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PR01694

Identifier
BAIPRECURSOR  [View Relations]  [View Alignment]  
Accession
PR01694
No. of Motifs
13
Creation Date
06-MAR-2002
Title
Brain-specific angiogenesis inhibitor precursor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00249 GPCRSECRETIN
Literature References
1. ATTWOOD, T.K. AND FINDLAY, J.B.C.
Fingerprinting G protein-coupled receptors.
PROTEIN ENG. 7(2) 195-203 (1994). 
 
2. ISHIHARA T., NAKAMURA S., KAZIRO, Y., TAKAHASHI, T., TAKAHASHI, K.
AND NAGATA, S.
Molecular cloning and expression of a cDNA encoding the secretin receptor.
EMBO J. 10 1635-1641 (1991).
 
3. LIN, H.Y., HARRIS, T.L., FLANNERY, M.S., ARUFFO, A., KAJI, E.H., 
GORN, A., KOLAKOWSKI, L.F., LODISH, H.F. AND GOLDRING, S.R.
Expression cloning of adenylate cyclase-coupled calcitonin receptor.
SCIENCE 254 1022-1024 (1991).
 
4. JUEPPNER, H., ABOU-SAMRA, A.-B., FREEMAN, M., KONG, X.F., 
SCHIPANI, E., RICHARDS, J., KOLALOWSKI, L.F., HOCK, J., POTTS, J.T.,
KRONENBERG, H.M. AND SEGRE, G.E.
A G protein linked receptor for parathyroid hormone and parathyroid
hormone-related peptide.
SCIENCE 254 1024-1026 (1991).
 
5. ISHIHARA, T., SHIGEMOTO, R., MORI, K., TAKAHASHI, K. AND NAGATA, S.
Functional expression and tissue distribution of a novel receptor for
vasoactive intestinal polypeptide.
NEURON 8(4) 811-819 (1992).
 
6. NISHIMORI, H., SHIRATSUCHI, T., URANO, T., KIMURA, Y., KIYONO, K.,
TATSUMI, K., YOSHIDA, S., ONO, M., KUWANO, M., NAKAMURA, Y. AND TOKINO, T.
A novel brain-specific p53-target gene, BAI1, containing thrombospondin type
1 repeats inhibits experimental angiogenesis.
ONCOGENE 15(18) 2145-2150 (1997).
 
7. SHIRATSUCHI, T., NISHIMORI, H., ICHISE, H., NAKAMURA, Y. AND TOKINO, T.
Cloning and characterization of BAI2 and BAI3, novel genes homologous to
brain-specific angiogenesis inhibitor 1 (BAI1).
CYTOGENET.CELL GENET. 79(1-2) 103-108 (1997).

Documentation
G protein-coupled receptors (GPCRs) constitute a vast protein family that 
encompasses a wide range of functions (including various autocrine, para-
crine and endocrine processes). They show considerable diversity at the 
sequence level, on the basis of which they can be separated into distinct 
groups. We use the term clan to describe the GPCRs, as they embrace a group
of families for which there are indications of evolutionary relationship, 
but between which there is no statistically significant similarity in 
sequence [1]. The currently known clan members include the rhodopsin-like 
GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating
pheromone receptors, and the metabotropic glutamate receptor family.
 
The secretin-like GPCRs include secretin [2], calcitonin [3], parathyroid
hormone/parathyroid hormone-related peptides [4] and vasoactive intestinal
peptide [5], all of which activate adenylyl cyclase and the phosphatidyl-
inositol-calcium pathway. The amino acid sequences of the receptors contain
high proportions of hydrophobic residues grouped into 7 domains, in a
manner reminiscent of the rhodopsins and other receptors believed to inter-
act with G proteins. However, while a similar 3D framework has been
proposed to account for this, there is no significant sequence similarity
between these families: the secretin-like receptors thus bear their own
unique '7TM' signature.
 
Three human secretin-like GPCRs that are expressed specifically in the
brain, and appear to have a role in the inhibition of angiogenesis, have
been identified and named BAI (brain-specific angiogenesis inhibitor) 1-3
[6,7]. In addition to the characteristic 7 TM domains, the BAIs also have a
large extracellular domain containing a number of thrombospondin type 1 
repeats - these have been shown to inhibit in vivo angiogenesis induced by
bFGF in rat cornea [6]. BAI1 has been found to be transcriptionally 
regulated by p53 and is absent in many glioblastoma cell lines, suggesting
that it may play an important role in suppression of the disease [6].
 
BAIPRECURSOR is a 13-element fingerprint that provides a signature for the
brain-specific angiogenesis inhibitor precursors. The fingerprint was 
derived from an initial alignment of 3 sequences: the motifs were drawn from
conserved regions spanning virtually the full alignment length, focusing on
those sections that characterise the brain-specific angiogenesis inhibitors
but distinguish them from the rest of the secretin-like superfamily - motif 
1 lies at the N-terminus of the extracellular domain; motifs 2-6 lie in the
C-terminal portion of the extracellular domain, between the thrombospondin
repeats and TM domain 1; motif 7 encodes the first cytoplasmic loop; motif 8
spans the second cytoplasmic loop; motif 9 lies in the second external loop;
motif 10 spans the third external loop; and motifs 11-13 lie at the
C-terminus. A single iteration on SPTR40_18f was required to reach
convergence, no further sequences being identified beyond the starting set.
Summary Information
3 codes involving 13 elements
0 codes involving 12 elements
0 codes involving 11 elements
0 codes involving 10 elements
0 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
0 codes involving 2 elements
Composite Feature Index
133333333333333
120000000000000
110000000000000
100000000000000
90000000000000
80000000000000
70000000000000
60000000000000
50000000000000
40000000000000
30000000000000
20000000000000
12345678910111213
True Positives
BAI1_HUMAN    BAI2_HUMAN    BAI3_HUMAN    
Sequence Titles
BAI1_HUMAN  Brain-specific angiogenesis inhibitor 1 precursor - Homo sapiens (Human). 
BAI2_HUMAN Brain-specific angiogenesis inhibitor 2 precursor - Homo sapiens (Human).
BAI3_HUMAN Brain-specific angiogenesis inhibitor 3 precursor - Homo sapiens (Human).
Scan History
SPTR40_18f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
CTWTLENPDPTKYSIYLK BAI3_HUMAN 55 55 -
CSWTLENPDPTKYSLYLR BAI2_HUMAN 53 53 -
CSWTLRNPDPRRYTLYMK BAI1_HUMAN 68 68 -

Motif 2 width=13
Element Seqn Id St Int Rpt
CPLNATGTTSRRC BAI3_HUMAN 537 464 -
CPPNASGSASRRC BAI2_HUMAN 545 474 -
CPRNATGLILRRC BAI1_HUMAN 604 518 -

Motif 3 width=17
Element Seqn Id St Int Rpt
AFWEQPSFARCISNEYR BAI3_HUMAN 557 7 -
AYWGLPSFARCISHEYR BAI2_HUMAN 565 7 -
AYWEPPTYIRCVSIDYR BAI1_HUMAN 624 7 -

Motif 4 width=20
Element Seqn Id St Int Rpt
GDLLMSVEILRNVTDTFKRA BAI3_HUMAN 614 40 -
GDLLFSVDILRNVTDTFKRA BAI2_HUMAN 622 40 -
GDLLSTIDVLRNMTEIFRRA BAI1_HUMAN 681 40 -

Motif 5 width=10
Element Seqn Id St Int Rpt
ENKEKWEDAQ BAI3_HUMAN 656 22 -
ENKEKWDDAQ BAI2_HUMAN 664 22 -
ENRDKWEEAQ BAI1_HUMAN 723 22 -

Motif 6 width=22
Element Seqn Id St Int Rpt
DINFPMKGRKGMVDWARNSEDR BAI3_HUMAN 717 51 -
DITFPMRGRRGMKDWVRHSEDR BAI2_HUMAN 725 51 -
DISFPMKGWRATGDWAKVPEDR BAI1_HUMAN 783 50 -

Motif 7 width=11
Element Seqn Id St Int Rpt
WRYIRSERSII BAI3_HUMAN 903 164 -
WRFIKSERSII BAI2_HUMAN 946 199 -
WRYIRSERSVI BAI1_HUMAN 973 168 -

Motif 8 width=14
Element Seqn Id St Int Rpt
YMAVTGKIRTRLIR BAI3_HUMAN 967 53 -
YLAVIGRMRTRLVR BAI2_HUMAN 1010 53 -
YMAVTGHLRNRLIR BAI1_HUMAN 1037 53 -

Motif 9 width=18
Element Seqn Id St Int Rpt
GYGTDHYCWLSLEGGLLY BAI3_HUMAN 1006 25 -
GYGTSSYCWLSLEGGLLY BAI2_HUMAN 1049 25 -
GYSTMNYCWLSLEGGLLY BAI1_HUMAN 1076 25 -

Motif 10 width=11
Element Seqn Id St Int Rpt
AMTDKRSILFQ BAI3_HUMAN 1119 95 -
AMTDRRSVLFQ BAI2_HUMAN 1162 95 -
AVTDRRSALFQ BAI1_HUMAN 1156 62 -

Motif 11 width=14
Element Seqn Id St Int Rpt
QIMTDFEKDVDIAC BAI3_HUMAN 1183 53 -
QILSDFEKDVDLAC BAI2_HUMAN 1226 53 -
QLMTDFEKDVDLAC BAI1_HUMAN 1220 53 -

Motif 12 width=15
Element Seqn Id St Int Rpt
SLERRKSRYSDLDFE BAI3_HUMAN 1411 214 -
SLERKKLRYSDLDFE BAI2_HUMAN 1446 206 -
SLERRKSRYAELDFE BAI1_HUMAN 1469 235 -

Motif 13 width=15
Element Seqn Id St Int Rpt
MHTRKRHMELFQELN BAI3_HUMAN 1428 2 -
MHTRKRHSELYHELN BAI2_HUMAN 1462 1 -
MHTRKRHQDMFQDLN BAI1_HUMAN 1486 2 -
Final Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
CTWTLENPDPTKYSIYLK BAI3_HUMAN 55 55 -
CSWTLENPDPTKYSLYLR BAI2_HUMAN 53 53 -
CSWTLRNPDPRRYTLYMK BAI1_HUMAN 68 68 -

Motif 2 width=13
Element Seqn Id St Int Rpt
CPLNATGTTSRRC BAI3_HUMAN 537 464 -
CPPNASGSASRRC BAI2_HUMAN 545 474 -
CPRNATGLILRRC BAI1_HUMAN 604 518 -

Motif 3 width=17
Element Seqn Id St Int Rpt
AFWEQPSFARCISNEYR BAI3_HUMAN 557 7 -
AYWGLPSFARCISHEYR BAI2_HUMAN 565 7 -
AYWEPPTYIRCVSIDYR BAI1_HUMAN 624 7 -

Motif 4 width=20
Element Seqn Id St Int Rpt
GDLLMSVEILRNVTDTFKRA BAI3_HUMAN 614 40 -
GDLLFSVDILRNVTDTFKRA BAI2_HUMAN 622 40 -
GDLLSTIDVLRNMTEIFRRA BAI1_HUMAN 681 40 -

Motif 5 width=10
Element Seqn Id St Int Rpt
ENKEKWEDAQ BAI3_HUMAN 656 22 -
ENKEKWDDAQ BAI2_HUMAN 664 22 -
ENRDKWEEAQ BAI1_HUMAN 723 22 -

Motif 6 width=22
Element Seqn Id St Int Rpt
DINFPMKGRKGMVDWARNSEDR BAI3_HUMAN 717 51 -
DITFPMRGRRGMKDWVRHSEDR BAI2_HUMAN 725 51 -
DISFPMKGWRATGDWAKVPEDR BAI1_HUMAN 783 50 -

Motif 7 width=11
Element Seqn Id St Int Rpt
WRYIRSERSII BAI3_HUMAN 903 164 -
WRFIKSERSII BAI2_HUMAN 946 199 -
WRYIRSERSVI BAI1_HUMAN 973 168 -

Motif 8 width=14
Element Seqn Id St Int Rpt
YMAVTGKIRTRLIR BAI3_HUMAN 967 53 -
YLAVIGRMRTRLVR BAI2_HUMAN 1010 53 -
YMAVTGHLRNRLIR BAI1_HUMAN 1037 53 -

Motif 9 width=18
Element Seqn Id St Int Rpt
GYGTDHYCWLSLEGGLLY BAI3_HUMAN 1006 25 -
GYGTSSYCWLSLEGGLLY BAI2_HUMAN 1049 25 -
GYSTMNYCWLSLEGGLLY BAI1_HUMAN 1076 25 -

Motif 10 width=11
Element Seqn Id St Int Rpt
AMTDKRSILFQ BAI3_HUMAN 1119 95 -
AMTDRRSVLFQ BAI2_HUMAN 1162 95 -
AVTDRRSALFQ BAI1_HUMAN 1156 62 -

Motif 11 width=14
Element Seqn Id St Int Rpt
QIMTDFEKDVDIAC BAI3_HUMAN 1183 53 -
QILSDFEKDVDLAC BAI2_HUMAN 1226 53 -
QLMTDFEKDVDLAC BAI1_HUMAN 1220 53 -

Motif 12 width=15
Element Seqn Id St Int Rpt
SLERRKSRYSDLDFE BAI3_HUMAN 1411 214 -
SLERKKLRYSDLDFE BAI2_HUMAN 1446 206 -
SLERRKSRYAELDFE BAI1_HUMAN 1469 235 -

Motif 13 width=15
Element Seqn Id St Int Rpt
MHTRKRHMELFQELN BAI3_HUMAN 1428 2 -
MHTRKRHSELYHELN BAI2_HUMAN 1462 1 -
MHTRKRHQDMFQDLN BAI1_HUMAN 1486 2 -