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PR00767

Identifier
DBMONOXGNASE  [View Relations]  [View Alignment]  
Accession
PR00767
No. of Motifs
9
Creation Date
07-SEP-1997  (UPDATE 10-JUN-1999)
Title
Dopamine-beta-monooxygenase signature
Database References

PROSITE; PS00084 CU2_MONOOXYGENASE_1; PS00085 CU2_MONOOXYGENASE_2
BLOCKS; BL00084
INTERPRO; IPR000945
Literature References
1. OUAFIK, L.H., STOFFERS, D.A., CAMPBELL, T.A., JOHNSON, R.C., BLOOMQUIST,
B.T., MAINS, R.E. AND EIPPER, B.A.
The multifunctional peptidylglycine alpha-amidating monooxygenase gene:
exon/intron organization of catalytic, processing, and routing domains.
MOL.ENDOCRINOL. 6(10) 1571-1584 (1992).
 
2. STOFFERS, D.A., OUAFIK, L. AND EIPPER, B.A. 
Characterization of novel mRNAs encoding enzymes involved in peptide 
alpha-amidation. 
J.BIOL.CHEM. 266(3) 1701-1707 (1991).
 
3. ROBERTSON, J.G., DESAI, P.R., KUMAR, A., FARRINGTON, G.K., FITZPATRICK,
P.F. AND VILLAFRANCA, J.J.
Primary amino acid sequence of bovine dopamine beta-hydroxylase. 
J.BIOL.CHEM. 265(2) 1029-1035 (1990).

Documentation
Peptidylglycine alpha-amidating monooxygenase (PAM) is a multifunctional
protein found in secretory granules. The protein contains two enzymes that
act sequentially to catalyse the alpha-amidation of neuroendocrine peptides 
[1,2]: peptidylglycine + ascorbate + O(2) = peptidyl(2-hydroxyglycine) + 
dehydroascorbate + H(2)O. The product is unstable and dismutates to
glyoxylate and the corresponding desglycine peptide amide. The first step
of the reaction is catalysed by peptidylglycine alpha-hydroxylating mono-
oxygenase (PHM), and is dependent on copper, ascorbate and molecular oxygen;
peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) catalyses the
second step of the reaction [1]. 
 
Sequence analysis shows the protein to be similar to dopamine-beta-mono-
oxygenases (DBH), a class of ascorbate-dependent enzymes from the 
catecholamine biosynthetic pathway that requires copper as a cofactor and
uses ascorbate as an electron donor. DBH catalyses the conversion of 
dopamine to the neurotransmitter norepinephrine: 3,4-dihydroxyphenethylamine
+ ascorbate + O(2) = noradrenaline + dehydroascorbate + H(2)O.
 
DBH exists in both soluble (in chromaffin granules) and membane bound
forms. The protein functions as a homotetramer. DBH and PAM share a few
regions of sequence similarity, some of which contain clusters of conserved
histidine residues that may be involved in copper binding [3].
 
DBMONOXGNASE is a 9-element fingerprint that provides a signature for
dopamine beta-monooxygenases. The fingerprint was derived from an initial
alignment of 7 sequences: the motifs were drawn from virtually the full
alignment length - motif 4 includes a putative active site tyrosine; and
motif 5 includes the region encoded by PROSITE pattern CU2_MONOOXYGENASE_1
(PS00084), which contains conserved histidine residues that may be involved
in copper binding. A single iteration on OWL29.4 was required to reach
convergence, no further sequences being identified beyond the starting
set. A single partial match was found, DMTBHMR, a Drosophila tyramine-beta-
hydroxylase that fails to make significant matches with motifs 1,2,4 and 6.
 
An update on SPTR37_9f identified a true set of 4 sequences, and 1
partial match.
Summary Information
   4 codes involving  9 elements
0 codes involving 8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
9444444444
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000110
123456789
True Positives
DOPO_BOVIN    DOPO_HUMAN    DOPO_MOUSE    DOPO_RAT      
True Positive Partials
Codes involving 2 elements
Q24549
Sequence Titles
DOPO_BOVIN  DOPAMINE BETA-MONOOXYGENASE PRECURSOR (EC 1.14.17.1) (DOPAMINE BETA- HYDROXYLASE) (DBH) - BOS TAURUS (BOVINE). 
DOPO_HUMAN DOPAMINE BETA-MONOOXYGENASE PRECURSOR (EC 1.14.17.1) (DOPAMINE BETA- HYDROXYLASE) (DBH) - HOMO SAPIENS (HUMAN).
DOPO_MOUSE DOPAMINE BETA-MONOOXYGENASE PRECURSOR (EC 1.14.17.1) (DOPAMINE BETA- HYDROXYLASE) (DBH) - MUS MUSCULUS (MOUSE).
DOPO_RAT DOPAMINE BETA-MONOOXYGENASE PRECURSOR (EC 1.14.17.1) (DOPAMINE BETA- HYDROXYLASE) (DBH) - RATTUS NORVEGICUS (RAT).

Q24549 TYRAMINE-BETA-HYDROXYLASE - DROSOPHILA MELANOGASTER (FRUIT FLY).
Scan History
OWL29_4    1  100  NSINGLE    
SPTR37_9f 2 5 NSINGLE
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
PYHIPLDPEGSLELSWNVSY DOPO_HUMAN 34 34 -
PYHIPLDPEGTLELSWNVSY DOPO_RAT 51 51 -
PFHIPLDPEGTLELSWNISY BOVDBH 28 28 -
PYHIPLDPEGILELSWNVSY JC1346 52 52 -
PYHIPLDPEGSLELSWNVSY HSDBH 34 34 -
PFHIPLDPEGTLELSWNISY BOVDBHZ 3 3 -
PFHIPLDPEGTLELSWNISY DOPO_BOVIN 41 41 -

Motif 2 width=23
Element Seqn Id St Int Rpt
RAGVLFGMSDRGEMENADLIMLW JC1346 86 14 -
KAGVLFGMSDRGELENADLVVLW DOPO_BOVIN 75 14 -
KAGVLFGMSDRGELENADLVVLW DOPO_HUMAN 68 14 -
KAGVLFGMSDRGELENADLVVLW BOVDBH 62 14 -
KAGVLFGMSDRGELENADLVVLW BOVDBHZ 37 14 -
KAGVLFGMSDRGELENADLVVLW HSDBH 68 14 -
RAGVLFGMSDRGEMENADLVMLW DOPO_RAT 85 14 -

Motif 3 width=19
Element Seqn Id St Int Rpt
LLFKRPFGTCDPKDYLIED HSDBH 131 40 -
LLFKRPFGTCDPKDYLIED DOPO_HUMAN 131 40 -
LLFKRPFGTCDPNDYLIED DOPO_BOVIN 138 40 -
LLFKRPFGTCDPNDYLIED BOVDBH 125 40 -
LLFKRPFGTCDPNDYLIED BOVDBHZ 100 40 -
LLFKRPFVTCDPKDYVIED DOPO_RAT 148 40 -
LLFKRPFVTCDPKDYVIED JC1346 149 40 -

Motif 4 width=21
Element Seqn Id St Int Rpt
YWCYVTELPDGFPRHHIVMYE DOPO_BOVIN 223 66 -
YWCYITELPPRFPRHHIIMYE JC1346 234 66 -
YWCYIKELPKGFSRHHIIKYE HSDBH 216 66 -
YWCYVTELPDGFPRHHIVMYE BOVDBHZ 185 66 -
YWCYVTELPDGFPRHHIVMYE BOVDBH 210 66 -
YWCYIKELPKGFSRHHIIKYE DOPO_HUMAN 216 66 -
YWCYITELPLHFPRHHIIMYE DOPO_RAT 233 66 -

Motif 5 width=19
Element Seqn Id St Int Rpt
IVTEGNEALVHHMEVFQCA BOVDBH 232 1 -
IVTEGNEALVHHMEVFQCA JC1346 256 1 -
IVTKGNEALVHHMEVFQCA HSDBH 238 1 -
IVTEGNEALVHHMEVFQCA BOVDBHZ 207 1 -
IVTEGNEALVHHMEVFQCA DOPO_BOVIN 245 1 -
IVTKGNEALVHHMEVFQCA DOPO_HUMAN 238 1 -
IVTEGNEALVHHMEVFQCT DOPO_RAT 255 1 -

Motif 6 width=19
Element Seqn Id St Int Rpt
FNGPCDSKMKPDRLNYCRH DOPO_RAT 282 8 -
FSGPCDSKMKPDRLNYCRH HSDBH 265 8 -
FNGPCDSKMKPDRLNYCRH JC1346 283 8 -
FSGPCDSKMKPQRLNFCRH BOVDBH 259 8 -
FSGPCDSKMKPQRLNFCRH DOPO_BOVIN 272 8 -
FSGPCDSKMKPDRLNYCRH DOPO_HUMAN 265 8 -
FSGPCDSKMKPQRLNFCRH BOVDBHZ 234 8 -

Motif 7 width=20
Element Seqn Id St Int Rpt
VLAAWALGAKAFYYPEEAGL DOPO_HUMAN 284 0 -
VLAAWALGAKAFYYPEEAGL BOVDBH 278 0 -
VLAAWALGAKAFYYPEEAGL BOVDBHZ 253 0 -
VLAAWALGAKAFYYPEEAGL HSDBH 284 0 -
VLAAWALGAKAFYYPKEAGV JC1346 302 0 -
VLAAWALGAKAFYYPEEAGV DOPO_RAT 301 0 -
VLAAWALGAKAFYYPEEAGL DOPO_BOVIN 291 0 -

Motif 8 width=18
Element Seqn Id St Int Rpt
AGIMELGLVYTPVMAIPP HSDBH 348 44 -
AGIMELGLVYTPLMAIPP DOPO_RAT 365 44 -
AGIMELGLVYTPVMAIPP DOPO_HUMAN 348 44 -
AGIMELGLAYTPVMAIPP DOPO_BOVIN 355 44 -
AGIMELGLAYTPVMAIPP BOVDBHZ 317 44 -
AGIMELGLVYTPLMAIPP JC1346 366 44 -
AGIMELGLAYTPVMAIPP BOVDBH 342 44 -

Motif 9 width=21
Element Seqn Id St Int Rpt
LKALYSFAPISMHCNKSSAVR HSDBH 538 172 -
LKALYGFAPISMHCNRSSAVR BOVDBH 532 172 -
LKALYSFAPISMHCNKSSAVR DOPO_HUMAN 538 172 -
LKALYGFAPISMHCNRSSAVR DOPO_BOVIN 545 172 -
LKALYNYAPISVHCNKTSAVR DOPO_RAT 555 172 -
LKALYDYAPISMHCNKTSAVR JC1346 556 172 -
LKALYGFAPISMHCNRSSAVR BOVDBHZ 507 172 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
PYHIPLDPEGTLELSWNVSY DOPO_RAT 51 51 -
PYHIPLDPEGILELSWNVSY DOPO_MOUSE 52 52 -
PYHIPLDPEGSLELSWNVSY DOPO_HUMAN 34 34 -
PFHIPLDPEGTLELSWNISY DOPO_BOVIN 41 41 -

Motif 2 width=23
Element Seqn Id St Int Rpt
RAGVLFGMSDRGEMENADLVMLW DOPO_RAT 85 14 -
RAGVLFGMSDRGEMENADLIMLW DOPO_MOUSE 86 14 -
KAGVLFGMSDRGELENADLVVLW DOPO_HUMAN 68 14 -
KAGVLFGMSDRGELENADLVVLW DOPO_BOVIN 75 14 -

Motif 3 width=19
Element Seqn Id St Int Rpt
LLFKRPFVTCDPKDYVIED DOPO_RAT 148 40 -
LLFKRPFVTCDPKDYVIED DOPO_MOUSE 149 40 -
LLFKRPFGTCDPKDYLIED DOPO_HUMAN 131 40 -
LLFKRPFGTCDPNDYLIED DOPO_BOVIN 138 40 -

Motif 4 width=21
Element Seqn Id St Int Rpt
YWCYITELPLHFPRHHIIMYE DOPO_RAT 233 66 -
YWCYITELPPRFPRHHIIMYE DOPO_MOUSE 234 66 -
YWCYIKELPKGFSRHHIIKYE DOPO_HUMAN 216 66 -
YWCYVTELPDGFPRHHIVMYE DOPO_BOVIN 223 66 -

Motif 5 width=19
Element Seqn Id St Int Rpt
IVTEGNEALVHHMEVFQCT DOPO_RAT 255 1 -
IVTEGNEALVHHMEVFQCA DOPO_MOUSE 256 1 -
IVTKGNEALVHHMEVFQCA DOPO_HUMAN 238 1 -
IVTEGNEALVHHMEVFQCA DOPO_BOVIN 245 1 -

Motif 6 width=19
Element Seqn Id St Int Rpt
FNGPCDSKMKPDRLNYCRH DOPO_RAT 282 8 -
FNGPCDSKMKPDRLNYCRH DOPO_MOUSE 283 8 -
FSGPCDSKMKPDRLNYCRH DOPO_HUMAN 265 8 -
FSGPCDSKMKPQRLNFCRH DOPO_BOVIN 272 8 -

Motif 7 width=20
Element Seqn Id St Int Rpt
VLAAWALGAKAFYYPEEAGV DOPO_RAT 301 0 -
VLAAWALGAKAFYYPKEAGV DOPO_MOUSE 302 0 -
VLAAWALGAKAFYYPEEAGL DOPO_HUMAN 284 0 -
VLAAWALGAKAFYYPEEAGL DOPO_BOVIN 291 0 -

Motif 8 width=18
Element Seqn Id St Int Rpt
AGIMELGLVYTPLMAIPP DOPO_RAT 365 44 -
AGIMELGLVYTPLMAIPP DOPO_MOUSE 366 44 -
AGIMELGLVYTPVMAIPP DOPO_HUMAN 348 44 -
AGIMELGLAYTPVMAIPP DOPO_BOVIN 355 44 -

Motif 9 width=21
Element Seqn Id St Int Rpt
LKALYNYAPISVHCNKTSAVR DOPO_RAT 555 172 -
LKALYDYAPISMHCNKTSAVR DOPO_MOUSE 556 172 -
LKALYSFAPISMHCNKSSAVR DOPO_HUMAN 538 172 -
LKALYGFAPISMHCNRSSAVR DOPO_BOVIN 545 172 -