SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR01238

Identifier
MITP450CC24  [View Relations]  [View Alignment]  
Accession
PR01238
No. of Motifs
5
Creation Date
09-DEC-1999
Title
CC24 mitochondrial P450 signature
Database References
PRINTS; PR00385 P450; PR00408 MITP450
INTERPRO; IPR002949
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. NELSON, D.R.
Metazoan Cytochrome P450 evolution.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY PART C 121 (1998).
 
3. DEGTYARENKO, K.N. AND ARCHAKOV, A.I.
Molecular evolution of P450 superfamily and P450-containing monooxygenase
systems.
FEBS LETT. 322 1-8 (1993).
 
4. RUETTINGER, R.T., WEN, L.P. AND FULCO, A.J.
Coding nucleotide, 5' regulatory, and deduced amino acid sequences of
P450BM-3, a single peptide cytochrome P450:NADPH-P450 reductase from
Bactillus megaterium.
J.BIOL.CHEM. 264 10987-10995 (1989).
 
5. 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 NERBERT, 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).
 
6. HANUKOGLU, I.
Steroidogenic enzymes: structure, function and regulation of expression.
J.STEROID BIOCHEM.MOL.BIOL. 43 770-804 M(1992).
 
7. SAKAGUCHI, M. AND OMURA, T.
Topology and biogenesis of microsomal cytochrome P-450s.
FRONTI.BIOTRANSFORM. 8 60-73 (1993).
 
8. MATTESON, K.J., CHUNG, B.C., URDEA, M.S. AND MILLER, W.L.
Study of cholestrol side chain cleavage (20,22 desmolase) deficiency causing
congenital lipid adrenal hyperplasia using bovine sequence P450scc
oligodeoxyribonucleotide probes.
ENDOCRINOLOGY 118 1296-1305 (1986).
 
9. NOMURA, M., MOROHASHI, K., KIRITA, S., NONAKA, Y., OKAMOTO, M.M.,
NAWATA, H. AND OMURA, T.
Three forms of rat CYP11B genes: 11 beta-hydroxylase gene, aldosterone
synthase gene and a novel gene.
J.BIOCHEMISTRY 113 144-152 (1993).
 
10. CALI, J.J. AND RUSSELL, D.W.
Characterization of human sterol 27 hydroxylase.  A mitochondrial cytochrome
P450 that catalyses multiple oxidation reaction in bile acid biosynthesis.
J.BIOL.CHEM. 266 7774-7778 (1991).
 
11. TEUNISSEN, Y., GERAERTS, W.P., VAN HEERIKHUIZEN, H., PLANTA, R.J. AND
JOOSSE, J.
Molecular cloning of a cDNA encoding a member of a novel cytochrome P450
family in the mollusc Lymnaea stagnalis.
J.BIOCHEMISTRY 112 249-252 (1992).
 
12. OHYAMA, Y., NOSHIRO, M. AND OKUDA, K.
Cloning and expression of cDNA encoding 25-hydroxyvitamin D3 24-hydroxylase.
FEBS LETT. 278 195-198 (1991). 
 
13. AKENO, N., SAIKATSU, S., KAWANE, T. AND HORIUCHI, N.
Mouse vitamin D-24-hydroxylase: molecular cloning, tissue distribution, and
transcriptional regulation by 1alpha,25-dihydroxyvitamin D3.
ENDOCRINOLOGY 138 2233-2240 (1997). 

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. 
 
P450-containing monooxygenase systems primarily fall into 2 major classes:
bacterial/mitochondrial (type I); and microsomal (type II). Alternatively,
P450-containing systems can be classified according to the number of their
protein components [3]: mitochondrial and most bacterial P450 systems have
3 components - an FAD-containing flavoprotein (NADPH or NADH-dependent
reductase), an iron-sulphur protein, and P450; the eukaryotic microsomal 
P450 system contains 2 components - NADPH:P450 reductase (a flavoprotein
containing both FAD and FMN) and P450; and a soluble monooxygenase P450BM-3
from Bacillus megaterium exists as a single polypeptide chain with 2 
functional parts (the haem and flavin domains), and represents a unique 
bacterial one-component system - sequence and functional comparisons show
that these domains are more similar to P450 and the flavoprotein of the
microsomal 2-component P450 monooxygenase system than to the relevant
proteins of the 3-component system [4].
 
Current P450 nomenclature, based on divergent evolution of the P450 
superfamily, was proposed and developed by Nebert et al. [5]. On the basis 
of sequence similarity, all P450s can be categorised into 2 main groups, 
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. 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. 
 
By contrast with the B-class, containing water-soluble haemoproteins, 
most E-class P450s are membrane-bound. Membranous P450s can be divided into
those from the inner mitochondrial membrane (mitochondrial type), and those
from membranes of the endoplasmic reticulum (ER) (microsomal type). In the
mitochondrial P450-containing monooxygenase system, P450 can be reduced by
the 2Fe-2S iron-sulphur protein adrenodoxin, which can accept electrons
from NADPH-dependent adrenodoxin reductase. Both adrenodoxin and
adrenodoxin reductase are soluble, and located in the mitochondrial matrix 
[6]. Microsomal P450s depend on a single NADPH:P450 reductase; the P450s
and the reductase are located on the cytosolic side of the ER membrane, and
are anchored to the membrane by hydrophobic amino-terminal segments [7].  
 
To date, only animal mitochondrial P450s have been sequenced. P450scc
(CYP11A) is responsible for conversion of cholesterol to pregnenolone [8].
P450s from the CYP11B subfamily catalyse 11-beta- or 18-hydroxylation of
steroids [9]. The CYP27 family contain enzymes involved in 25-hydroxylation
of vitamin D3 and sterol 26- and 27-hydroxylation [10]. P450 from pond
snail (CYP10) is highly similar to the mitochondrial P450, although its
cellular location is unknown [11].
 
A cDNA encoding 25-hydroxyvitamin D3 24-hydroxylase (P450cc24) has been
isolated from rat kidney [12]. The cDNA contained a 1542bp open reading
frame encoding 514 amino acids, including an N-terminal presequence typical
of mitochondrial enzymes [12]. The sequence shows less than 30% similarity 
to those of other cytochrome P450s, and hence P450cc24 constitutes a novel
P450 family [12]. The enzyme catalyses the conversion of 25-hydroxyvitamin
D3 and 1-alpha, 25-dihydroxyvitamin D3 to 24,25-dihydroxyvitamin D3 and
1,24,25-trihydroxyvitamin D3, respectively [13].
 
MITP450CC24 is a 5-element fingerprint that provides a signature for the
mammalian CC24 mitochondrial P450. The fingerprint was derived from an 
initial alignment of 3 sequences: the motifs were drawn from short conserved 
regions, focusing on those sections of the alignment that characterise CC24 
P450s but distinguish them from other mitochondrial P450s. A single
iteration on SPTR37_10f was required to reach convergence, no further 
sequences being identifed beyond the starting set. A single partial match
was found, O73684, a chicken 25-hydroxyvitamin D(3) 24-hydroxylase that
matches motifs 1,2 and 4.
Summary Information
   3 codes involving  5 elements
0 codes involving 4 elements
1 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
533333
400000
311010
200000
12345
True Positives
CP24_HUMAN    CP24_MOUSE    CP24_RAT      
True Positive Partials
Codes involving 3 elements
O73684
Sequence Titles
CP24_HUMAN  CYTOCHROME P450-CC24, MITOCHONDRIAL PRECURSOR (EC 1.14.-.-) (P450- CC24) (VITAMI 
CP24_MOUSE CYTOCHROME P450-CC24, MITOCHONDRIAL PRECURSOR (EC 1.14.-.-) (P450- CC24) (VITAMI
CP24_RAT CYTOCHROME P450-CC24, MITOCHONDRIAL PRECURSOR (EC 1.14.-.-) (P450- CC24) (VITAMI

O73684 25-HYDROXYVITAMIN D3 24-HYDROXYLASE - GALLUS GALLUS (CHICKEN).
Scan History
SPTR37_10f 1  30   NSINGLE    
Initial Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
EYHKKYGQIFRMKLGSFD CP24_RAT 88 88 -
EYHKKYGQIFRMKLGSFD CP24_MOUSE 88 88 -
EYHKKYGKIFRMKLGSFE CP24_HUMAN 88 88 -

Motif 2 width=12
Element Seqn Id St Int Rpt
SAFQKKLMKPVE CP24_RAT 160 54 -
SAFQKKLMKPVE CP24_MOUSE 160 54 -
SAFQKKLMKPGE CP24_HUMAN 159 53 -

Motif 3 width=9
Element Seqn Id St Int Rpt
CDERGRIPD CP24_RAT 194 22 -
RDERGRIQD CP24_MOUSE 194 22 -
CDERGHVED CP24_HUMAN 193 22 -

Motif 4 width=11
Element Seqn Id St Int Rpt
RLNTKVWQAHT CP24_RAT 262 59 -
RLNTKVWQAHT CP24_MOUSE 262 59 -
SLNTKVWQGHT CP24_HUMAN 261 59 -

Motif 5 width=10
Element Seqn Id St Int Rpt
SQQPGADFLC CP24_RAT 294 21 -
SQQPGADFLC CP24_MOUSE 294 21 -
SQQPSADFLC CP24_HUMAN 293 21 -
Final Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
EYHKKYGQIFRMKLGSFD CP24_RAT 88 88 -
EYHKKYGQIFRMKLGSFD CP24_MOUSE 88 88 -
EYHKKYGKIFRMKLGSFE CP24_HUMAN 88 88 -

Motif 2 width=12
Element Seqn Id St Int Rpt
SAFQKKLMKPVE CP24_RAT 160 54 -
SAFQKKLMKPVE CP24_MOUSE 160 54 -
SAFQKKLMKPGE CP24_HUMAN 159 53 -

Motif 3 width=9
Element Seqn Id St Int Rpt
CDERGRIPD CP24_RAT 194 22 -
RDERGRIQD CP24_MOUSE 194 22 -
CDERGHVED CP24_HUMAN 193 22 -

Motif 4 width=11
Element Seqn Id St Int Rpt
RLNTKVWQAHT CP24_RAT 262 59 -
RLNTKVWQAHT CP24_MOUSE 262 59 -
SLNTKVWQGHT CP24_HUMAN 261 59 -

Motif 5 width=10
Element Seqn Id St Int Rpt
SQQPGADFLC CP24_RAT 294 21 -
SQQPGADFLC CP24_MOUSE 294 21 -
SQQPSADFLC CP24_HUMAN 293 21 -