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PR00466

Identifier
GP91PHOX  [View Relations]  [View Alignment]  
Accession
PR00466
No. of Motifs
6
Creation Date
30-MAR-1996  (UPDATE 07-JUN-1999)
Title
Cytochrome B-245 heavy chain signature
Database References

INTERPRO; IPR000778
Literature References
1. SEGAL, A.W.
The NADPH oxidase and chronic granulomatous disease.
MOL.MED.TODAY 2(3) 129-135 (1996).
 
2. TAYLOR, W.R., JONES, D.T. AND SEGAL, A.W.
A structural model for the nucleotide binding domain of the cytochrome
b-245 beta-chain.
PROTEIN SCI. 2 1675-1685 (1993).

Documentation
Phagocytes form the first line of defence against invasion by micro-
organisms. Engulfing of bacteria by neutrophils is accompanied by the
consumption of large amounts of oxygen - a so-called respiratory burst.
Defects in phagocytosis involving the lack of a respiratory burst give
rise to chronic granulomatous disease (CGD), in which patients are pre-
disposed to infection, often from otherwise non-pathogenic bacteria [1].
 
Regulation of the respiratory burst takes place at the phagocytic vacuole.
The process is mediated by NADPH oxidase, which transports electrons across
the plasma membrane to form superoxide (an oxygen molecule with an extra
electron that is toxic to normal cells) in the vacuole interior. The
electrons are carried across the membrane by a short electron transport
chain in the form of an unusual flavocytochrome b [1].
 
The flavoprotein comprises 2 subunits, p21phox and gp91phox. Gp91phox
has 2 major domains: an N-terminal, hydrophobic domain with a number of
putative transmembrane helices that could associate to form a barrel-like
pore in the membrane [1]; and a more hydrophilic C-terminal domain, which
probably lies on the cytosolic side of the membrane, capping the trans-
membrane structure [1]. The C-terminal domain is similar to a number of
electron-transport proteins, one of which (ferredoxin-NADP reductase)
has provided a structural framework upon which to model this domain [2].
 
Around two thirds of individuals with CGD inherit the disease in an
X-linked, recessive manner. The gene responsible for X-linked CGD is that
coding for the large subunit of flavocytochrome b, gp91phox.
 
GP91PHOX is a 6-element fingerprint that provides a signature for the
cytochrome b-245 heavy chain (gp91phox). The fingerprint was derived from
an initial alignment of 2 sequences: the motifs were drawn from conserved
regions spanning the full alignment length, motifs 1-3 lying in the 
N-terminal domain and motifs 4-6 spanning the C-terminal nucleotide-
binding domain. A single iteration on OWL27.1 was required to reach
convergence, no further sequences being identified beyond the starting set.
Several partial matches were also found, all of which are proteins known
to contain nucleotide-binding domains. 
 
An update on SPTR37_9f identified a true set of 4 sequences, and 10
partial matches.
Summary Information
   4 codes involving  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
9 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
6444444
5000000
4000000
3307098
2100010
123456
True Positives
C24B_HUMAN    C24B_PIG      O46522        Q61093        
True Positive Partials
Codes involving 3 elements
O01793 O04020 O48538 O61213
O80342 O81209 O81210 O81211
O81212
Codes involving 2 elements
O01795
Sequence Titles
C24B_HUMAN  CYTOCHROME B-245 HEAVY CHAIN (P22 PHAGOCYTE B-CYTOCHROME) (NEUTROPHIL CYTOCHROME B, 91 KD POLYPEPTIDE) (CGD91-PHOX) (GP91-PHOX) (CYTOCHROME B(558) BETA CHAIN) (SUPEROXIDE-GENERATING NADPH OXIDASE HEAVY CHAIN SUBUNIT) - HOMO SAPIENS (HUMAN). 
C24B_PIG CYTOCHROME B-245 HEAVY CHAIN (P22 PHAGOCYTE B-CYTOCHROME) (NEUTROPHIL CYTOCHROME B, 91 KD POLYPEPTIDE) (CGD91-PHOX) (GP91-PHOX) (CYTOCHROME B(558) BETA CHAIN) (SUPEROXIDE-GENERATING NADPH OXIDASE HEAVY CHAIN SUBUNIT) - SUS SCROFA (PIG).
O46522 FLAVOCYTOCHROME B SUBUNIT - BOS TAURUS (BOVINE).
Q61093 CYTOCHROME B-245, BETA POLYPEPTIDE (HEME BINDING MEMBRANE GLYCOPROTEIN GP91PHOX) - MUS MUSCULUS (MOUSE).

O01793 SIMILARITY TO NADPH OXIDASES - CAENORHABDITIS ELEGANS.
O04020 HYPOTHETICAL 66.6 KD PROTEIN - ARABIDOPSIS THALIANA (MOUSE-EAR CRESS).
O48538 RBOHAP108 - ARABIDOPSIS THALIANA (MOUSE-EAR CRESS).
O61213 F56C11.1 PROTEIN - CAENORHABDITIS ELEGANS.
O80342 ATRBOH F PROTEIN - ARABIDOPSIS THALIANA (MOUSE-EAR CRESS).
O81209 RESPIRATORY BURST OXIDASE PROTEIN A - ARABIDOPSIS THALIANA (MOUSE-EAR CRESS).
O81210 RESPIRATORY BURST OXIDASE PROTEIN C - ARABIDOPSIS THALIANA (MOUSE-EAR CRESS).
O81211 RESPIRATORY BURST OXIDASE PROTEIN E - ARABIDOPSIS THALIANA (MOUSE-EAR CRESS).
O81212 RESPIRATORY BURST OXIDASE PROTEIN D - ARABIDOPSIS THALIANA (MOUSE-EAR CRESS).

O01795 SIMILAR IN THE AMINO-HALF TO PEROXIDASES AND IN THE CARBOXY-HALF TO NAPDH OXIDASES - CAENORHABDITIS ELEGANS.
Scan History
OWL27_1    1  100  NSINGLE    
SPTR37_9f 2 59 NSINGLE
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
VAWMIALHATIHTIAHLFN S52077 2 2 -
VAWMIALHSAIHTIAHLFN C24B_HUMAN 103 103 -

Motif 2 width=24
Element Seqn Id St Int Rpt
ITGVVITLCLILIITSSTKTIRRS S52077 75 54 -
ITGVVITLCLILIITSSTKTIRRS C24B_HUMAN 176 54 -

Motif 3 width=21
Element Seqn Id St Int Rpt
FEVFWYTHHLFVIFFIGLAIH S52077 100 1 -
FEVFWYTHHLFVIFFIGLAIH C24B_HUMAN 201 1 -

Motif 4 width=14
Element Seqn Id St Int Rpt
PKIAVDGPFGTASE S52077 281 160 -
PKIAVDGPFGTASE C24B_HUMAN 382 160 -

Motif 5 width=18
Element Seqn Id St Int Rpt
LVGAGIGVTPFASILKSV S52077 304 9 -
LVGAGIGVTPFASILKSV C24B_HUMAN 405 9 -

Motif 6 width=19
Element Seqn Id St Int Rpt
PTTRIGVFLCGPEALAETL S52077 426 104 -
PNTRIGVFLCGPEALAETL C24B_HUMAN 527 104 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
VAWMIALHSAIHTIAHLFN C24B_HUMAN 103 103 -
VAWMIALHTAIHTIAHLFN O46522 104 104 -
VAWMIALHTAIHTIAHLFN Q61093 104 104 -
VAWMIALHATIHTIAHLFN C24B_PIG 2 2 -

Motif 2 width=24
Element Seqn Id St Int Rpt
ITGVVITLCLILIITSSTKTIRRS C24B_HUMAN 176 54 -
ITGVVITLCLILIITSSTKTIRRS O46522 177 54 -
ITGIVITLCLILIITSSTKTIRRS Q61093 177 54 -
ITGVVITLCLILIITSSTKTIRRS C24B_PIG 75 54 -

Motif 3 width=21
Element Seqn Id St Int Rpt
FEVFWYTHHLFVIFFIGLAIH C24B_HUMAN 201 1 -
FEVFWYTHHLFVIFFIGLAIH O46522 202 1 -
FEVFWYTHHLFVIFFIGLAIH Q61093 202 1 -
FEVFWYTHHLFVIFFIGLAIH C24B_PIG 100 1 -

Motif 4 width=14
Element Seqn Id St Int Rpt
PKIAVDGPFGTASE C24B_HUMAN 382 160 -
PKIAVDGPFGTASE O46522 383 160 -
PKIAVDGPFGTASE Q61093 383 160 -
PKIAVDGPFGTASE C24B_PIG 281 160 -

Motif 5 width=18
Element Seqn Id St Int Rpt
LVGAGIGVTPFASILKSV C24B_HUMAN 405 9 -
LVGAGIGVTPFASILKSV O46522 406 9 -
LVGAGIGVTPFASILKSV Q61093 406 9 -
LVGAGIGVTPFASILKSV C24B_PIG 304 9 -

Motif 6 width=19
Element Seqn Id St Int Rpt
PNTRIGVFLCGPEALAETL C24B_HUMAN 527 104 -
PNTRIGVFLCGPEALADTL O46522 528 104 -
PNTTIGVFLCGPEALAETL Q61093 528 104 -
PTTRIGVFLCGPEALAETL C24B_PIG 426 104 -