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PR01639

Identifier
PROFILINMAML  [View Relations]  [View Alignment]  
Accession
PR01639
No. of Motifs
6
Creation Date
12-DEC-2001
Title
Mammal profilin signature
Database References
PRINTS; PR00392 PROFILIN
PDB; 1D1J; 1FIK; 1FIL; 1PFL; 1PNE
SCOP; 1D1J; 1FIK; 1FIL; 1PFL; 1PNE
CATH; 1D1J; 1FIK; 1FIL; 1PFL; 1PNE
Literature References
1. GOLDSCHMIDT-CLERMONT, P.J. AND JAMMEY, P.A.
Profilin, a weak CAP for actin and RAS.
CELL 66 419-421 (1991).
 
2. THERIOT, J.A. AND MITCHISON, T.J.
The three faces of profilin.
CELL 75 835-838 (1993).
 
3. METZIER, W.J., FARMER, B.T., CONSTANTINE, K.L., FRIEDRICHS, M.S.,
LAVOLE, T. AND MUELLER, L.
Refined solution structure of human profilin I.
PROTEIN SCI. 4 450-459 (1995).
 
4. ASTURIAS, J.A., ARILLA, M.C., GOMEZ-BAYON, N., MARTINEZ, A. AND 
PALACIOS, R.
Recombinant DNA technology in allergology: cloning and expression of plant 
profilins.
ALLERGOL.IMMUNOPATHOL. 25 127-134 (1997).

Documentation
Profilin is a ubiquitous eukaryotic protein that plays an active role in
the regulation of actin polymerisation. In view of its relatively small
molecular mass (12-15kDa), the functions of profilin are complex and
diverse. Under some circumstances, the protein sequesters actin monomers 
and inhibits filament growth; under others, it "desequesters" actin monomers
and actively promotes filament growth. Desequestering involves binding of
profilin to the fast-growing ends of actin-filaments, which accelerates the
exchange of the adenine nucleotide bound to monomeric actin. ATP-actin
monomers polymerise faster than ADP-actin, and make stiffer filaments. 
Therefore, under conditions of rapid filament reorganisation, where large 
amounts of ADP-actin monomers are produced, and in the presence of a large
excess of ATP over ADP, profilin may actually promote polymerisation [1,2].
 
Profilin is probably also involved in some signalling pathways. It has been
shown to bind tightly and specifically to phosphoinositides (PIP). Its 
binding to PIP2 in lipid bilayers protects PIP2 from hydrolysis by soluble
phosphoinositol-specific phospholipase C. Interestingly, the activity of RAS
is controlled by mitogenically active phospholipids. Two proteins that
regulate the GTPase activity of H-Ras (GAP and GIP) are regulated in 
opposite ways by specific phospholipids, including polyphosphoinositides and 
diacylglycerol. The net result of the phospholipid regulation of these two
proteins is the activation of H-Ras. This suggests that profilin may 
participate in the pathway activated by receptor tyrosine kinases and may
be part of the mechanism by which receptor tyrosine kinases control the
reorganisation of the cytoskeleton. Thus, the regulation of profilin may
be an important link between growth factor signals from the outside world
and the internal state of the actin cytoskeleton [1,2].
 
Profilin homologues are present in organisms ranging from fungi and amoebae,
to trees and mammals; a protein structurally similar to profilin is also
present in the genome of variola and vaccinia viruses. Profilin is, in part,
responsible for cross-reactivities in pollen and food allergic patients.
 
Although the N-terminal region of profilins, which is thought to be involved 
in actin binding, is relatively well conserved, in general, sequence 
similarities between profilins from different species is low. The 
differences are especially pronounced between mammal-specific and all
other profilins. 
 
The structure of profilin has been determined by NMR [3]. The protein folds
into a single compact globular domain, which is bisected by an extended 
anti-parallel beta-sheet. Two alpha-helices (which include the N- and
C-terminal residues) lie on the convex face of the sheet, and 3 smaller
helices lie on the concave face [3,4].
 
PROFILINMAML is a 6-element fingerprint that provides a signature for
mammal profilins. The fingerprint was derived from an initial alignment of
6 sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length, focusing on those sections that characterise the 
mammalian profilins but distinguish them from the rest of the profilin 
family - motif 1 spans alpha-helix 1 and the N-terminus of beta-strand 1;
motif 2 spans strand 2 and helix 2; motif 3 encompasses helix 4 and strand 3;
motif 4 encodes strand 4; motif 5 encodes strand 6; and motif 6 spans the
C-terminus of strand 7 and the N-terminus of helix 5. Three iterations on 
SPTR39_17f were required to reach convergence, at which point a true set
comprising 10 sequences was identified. Three partial matches were also
found, all of which are C-terminal mouse profilin fragments. 
Summary Information
  10 codes involving  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
3 codes involving 2 elements
Composite Feature Index
6101010101010
5000000
4000000
3000000
2000123
123456
True Positives
PRO1_BOVIN    PRO1_HUMAN    PRO1_MOUSE    PRO2_HUMAN    
PRO2_MOUSE Q9EPC6 Q9ES49 Q9ES50
Q9HBK2 Q9JHU7
True Positive Partials
Codes involving 2 elements
Q9DAD6 Q9ES47 Q9ES48
Sequence Titles
PRO1_BOVIN  PROFILIN I - Bos taurus (Bovine).             
PRO1_HUMAN PROFILIN I - Homo sapiens (Human).
PRO1_MOUSE PROFILIN I - Mus musculus (Mouse), and Rattus norvegicus (Rat).
PRO2_HUMAN PROFILIN II - Homo sapiens (Human).
PRO2_MOUSE PROFILIN II - Mus musculus (Mouse).
Q9EPC6 PROFILIN IIA - Rattus norvegicus (Rat).
Q9ES49 PROFILIN II - Mus musculus (Mouse).
Q9ES50 PROFILIN II - Mus musculus (Mouse).
Q9HBK2 PROFILIN IIA (PROFILIN 2) - Homo sapiens (Human).
Q9JHU7 PROFILIN II - Rattus norvegicus (Rat).

Q9DAD6 1700012P12RIK PROTEIN - Mus musculus (Mouse).
Q9ES47 PROFILIN II - Mus musculus (Mouse).
Q9ES48 PROFILIN II - Mus musculus (Mouse).
Scan History
SPTR39_17f 3  100  NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
GWQSYVDNLMCDGCCQE Q9EPC6 3 3 -
GWQSYVDNLMCDGCCQE Q9JHU7 3 3 -
GWQSYVDNLMCDGCCQE PRO2_HUMAN 2 2 -
GWQSYVDNLMCDGCCQE Q9ES49 3 3 -
GWNAYIDSLMADGTCQD PRO1_MOUSE 2 2 -
GWNAYIDNLMADGTCQD PRO1_BOVIN 2 2 -

Motif 2 width=16
Element Seqn Id St Int Rpt
WAATAGGVFQSITPAE Q9EPC6 32 12 -
WAATAGGVFQSITPAE Q9JHU7 32 12 -
WAATAGGVFQSITPIE PRO2_HUMAN 31 12 -
WAATGGGVFQSITPVE Q9ES49 32 12 -
WAAVPGKTFVSITPAE PRO1_MOUSE 31 12 -
WAAVPGKTFVNITPAE PRO1_BOVIN 31 12 -

Motif 3 width=15
Element Seqn Id St Int Rpt
GKDREGFFTNGLTLG Q9EPC6 53 5 -
GKDREGFFTNGLTLG Q9JHU7 53 5 -
GKDREGFFTNGLTLG PRO2_HUMAN 52 5 -
GKDREGFFTNGLTLG Q9ES49 53 5 -
GKDRSSFFVNGLTLG PRO1_MOUSE 52 5 -
GKDRSSFFVNGLTLG PRO1_BOVIN 52 5 -

Motif 4 width=14
Element Seqn Id St Int Rpt
KCSVIRDSLYVDSD Q9EPC6 70 2 -
KCSVIRDSLYVDSD Q9JHU7 70 2 -
KCSVIRDSLYVDGD PRO2_HUMAN 69 2 -
KCSVIRDSLYVDGD Q9ES49 70 2 -
KCSVIRDSLLQDGE PRO1_MOUSE 69 2 -
KCSVIRDSLLQDGE PRO1_BOVIN 69 2 -

Motif 5 width=10
Element Seqn Id St Int Rpt
MDIRTKSQGG Q9EPC6 86 2 -
MDIRTKSQGG Q9JHU7 86 2 -
MDIRTKSQGG PRO2_HUMAN 85 2 -
MDIRTKSQGG Q9ES49 86 2 -
MDLRTKSTGG PRO1_MOUSE 85 2 -
MDLRTKSTGG PRO1_BOVIN 85 2 -

Motif 6 width=14
Element Seqn Id St Int Rpt
MGKEGVHGGGLNKK Q9EPC6 114 18 -
MGKEGVHGGGLNKK Q9JHU7 114 18 -
MGKEGVHGGTLNKK PRO2_HUMAN 113 18 -
MGKEGVHAGTINKK Q9ES49 114 18 -
MGKEGVHGGLINKK PRO1_MOUSE 113 18 -
MGKEGVHGGMINKK PRO1_BOVIN 113 18 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
GWQSYVDNLMCDGCCQE Q9EPC6 3 3 -
GWQSYVDNLMCDGCCQE Q9JHU7 3 3 -
GWQSYVDNLMCDGCCQE PRO2_HUMAN 2 2 -
GWQSYVDNLMCDGCCQE Q9HBK2 3 3 -
GWQSYVDNLMCDGCCQE PRO2_MOUSE 2 2 -
GWQSYVDNLMCDGCCQE Q9ES50 3 3 -
GWQSYVDNLMCDGCCQE Q9ES49 3 3 -
GWNAYIDSLMADGTCQD PRO1_MOUSE 2 2 -
GWNAYIDNLMADGTCQD PRO1_BOVIN 2 2 -
GWNAYIDNLMADGTCQD PRO1_HUMAN 2 2 -

Motif 2 width=16
Element Seqn Id St Int Rpt
WAATAGGVFQSITPAE Q9EPC6 32 12 -
WAATAGGVFQSITPAE Q9JHU7 32 12 -
WAATAGGVFQSITPIE PRO2_HUMAN 31 12 -
WAATAGGVFQSITPIE Q9HBK2 32 12 -
WAATAGGVFQSITPVE PRO2_MOUSE 31 12 -
WAATGGGVFQSITPVE Q9ES50 32 12 -
WAATGGGVFQSITPVE Q9ES49 32 12 -
WAAVPGKTFVSITPAE PRO1_MOUSE 31 12 -
WAAVPGKTFVNITPAE PRO1_BOVIN 31 12 -
WAAVPGKTFVNITPAE PRO1_HUMAN 31 12 -

Motif 3 width=15
Element Seqn Id St Int Rpt
GKDREGFFTNGLTLG Q9EPC6 53 5 -
GKDREGFFTNGLTLG Q9JHU7 53 5 -
GKDREGFFTNGLTLG PRO2_HUMAN 52 5 -
GKDREGFFTNGLTLG Q9HBK2 53 5 -
GKDREGFFTNGLTLG PRO2_MOUSE 52 5 -
GKDREGFFTNGLTLG Q9ES50 53 5 -
GKDREGFFTNGLTLG Q9ES49 53 5 -
GKDRSSFFVNGLTLG PRO1_MOUSE 52 5 -
GKDRSSFFVNGLTLG PRO1_BOVIN 52 5 -
GKDRSSFYVNGLTLG PRO1_HUMAN 52 5 -

Motif 4 width=14
Element Seqn Id St Int Rpt
KCSVIRDSLYVDSD Q9EPC6 70 2 -
KCSVIRDSLYVDSD Q9JHU7 70 2 -
KCSVIRDSLYVDGD PRO2_HUMAN 69 2 -
KCSVIRDSLYVDGD Q9HBK2 70 2 -
KCSVIRDSLYVDGD PRO2_MOUSE 69 2 -
KCSVIRDSLYVDGD Q9ES50 70 2 -
KCSVIRDSLYVDGD Q9ES49 70 2 -
KCSVIRDSLLQDGE PRO1_MOUSE 69 2 -
KCSVIRDSLLQDGE PRO1_BOVIN 69 2 -
KCSVIRDSLLQDGE PRO1_HUMAN 69 2 -

Motif 5 width=10
Element Seqn Id St Int Rpt
MDIRTKSQGG Q9EPC6 86 2 -
MDIRTKSQGG Q9JHU7 86 2 -
MDIRTKSQGG PRO2_HUMAN 85 2 -
MDIRTKSQGG Q9HBK2 86 2 -
MDIRTKSQGG PRO2_MOUSE 85 2 -
MDIRTKSQGG Q9ES50 86 2 -
MDIRTKSQGG Q9ES49 86 2 -
MDLRTKSTGG PRO1_MOUSE 85 2 -
MDLRTKSTGG PRO1_BOVIN 85 2 -
MDLRTKSTGG PRO1_HUMAN 85 2 -

Motif 6 width=14
Element Seqn Id St Int Rpt
MGKEGVHGGGLNKK Q9EPC6 114 18 -
MGKEGVHGGGLNKK Q9JHU7 114 18 -
MGKEGVHGGTLNKK PRO2_HUMAN 113 18 -
MGKEGVHGGGLNKK Q9HBK2 114 18 -
MGKEGVHGGGLNKK PRO2_MOUSE 113 18 -
MGKEGVHGGGLNKK Q9ES50 114 18 -
MGKEGVHAGTINKK Q9ES49 114 18 -
MGKEGVHGGLINKK PRO1_MOUSE 113 18 -
MGKEGVHGGMINKK PRO1_BOVIN 113 18 -
MGKEGVHGGLINKK PRO1_HUMAN 113 18 -