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PR01685

Identifier
EP450ICYP2B  [View Relations]  [View Alignment]  
Accession
PR01685
No. of Motifs
4
Creation Date
13-MAR-2002
Title
CYP2B 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. 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. 
 
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]. 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, particularly between the 2B and 2C subfamilies. Although primarily
associated with detoxification, 2B has been also linked with toxic effects
produced by generation of reactive oxygen species (ROS) via a mechanism
known as futile cycling in rodent. The likelihood of toxic activation
mediated by 2B is minimal in man, as the relevant orthologue is poorly
expressed in human liver and is only associated with the toxicity of a very
small number of carcinogens and cytotoxic agents [7]. The CYP2B gene is
located on chromosome 19 in mouse and man [3].
 
EP450ICYP2B is a 4-element fingerprint that provides a signature for the
CYP2B P450 family. The fingerprint was derived from an initial alignment of
11 sequences: the motifs were drawn from conserved regions spanning the
N-terminal half of the alignment, focusing on those sections that 
characterise the CYP2B proteins but distinguish them from the rest of the
CYP2 family - using the model of Szklarz et al. [8], motif 1 spans the
N-terminal membrane anchor domain; motif 2 spans the C-terminus of the F
helix, corresponding to substrate recognition site (SRS) 2; motif 3 lies at
the N-terminus of the G helix, located between SRS 2 and 3; and motif 4
encodes the K' helix between the K and E1 helices. 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, Q14097, a truncated CYP2B family member from human that matches
motifs 1-3.
Summary Information
  19 codes involving  4 elements
1 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
419191919
31110
20000
1234
True Positives
CPB1_RAT      CPB2_RAT      CPB3_RAT      CPB4_RABIT    
CPB5_RABIT CPB6_HUMAN CPB9_MOUSE CPBA_MOUSE
CPBB_CANFA CPBC_RAT CPBJ_MOUSE Q29516
Q29532 Q64460 Q64463 Q64584
Q9JJ02 Q9UK46 Q9WUD0
True Positive Partials
Codes involving 3 elements
Q14097
Sequence Titles
CPB1_RAT    Cytochrome P450 2B1 (EC 1.14.14.1) (CYPIIB1) (P450-B) (P450-PB1 and P450-PB2) (P450-LM2) - Rattus norvegicus (Rat). 
CPB2_RAT Cytochrome P450 2B2 (EC 1.14.14.1) (CYPIIB2) (P450E) (P450 PB4) - Rattus norvegicus (Rat).
CPB3_RAT Cytochrome P450 2B3 (EC 1.14.14.1) (CYPIIB3) - Rattus norvegicus (Rat).
CPB4_RABIT Cytochrome P450 2B4 (EC 1.14.14.1) (CYPIIB4) (P450-LM2) (Isozyme 2) (P450 types B0 and B1) - Oryctolagus cuniculus (Rabbit).
CPB5_RABIT Cytochrome P450 2B5 (EC 1.14.14.1) (CYPIIB5) (P450 type B2) (P450 form HP1) - Oryctolagus cuniculus (Rabbit).
CPB6_HUMAN Cytochrome P450 2B6 (EC 1.14.14.1) (CYPIIB6) (P450 IIB1) - Homo sapiens (Human).
CPB9_MOUSE Cytochrome P450 2B9 (EC 1.14.14.1) (CYPIIB9) (Testosterone 16-alpha hydroxylase) (P450-16-alpha) (Clone PF26) - Mus musculus (Mouse).
CPBA_MOUSE Cytochrome P450 2B10 (EC 1.14.14.1) (CYPIIB10) (Testosterone 16-alpha hydroxylase) (P450-16-alpha) (Clone PF3/46) - Mus musculus (Mouse).
CPBB_CANFA Cytochrome P450 2B11 (EC 1.14.14.1) (CYPIIB11) (P450 PBD-2) - Canis familiaris (Dog).
CPBC_RAT Cytochrome P450 2B12 (EC 1.14.14.1) (CYPIIB12) - Rattus norvegicus (Rat).
CPBJ_MOUSE Cytochrome P450 2B19 (EC 1.14.14.1) (CYPIIB19) - Mus musculus (Mouse).
Q29516 CYTOCHROME P450 (P450IIB) (EC 1.14.14.1) - Oryctolagus cuniculus (Rabbit).
Q29532 CYTOCHROME P450 2B-BX (EC 1.14.14.1) - Oryctolagus cuniculus (Rabbit).
Q64460 CYTOCHROME P450 (TESTOSTERONE 16-ALPHA HYDROXYLASE TYPE B) (EC 1.14.14.1) - Mus musculus (Mouse).
Q64463 CYTOCHROME P450 (TESTOSTERONE 16-ALPHA HYDROXYLASE TYPE A) (EC 1.14.14.1) - Mus musculus (Mouse).
Q64584 CYTOCHROME P450 B (EC 1.14.14.1) - Rattus norvegicus (Rat).
Q9JJ02 CYTOCHROME P450 CYP2BOES - Rattus norvegicus (Rat).
Q9UK46 CYTOCHROME P450-2B6 (EC 1.14.14.1) - Homo sapiens (Human).
Q9WUD0 CYTOCHROME P450 2B10 RELATED PROTEIN - Mus musculus (Mouse).

Q14097 CYTOCHROME P450-IIB (HIIB3) - Homo sapiens (Human).
Scan History
SPTR40_18f 2  200  NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
VLLLLALLVGFLLLL CPBA_MOUSE 5 5 -
ILLLLALLVGFLLLL CPB1_RAT 5 5 -
ILLLLALLVGFLLLL CPB2_RAT 5 5 -
LLLLLAFLAGLLLLL CPB4_RABIT 5 5 -
LLLLLAFLAGLLLLL CPB5_RABIT 5 5 -
VLLLLAVLLSFLLFL CPB3_RAT 5 5 -
VLLLLAVLLSLFLLL CPB9_MOUSE 5 5 -
VLLLLALTTGFLIFL CPBJ_MOUSE 5 5 -
VLLLLALLTGLLLLM CPBB_CANFA 5 5 -
VLLFLALLTGLLLLL CPB6_HUMAN 5 5 -
VLLLLTLTVGFLLFL CPBC_RAT 5 5 -

Motif 2 width=11
Element Seqn Id St Int Rpt
LISSFSSQMFE CPBA_MOUSE 208 188 -
LLSSFSSQVFE CPB1_RAT 208 188 -
LLSSFSSQVFE CPB2_RAT 208 188 -
LISSFSSQVFE CPB4_RABIT 208 188 -
LISSFSSQVFE CPB5_RABIT 208 188 -
LISSFSSQMFE CPB3_RAT 208 188 -
LLSSFSGQMFE CPB9_MOUSE 208 188 -
LMSSLSSQVFE CPBJ_MOUSE 209 189 -
LISSFSSQMFE CPBB_CANFA 208 188 -
LISSVFGQLFE CPB6_HUMAN 208 188 -
LMGSLSSQVFE CPBC_RAT 209 189 -

Motif 3 width=11
Element Seqn Id St Int Rpt
LKYFPGAHRQI CPBA_MOUSE 224 5 -
LKYFPGAHRQI CPB1_RAT 224 5 -
LKYFPGAHRQI CPB2_RAT 224 5 -
LKHFPGTHRQI CPB4_RABIT 224 5 -
LKHFPGTHRQI CPB5_RABIT 224 5 -
LKYFPGVHREI CPB3_RAT 224 5 -
LKYFPGVHRQI CPB9_MOUSE 224 5 -
LKYFPGAHRQI CPBJ_MOUSE 225 5 -
LKYFPGTHRQV CPBB_CANFA 224 5 -
LKYFPGAHRQV CPB6_HUMAN 224 5 -
LKYFPGAHKQI CPBC_RAT 225 5 -

Motif 4 width=13
Element Seqn Id St Int Rpt
ILSSALHDPQYFE CPBA_MOUSE 391 156 -
ILSSALHDPQYFD CPB1_RAT 391 156 -
ILSSALHDPQYFD CPB2_RAT 391 156 -
VLSSALHDPRYFE CPB4_RABIT 391 156 -
VLSSALHDPRYFE CPB5_RABIT 391 156 -
ILSSALHDPQYFE CPB3_RAT 391 156 -
VLSSALHDPQYFE CPB9_MOUSE 391 156 -
ILSSALHDPRYFE CPBJ_MOUSE 392 156 -
ILHSALNDPHYFE CPBB_CANFA 391 156 -
ILSTALHDPHYFE CPB6_HUMAN 391 156 -
ILSSALHDPRYFE CPBC_RAT 392 156 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
VLLLLALLVGFLLLL CPBA_MOUSE 5 5 -
VLLLLALLVGFLLLL Q9WUD0 5 5 -
ILLLLALLVGFLLLL CPB1_RAT 5 5 -
ILLLLALLVGFLLLL CPB2_RAT 5 5 -
ILLLLALLVGFLLLL Q64584 5 5 -
LLLLLAFLAGLLLLL CPB4_RABIT 5 5 -
LLLLLAFLAGLLLLL CPB5_RABIT 5 5 -
VLLLFALLTGFLLLL Q9JJ02 5 5 -
LLLLLAFLAGLLLLL Q29516 5 5 -
LLLLLAFLAGLLLLL Q29532 5 5 -
VLLLLAVLLSFLLFL CPB3_RAT 5 5 -
VLLLLAVLLSLFLLL CPB9_MOUSE 5 5 -
VLLLLAVLLSLFLLL Q64463 5 5 -
VLLLLALTTGFLIFL CPBJ_MOUSE 5 5 -
VLLLLALLTGLLLLM CPBB_CANFA 5 5 -
VLLLLAVLLSLFLLL Q64460 5 5 -
VLLFLALLTGLLLLL CPB6_HUMAN 5 5 -
VLLFLALLTGLLLLL Q9UK46 5 5 -
VLLLLTLTVGFLLFL CPBC_RAT 5 5 -

Motif 2 width=11
Element Seqn Id St Int Rpt
LISSFSSQMFE CPBA_MOUSE 208 188 -
LISSFSSQMFE Q9WUD0 208 188 -
LLSSFSSQVFE CPB1_RAT 208 188 -
LLSSFSSQVFE CPB2_RAT 208 188 -
LLSSFSSQVFE Q64584 208 188 -
LISSFSSQVFE CPB4_RABIT 208 188 -
LISSFSSQVFE CPB5_RABIT 208 188 -
LVSSFSSQVFE Q9JJ02 208 188 -
LTSSFSSQVFE Q29516 208 188 -
LISSFSSQVFE Q29532 208 188 -
LISSFSSQMFE CPB3_RAT 208 188 -
LLSSFSGQMFE CPB9_MOUSE 208 188 -
LLSSFSGQMFE Q64463 208 188 -
LMSSLSSQVFE CPBJ_MOUSE 209 189 -
LISSFSSQMFE CPBB_CANFA 208 188 -
LLRSFSCQMFE Q64460 208 188 -
LISSVFGQLFE CPB6_HUMAN 208 188 -
LISSVFGQLFE Q9UK46 208 188 -
LMGSLSSQVFE CPBC_RAT 209 189 -

Motif 3 width=11
Element Seqn Id St Int Rpt
LKYFPGAHRQI CPBA_MOUSE 224 5 -
LKYFPGAHRQI Q9WUD0 224 5 -
LKYFPGAHRQI CPB1_RAT 224 5 -
LKYFPGAHRQI CPB2_RAT 224 5 -
LKYFPGAHRQI Q64584 224 5 -
LKHFPGTHRQI CPB4_RABIT 224 5 -
LKHFPGTHRQI CPB5_RABIT 224 5 -
LKYFPGTHRHI Q9JJ02 224 5 -
LKHFPGTHRQI Q29516 224 5 -
LKHFPGTHRQI Q29532 224 5 -
LKYFPGVHREI CPB3_RAT 224 5 -
LKYFPGVHRQI CPB9_MOUSE 224 5 -
LKYFPGVHRQI Q64463 224 5 -
LKYFPGAHRQI CPBJ_MOUSE 225 5 -
LKYFPGTHRQV CPBB_CANFA 224 5 -
LKYFPGVHRQI Q64460 224 5 -
LKYFPGAHRQV CPB6_HUMAN 224 5 -
LKYFPGAHRQV Q9UK46 224 5 -
LKYFPGAHKQI CPBC_RAT 225 5 -

Motif 4 width=13
Element Seqn Id St Int Rpt
ILSSALHDPQYFE CPBA_MOUSE 391 156 -
ILSSALHDPQYFE Q9WUD0 391 156 -
ILSSALHDPQYFD CPB1_RAT 391 156 -
ILSSALHDPQYFD CPB2_RAT 391 156 -
IRSSALHDPQYFD Q64584 391 156 -
VLSSALHDPRYFE CPB4_RABIT 391 156 -
VLSSALHDPRYFE CPB5_RABIT 391 156 -
ILSSALHDPQYFE Q9JJ02 391 156 -
VLSSALHDPRYFE Q29516 391 156 -
VLSSALHDPRYFK Q29532 391 156 -
ILSSALHDPQYFE CPB3_RAT 391 156 -
VLSSALHDPQYFE CPB9_MOUSE 391 156 -
VLSSALHDPQYFE Q64463 391 156 -
ILSSALHDPRYFE CPBJ_MOUSE 392 156 -
ILHSALNDPHYFE CPBB_CANFA 391 156 -
ILSSALHDPQYFE Q64460 391 156 -
ILSTALHDPHYFE CPB6_HUMAN 391 156 -
ILSTALHDPHYFE Q9UK46 391 156 -
ILSSALHDPRYFE CPBC_RAT 392 156 -