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PR01688

Identifier
EP450ICYP2J  [View Relations]  [View Alignment]  
Accession
PR01688
No. of Motifs
4
Creation Date
13-MAR-2002
Title
CYP2J 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. XIE, Q., ZHANG, Q.Y., ZHANG, Y., SU, T., GU, J., KAMINSKY, L.S. AND DING, X.
Induction of mouse CYP2J by pyrazole in the eye, kidney, liver, lung,
olfactory mucosa, and small intestine, but not in the heart.
DRUG METAB.DISPOS. 28 1311-1316 (2000).
 
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 [3] 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 [5,6]. 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, whereas 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]. Ten CYP2J1 isoforms have been reported, including rabbit
CYP2J1; human CYP2J2; rat 2J3 and 2J4; mouse 2J5, 2J6, 2J7, 2J8 and 2J9; and
rat CYP2J10 [7]. The metabolic activities of CYP2J2, 2J3, 2J4 and 2J5 have
been characterised; all isoforms are active toward arachidonic acid, forming
metabolites believed to be important for cellular functions. In addition,
CYP2J4 is active in the biosynthesis of retinoic acid from retinal.
 
EP450ICYP2J is a 4-element fingerprint that provides a signature for the
CYP2J P450 family. The fingerprint was derived from an initial alignment of
5 sequences: the motifs were drawn from conserved regions spanning the N- 
and C-terminal portions of the alignment, focusing on those sections that
characterise the CYP2J 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 encodes the B helix; motif 3
spans the E1 and F1 helices, and lies at the N-terminus of the haem-binding
domain; and motif 4 spans the C-terminus, including substrate recognition
site (SRS) 6. Two iterations on SPTR40_18f were required to reach
convergence, at which point a true set comprising 6 sequences was identified.
Summary Information
6 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
46666
30000
20000
1234
True Positives
CPJ1_RABIT    CPJ2_HUMAN    CPJ3_RAT      CPJ5_MOUSE    
CPJ6_MOUSE Q9QXF7
Sequence Titles
CPJ1_RABIT  Cytochrome P450 2J1 (EC 1.14.14.1) (CYPIIJ1) (P-450IB) - Oryctolagus cuniculus (Rabbit). 
CPJ2_HUMAN Cytochrome P450 2J2 (EC 1.14.14.1) (CYPIIJ2) (Arachidonic acid epoxygenase) - Homo sapiens (Human).
CPJ3_RAT Cytochrome P450 2J3 (EC 1.14.14.1) (CYPIIJ3) - Rattus norvegicus (Rat).
CPJ5_MOUSE Cytochrome P450 2J5 (EC 1.14.14.1) (CYPIIJ5) (Arachidonic acid epoxygenase) - Mus musculus (Mouse).
CPJ6_MOUSE Cytochrome P450 2J6 (EC 1.14.14.1) (CYPIIJ6) (Arachidonic acid epoxygenase) - Mus musculus (Mouse).
Q9QXF7 CYP2J4 PROTEIN - Rattus norvegicus (Rat).
Scan History
SPTR40_18f 2  125  NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
LHPRTLLVAAVTFL CPJ6_MOUSE 16 16 -
LHLRILLLAAVTFL CPJ3_RAT 16 16 -
LHPKTLLLGAVAFL CPJ1_RABIT 15 15 -
VHPRTLLLGTVAFL CPJ2_HUMAN 16 16 -
LHLKTLVLAVVTFL CPJ5_MOUSE 16 16 -

Motif 2 width=12
Element Seqn Id St Int Rpt
VVITGLPLIKEA CPJ6_MOUSE 89 59 -
VVVTGMPLIKEI CPJ3_RAT 89 59 -
VIVTGLPLIKEV CPJ1_RABIT 88 59 -
VLITGLPLIKEA CPJ2_HUMAN 89 59 -
VVVSGLPLIKEM CPJ5_MOUSE 89 59 -

Motif 3 width=16
Element Seqn Id St Int Rpt
FNPEHFLENGQFKKRE CPJ6_MOUSE 420 319 -
FNPEHFLENGQFKKRE CPJ3_RAT 421 320 -
FNPEHFLENGQFKKKE CPJ1_RABIT 419 319 -
FNPDHFLENGQFKKRE CPJ2_HUMAN 421 320 -
FNPEHFLENGQFKKRE CPJ5_MOUSE 420 319 -

Motif 4 width=12
Element Seqn Id St Int Rpt
LSPVSHRICAVP CPJ6_MOUSE 488 52 -
ISPVSHRLCAIP CPJ3_RAT 489 52 -
LSPVKHRICAIP CPJ1_RABIT 487 52 -
ISPVSHRLCAVP CPJ2_HUMAN 489 52 -
LSPASYRICAIP CPJ5_MOUSE 488 52 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
LHPRTLLVAAVTFL CPJ6_MOUSE 16 16 -
LHLRTLLVAALTFL Q9QXF7 16 16 -
LHLRILLLAAVTFL CPJ3_RAT 16 16 -
LHPKTLLLGAVAFL CPJ1_RABIT 15 15 -
VHPRTLLLGTVAFL CPJ2_HUMAN 16 16 -
LHLKTLVLAVVTFL CPJ5_MOUSE 16 16 -

Motif 2 width=12
Element Seqn Id St Int Rpt
VVITGLPLIKEA CPJ6_MOUSE 89 59 -
VVITGLPLIKET Q9QXF7 89 59 -
VVVTGMPLIKEI CPJ3_RAT 89 59 -
VIVTGLPLIKEV CPJ1_RABIT 88 59 -
VLITGLPLIKEA CPJ2_HUMAN 89 59 -
VVVSGLPLIKEM CPJ5_MOUSE 89 59 -

Motif 3 width=16
Element Seqn Id St Int Rpt
FNPEHFLENGQFKKRE CPJ6_MOUSE 420 319 -
FNPEHFLENGQFKKRE Q9QXF7 420 319 -
FNPEHFLENGQFKKRE CPJ3_RAT 421 320 -
FNPEHFLENGQFKKKE CPJ1_RABIT 419 319 -
FNPDHFLENGQFKKRE CPJ2_HUMAN 421 320 -
FNPEHFLENGQFKKRE CPJ5_MOUSE 420 319 -

Motif 4 width=12
Element Seqn Id St Int Rpt
LSPVSHRICAVP CPJ6_MOUSE 488 52 -
LSPVTHRICAVP Q9QXF7 488 52 -
ISPVSHRLCAIP CPJ3_RAT 489 52 -
LSPVKHRICAIP CPJ1_RABIT 487 52 -
ISPVSHRLCAVP CPJ2_HUMAN 489 52 -
LSPASYRICAIP CPJ5_MOUSE 488 52 -