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PR00041

Identifier
LEUZIPPRCREB  [View Relations]  [View Alignment]  
Accession
PR00041
No. of Motifs
6
Creation Date
29-APR-1993  (UPDATE 10-JUN-1999)
Title
cAMP response element binding (CREB) protein signature
Database References

PROSITE; PS00029 LEUCINE_ZIPPER
INTERPRO; IPR001630
Literature References
1. FOULKES, N.S., BORRELLI, E. AND SASSONECORSI, P.
CREM gene - Use of alternative DNA-binding domains generates multiple
antagonists of cAMP-inducd transcription.
CELL 64 80-84 (1991).
 
2. QUINN, P.G. AND GRANNER, D.K.
Cyclic AMP-dependent protein kinase regulates transcription of the 
phosphoenolpyruvate carboxykinase gene but not binding of nuclear factors
to the cyclic AMP regulatory element.
MOL.CELL.BIOL. 10 3357-3364 (1990).
 
3. GONZLAEZ, G.A., YAMAMOTO, K.K., FISCHER, W.H., KARR, D., MENZEL, P.,
BIGGS, W., YALE, W.W. AND MONTMINY, M.R.
A cluster of phosphorylation sites on the cyclic AMP regulated nuclear 
factor creb predicted by its sequence.
NATURE 337 749-752 (1989).

Documentation
Transcription initiation is dictated by the presence and activity of 
specific nuclear factors that bind to DNA regulatory sequences and interact
with the transcriptional machinery. The functions of some of these factors
can be altered by phosphorylation, which affects both DNA binding and
transcriptional activation [1]. Phosphorylation is effected by specific
protein kinases that have been activated by the stimulus of signal
transduction pathways, resulting in the regulation of gene transcription
by modulating the phosphorylation sites of transcription factors.
 
Cyclic AMP (cAMP) regulates the expression of many genes via a conserved
gene promoter element CRE (cAMP response element) [2], which has the
sequence 5'-TGACGTCA-3' [3]. The cAMP response element binding protein
(CREB) is a nuclear factor that is regulated by protein kinase A phos-
phorylation. Transcription is stimulated on binding to the CRE of a phos-
phorylated CREB dimer, which is held together by leucine zippers. Dimer-
isation and transcriptional efficacy have been found to be stimulated by
phosphorylation at several distinct sites, and it has thus been suggested 
[2] that CREB may be regulated by multiple kinases. Sequence analysis of 
the gene has revealed a cluster of protein kinase A, protein kinase C, and 
casein kinase II consensus recognition sites near the N-terminus of the 
protein sequence, and the proximity of these sites to one another indicates
the possibility of interaction in a positive or negative fashion to 
regulate CREB bioactivity.
 
The `leucine zipper' is a structure that is believed to mediate the
function of several eukaryotic gene regulatory proteins. The zipper
consists of a periodic repetition of leucine residues at every seventh
position, and regions containing them appear to span 8 turns of alpha-
helix. The leucine side chains that extend from one helix interact with
those from a similar helix, hence facilitating dimerisation in the form
of a coiled-coil. Leucine zippers are present in many gene regulatory
proteins, including the CREB proteins, Jun/AP1 transcription factors,
fos oncogene and fos-related proteins, C-myc, L-myc and N-myc oncogenes,
and so on.
 
LEUZIPPRCREB is a 6-element fingerprint that provides a signature for the 
leucine zipper and DNA-binding domains characteristic of CREB proteins. 
The fingerprint was derived from an initial alignment of 7 sequences: 
motifs 4 and 5 encode the highly basic DNA-binding domain, while motifs 5
and 6 span the zipper region (cf. PROSITE pattern LEUCINE_ZIPPER (PS00029)).
Two iterations on OWL19.1 were required to reach convergence, at which
point a true set comprising 17 sequences was identified. Two partial
matches were also found: the first (ATF6_HUMAN) is a CREB protein fragment,
and the second (S15664) is an AP1-like transcription factor.
 
An update on SPTR37_9f identified a true set of 15 sequences, and 14
partial matches.
Summary Information
  15 codes involving  6 elements
0 codes involving 5 elements
12 codes involving 4 elements
0 codes involving 3 elements
2 codes involving 2 elements
Composite Feature Index
6151515151515
5000000
43110121111
3000000
2100111
123456
True Positives
ATF1_HUMAN    ATF1_MOUSE    CREA_HUMAN    CREA_MOUSE    
CREB_BOVIN CREB_HUMAN CREB_MOUSE CREB_RAT
CREM_CANFA CREM_MOUSE CREM_RAT O18957
Q14501 Q62347 Q63884
True Positive Partials
Codes involving 4 elements
CREB_CHLVR O75519 Q14503 Q14504
Q14505 Q14506 Q15731 Q26329
Q61442 Q62613 Q63897 Q63925
Codes involving 2 elements
CREB_HYDAT Q14502
Sequence Titles
ATF1_HUMAN  CYCLIC-AMP-DEPENDENT TRANSCRIPTION FACTOR ATF-1 (TREB36 PROTEIN) - HOMO SAPIENS (HUMAN). 
ATF1_MOUSE CYCLIC-AMP-DEPENDENT TRANSCRIPTION FACTOR ATF-1 (TCR-ATF1) - MUS MUSCULUS (MOUSE).
CREA_HUMAN CAMP-RESPONSIVE ELEMENT MODULATOR, ALPHA ISOFORM (CREM) - HOMO SAPIENS (HUMAN).
CREA_MOUSE CAMP-RESPONSIVE ELEMENT MODULATOR, ALPHA ISOFORM (CREM) - MUS MUSCULUS (MOUSE).
CREB_BOVIN CAMP-RESPONSE ELEMENT BINDING PROTEIN 2 (CREB2) - BOS TAURUS (BOVINE).
CREB_HUMAN CAMP-RESPONSE ELEMENT BINDING PROTEIN (CREB) - HOMO SAPIENS (HUMAN).
CREB_MOUSE CAMP-RESPONSE ELEMENT BINDING PROTEIN (CREB) - MUS MUSCULUS (MOUSE).
CREB_RAT CAMP-RESPONSE ELEMENT BINDING PROTEIN (CREB) - RATTUS NORVEGICUS (RAT).
CREM_CANFA CAMP-RESPONSIVE ELEMENT MODULATOR, DELTA ISOFORM - CANIS FAMILIARIS (DOG).
CREM_MOUSE CAMP-RESPONSIVE ELEMENT MODULATOR, DELTA, BETA, AND GAMMA ISOFORMS (CREM) - MUS MUSCULUS (MOUSE).
CREM_RAT CAMP-RESPONSIVE ELEMENT MODULATOR, DELTA ISOFORM - RATTUS NORVEGICUS (RAT).
O18957 CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN - BOS TAURUS (BOVINE).
Q14501 HCREM 1ALPHA PROTEIN - HOMO SAPIENS (HUMAN).
Q62347 TRANSCRIPTION FACTOR/DNA BINDING PROTEIN - MUS MUSCULUS (MOUSE).
Q63884 CREM-EPSILON - MUS MUSCULUS (MOUSE).

CREB_CHLVR CAMP RESPONSE ELEMENT BINDING PROTEIN - CHLOROHYDRA VIRIDISSIMA (HYDRA).
O75519 INDUCIBLE CAMP EARLY REPRESSOR TYPE 1 - HOMO SAPIENS (HUMAN).
Q14503 HCREM 2BETA-A PROTEIN - HOMO SAPIENS (HUMAN).
Q14504 HCREM 2ALPHA-A PROTEIN - HOMO SAPIENS (HUMAN).
Q14505 HCREM 2ALPHA-B PROTEIN - HOMO SAPIENS (HUMAN).
Q14506 HCREM 2BETA-B PROTEIN - HOMO SAPIENS (HUMAN).
Q15731 INDUCIBLE CAMP EARLY REPRESSOR - HOMO SAPIENS (HUMAN).
Q26329 CAMP-REGULATED ENHANCER-BINDING PROTEIN - DROSOPHILA MELANOGASTER (FRUIT FLY).
Q61442 C-AMP-RESPONSIVE-ELEMENT BINDING PROTEIN OMEGA - MUS MUSCULUS (MOUSE).
Q62613 CREMDELTAC-G - RATTUS NORVEGICUS (RAT).
Q63897 TRANSCRIPTIONAL REPRESSOR CREM - RATTUS NORVEGICUS (RAT).
Q63925 ICER - MUS MUSCULUS (MOUSE).

CREB_HYDAT CAMP RESPONSE ELEMENT BINDING PROTEIN - HYDRA ATTENUATA (HYDRA) (HYDRA VULGARIS).
Q14502 HCREM-1 PROTEIN - HOMO SAPIENS (HUMAN).
Scan History
OWL19_1    2  100  NSINGLE    
OWL26_0 1 200 NSINGLE
SPTR37_9f 2 30 NSINGLE
Initial Motifs
Motif 1  width=23
Element Seqn Id St Int Rpt
IGSSQKAAGILARRPSYRKILKD ATF1_HUMAN 10 10 -
VIDSHKRREILSRRPSYRKILNE CREM_MOUSE 102 102 -
VTDSQKRREILSRRPSYRKILND CREB_RAT 118 118 -
VTDSQKRREILSRRPSYRKILND CREB_BOVIN 102 102 -
VIDSHKRREILSRRPSYRKILNE RNCREM 102 102 -
VTDSQKRRGILSRRPSYRKILND A35663 105 105 -
VIDSHKRREILSRRPSYRKILNE C37944 53 53 -

Motif 2 width=16
Element Seqn Id St Int Rpt
TVTVPTPIYQTSSGQY CREB_RAT 167 26 -
TMAVPTSIYQTSTGQY C37944 102 26 -
TVTVPTPIYQTSSGQY CREB_BOVIN 151 26 -
SMSVPTPIYQTSSGQY ATF1_HUMAN 56 23 -
TMAVPTSIYQTSTGQY RNCREM 151 26 -
TVTVPTPIYQTSSGQY A35663 154 26 -
TMAVPTSIYQTSTGQY CREM_MOUSE 151 26 -

Motif 3 width=12
Element Seqn Id St Int Rpt
AASGDVQTYQIR CREB_BOVIN 228 61 -
TATGDMPTYQIR C37944 118 0 -
AATGDMPTYQIR RNCREM 242 75 -
AASGDVQTYQIR A35663 231 61 -
AASGDVQTYQIR CREB_RAT 244 61 -
AATGDMPTYQIR CREM_MOUSE 242 75 -
TASGDMQTYQIR ATF1_HUMAN 133 61 -

Motif 4 width=17
Element Seqn Id St Int Rpt
EEATRKRELRLMKNREA CREM_MOUSE 280 26 -
EEAARKREVRLMKNREA CREB_RAT 280 24 -
EEAARKREVRLMKNREA CREB_BOVIN 264 24 -
EEAARKREVRLMKNREA A35663 267 24 -
EEATRKRELRLMKNREA RNCREM 280 26 -
EEATRKRELRLMKNREA C37944 156 26 -
DDPQLKREIRLMKNREA ATF1_HUMAN 172 27 -

Motif 5 width=21
Element Seqn Id St Int Rpt
RECRRKKKEYVKCLENRVAVL A35663 285 1 -
RECRRKKKEYVKCLENRVAVL RNCREM 298 1 -
KECRRRKKEYVKCLESRVAVL C37944 174 1 -
RECRRKKKEYVKCLENRVAVL CREB_BOVIN 282 1 -
RECRRKKKEYVKCLENRVAVL CREB_RAT 298 1 -
KECRRRKKEYVKCLESRVAVL CREM_MOUSE 298 1 -
RECRRKKKEYVKCLENRVAVL ATF1_HUMAN 189 0 -

Motif 6 width=18
Element Seqn Id St Int Rpt
LENQNKTLIEELKALKDL A35663 305 -1 -
LESQNKTLIEELKALKDL RNCREM 318 -1 -
LEVQNKKLIEELETLKDI C37944 194 -1 -
LENQNKTLIEELKTLKDL ATF1_HUMAN 209 -1 -
LEVQNKKLIEELETLKDI CREM_MOUSE 318 -1 -
LENQNKTLIEELKALKDL CREB_RAT 318 -1 -
LENQNKTLIEELKALKDL CREB_BOVIN 302 -1 -
Final Motifs
Motif 1  width=23
Element Seqn Id St Int Rpt
VIDSHKRREILSRRPSYRKILNE CREA_MOUSE 53 53 -
VIDSHKRREILSRRPSYRKILNE CREM_CANFA 105 105 -
VIDSHKRREILSRRPSYRKILNE Q14501 72 72 -
VIDSHKRREILSRRPSYRKILNE Q63884 102 102 -
VTDSQKRREILSRRPSYRKILND CREB_BOVIN 102 102 -
VTDSQKRREILSRRPSYRKILND Q62347 64 64 -
VTDSQKRREILSRRPSYRKILND O18957 102 102 -
VTDSQKRREILSRRPSYRKILND CREB_RAT 118 118 -
VTDSQKRREILSRRPSYRKILND CREB_MOUSE 118 118 -
VTDSQKRREILSRRPSYRKILND CREB_HUMAN 118 118 -
VIDSHKRREILSRRPSYRKILNE CREM_RAT 102 102 -
VIDSHKRREILSRRPSYRKILNE CREM_MOUSE 102 102 -
VIDSHKRREILSRRPSYRKILNE CREA_HUMAN 56 56 -
IGSSQKAAGILARRPSYRKILKD ATF1_HUMAN 10 10 -
IGSSQKAHGILARRPSYRKILKD ATF1_MOUSE 48 48 -

Motif 2 width=16
Element Seqn Id St Int Rpt
TMAVPTSIYQTSTGQY CREA_MOUSE 102 26 -
TMAVPTSIYQTSTGQY CREM_CANFA 154 26 -
TMAVPTSIYQTSTGQY Q14501 121 26 -
TMAVPTSIYQTSTGQY Q63884 151 26 -
TVTVPTPIYQTSSGQY CREB_BOVIN 151 26 -
TVTVPTPIYQTSSGQY Q62347 113 26 -
TVTVPTPIYQTSSGQY O18957 151 26 -
TVTVPTPIYQTSSGQY CREB_RAT 167 26 -
TVTVPTPIYQTSSGQY CREB_MOUSE 167 26 -
TVTVPTPIYQTSSGQY CREB_HUMAN 167 26 -
TMAVPTSIYQTSTGQY CREM_RAT 151 26 -
TMAVPTSIYQTSTGQY CREM_MOUSE 151 26 -
TMAVPTSIYQTSTGQY CREA_HUMAN 105 26 -
SMSVPTPIYQTSSGQY ATF1_HUMAN 56 23 -
SMSVPAPIYQTSSGQY ATF1_MOUSE 93 22 -

Motif 3 width=12
Element Seqn Id St Int Rpt
AATGDMPTYQIR CREA_MOUSE 130 12 -
AATGDMPTYQIR CREM_CANFA 245 75 -
AATGDMPTYQIR Q14501 149 12 -
AATGDMPTYQIR Q63884 179 12 -
AASGDVQTYQIR CREB_BOVIN 228 61 -
AASGDVQTYQIR Q62347 190 61 -
AASGDVQTYQIR O18957 228 61 -
AASGDVQTYQIR CREB_RAT 244 61 -
AASGDVQTYQIR CREB_MOUSE 244 61 -
AASGDVQTYQIR CREB_HUMAN 244 61 -
AATGDMPTYQIR CREM_RAT 242 75 -
AATGDMPTYQIR CREM_MOUSE 242 75 -
TATGDMPTYQIR CREA_HUMAN 121 0 -
TASGDMQTYQIR ATF1_HUMAN 133 61 -
TASGDMQTYQIR ATF1_MOUSE 169 60 -

Motif 4 width=17
Element Seqn Id St Int Rpt
EEATRKRELRLMKNREA CREA_MOUSE 168 26 -
EEATRKRELRLMKNREA CREM_CANFA 283 26 -
EEATRKRELRLMKNREA Q14501 187 26 -
EEATRKRELRLMKNREA Q63884 217 26 -
EEAARKREVRLMKNREA CREB_BOVIN 264 24 -
EEAARKREVRLMKNREA Q62347 226 24 -
EEAARKREVRLMKNREA O18957 264 24 -
EEAARKREVRLMKNREA CREB_RAT 280 24 -
EEAARKREVRLMKNREA CREB_MOUSE 280 24 -
EEAARKREVRLMKNREA CREB_HUMAN 280 24 -
EEATRKRELRLMKNREA CREM_RAT 280 26 -
EEATRKRELRLMKNREA CREM_MOUSE 280 26 -
EEATRKRELRLMKNREA CREA_HUMAN 159 26 -
DDPQLKREIRLMKNREA ATF1_HUMAN 172 27 -
DDPQLRREIRLMKNREA ATF1_MOUSE 208 27 -

Motif 5 width=21
Element Seqn Id St Int Rpt
RECRRKKKEYVKCLENRVAVL CREA_MOUSE 186 1 -
RECRRKKKEYVKCLENRVAVL CREM_CANFA 301 1 -
RECRRKKKEYVKCLENRVAVL Q14501 205 1 -
RECRRKKKEYVKCLENRVAVL Q63884 235 1 -
RECRRKKKEYVKCLENRVAVL CREB_BOVIN 282 1 -
RECRRKKKEYVKCLENRVAVL Q62347 244 1 -
RECRRKKKEYVKCLENRVAVL O18957 282 1 -
RECRRKKKEYVKCLENRVAVL CREB_RAT 298 1 -
RECRRKKKEYVKCLENRVAVL CREB_MOUSE 298 1 -
RECRRKKKEYVKCLENRVAVL CREB_HUMAN 298 1 -
RECRRKKKEYVKCLENRVAVL CREM_RAT 298 1 -
KECRRRKKEYVKCLESRVAVL CREM_MOUSE 298 1 -
KECRRRKKEYVKCLESRVAVL CREA_HUMAN 177 1 -
RECRRKKKEYVKCLENRVAVL ATF1_HUMAN 189 0 -
RECRRKKKEYVKCLENRVAVL ATF1_MOUSE 226 1 -

Motif 6 width=18
Element Seqn Id St Int Rpt
LENQNKTLIEELKALKDL CREA_MOUSE 206 -1 -
LENQNKTLIEELKALKDL CREM_CANFA 321 -1 -
LENQNKTLIEELKALKDL Q14501 225 -1 -
LENQNKTLIEELKALKDL Q63884 255 -1 -
LENQNKTLIEELKALKDL CREB_BOVIN 302 -1 -
LENQNKTLIEELKALKDL Q62347 264 -1 -
LENQNKTLIEELKALKDL O18957 302 -1 -
LENQNKTLIEELKALKDL CREB_RAT 318 -1 -
LENQNKTLIEELKALKDL CREB_MOUSE 318 -1 -
LENQNKTLIEELKALKDL CREB_HUMAN 318 -1 -
LESQNKTLIEELKALKDL CREM_RAT 318 -1 -
LEVQNKKLIEELETLKDI CREM_MOUSE 318 -1 -
LEVQNKKLIEELETLKDI CREA_HUMAN 197 -1 -
LENQNKTLIEELKTLKDL ATF1_HUMAN 209 -1 -
LENQNKTLIEELKTLKDL ATF1_MOUSE 246 -1 -