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PR00963

Identifier
MARCKS  [View Relations]  [View Alignment]  
Accession
PR00963
No. of Motifs
4
Creation Date
13-AUG-1998  (UPDATE 07-JUN-1999)
Title
MARCKS family signature
Database References

PROSITE; PS00826 MARCKS_1; PS00827 MARCKS_2
BLOCKS; BL00826
INTERPRO; IPR002101
Literature References
1. BLACKSHEAR, P.J.
The MARCKS family of cellular protein kinase C substrates.
J.BIOL.CHEM. 268 1501-1504 (1993).
 
2. THELEN, M., ROSEN, A., NAIRN, A.C. AND ADEREM, A.
Regulation by phosphorylation of reversible association of a myristoylated 
protein kinase C substrate with the plasma membrane. 
NATURE 351 320-322 (1991). 
 
3. HARTWIG, J.H., THELEN, M., ROSEN, A., JANMEY, P.A., NAIRN, A.C.
AND ADEREM, A.
MARCKS is an actin filament crosslinking protein regulated by protein
kinase C and calcium-calmodulin. 
NATURE 356 618-622 (1992).
 
4. UMEKAGE, T. AND KATO, K.
A mouse brain cDNA encodes a novel protein with the protein kinase C
phosphorylation site domain common to MARCKS.
FEBS LETT. 286 147-151 (1991). 

Documentation
Myristoylated alanine-rich C-kinase substrate (MARCKS) is a predominent
cellular substrate for protein kinase C (PKC) that has been implicated in
macrophage activation, neuro-secretion and growth factor-dependent
mitogenesis [1-3]. The N-terminal glycine is the site of myristoylation, 
which allows effective binding of the protein to the plasma membrane, where
it co-localises with PKC [2]. MARCKS binds calmodulin in a calcium-dependent
manner; the region responsible for calcium-binding is highly basic, a domain
of 25 amino acids known as the PSD domain, which also contains the PKC
phosphorylation sites. When not phosphorylated, the PSD domain can bind
to filamentous actin [3]. It is believed that MARCKS may be a regulated 
crossbridge between actin and the plasma membrane; modulation of the actin
cross-linking activity by calmodulin and phosphorylation, represent a
potential convergence of the calcium-calmodulin and PKC signal transduction
pathways in regulation of the actin cytoskeleton [3]. 
 
MARCKS-related protein (MRP) is similar to MARCKS in terms of properties
such as its myristoylation, phosphorylation and calmodulin-binding, and
shares a high degree of sequence similarity. Two regions that show highest
similarity are the kinase C phosphorylation site domain and the N-terminal
region containing the myristoylation site [4]. MARCKS and MRP amino acid 
compositions are similar, but the alanine content of the latter is lower [4].
 
MARCKS is a 4-element fingerprint that provides a signature for the 
myristoylated alanine-rich C-kinase substrate proteins. The fingerprint
was derived from an initial alignment of 5 sequences: the motifs were
drawn from short conserved regions spanning the full alignment length,
motifs 2 and 3 including the regions encoded by PROSITE patterns MARCKS_1
(PS00826) and MARCKS_2 (PS00827), the latter corresponding to the PSD domain.
Two iterations on OWL30.2 were required to reach convergence, at which point
a true set comprising 10 sequences was identified.
 
An update on SPTR37_9f identified a true set of 9 sequences.
Summary Information
9 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
49999
30000
20000
1234
True Positives
MACS_BOVIN    MACS_CHICK    MACS_HUMAN    MACS_MOUSE    
MACS_RAT MRP_HUMAN MRP_MOUSE MRP_RABIT
O93503
Sequence Titles
MACS_BOVIN  MYRISTOYLATED ALANINE-RICH C-KINASE SUBSTRATE (MARCKS) (ACAMP-81) - BOS TAURUS (BOVINE). 
MACS_CHICK MYRISTOYLATED ALANINE-RICH C-KINASE SUBSTRATE (MARCKS) - GALLUS GALLUS (CHICKEN).
MACS_HUMAN MYRISTOYLATED ALANINE-RICH C-KINASE SUBSTRATE (MARCKS) (PROTEIN KINASE C SUBSTRATE, 80 KD PROTEIN, LIGHT CHAIN) (PKCSL) (80K-L PROTEIN) - HOMO SAPIENS (HUMAN).
MACS_MOUSE MYRISTOYLATED ALANINE-RICH C-KINASE SUBSTRATE (MARCKS) - MUS MUSCULUS (MOUSE).
MACS_RAT MYRISTOYLATED ALANINE-RICH C-KINASE SUBSTRATE (MARCKS) - RATTUS NORVEGICUS (RAT).
MRP_HUMAN MARCKS-RELATED PROTEIN (MAC-MARCKS) - HOMO SAPIENS (HUMAN).
MRP_MOUSE MARCKS-RELATED PROTEIN (MAC-MARCKS) (BRAIN PROTEIN F52) - MUS MUSCULUS (MOUSE).
MRP_RABIT MARCKS-RELATED PROTEIN (MAC-MARCKS) - ORYCTOLAGUS CUNICULUS (RABBIT).
O93503 MYRISTOYLATED ALANINE-RICH C KINASE SUBSTRATE - XENOPUS LAEVIS (AFRICAN CLAWED FROG).
Scan History
OWL30_2    2  100  NSINGLE    
SPTR37_9f 2 10 NSINGLE
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
SKTAAKGEATAE MACS_BOVIN 5 5 -
SKTAAKGEAAAE MACS_HUMAN 5 5 -
SKTAAKGEAAAE MACS_CHICK 5 5 -
SSKAPRGDVTAE MRP_RABIT 4 4 -
SSKAPRGDVTAE MRP_MOUSE 4 4 -

Motif 2 width=21
Element Seqn Id St Int Rpt
SPSKANGQENGHVKVNGDASP MACS_BOVIN 26 9 -
SPSKANGQENGHVKVNGDASP MACS_HUMAN 26 9 -
SPSKANGQENGHVKVNGDASP MACS_CHICK 25 8 -
SPAKANGQENGHVKSNGDLTP MRP_RABIT 21 5 -
SPAKANGQENGHVRSNGDLTP MRP_MOUSE 21 5 -

Motif 3 width=22
Element Seqn Id St Int Rpt
KRFSFKKSFKLSGFSFKKNKKE MACS_BOVIN 154 107 -
KRFSFKKSFKLSGFSFKKNKKE MACS_HUMAN 155 108 -
KRFSFKKSFKLSGFSFKKNKKE MACS_CHICK 120 74 -
KKFSFKKPFKLSGLSFKRNRKE MRP_RABIT 89 47 -
KKFSFKKPFKLSGLSFKRNRKE MRP_MOUSE 89 47 -

Motif 4 width=12
Element Seqn Id St Int Rpt
EAQPECSPEAPP MACS_BOVIN 315 139 -
EAQPECSPEAPP MACS_HUMAN 315 138 -
EAPSESSPEGPA MACS_CHICK 265 123 -
EPSTPSGPESGP MRP_RABIT 178 67 -
EPSTPSGPESGP MRP_MOUSE 179 68 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
SKTAAKGEATAE MACS_BOVIN 5 5 -
SKTAAKGEAAAE MACS_HUMAN 5 5 -
SKTAAKGEATAE MACS_MOUSE 5 5 -
SKTAAKGEAAAE MACS_RAT 5 5 -
SKTAAKGEAAAE MACS_CHICK 5 5 -
SKTAAKGEAATA O93503 6 6 -
SSKAPRGDVTAE MRP_HUMAN 4 4 -
SSKAPRGDVTAE MRP_RABIT 4 4 -
SSKAPRGDVTAE MRP_MOUSE 4 4 -

Motif 2 width=21
Element Seqn Id St Int Rpt
SPSKANGQENGHVKVNGDASP MACS_BOVIN 26 9 -
SPSKANGQENGHVKVNGDASP MACS_HUMAN 26 9 -
SPSKANGQENGHVKVNGDASP MACS_MOUSE 26 9 -
SPSKANGQENGHVKVNGDASP MACS_RAT 26 9 -
SPSKANGQENGHVKVNGDASP MACS_CHICK 25 8 -
SPSKANGQENGHVKVNGDASP O93503 27 9 -
SPAKANGQENGHVKSNGDLSP MRP_HUMAN 21 5 -
SPAKANGQENGHVKSNGDLTP MRP_RABIT 21 5 -
SPAKANGQENGHVRSNGDLTP MRP_MOUSE 21 5 -

Motif 3 width=22
Element Seqn Id St Int Rpt
KRFSFKKSFKLSGFSFKKNKKE MACS_BOVIN 154 107 -
KRFSFKKSFKLSGFSFKKNKKE MACS_HUMAN 155 108 -
KRFSFKKSFKLSGFSFKKSKKE MACS_MOUSE 148 101 -
KRFSFKKSFKLSGFSFKKSKKE MACS_RAT 148 101 -
KRFSFKKSFKLSGFSFKKNKKE MACS_CHICK 120 74 -
KRFSFKKSFKLSGFSFKKNKKE O93503 129 81 -
KKFSFKKPFKLSGLSFKRNRKE MRP_HUMAN 89 47 -
KKFSFKKPFKLSGLSFKRNRKE MRP_RABIT 89 47 -
KKFSFKKPFKLSGLSFKRNRKE MRP_MOUSE 89 47 -

Motif 4 width=12
Element Seqn Id St Int Rpt
EAQPECSPEAPP MACS_BOVIN 315 139 -
EAQPECSPEAPP MACS_HUMAN 315 138 -
EPQPECSPEAPP MACS_MOUSE 292 122 -
EPQPECSPEAPP MACS_RAT 292 122 -
EAPSESSPEGPA MACS_CHICK 265 123 -
EATSESSPAADS O93503 274 123 -
EPSTPSGPESGP MRP_HUMAN 174 63 -
EPSTPSGPESGP MRP_RABIT 178 67 -
EPSTPSGPESGP MRP_MOUSE 179 68 -