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PR01080

Identifier
HYPOXIAIF1A  [View Relations]  [View Alignment]  
Accession
PR01080
No. of Motifs
4
Creation Date
25-FEB-1999  (UPDATE 07-JUN-1999)
Title
Hypoxia-inducible factor-1 alpha signature
Database References

INTERPRO; IPR001321
Literature References
1. SRINIVAS, V., ZHU, X., SALCEDA, S., NAKAMURA, R. AND CARO, J.
Hypoxia-inducible factor 1 (HIF-1) is a non-heme iron protein. Implications
for oxygen sensing.
J.BIOL.CHEM. 273 18019-18022 (1988).
 
2. WANG, G.L., JIANG, B.-H., RUE, E.A. AND SEMENZA, G.L.
Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer
regulated by cellular O2 tension.
PROC.NATL.ACAD.SCI.U.S.A. 92 5510-5514 (1995).
 
3. ZELZER, E., LEVY, Y., KAHANA, C., SHILO, B-Z., RUBINSTEIN, M. AND 
COHEN, B.
Insulin induces transcription of target genes through the hypoxia-inducible
factor HIF-1alpha/ARNT.
EMBO J. 17 5085-5094 (1998).
 
4. DANG, C.V. AND SEMENZA, G.L.
Oncogenic alterations of metabolism.
TRENDS BIOCHEM.SCI. 24 68-72 (1999).
 
5. CARMELIET, P., DOR, Y., HERBERT, J-M., FUKUMURA, D.,  BRUSSELMANS, K.,
DEWERCHIN, M., NEEMAN, M., BONO, F., ABRAMOVITCH, R., MAXWELL, P., KOCH,
C.J., RATCLIFFE, P., MOONS, L., JAIN, R.K., COLLEN, D. AND KESHERT E.
Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and
tumour angiogenesis.
NATURE 394 485-490 (1998).

Documentation
Hypoxia inducible factor 1 alpha (HIF-1alpha) is a basic-helix-loop-helix-
PAS (bHLH-PAS) protein. It is an obligatory component of hypoxia-inducible
factor 1 (HIF-1), which exists as a heterodimer of HIF-1alpha and another
bHLH-PAS protein, the arylhydrocarbon receptor nuclear translocator
(HIF-1beta, ARNT) [1,2]. HIF-1 acts to regulate the response to hypoxia,
both at the cellular and system (body) level. On binding to DNA, it increases
the expression of genes that encode glycolytic enzymes, certain glucose
transporters, erythropoietin, and vascular endothelial growth factor
(VEGF). Thus it acts at the cellular level to promote glycolysis, and at the
organ and body level to promote red blood cell production, and formation of
new blood vessels. Besides being stimulated by low oxygen conditions, HIF-1
activity has also been found to be stimulated by insulin and insulin-like
growth factor-1; however, the mechanism(s) whereby any of these agents can
promote its activity remain to be determined [3].
 
HIF-1 induction has also been implicated in the vascularisation of tumours,
which depend for their survival on the recruitment of new blood microvessels,
in part through angiogenic factors such as VEGF. Furthermore, recent
molecular studies of cancer have suggested that HIF-1alpha may have a role
in regulating hypoxic control of cell growth and apoptosis, suggesting there
may be an interplay between it and tumour supressors such as p53, and other
apoptotic regulators, including p21 and Bcl-2 [4,5].
 
HYPOXIAIF1A is a 4-element fingerprint that provides a signature for hypoxia
inducible factor 1 alpha (HIF-1alpha). The fingerprint was derived from an
initial alignment of 2 sequences: the motifs were drawn from conserved
regions within the N-terminal half of the alignment - motif 1 lies between 
PAS repeats 1 and 2; and motifs 2-4 reside between the PAC-motif and a
poly-threonine motif. Two iterations on OWL31.1 were required to reach 
convergence, at which point a true set comprising 8 sequences was 
identified.
 
An update on SPTR37_9f identified a true set of 3 sequences.
Summary Information
3 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
43333
30000
20000
1234
True Positives
HIFA_HUMAN    HIFA_MOUSE    O35800        
Sequence Titles
HIFA_HUMAN  HYPOXIA-INDUCIBLE FACTOR 1 ALPHA (HIF-1 ALPHA) (ARNT INTERACTING PROTEIN) (MEMBER OF PAS PROTEIN 1) (MOP1) (HIF1 ALPHA) - HOMO SAPIENS (HUMAN). 
HIFA_MOUSE HYPOXIA-INDUCIBLE FACTOR 1 ALPHA (HIF-1 ALPHA) (ARNT INTERACTING PROTEIN) - MUS MUSCULUS (MOUSE).
O35800 HYPOXIA-INDUCIBLE FACTOR 1 - RATTUS NORVEGICUS (RAT).
Scan History
OWL31_1    2  150  NSINGLE    
SPTR37_9f 2 4 NSINGLE
Initial Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
YDTNSNQPQCGYKKPPMTCLVLIC HIFA_MOUSE 201 201 -
YDTNSNQPQCGYKKPPMTCLVLIC HIFA_HUMAN 201 201 -

Motif 2 width=19
Element Seqn Id St Int Rpt
VLKPVESSDMKMTQLFTKV HIFA_MOUSE 360 135 -
VLKPVESSDMKMTQLFTKV HIFA_HUMAN 360 135 -

Motif 3 width=19
Element Seqn Id St Int Rpt
DTETEDQQLEDVPLYNDVM HIFA_MOUSE 417 38 -
DTETDDQQLEEVPLYNDVM HIFA_HUMAN 417 38 -

Motif 4 width=21
Element Seqn Id St Int Rpt
ETPKPLRSSADPALNQEVALK HIFA_MOUSE 456 20 -
ETPKPLRSSADPALNQEVALK HIFA_HUMAN 457 21 -
Final Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
YDTNSNQPQCGYKKPPMTCLVLIC HIFA_MOUSE 201 201 -
YDTSSNQPQCGYKKPPMTCLVLIC O35800 201 201 -
YDTNSNQPQCGYKKPPMTCLVLIC HIFA_HUMAN 201 201 -

Motif 2 width=19
Element Seqn Id St Int Rpt
VLKPVESSDMKMTQLFTKV HIFA_MOUSE 360 135 -
VLKPVESSDMKMTQLFTKV O35800 360 135 -
VLKPVESSDMKMTQLFTKV HIFA_HUMAN 360 135 -

Motif 3 width=19
Element Seqn Id St Int Rpt
DTETEDQQLEDVPLYNDVM HIFA_MOUSE 417 38 -
DTETEDQQLEDVPLYNDVM O35800 417 38 -
DTETDDQQLEEVPLYNDVM HIFA_HUMAN 417 38 -

Motif 4 width=21
Element Seqn Id St Int Rpt
ETPKPLRSSADPALNQEVALK HIFA_MOUSE 456 20 -
ETPKPLRSSADPALNQEVALK O35800 456 20 -
ETPKPLRSSADPALNQEVALK HIFA_HUMAN 457 21 -