##gff-version 3 Q16665 UniProtKB Chain 1 826 . . . ID=PRO_0000127220;Note=Hypoxia-inducible factor 1-alpha Q16665 UniProtKB Domain 17 70 . . . Note=BHLH;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00981 Q16665 UniProtKB Domain 85 158 . . . Note=PAS 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00140 Q16665 UniProtKB Domain 228 298 . . . Note=PAS 2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00140 Q16665 UniProtKB Domain 302 345 . . . Note=PAC Q16665 UniProtKB Region 1 401 . . . Note=Interaction with TSGA10;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q61221 Q16665 UniProtKB Region 1 30 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite Q16665 UniProtKB Region 21 30 . . . Note=DNA-binding;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q61221 Q16665 UniProtKB Region 170 191 . . . Note=Required for heterodimer formation with ARNT;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q61221 Q16665 UniProtKB Region 380 417 . . . Note=N-terminal VHL recognition site Q16665 UniProtKB Region 401 603 . . . Note=ODD;Ontology_term=ECO:0000303;evidence=ECO:0000303|PubMed:16288748;Dbxref=PMID:16288748 Q16665 UniProtKB Region 494 520 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite Q16665 UniProtKB Region 531 575 . . . Note=NTAD;Ontology_term=ECO:0000303,ECO:0000303;evidence=ECO:0000303|PubMed:10202154,ECO:0000303|PubMed:9235919;Dbxref=PMID:10202154,PMID:9235919 Q16665 UniProtKB Region 556 572 . . . Note=C-terminal VHL recognition site Q16665 UniProtKB Region 576 785 . . . Note=ID Q16665 UniProtKB Region 642 688 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite Q16665 UniProtKB Region 786 826 . . . Note=CTAD;Ontology_term=ECO:0000303,ECO:0000303;evidence=ECO:0000303|PubMed:10202154,ECO:0000303|PubMed:9235919;Dbxref=PMID:10202154,PMID:9235919 Q16665 UniProtKB Motif 718 721 . . . Note=Nuclear localization signal;Ontology_term=ECO:0000255;evidence=ECO:0000255 Q16665 UniProtKB Compositional bias 494 516 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite Q16665 UniProtKB Compositional bias 645 670 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite Q16665 UniProtKB Modified residue 247 247 . . . Note=Phosphoserine%3B by CK1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20699359;Dbxref=PMID:20699359 Q16665 UniProtKB Modified residue 402 402 . . . Note=4-hydroxyproline;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11566883;Dbxref=PMID:11566883 Q16665 UniProtKB Modified residue 532 532 . . . Note=N6-acetyllysine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:24681946;Dbxref=PMID:24681946 Q16665 UniProtKB Modified residue 551 551 . . . Note=Phosphoserine%3B by GSK3-beta;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20889502;Dbxref=PMID:20889502 Q16665 UniProtKB Modified residue 555 555 . . . Note=Phosphothreonine%3B by GSK3-beta;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20889502;Dbxref=PMID:20889502 Q16665 UniProtKB Modified residue 564 564 . . . Note=4-hydroxyproline;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11292861,ECO:0000269|PubMed:11566883,ECO:0000269|PubMed:12351678,ECO:0000269|PubMed:25974097;Dbxref=PMID:11292861,PMID:11566883,PMID:12351678,PMID:25974097 Q16665 UniProtKB Modified residue 576 576 . . . Note=Phosphoserine%3B by PLK3;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20889502;Dbxref=PMID:20889502 Q16665 UniProtKB Modified residue 589 589 . . . Note=Phosphoserine%3B by GSK3-beta;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20889502;Dbxref=PMID:20889502 Q16665 UniProtKB Modified residue 657 657 . . . Note=Phosphoserine%3B by PLK3;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20889502;Dbxref=PMID:20889502 Q16665 UniProtKB Modified residue 709 709 . . . Note=N6-acetyllysine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:24681946;Dbxref=PMID:24681946 Q16665 UniProtKB Modified residue 800 800 . . . Note=S-nitrosocysteine;Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:12914934;Dbxref=PMID:12914934 Q16665 UniProtKB Modified residue 803 803 . . . Note=(3S)-3-hydroxyasparagine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:12080085;Dbxref=PMID:12080085 Q16665 UniProtKB Glycosylation 18 18 . . . Note=(Microbial infection) N-beta-linked (GlcNAc) arginine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:30125331;Dbxref=PMID:30125331 Q16665 UniProtKB Cross-link 391 391 . . . Note=Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO);Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:15465032,ECO:0000269|PubMed:17610843;Dbxref=PMID:15465032,PMID:17610843 Q16665 UniProtKB Cross-link 477 477 . . . Note=Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO);Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:15465032,ECO:0000269|PubMed:17610843;Dbxref=PMID:15465032,PMID:17610843 Q16665 UniProtKB Cross-link 532 532 . . . Note=Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin);Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:16862177;Dbxref=PMID:16862177 Q16665 UniProtKB Cross-link 538 538 . . . Note=Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin);Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:16862177;Dbxref=PMID:16862177 Q16665 UniProtKB Cross-link 547 547 . . . Note=Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin);Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:16862177;Dbxref=PMID:16862177 Q16665 UniProtKB Alternative sequence 1 12 . . . ID=VSP_044942;Note=In isoform 3. MEGAGGANDKKK->MSSQCRSLENKFVFLKEGLGNSKPEELEEIRIENGR;Ontology_term=ECO:0000303;evidence=ECO:0000303|PubMed:18638657;Dbxref=PMID:18638657 Q16665 UniProtKB Alternative sequence 735 735 . . . ID=VSP_047335;Note=In isoform 2. G->I;Ontology_term=ECO:0000303;evidence=ECO:0000303|Ref.7 Q16665 UniProtKB Alternative sequence 736 826 . . . ID=VSP_007738;Note=In isoform 2. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303|Ref.7 Q16665 UniProtKB Natural variant 582 582 . . . ID=VAR_049541;Note=P->S;Dbxref=dbSNP:rs11549465 Q16665 UniProtKB Natural variant 588 588 . . . ID=VAR_049542;Note=A->T;Dbxref=dbSNP:rs11549467 Q16665 UniProtKB Natural variant 796 796 . . . ID=VAR_015854;Note=T->A;Dbxref=dbSNP:rs1802821 Q16665 UniProtKB Mutagenesis 18 18 . . . Note=Strongly reduced GlcNAcylation by E.coli NleB1. R->K;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:30125331;Dbxref=PMID:30125331 Q16665 UniProtKB Mutagenesis 247 247 . . . Note=Constitutive kinase activity. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20699359;Dbxref=PMID:20699359 Q16665 UniProtKB Mutagenesis 247 247 . . . Note=Impaired kinase activity. S->D;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20699359;Dbxref=PMID:20699359 Q16665 UniProtKB Mutagenesis 377 377 . . . Note=No change in HIF1A protein turnover rate but increased transcriptional activity%3B when associated with R-391%3B R-477 and R-532. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17610843;Dbxref=PMID:17610843 Q16665 UniProtKB Mutagenesis 389 389 . . . Note=No change in sumoylation. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:15465032;Dbxref=PMID:15465032 Q16665 UniProtKB Mutagenesis 391 391 . . . Note=Abolishes 1 sumoylation. Abolishes 1 sumoylation%3B when associated with R-532. Abolishes 2 sumoylations%3B when associated with R-477. No change in HIF1A protein turnover rate but increased transcriptional activity%3B when associated with R-377%3B R-477 and R-532. K->R;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:15465032,ECO:0000269|PubMed:17610843;Dbxref=PMID:15465032,PMID:17610843 Q16665 UniProtKB Mutagenesis 392 392 . . . Note=No change in sumoylation. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:15465032;Dbxref=PMID:15465032 Q16665 UniProtKB Mutagenesis 394 394 . . . Note=No change in VHLE3-dependent ubiquitination. P->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11566883;Dbxref=PMID:11566883 Q16665 UniProtKB Mutagenesis 397 397 . . . Note=Abolishes VHLE3-dependent ubiquitination%3B when associated with A-400. L->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11566883;Dbxref=PMID:11566883 Q16665 UniProtKB Mutagenesis 400 400 . . . Note=Abolishes VHLE3-dependent ubiquitination%3B when associated with A-397. L->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11566883;Dbxref=PMID:11566883 Q16665 UniProtKB Mutagenesis 402 402 . . . Note=Abolishes in VHLE3-dependent ubiquitination%2C abolishes oxygen-dependent regulation of VP16%2C partially reduced VHLE target site ubiquitination and no interaction with VHL. No VHLE target site ubiquitination%3B when associated with G-564. Increases HIF1A instability and reduces HIF1A-induced target gene transcriptional activation%3B when associated with A-564. P->A;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11566883,ECO:0000269|PubMed:16862177,ECO:0000269|PubMed:24681946;Dbxref=PMID:11566883,PMID:16862177,PMID:24681946 Q16665 UniProtKB Mutagenesis 442 442 . . . Note=No change in sumoylation. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:15465032;Dbxref=PMID:15465032 Q16665 UniProtKB Mutagenesis 460 460 . . . Note=No change in sumoylation nor in ARD1-mediated acetylation. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:15465032;Dbxref=PMID:15465032 Q16665 UniProtKB Mutagenesis 477 477 . . . Note=Abolishes 1 sumoylation. Abolishes 2 sumoylations%3B when associated with R-391. No change in HIF1A protein turnover rate but increased transcriptional activity%3B when associated with R-377%3B R-391 and R-532. K->R;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:15465032,ECO:0000269|PubMed:17610843;Dbxref=PMID:15465032,PMID:17610843 Q16665 UniProtKB Mutagenesis 532 532 . . . Note=Reduced ubiquitination. No change in sumoylation nor on interaction with NAA10. No change in HIF1A protein turnover rate but increased transcriptional activity%3B when associated with R-377%3B R-391 and R-477. Complete loss of ubiquitination%2C but no change in VHL binding%3B when associated with K-538 and K-547. K->R;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10944113,ECO:0000269|PubMed:15465032,ECO:0000269|PubMed:16288748,ECO:0000269|PubMed:16862177,ECO:0000269|PubMed:17610843;Dbxref=PMID:10944113,PMID:15465032,PMID:16288748,PMID:16862177,PMID:17610843 Q16665 UniProtKB Mutagenesis 538 538 . . . Note=No change in sumoylation%2C but reduced ubiquitination. Complete loss of ubiquitination%2C but no change in VHL binding%3B when associated with K-532 and K-547. K->R;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10944113,ECO:0000269|PubMed:15465032,ECO:0000269|PubMed:16862177;Dbxref=PMID:10944113,PMID:15465032,PMID:16862177 Q16665 UniProtKB Mutagenesis 547 547 . . . Note=No change in sumoylation%2C but reduced ubiquitination. Complete loss of ubiquitination%2C but no change in VHL binding%3B when associated with K-532 and K-538. K->R;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10944113,ECO:0000269|PubMed:15465032,ECO:0000269|PubMed:16862177;Dbxref=PMID:10944113,PMID:15465032,PMID:16862177 Q16665 UniProtKB Mutagenesis 551 551 . . . Note=Constitutive expression under nonhypoxic conditions by decreasing ubiquitination. S->G;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10758161;Dbxref=PMID:10758161 Q16665 UniProtKB Mutagenesis 552 552 . . . Note=Constitutive expression under nonhypoxic conditions by decreasing ubiquitination. T->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10758161;Dbxref=PMID:10758161 Q16665 UniProtKB Mutagenesis 564 564 . . . Note=Increases HIF1A instability and reduces HIF1A-induced target gene transcriptional activation%3B when associated with A-402. P->A;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11566883,ECO:0000269|PubMed:16862177,ECO:0000269|PubMed:24681946;Dbxref=PMID:11566883,PMID:16862177,PMID:24681946 Q16665 UniProtKB Mutagenesis 564 564 . . . Note=No change in VHL-dependent ubiquitination. Partially reduced VHLE target site ubiquitination. No VHLE target site ubiquitination%3B when associated with A-402. P->G;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11566883,ECO:0000269|PubMed:16862177,ECO:0000269|PubMed:24681946;Dbxref=PMID:11566883,PMID:16862177,PMID:24681946 Q16665 UniProtKB Mutagenesis 576 576 . . . Note=Induces stabilization of the protein. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20889502;Dbxref=PMID:20889502 Q16665 UniProtKB Mutagenesis 657 657 . . . Note=Induces stabilization of the protein. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20889502;Dbxref=PMID:20889502 Q16665 UniProtKB Mutagenesis 709 709 . . . Note=Abolishes SIRT2-mediated deacetylation%2C increases HIF1A instability and reduces HIF1A-induced target gene transcriptional activation. Increases interaction with EGLN1. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:24681946;Dbxref=PMID:24681946 Q16665 UniProtKB Mutagenesis 719 719 . . . Note=Dramatic reduction of accumulation in the nucleus in response to hypoxia. K->T;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10944113,ECO:0000269|PubMed:9822602;Dbxref=PMID:10944113,PMID:9822602 Q16665 UniProtKB Mutagenesis 795 795 . . . Note=Inhibits interaction with EP300 and transactivation activity. L->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:12778114;Dbxref=PMID:12778114 Q16665 UniProtKB Mutagenesis 800 800 . . . Note=Blocks increase in transcriptional activation caused by nitrosylation. C->A;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10202154,ECO:0000269|PubMed:12914934;Dbxref=PMID:10202154,PMID:12914934 Q16665 UniProtKB Mutagenesis 800 800 . . . Note=Abolishes hypoxia-inducible transcriptional activation of ctaD. C->S;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10202154,ECO:0000269|PubMed:12914934;Dbxref=PMID:10202154,PMID:12914934 Q16665 UniProtKB Mutagenesis 803 803 . . . Note=Recruits CREBBP. No enhancement of CREBBP by Clioquinol in the presence of FIH1. No change in nuclear location nor on repression of transcriptional activity in the presence of histone deacetylase inhibitor. N->A;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:16543236,ECO:0000269|PubMed:16973622;Dbxref=PMID:16543236,PMID:16973622 Q16665 UniProtKB Sequence conflict 572 572 . . . Note=F->L;Ontology_term=ECO:0000305;evidence=ECO:0000305 Q16665 UniProtKB Beta strand 241 246 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4H6J Q16665 UniProtKB Beta strand 251 255 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4H6J Q16665 UniProtKB Helix 258 263 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4H6J Q16665 UniProtKB Helix 267 270 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4H6J Q16665 UniProtKB Helix 275 277 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4H6J Q16665 UniProtKB Turn 281 283 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4H6J Q16665 UniProtKB Helix 284 297 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4H6J Q16665 UniProtKB Beta strand 298 301 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4H6J Q16665 UniProtKB Beta strand 305 308 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4H6J Q16665 UniProtKB Beta strand 310 325 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4H6J Q16665 UniProtKB Turn 327 329 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4H6J Q16665 UniProtKB Beta strand 332 341 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:4H6J Q16665 UniProtKB Helix 397 400 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5L9V Q16665 UniProtKB Beta strand 408 410 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5LA9 Q16665 UniProtKB Helix 559 562 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5L9B Q16665 UniProtKB Turn 779 783 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1L8C Q16665 UniProtKB Helix 784 787 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1L8C Q16665 UniProtKB Beta strand 789 792 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1L8C Q16665 UniProtKB Helix 797 803 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7QGS Q16665 UniProtKB Helix 809 811 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7LVS Q16665 UniProtKB Helix 817 821 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7QGS Q16665 UniProtKB Turn 822 824 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7QGS