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PR01749

Identifier
AP2ATNSCPFCT  [View Relations]  [View Alignment]  
Accession
PR01749
No. of Motifs
3
Creation Date
22-MAY-2002
Title
Transcription factor AP-2 alpha signature
Database References
PRINTS; PR01748 AP2TNSCPFCT
MIM; 107580
Literature References
1. WILLIAMS, T. AND TJIAN, R.
Analysis of the DNA-binding and activation properties of the human
transcription factor AP-2.
GENES DEV. 5 670-682 (1991).
 
2. WILLIAMS, T. AND TJIAN, R.
Characterization of a dimerization motif in AP-2 and its function in
heterologous DNA-binding proteins.
SCIENCE 251 1067-1071 (1991).
 
3. HILGER-EVERSHEIM, K., MOSER, M., SCHORLE, H. AND BUETTNER, R. 
Regulation roles of AP-2 transcription factors in vertebrate development, 
apoptosis and cell-cycle control, 
GENE 260 1-12 (2000).
 
4. JEAN, D., GERSHENWALD, J., HUANG, S., LUCA, M., HUDSON, M., TAINSKY, M.
AND BAR-ELI, M.
Loss of AP-2 results in up-regulation of MCAM/MUC18 and an increase in tumor
growth and metastasis of human melanoma cells.
J.BIOL.CHEM. 273 16501-16508 (1998).
 
5. ANTTILA, M., KELLOKOSKI, J., MOISIO, K., MITCHELL, P., SAARIKOSKI, S., 
SYRJANEN, K. AND KOSMA, V.
Expression of transcription factor AP-2alpha predicts survival in epithelial
ovarian cancer.
BR.J.CANCER 82 1974-1983 (2000).
 
6. MITCHELL P., WANG, C. AND TJIAN, R.
Positive and negative regulation of transcription in vitro: enhancer-binding
protein AP-2 is inhibited by SV40 T antigen.
CELL 50 847-861 (1987).
 
7. ZHANG, J., HAGOPIAN-DONALDSON, S., SERBEDZIJA, G., ELSEMORE, J., 
PLEHN-DUJOWICH, D., MCMAHON, A., FLAVELL, R. AND WILLIAMS, T.
Neural tube, skeletal and body wall defects in mice lacking transcription 
factor AP-2.
NATURE 381 238-241 (1996).
 
8. DAVIES, A., MIRZA, G., FLINTER, F. AND RAGOUSSIS, J.
An interstitial deletion of 6p24-p25 proximal to the FKHL7 locus and 
including AP-2-alpha that affects anterior eye chamber development. 
J.MED.GENET. 36 708-710 (1999).

Documentation
Activator protein-2 (AP-2) transcription factors constitute a family of
closely related and evolutionarily conserved proteins that bind to the DNA 
consensus sequence GCCNNNGGC and stimulate target gene transcription [1,2].
Four different isoforms of AP-2 have been identifed in mammals, termed AP-2
alpha, beta, gamma and delta. Each family member shares a common structure, 
possessing a proline/glutamine-rich domain in the N-terminal region, which 
is responsible for transcriptional activation [1], and a helix-span-helix
domain in the C-terminal region, which mediates dimerisation and site-
specific DNA binding [2].
 
The AP-2 family have been shown to be critical regulators of gene expression
during embryogenesis. They regulate the development of facial prominence and
limb buds, and are essential for cranial closure and development of the lens
[3]; they have also been implicated in tumorigenesis. AP-2 protein 
expression levels have been found to affect cell transformation, tumour 
growth and metastasis, and may predict survival in some types of cancer [4,5].
 
AP-2 alpha was initially isolated from human HeLa cells [6]. The protein was
shown to bind to enhancer regions of the SV40 and human metallothionein IIA 
promoters, and to stimulate RNA synthesis [6]. AP-2 alpha gene knockout in 
mice causes neural-tube defects during embryogenesis, leading to craniofacial
abnormalities and anencephaly [7]. In humans, deletion of chromosome 6
region 6p24-p25, which includes the AP-2 alpha gene, is associated with
microphthalmia, corneal clouding and a number of other dysmorphic features, 
including hypertelorism, micrognathia, dysplastic ears, thin limbs, and 
congenital cardiac defects [8].
 
AP2ATNSCPFCT is a 3-element fingerprint that provides a signature for
transcription factor AP-2 alpha proteins. The fingerprint was derived from
an initial alignment of 6 sequences: the motifs were drawn from conserved 
regions in the N-terminal half of the alignment, focusing on those sections
that characterise AP-2 alpha but distinguish it from other family members - 
motifs 1-3 span the transcriptional activation domain. Two iterations on
SPTR40_20f were required to reach convergence, at which point a true set
comprising 10 sequences was identified. 
Summary Information
10 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3101010
2000
123
True Positives
AP2A_HUMAN    AP2A_MOUSE    AP2A_RAT      AP2A_SHEEP    
O13111 Q8UVE5 Q8UVE6 Q91867
Q96SH0 Q96SH1
Sequence Titles
AP2A_HUMAN  Transcription factor AP-2 alpha (AP2-alpha) (Activating enhancer- binding protein 2 alpha) (AP-2 transcription factor) (Activator protein-2) (AP-2) - Homo sapiens (Human). 
AP2A_MOUSE Transcription factor AP-2 alpha (AP2-alpha) (Activating enhancer- binding protein 2 alpha) (Activator protein-2) (AP-2) - Mus musculus (Mouse).
AP2A_RAT Transcription factor AP-2 alpha (AP2-alpha) (Activating enhancer- binding protein 2 alpha) (Activator protein-2) (AP-2) - Rattus norvegicus (Rat).
AP2A_SHEEP Transcription factor AP-2 alpha (AP2-alpha) (Activating enhancer- binding protein 2 alpha) (Activator protein-2) (AP-2) - Ovis aries (Sheep).
O13111 AP-2 TRANSCRIPTION FACTOR - Gallus gallus (Chicken).
Q8UVE5 TRANSCRIPTION FACTOR AP2 ALPHA 2 - Brachydanio rerio (Zebrafish) (Zebra danio).
Q8UVE6 TRANSCRIPTION FACTOR AP2 ALPHA 1 - Brachydanio rerio (Zebrafish) (Zebra danio).
Q91867 TRANSCRIPTION FACTOR - Xenopus laevis (African clawed frog).
Q96SH0 DJ290I10.2.2 (TRANSCRIPTION FACTOR AP-2 ALPHA (ACTIVATING ENHANCER-BINDING PROTEIN 2 ALPHA), ISOFORM 2) - Homo sapiens (Human).
Q96SH1 DJ290I10.2.1 (TRANSCRIPTION FACTOR AP-2 ALPHA (ACTIVATING ENHANCER-BINDING PROTEIN 2 ALPHA), ISOFORM 1) - Homo sapiens (Human).
Scan History
SPTR40_20f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
GTARLPQLGTVGQSP Q96SH1 26 26 -
GTARLPQLGTVGQSP Q96SH0 26 26 -
GTGRLPQLGSVGQSP Q91867 13 13 -
GTARLPQLGSVGQSP Q8UVE5 30 30 -
GTARLPQLGSVGQSP Q8UVE6 24 24 -
GTARLPQLGAVGQSP O13111 24 24 -

Motif 2 width=11
Element Seqn Id St Int Rpt
HAQPQPQHPGW Q96SH1 88 47 -
HAQPQPQHPGW Q96SH0 88 47 -
HAQPQPQHPGW Q91867 75 47 -
HAQSQPQHPGW Q8UVE5 92 47 -
HAQSQPQHPGW Q8UVE6 86 47 -
HTQPQPQHPAW O13111 86 47 -

Motif 3 width=12
Element Seqn Id St Int Rpt
GLLHTHRGLPHQ Q96SH1 108 9 -
GLLHTHRGLPHQ Q96SH0 108 9 -
SLLHTHRGLPHQ Q91867 95 9 -
SLLHQHRGLPHQ Q8UVE5 112 9 -
SLLHQHRGLPHQ Q8UVE6 106 9 -
SLLHAHRGLPHQ O13111 106 9 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
GTARLPQLGTVGQSP AP2A_HUMAN 24 24 -
GTARLPQLGTVGQSP Q96SH1 26 26 -
GTARLPQLGTVGQSP Q96SH0 26 26 -
GTARLPQLGTVGQSP AP2A_SHEEP 78 78 -
GTARLPQLGTVGQSP AP2A_RAT 24 24 -
GTARLPQLGTVGQSP AP2A_MOUSE 24 24 -
GTGRLPQLGSVGQSP Q91867 13 13 -
GTARLPQLGSVGQSP Q8UVE5 30 30 -
GTARLPQLGSVGQSP Q8UVE6 24 24 -
GTARLPQLGAVGQSP O13111 24 24 -

Motif 2 width=11
Element Seqn Id St Int Rpt
HAQPQPQHPGW AP2A_HUMAN 86 47 -
HAQPQPQHPGW Q96SH1 88 47 -
HAQPQPQHPGW Q96SH0 88 47 -
HAQPQPQHPGW AP2A_SHEEP 140 47 -
HAQPQPQHPGW AP2A_RAT 86 47 -
HAQPQPQHPGW AP2A_MOUSE 86 47 -
HAQPQPQHPGW Q91867 75 47 -
HAQSQPQHPGW Q8UVE5 92 47 -
HAQSQPQHPGW Q8UVE6 86 47 -
HTQPQPQHPAW O13111 86 47 -

Motif 3 width=12
Element Seqn Id St Int Rpt
GLLHTHRGLPHQ AP2A_HUMAN 106 9 -
GLLHTHRGLPHQ Q96SH1 108 9 -
GLLHTHRGLPHQ Q96SH0 108 9 -
GLLHTHRGLPHQ AP2A_SHEEP 160 9 -
GLLHTHRGLPHQ AP2A_RAT 106 9 -
GLLHTHRGLPHQ AP2A_MOUSE 106 9 -
SLLHTHRGLPHQ Q91867 95 9 -
SLLHQHRGLPHQ Q8UVE5 112 9 -
SLLHQHRGLPHQ Q8UVE6 106 9 -
SLLHAHRGLPHQ O13111 106 9 -