UniProt Accession

 EPAS1_HUMAN; Q99814; Q86VA2; Q99630 

Genbank Protein ID

 U81984; U51626; BC051338 

Genbank Nucleotide ID

 AAB41495.1; AAC51212.1; AAH51338.1 

Protein Name

 Endothelial PAS domain-containing protein 1 

Protein Synonyms/Alias

 EPAS-1; Basic-helix-loop-helix-PAS protein MOP2; Class E basic helix-loop-helix protein 73; bHLHe73; HIF-1-alpha-like factor; HLF; Hypoxia-inducible factor 2-alpha; HIF-2-alpha; HIF2-alpha; Member of PAS protein 2; PAS domain-containing protein 2 

Gene Name

 EPAS1 

Gene Synonyms/Alias

 BHLHE73; HIF2A; MOP2; PASD2 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
253	SRHSMDMKFTYCDDR	ubiquitination	[1]
291	LDSENMTKSHQNLCT	ubiquitination	[1]
299	SHQNLCTKGQVVSGQ	ubiquitination	[1]
385	GKGAVSEKSNFLFTK	acetylation	[2]
385	GKGAVSEKSNFLFTK	ubiquitination	[3]
392	KSNFLFTKLKEEPEE	ubiquitination	[1, 3]
394	NFLFTKLKEEPEELA	sumoylation	[4]
503	LKIEVIEKLFAMDTE	ubiquitination	[3]
685	TFKTRSAKGFGARGP	acetylation	[2]
741	HLMWKRMKNLRGGSC	acetylation	[2]

Reference

 [1] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [2] Regulation of hypoxia-inducible factor 2alpha signaling by the stress-responsive deacetylase sirtuin 1.
 Dioum EM, Chen R, Alexander MS, Zhang Q, Hogg RT, Gerard RD, Garcia JA.
 Science. 2009 Jun 5;324(5932):1289-93. [PMID: 19498162]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] RNF4 and VHL regulate the proteasomal degradation of SUMO-conjugated Hypoxia-Inducible Factor-2alpha.
 van Hagen M, Overmeer RM, Abolvardi SS, Vertegaal AC.
 Nucleic Acids Res. 2010 Apr;38(6):1922-31. [PMID: 20026589] 

Functional Description

 Transcription factor involved in the induction of oxygen regulated genes. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation seems to require recruitment of transcriptional coactivators such as CREBPB and probably EP300. Interaction with redox regulatory protein APEX seems to activate CTAD. 

Sequence Annotation

 DOMAIN 14 67 bHLH.
 DOMAIN 84 154 PAS 1.
 DOMAIN 230 300 PAS 2.
 DOMAIN 304 347 PAC.
 REGION 496 542 NTAD.
 REGION 830 870 CTAD.
 MOD_RES 405 405 4-hydroxyproline (By similarity).
 MOD_RES 531 531 4-hydroxyproline (By similarity).
 MOD_RES 840 840 Phosphothreonine (By similarity).
 MOD_RES 847 847 (3S)-3-hydroxyasparagine (By similarity).  

Keyword

 3D-structure; Activator; Angiogenesis; Complete proteome; Congenital erythrocytosis; Developmental protein; Differentiation; Disease mutation; DNA-binding; Hydroxylation; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Transcription; Transcription regulation; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 870 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005667; C:transcription factor complex; IDA:MGI.
 GO:0003677; F:DNA binding; IGI:MGI.
 GO:0001077; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription; IEA:Compara.
 GO:0004871; F:signal transducer activity; IEA:InterPro.
 GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
 GO:0001974; P:blood vessel remodeling; IEA:Compara.
 GO:0048469; P:cell maturation; IEA:Compara.
 GO:0001892; P:embryonic placenta development; IEA:Compara.
 GO:0030218; P:erythrocyte differentiation; IEA:Compara.
 GO:0030324; P:lung development; IEA:Compara.
 GO:0007005; P:mitochondrion organization; IEA:Compara.
 GO:0048625; P:myoblast fate commitment; ISS:BHF-UCL.
 GO:0042415; P:norepinephrine metabolic process; IEA:Compara.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IGI:MGI.
 GO:0002027; P:regulation of heart rate; IEA:Compara.
 GO:0061418; P:regulation of transcription from RNA polymerase II promoter in response to hypoxia; TAS:Reactome.
 GO:0043619; P:regulation of transcription from RNA polymerase II promoter in response to oxidative stress; IEA:Compara.
 GO:0007165; P:signal transduction; TAS:ProtInc.
 GO:0043129; P:surfactant homeostasis; IEA:Compara.
 GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc.
 GO:0007601; P:visual perception; IEA:Compara. 

Interpro

 IPR011598; bHLH_dom.
 IPR014887; HIF-1_TAD_C.
 IPR021537; HIF_alpha_subunit.
 IPR001067; Nuc_translocat.
 IPR001610; PAC.
 IPR000014; PAS.
 IPR013767; PAS_fold.
 IPR013655; PAS_fold_3. 

Pfam

 PF11413; HIF-1
 PF08778; HIF-1a_CTAD
 PF00989; PAS
 PF08447; PAS_3 

SMART

 SM00353; HLH
 SM00086; PAC
 SM00091; PAS 

PROSITE

 PS50888; BHLH
 PS50113; PAC
 PS50112; PAS 

PRINTS

 PR00785; NCTRNSLOCATR.