505 Q27506