Basic-helix-loop-helix-PAS protein MOP1;ARNT-interacting protein;Member of PAS protein 1;Class E basic helix-loop-helix protein 78(bHLHe78);PAS domain-containing protein 8;
Organism:
Human (Homo sapiens).
General Annotation
Sub Unit:
Interacts with the HIF1A beta/ARNT subunit; heterodimerization is required for DNA binding. Interacts with COPS5; the interaction increases the transcriptional activity of HIF1A through increased stability (By similarity). Interacts with EP300 (via TAZ-type 1 domains); the interaction is stimulated in response to hypoxia and inhibited by CITED2. Interacts with CREBBP (via TAZ-type 1 domains). Interacts with NCOA1, NCOA2, APEX and HSP90. Interacts (hydroxylated within the ODD domain) with VHLL (via beta domain); the interaction, leads to polyubiquitination and subsequent HIF1A proteasomal degradation. During hypoxia, sumoylated HIF1A also binds VHL; the interaction promotes the ubiquitination of HIF1A. Interacts with SENP1; the interaction desumoylates HIF1A resulting in stabilization and activation of transcription. Interacts (Via the ODD domain) with ARD1A; the interaction appears not to acetylate HIF1A nor have any affect on protein stability, during hypoxia. Interacts with RWDD3; the interaction enhances HIF1A sumoylation. Interacts with TSGA10 (By similarity). Interacts with RORA (via the DNA binding domain); the interaction enhances HIF1A transcription under hypoxia through increasing protein stability. Interaction with PSMA7 inhibits the transactivation activity of HIF1A under both normoxic and hypoxia-mimicking conditions. Interacts with USP20. Interacts with GNB2L1/RACK1; promotes HIF1A ubiquitination and proteasome-mediated degradation.
Function:
Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions activates the transcription of over 40 genes, including, erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP.
Subcellular Location:
Cytoplasm
Nucleus
Cytoplasmic in normoxia, nuclear translocation in response to hypoxia. Colocalizes with SUMO1 in the nucleus, under hypoxia.
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Cited for: FUNCTION;SUBCELLULAR LOCATION;TISSUE SPECIFICITY;INDUCTION
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Cited for: NUCLEOTIDE SEQUENCE [MRNA];PROTEIN SEQUENCE OF 166-170; 259-289 AND 771-781
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Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3);ALTERNATIVE SPLICING
6.
"HIF1a sequence in the Quechua, a high altitude population." Rupert J.L.
,
Hochachka P.W.
Submitted (1999-11) to the EMBL/GenBank/DDBJ databases
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Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]
"Hypoxia-inducible factor-1 alpha variant isolated from human liver tissue." Tanaka S.
,
Sugimachi K.
Submitted (2001-10) to the EMBL/GenBank/DDBJ databases
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Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)
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Cited for: IDENTIFICATION IN COMPLEX WITH EP300 AND CREBBP;INTERACTION WITH EP300
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Cited for: TRANSACTIVATION DOMAINS NTAD AND CTAD;INTERACTION WITH APEX;MUTAGENESIS OF CYS-800
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Cited for: INTERACTION WITH VHL AND ARNT;MUTAGENESIS OF LYS-532; LYS-538; LYS-547 AND LYS-719
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Cited for: MUTAGENESIS OF SER-551 AND THR-552;UBIQUITINATION
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Cited for: HYDROXYLATION AT PRO-402 AND PRO-564;UBIQUITINATION;INTERACTION WITH THE VHLE COMPLEX;FUNCTION;MUTAGENESIS OF PRO-394; LEU-397; LEU-400; PRO-402 AND PRO-564
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Cited for: UBIQUITINATION;FUNCTION;HYDROXYLATION AT PRO-564
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Cited for: HYDROXYLATION AT ASN-803;IDENTIFICATION BY MASS SPECTROMETRY
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Cited for: HYDROXYLATION AT PRO-564;IDENTIFICATION BY MASS SPECTROMETRY
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Cited for: S-NITROSYLATION AT CYS-800;MUTAGENESIS OF CYS-800
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Cited for: SUMOYLATION AT LYS-391 AND LYS-477;FUNCTION;MUTAGENESIS OF LYS-389; LYS-391; LYS-392; LYS-442; LYS-460; LYS-477; LYS-532; LYS-538 AND LYS-547
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Cited for: UBIQUITINATION;DEUBIQUITINATION BY USP20;INTERACTION WITH USP20
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Cited for: FUNCTION;INTERACTION WITH EP300 IN THE HIF1A/EP300/CREBBP COMPLEX;MUTAGENESIS OF ASN-803
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Cited for: UBIQUITINATION;HYDROXYLATION;FUNCTION;INTERACTION WITH CBPP;IDENTIFICATION BY MASS SPECTROMETRY;MUTAGENESIS OF ASN-803
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Cited for: SUMOYLATION AT LYS-391 AND LYS-477;FUNCTION;MUTAGENESIS OF LYS-377; LYS-391; LYS-477 AND LYS-532
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Cited for: UBIQUITINATION AT LYS-532; LYS-538 AND LYS-547;INTERACTION WITH VHL;MUTAGENESIS OF PRO-402; LYS-532; LYS-538; LYS-547 AND PRO-564
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Cited for: PHOSPHORYLATION AT SER-551; THR-555; SER-576; SER-589 AND SER-657;MUTAGENESIS OF SER-576 AND SER-657
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Cited for: PHOSPHORYLATION AT SER-247 BY CSNK1D/CK1;MUTAGENESIS OF SER-247;INTERACTION WITH ARNT
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Cited for: ACETYLATION;DEACETYLATION AT LYS-709 BY SIRT2;HYDROXYLATION;INTERACTION WITH SIRT2 AND EGLN1;MUTAGENESIS OF PRO-402; PRO-564 AND LYS-709
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Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 775-826 IN COMPLEX WITH HIF1AN
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Cited for: STRUCTURE BY NMR OF 786-826 IN COMPLEX WITH 302-418 OF EP300
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Cited for: STRUCTURE BY NMR OF 776-826 IN COMPLEX WITH 345-439 OF CREBBP
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Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 556-575 IN COMPLEX WITH TCEB1; TCEB2 AND 54-213 OF VHL
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Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 549-582 IN COMPLEX WITH 17-112 OF TCEB1; TCEB2 AND 52-213 OF VHL