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UniProt functional annotation for Q9NWT6 | ||
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| UniProt code: Q9NWT6. |
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| Organism: | |
Homo sapiens (Human). |
| Taxonomy: | |
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. |
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| Function: | |
Hydroxylates HIF-1 alpha at 'Asn-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation. {ECO:0000269|PubMed:12042299, ECO:0000269|PubMed:12080085, ECO:0000269|PubMed:17003112, ECO:0000269|PubMed:17573339, ECO:0000269|PubMed:18299578, ECO:0000269|PubMed:19245366, ECO:0000269|PubMed:21177872, ECO:0000269|PubMed:21251231}. |
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| Catalytic activity: | |
Reaction=2-oxoglutarate + L-asparaginyl-[hypoxia-inducible factor alpha subunit] + O2 = (3S)-3-hydroxy-L-asparaginyl-[hypoxia-inducible factor alpha subunit] + CO2 + succinate; Xref=Rhea:RHEA:54268, Rhea:RHEA-COMP:13833, Rhea:RHEA-COMP:13834, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:50347, ChEBI:CHEBI:138107; EC=1.14.11.30; Evidence={ECO:0000269|PubMed:12042299, ECO:0000269|PubMed:12080085, ECO:0000269|PubMed:14701857, ECO:0000269|PubMed:17573339}; |
| Catalytic activity: | |
Reaction=2-oxoglutarate + L-histidyl-[ankyrin-repeat domain protein] + O2 = (3S)-3-hydroxy-L-histidyl-[ankyrin-repeat domain protein] + CO2 + succinate; Xref=Rhea:RHEA:54264, Rhea:RHEA-COMP:13836, Rhea:RHEA- COMP:13837, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:29979, ChEBI:CHEBI:30031, ChEBI:CHEBI:138021; EC=1.14.11.n4; Evidence={ECO:0000269|PubMed:21251231}; |
| Catalytic activity: | |
Reaction=2-oxoglutarate + L-asparaginyl-[ankyrin-repeat domain protein] + O2 = (3S)-3-hydroxy-L-asparaginyl-[ankyrin-repeat domain protein] + CO2 + succinate; Xref=Rhea:RHEA:54272, Rhea:RHEA-COMP:13838, Rhea:RHEA-COMP:13839, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:50347, ChEBI:CHEBI:138107; EC=1.14.11.n4; Evidence={ECO:0000269|PubMed:17003112, ECO:0000269|PubMed:17573339, ECO:0000269|PubMed:18299578, ECO:0000269|PubMed:19245366, ECO:0000269|PubMed:21177872}; |
| Catalytic activity: | |
Reaction=2-oxoglutarate + L-aspartyl-[ankyrin-repeat domain protein] + O2 = (3S)-3-hydroxy-L-aspartyl-[ankyrin-repeat domain protein] + CO2 + succinate; Xref=Rhea:RHEA:54280, Rhea:RHEA-COMP:13843, Rhea:RHEA- COMP:13844, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:29961, ChEBI:CHEBI:30031, ChEBI:CHEBI:138111; EC=1.14.11.n4; Evidence={ECO:0000269|PubMed:21177872}; |
| Cofactor: | |
Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000269|PubMed:12432100, ECO:0000269|PubMed:12446723, ECO:0000269|PubMed:15913349, ECO:0000269|PubMed:17135241, ECO:0000269|PubMed:20396966, ECO:0000269|PubMed:20822901, ECO:0000269|PubMed:21251231, ECO:0000269|PubMed:21460794}; |
| Biophysicochemical properties: | |
Kinetic parameters: KM=100 uM for HIF1A (788-822) peptide {ECO:0000269|PubMed:14701857}; KM=160 uM for HIF2A (832-866) peptide {ECO:0000269|PubMed:14701857}; KM=0.5 uM for Fe(2+) {ECO:0000269|PubMed:14701857}; KM=25 uM for 2-oxoglutarate {ECO:0000269|PubMed:14701857}; KM=260 uM for ascorbate {ECO:0000269|PubMed:14701857}; KM=90 uM for O(2) {ECO:0000269|PubMed:14701857}; Note=The kinetic constants are determined for the recombinant FLAG- His-tagged protein.; |
| Subunit: | |
Homodimer; homodimerization is essential for catalytic activity. Interacts with VHL and HIF1A. Part of a complex with VHL, HIF1A and HDAC1 or HDAC2 or HDAC3. Interacts with NFKB1 and NFKBIA. Interacts with NOTCH1, NOTCH2 and NOTCH3 but not with NOTCH4. Interacts with APBA3; binding inhibits HIF1AN binding to HIF1A. Interacts with TNKS2. Interacts with PPP1R12A. Interacts with ASB4 (By similarity). Interacts with UBE3A. Interacts with ANKS3 (By similarity). Interacts with NECAB3; the interaction is indirect and seems to be mediated by APBA3. {ECO:0000250|UniProtKB:Q8BLR9, ECO:0000269|PubMed:11641274, ECO:0000269|PubMed:12432100, ECO:0000269|PubMed:12446723, ECO:0000269|PubMed:12482756, ECO:0000269|PubMed:14701857, ECO:0000269|PubMed:15913349, ECO:0000269|PubMed:17003112, ECO:0000269|PubMed:17135241, ECO:0000269|PubMed:17573339, ECO:0000269|PubMed:19245366, ECO:0000269|PubMed:19726677, ECO:0000269|PubMed:20396966, ECO:0000269|PubMed:20822901, ECO:0000269|PubMed:21177872, ECO:0000269|PubMed:21251231, ECO:0000269|PubMed:21460794, ECO:0000269|PubMed:22645313, ECO:0000269|PubMed:26948053}. |
| Subcellular location: | |
Nucleus. Cytoplasm. Cytoplasm, perinuclear region. Note=Mainly cytoplasmic localization, but interaction with NOTCH1 results in nuclear localization and interaction with ABPA3 results in perinuclear localization in macrophages. |
| Mass spectrometry: | |
Mass=40566; Method=Electrospray; Evidence={ECO:0000269|PubMed:15239670}; |
Annotations taken from UniProtKB at the EBI.