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PR01684

Identifier
EP450ICYP2A  [View Relations]  [View Alignment]  
Accession
PR01684
No. of Motifs
4
Creation Date
13-MAR-2002
Title
CYP2A P450 family signature
Database References
PRINTS; PR00385 P450; PR00463 EP450I
Literature References
1. NOMENCLATURE COMMITTEE OF THE INTERNATIONAL UNION OF BIOCHEMISTRY
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., 2ND ED., ISHIMURA, Y. AND FUJII-KURIYAMA, Y., EDS., 
KODANSHA, TOKYO, 1993, PP.255-272.
 
5. NELSON, D.R.
Cytochrome P450 homepage.
http://drnelson.utmem.edu/CytochromeP450.html
 
6. NELSON, D.R.
Metazoan Cytochrome P450 evolution.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY PART C 121 15-22 (1998).
 
7. LEWIS, D.F.V.
P450 substrate specificity and metabolism.
IN CYTOCHROMES P450: STRUCTURE, FUNCTION AND MECHANISM, TAYLOR AND FRANCIS
LTD., LONDON, 1996, PP.115-167.
 
8. DE GROOT, M.J., VERMEULEN, N.P.E. KRAMER, J.D., VAN ACKER, F.A.A. AND
DONNE-OP DEN KELDER, G.M. 
A three-dimensional protein model for human cytochrome P450 2D6 based on the
crystal structures of P450 101, P450 102, and P450 108.
CHEM.RES.TOXICOL. 9 1079-1091 (1996).

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. 
 
Due to the rapid increase in numbers of P450s, Nelson introduced the concept
of a higher order classification of P450 families into clans [5,6] based on 
sequence similarity. This is similar to the previous grouping into B- and
E-classes; both classifications are still used. According to Nelson's 
system, clan 2 contains the CYP2 plus CYP1, 17, 18, 21 and 71 families, and
corresponds to the E-class group I proteins [6]. 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, while CYP17
and CYP21 are involved in metabolism of endogenous physiologically-active
compounds. 
 
The CYP2 family, comprising 15 subfamilies (A-H, J-N, P and Q), is the most
dominant in clan 2. Six of these subfamilies are non-mammalian: 2H derives
from chicken; 2K, 2M, 2N and 2P are from fish; 2L is from lobster; and 2Q
from Xenopus [5]. The first five (A-E) are present in mammalian liver, but
in differing amounts and with different inducibilities [7]. These five 
subfamilies show varied substrate specificities, with some degree of 
overlap. The various mammalian orthologues of the CYP2A subfamily (of which
2A1, 2A2 and 2A3 are the rat forms, 2A4 and 2A5 are the mouse forms, and
2A6 and 2A7 represent those in human) exhibit some interesting inter-species
differences, indicating possible evolutionary modifications that may 
represent responses to dietary challenges [7]. The CYP2A gene is located on
chromosome 19 in mouse and man [3].
 
EP450ICYP2A is a 4-element fingerprint that provides a signature for the
CYP2A P450 family. The fingerprint was derived from an initial alignment of
13 sequences: the motifs were drawn from conserved regions spanning 
virtually the full alignment length, focusing on those sections that
characterise the CYP2A proteins but distinguish them from the rest of the
CYP2 family - using the model of de Groot et al. [8], motif 1 lies in the
N-terminal membrane anchor domain; motif 2 spans the N-terminal region of
the G helix, and is located between substrate recognition site (SRS) 2 and
SRS 3; motif 3 encodes the J' helix between the J and K helices; and motif 
4 encodes the K' helix between SRS 5 and the haem-binding domain. Two 
iterations on SPTR40_18f were required to reach convergence, at which point
a true set comprising 19 sequences was identified. A single partial match
was also found, Q92129, a P450 from Xenopus that matches motifs 3 and 4.
Summary Information
  19 codes involving  4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
419191919
30000
20011
1234
True Positives
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 Q13120 Q9H2X2 Q9JM91
Q9QZ50 Q9R0R6 Q9Z1H8
True Positive Partials
Codes involving 2 elements
Q92129
Sequence Titles
CPA1_RAT    Cytochrome P450 2A1 (EC 1.14.14.1) (CYPIIA1) (Steroid hormones 7- alpha-hydroxylase) (Testosterone 7-alpha-hydroxylase) (P450-UT-F) - Rattus norvegicus (Rat). 
CPA2_RAT Cytochrome P450 2A2 (EC 1.14.14.1) (CYPIIA2) (Testosterone 15-alpha- hydroxylase) (P450-UT-4) - Rattus norvegicus (Rat).
CPA3_RAT Cytochrome P450 2A3 (EC 1.14.14.1) (CYPIIA3) (Coumarin 7-hydroxylase) - Rattus norvegicus (Rat).
CPA4_MOUSE Cytochrome P450 2A4 (EC 1.14.14.1) (CYPIIA4) (Testosterone 15-alpha- hydroxylase) (P450-15-alpha) (P450-IIA3.1) - Mus musculus (Mouse).
CPA5_MOUSE Cytochrome P450 2A5 (EC 1.14.14.1) (CYPIIA5) (Coumarin 7-hydroxylase) (P450-15-COH) (P450-IIA3.2) - Mus musculus (Mouse).
CPA6_HUMAN Cytochrome P450 2A6 (EC 1.14.14.1) (CYPIIA6) (Coumarin 7-hydroxylase) (IIA3) (CYP2A3) (P450(I)) - Homo sapiens (Human).
CPA7_HUMAN Cytochrome P450 2A7 (EC 1.14.14.1) (CYPIIA7) (P450-IIA4) - Homo sapiens (Human).
CPA8_MESAU Cytochrome P450 2A8 (EC 1.14.14.1) (CYPIIA8) (P450-MC1) (P450-AFB) - Mesocricetus auratus (Golden hamster).
CPA9_MESAU Cytochrome P450 2A9 (EC 1.14.14.1) (CYPIIA9) (P450-MC1-R) (Testosterone 7-alpha-hydroxylase) - Mesocricetus auratus (Golden hamster).
CPAA_RABIT Cytochrome P450 2A10 (EC 1.14.14.1) (CYPIIA10) (P450-IIA10) - Oryctolagus cuniculus (Rabbit).
CPAB_RABIT Cytochrome P450 2A11 (EC 1.14.14.1) (CYPIIA11) (P450-IIA11) - Oryctolagus cuniculus (Rabbit).
CPAC_MOUSE Cytochrome P450 2A12 (EC 1.14.14.1) (CYPIIA12) (Steroid hormones 7- alpha-hydroxylase) (Testosterone 7-alpha-hydroxylase) - Mus musculus (Mouse).
CPAD_HUMAN Cytochrome P450 2A13 (EC 1.14.14.1) (CYPIIA13) - Homo sapiens (Human).
Q13120 CYTOCHROME P450 IIA6 W(EC 1.14.14.1) - Homo sapiens (Human).
Q9H2X2 CYTOCHROME P450 2A13 - Homo sapiens (Human).
Q9JM91 CYTOCHROME P450 2A17 - Cricetulus griseus (Chinese hamster).
Q9QZ50 CYTOCHROME P-450 - Mesocricetus auratus (Golden hamster).
Q9R0R6 CYTOCHROME P450 2A15 - Cricetulus griseus (Chinese hamster).
Q9Z1H8 CYTOCHROME P-450 2A14 - Cricetulus griseus (Chinese hamster).

Q92129 CYTOCHROME P-450 (EC 1.14.14.1) - Xenopus laevis (African clawed frog).
Scan History
SPTR40_18f 2  150  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
MLASGLLLAALLA CPAA_RABIT 1 1 -
MLASGLLLAALLA CPAB_RABIT 1 1 -
MLASGLLLVALLA CPA7_HUMAN 1 1 -
MLTSGLLLVAAVA CPA4_MOUSE 1 1 -
MLTSGLLLVAAVA CPA5_MOUSE 1 1 -
MLASGLLLVTLLA CPAD_HUMAN 1 1 -
MLASGLLLVASVA CPA3_RAT 1 1 -
MLASGMLLVALLV CPA6_HUMAN 1 1 -
MLGSGLILVAILA CPA9_MESAU 1 1 -
MLGSGLLLLAILA CPAC_MOUSE 1 1 -
MLDTGLLLVVILA CPA1_RAT 1 1 -
MLVSGMLLVVVLT CPA8_MESAU 1 1 -
MLDTGLLLVVILA CPA2_RAT 1 1 -

Motif 2 width=13
Element Seqn Id St Int Rpt
SVMKHLPGPQQQA CPAA_RABIT 225 211 -
SVMKHLPGPQQQA CPAB_RABIT 225 211 -
SVMKHLPGPQQQA CPA7_HUMAN 225 211 -
SVMKHLPGPQQQA CPA4_MOUSE 225 211 -
SVMKHLPGPQQQA CPA5_MOUSE 225 211 -
SVMKHLPGPQQQA CPAD_HUMAN 225 211 -
SVMKHLPGPQQQA CPA3_RAT 225 211 -
SVMKHLPGPQQQA CPA6_HUMAN 225 211 -
SVMKYLPGPQQQI CPA9_MESAU 224 210 -
SVMKYLPGPQQQI CPAC_MOUSE 224 210 -
SVMKYLPGPQQQI CPA1_RAT 224 210 -
SVMKHLPGCQHQA CPA8_MESAU 225 211 -
SVMKYLPGPQQQI CPA2_RAT 224 210 -

Motif 3 width=11
Element Seqn Id St Int Rpt
GRNRQPKFEDR CPAA_RABIT 336 98 -
GRNRQPKFEDR CPAB_RABIT 336 98 -
GKNRQPKFEDR CPA7_HUMAN 336 98 -
GRNRQPKYEDR CPA4_MOUSE 336 98 -
GRNRQPKYEDR CPA5_MOUSE 336 98 -
GKNRQPKFEDR CPAD_HUMAN 336 98 -
GRNRQAKYEDR CPA3_RAT 336 98 -
GKNRQPKFEDR CPA6_HUMAN 336 98 -
GRNRQPQFEDR CPA9_MESAU 335 98 -
GRNRQPQYEDH CPAC_MOUSE 334 97 -
GRNRQPQYEDH CPA1_RAT 334 97 -
GRNRQPKYEDH CPA8_MESAU 336 98 -
GRNRQPQYEDH CPA2_RAT 334 97 -

Motif 4 width=16
Element Seqn Id St Int Rpt
EVFPMLGSVLKDPKFF CPAA_RABIT 390 43 -
EVFPMLGSVLKDPKFF CPAB_RABIT 390 43 -
EVFPMLGSVLRDPSFF CPA7_HUMAN 390 43 -
EVFPMLGSVLKDPKFF CPA4_MOUSE 390 43 -
EVFPMLGSVLKDPKFF CPA5_MOUSE 390 43 -
EVFPMLGSELRDPRFF CPAD_HUMAN 390 43 -
EVFPMLGSVLKDPKFF CPA3_RAT 390 43 -
EVYPMLGSVLRDPSFF CPA6_HUMAN 390 43 -
DVYPILGSLLTDPKFF CPA9_MESAU 389 43 -
EVFPILGSLMTDPKFF CPAC_MOUSE 388 43 -
DVFPILGSLMTDPKFF CPA1_RAT 388 43 -
DVFPVLSSVLKDPKFF CPA8_MESAU 390 43 -
DVFPIIGSLMTEPKFF CPA2_RAT 388 43 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
MLASGLLLAALLA CPAA_RABIT 1 1 -
MLASGLLLAALLA CPAB_RABIT 1 1 -
MLASGLLLVTVLA Q9QZ50 1 1 -
MLASGLLLVALLA CPA7_HUMAN 1 1 -
MLASGLLLVTLLA Q9H2X2 1 1 -
MLTSGLLLVAAVA CPA4_MOUSE 1 1 -
MLTSGLLLVAAVA CPA5_MOUSE 1 1 -
MLASGLLLVTVLA Q9JM91 1 1 -
MLASGLLLVTLLA CPAD_HUMAN 1 1 -
MLASGLLLVASVA CPA3_RAT 1 1 -
MLASGMLLVALLA Q13120 1 1 -
MLASGLLLVSVLA Q9Z1H8 1 1 -
MLASGMLLVALLV CPA6_HUMAN 1 1 -
MLGSELLLVAILA Q9R0R6 1 1 -
MLGSGLILVAILA CPA9_MESAU 1 1 -
MLGSGLLLLAILA CPAC_MOUSE 1 1 -
MLDTGLLLVVILA CPA1_RAT 1 1 -
MLVSGMLLVVVLT CPA8_MESAU 1 1 -
MLDTGLLLVVILA CPA2_RAT 1 1 -

Motif 2 width=13
Element Seqn Id St Int Rpt
SVMKHLPGPQQQA CPAA_RABIT 225 211 -
SVMKHLPGPQQQA CPAB_RABIT 225 211 -
SVMKHLPGPQQQA Q9QZ50 225 211 -
SVMKHLPGPQQQA CPA7_HUMAN 225 211 -
SVMKHLPGPQQQA Q9H2X2 225 211 -
SVMKHLPGPQQQA CPA4_MOUSE 225 211 -
SVMKHLPGPQQQA CPA5_MOUSE 225 211 -
SVMKHLPGPQQKA Q9JM91 226 212 -
SVMKHLPGPQQQA CPAD_HUMAN 225 211 -
SVMKHLPGPQQQA CPA3_RAT 225 211 -
SVMKHLPGPQQQA Q13120 225 211 -
SVMKRLPGPQQQA Q9Z1H8 226 212 -
SVMKHLPGPQQQA CPA6_HUMAN 225 211 -
SVMKYLPGPQQQI Q9R0R6 224 210 -
SVMKYLPGPQQQI CPA9_MESAU 224 210 -
SVMKYLPGPQQQI CPAC_MOUSE 224 210 -
SVMKYLPGPQQQI CPA1_RAT 224 210 -
SVMKHLPGCQHQA CPA8_MESAU 225 211 -
SVMKYLPGPQQQI CPA2_RAT 224 210 -

Motif 3 width=11
Element Seqn Id St Int Rpt
GRNRQPKFEDR CPAA_RABIT 336 98 -
GRNRQPKFEDR CPAB_RABIT 336 98 -
GKNRQPKYEDR Q9QZ50 336 98 -
GKNRQPKFEDR CPA7_HUMAN 336 98 -
GKNRQPKFEDR Q9H2X2 336 98 -
GRNRQPKYEDR CPA4_MOUSE 336 98 -
GRNRQPKYEDR CPA5_MOUSE 336 98 -
GRNRQPKYEDR Q9JM91 337 98 -
GKNRQPKFEDR CPAD_HUMAN 336 98 -
GRNRQAKYEDR CPA3_RAT 336 98 -
GKNRQPKFEDR Q13120 336 98 -
GRNRQPKYEDR Q9Z1H8 336 97 -
GKNRQPKFEDR CPA6_HUMAN 336 98 -
GRNRQPQFEDR Q9R0R6 335 98 -
GRNRQPQFEDR CPA9_MESAU 335 98 -
GRNRQPQYEDH CPAC_MOUSE 334 97 -
GRNRQPQYEDH CPA1_RAT 334 97 -
GRNRQPKYEDH CPA8_MESAU 336 98 -
GRNRQPQYEDH CPA2_RAT 334 97 -

Motif 4 width=16
Element Seqn Id St Int Rpt
EVFPMLGSVLKDPKFF CPAA_RABIT 390 43 -
EVFPMLGSVLKDPKFF CPAB_RABIT 390 43 -
EVFPMLGSVLRDPKFF Q9QZ50 390 43 -
EVFPMLGSVLRDPSFF CPA7_HUMAN 390 43 -
EVFPMLGSVLRDPRFF Q9H2X2 390 43 -
EVFPMLGSVLKDPKFF CPA4_MOUSE 390 43 -
EVFPMLGSVLKDPKFF CPA5_MOUSE 390 43 -
EVFPMLGSVLNDPKFF Q9JM91 391 43 -
EVFPMLGSELRDPRFF CPAD_HUMAN 390 43 -
EVFPMLGSVLKDPKFF CPA3_RAT 390 43 -
EVFPMLGSVLRDLRFF Q13120 390 43 -
DVFPVLGSVLKDSKFF Q9Z1H8 390 43 -
EVYPMLGSVLRDPSFF CPA6_HUMAN 390 43 -
EVFPILGSLLTDPKFF Q9R0R6 389 43 -
DVYPILGSLLTDPKFF CPA9_MESAU 389 43 -
EVFPILGSLMTDPKFF CPAC_MOUSE 388 43 -
DVFPILGSLMTDPKFF CPA1_RAT 388 43 -
DVFPVLSSVLKDPKFF CPA8_MESAU 390 43 -
DVFPIIGSLMTEPKFF CPA2_RAT 388 43 -