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Protein

Endothelial PAS domain-containing protein 1

Gene

Epas1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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 (By similarity).By similarity

GO - Molecular functioni

  • cobalt ion binding Source: RGD
  • DNA binding Source: UniProtKB-KW
  • transcription factor activity, sequence-specific DNA binding Source: RGD

GO - Biological processi

  • angiogenesis Source: UniProtKB-KW
  • cell differentiation Source: UniProtKB-KW
  • cellular response to hypoxia Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: RGD
  • positive regulation of lung alveolus development Source: RGD
  • positive regulation of transcription from RNA polymerase II promoter Source: RGD
  • response to hypoxia Source: RGD
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Angiogenesis, Differentiation, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Endothelial PAS domain-containing protein 1
Short name:
EPAS-1
Alternative name(s):
Hypoxia-inducible factor 2-alpha
Short name:
HIF-2-alpha
Short name:
HIF2-alpha
Gene namesi
Name:Epas1
Synonyms:Hif2a
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi68404. Epas1.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotationBy similarity
  • Nucleus speckle By similarity

  • Note: Colocalizes with HIF3A in the nucleus and speckles.By similarity

GO - Cellular componenti

  • cytoplasm Source: RGD
  • nuclear speck Source: UniProtKB-SubCell
  • nucleus Source: RGD
  • transcription factor complex Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 874874Endothelial PAS domain-containing protein 1PRO_0000127421Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei405 – 40514-hydroxyprolineBy similarity
Modified residuei530 – 53014-hydroxyprolineBy similarity
Modified residuei844 – 8441PhosphothreonineBy similarity
Modified residuei851 – 8511(3S)-3-hydroxyasparagineBy similarity

Post-translational modificationi

In normoxia, is probably hydroxylated on Pro-405 and Pro-530 by EGLN1/PHD1, EGLN2/PHD2 and/or EGLN3/PHD3. The hydroxylated prolines promote interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation. Under hypoxia, proline hydroxylation is impaired and ubiquitination is attenuated, resulting in stabilization (By similarity).By similarity
In normoxia, is hydroxylated on Asn-851 by HIF1AN thus probably abrogating interaction with CREBBP and EP300 and preventing transcriptional activation.By similarity
Phosphorylated on multiple sites in the CTAD.By similarity
The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains.By similarity

Keywords - PTMi

Hydroxylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9JHS1.
PRIDEiQ9JHS1.

Interactioni

Subunit structurei

Interacts with HIF3A. Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerizes with ARNT.By similarity

Protein-protein interaction databases

BioGridi248095. 2 interactions.
STRINGi10116.ENSRNOP00000033874.

Structurei

3D structure databases

ProteinModelPortaliQ9JHS1.
SMRiQ9JHS1. Positions 239-350, 824-872.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini14 – 6754bHLHPROSITE-ProRule annotationAdd
BLAST
Domaini84 – 15471PAS 1PROSITE-ProRule annotationAdd
BLAST
Domaini230 – 30071PAS 2PROSITE-ProRule annotationAdd
BLAST
Domaini304 – 34744PACAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni495 – 54147NTADAdd
BLAST
Regioni834 – 87441CTADAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi474 – 4796Poly-Ser

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation
Contains 2 PAS (PER-ARNT-SIM) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3558. Eukaryota.
ENOG410YK57. LUCA.
HOGENOMiHOG000234306.
HOVERGENiHBG060456.
InParanoidiQ9JHS1.
KOiK09095.
PhylomeDBiQ9JHS1.

Family and domain databases

InterProiIPR011598. bHLH_dom.
IPR014887. HIF-1_TAD_C.
IPR021537. HIF_alpha_subunit.
IPR001067. Nuc_translocat.
IPR001610. PAC.
IPR000014. PAS.
IPR013655. PAS_fold_3.
[Graphical view]
PfamiPF11413. HIF-1. 1 hit.
PF08778. HIF-1a_CTAD. 1 hit.
PF08447. PAS_3. 1 hit.
PF13426. PAS_9. 1 hit.
[Graphical view]
PRINTSiPR00785. NCTRNSLOCATR.
SMARTiSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 2 hits.
TIGRFAMsiTIGR00229. sensory_box. 2 hits.
PROSITEiPS50888. BHLH. 1 hit.
PS50112. PAS. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9JHS1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTADKEKKRS SSELRKEKSR DAARCRRSKE TEVFYELAHE LPLPHSVSSH
60 70 80 90 100
LDKASIMRLA ISFLRTHKLL SSVCSENESE AEADQQMDNL YLKALEGFIA
110 120 130 140 150
VVTQDGDMIF LSENISKFMG LTQVELTGHS IFDFTHPCDH EEIRENLTLK
160 170 180 190 200
TGSGFGKKNK DRSTERDFFM RMKCTVTNRG RTVNLKSATW KVLHCTGQVR
210 220 230 240 250
VYNNCPPHSS LCGYKEPLLS CLIIMCEPIQ HPSHMDIPLD SKTFLSRHSM
260 270 280 290 300
DMKFTYCDDR ILELVGYHPE ELLGRSAYEF YHALDSENMT KSHQNLCTKG
310 320 330 340 350
QVVSGQYRML AKHGGYVWLE TQGTVVYNPR NLQPQCIMCV NYVLSEIEKN
360 370 380 390 400
DVVVSMDQTE SCSSHTLMAM NSIFDTSDDV ALSEKSNYLF TNLKEEPEDL
410 420 430 440 450
AQLAPTPGDA IISLDFGSQN FDESSTYGKA ILPPGQPWAT ELRSHSAQSE
460 470 480 490 500
SRSLPAFTVP QAGSPGNATP SATSSSSCST PSSPEDYYSS LENHLKIEVI
510 520 530 540 550
EKLFAMDTEA KDQCSTQTDF NELDLETLAP YIPMDGEDFQ LSPICPEEPL
560 570 580 590 600
VPESPQPNPQ HCFSTMSSIF QPLTPGASQG TFFLDKYPQQ LESRKTESEH
610 620 630 640 650
WPMSTIFFDA GSKGSLPPCC GQASTPLSSM GGRSNTPWPP DPPLHLGPTK
660 670 680 690 700
WSVGNQSAEP LGPLPLGTSQ LEPPSTPPHV SMFKMRSAKD FGARGPYMMS
710 720 730 740 750
PAMIALSNKL KLKRQLDYEE PAFQDTSGGD PPGTSSSHLM WKRMKSLMGG
760 770 780 790 800
TCPLMPDKTV SASMAPDEFT QKSMRGLGQP LRHLPPSQPP STRSPGENAK
810 820 830 840 850
SGFPPQCYAS PFQDYSPPGA QKGSGVASRL LGPSFEPYLL PELTRYDCEV
860 870
NVPEPGSSTL LQGRDLLRAL DQAT
Length:874
Mass (Da):96,718
Last modified:October 1, 2000 - v1
Checksum:iA1FF08EB24369796
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ277828 mRNA. Translation: CAB96612.1.
RefSeqiNP_075578.1. NM_023090.1.
UniGeneiRn.163791.
Rn.55138.

Genome annotation databases

GeneIDi29452.
KEGGirno:29452.
UCSCiRGD:68404. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ277828 mRNA. Translation: CAB96612.1.
RefSeqiNP_075578.1. NM_023090.1.
UniGeneiRn.163791.
Rn.55138.

3D structure databases

ProteinModelPortaliQ9JHS1.
SMRiQ9JHS1. Positions 239-350, 824-872.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248095. 2 interactions.
STRINGi10116.ENSRNOP00000033874.

Proteomic databases

PaxDbiQ9JHS1.
PRIDEiQ9JHS1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi29452.
KEGGirno:29452.
UCSCiRGD:68404. rat.

Organism-specific databases

CTDi2034.
RGDi68404. Epas1.

Phylogenomic databases

eggNOGiKOG3558. Eukaryota.
ENOG410YK57. LUCA.
HOGENOMiHOG000234306.
HOVERGENiHBG060456.
InParanoidiQ9JHS1.
KOiK09095.
PhylomeDBiQ9JHS1.

Miscellaneous databases

NextBioi609218.
PROiQ9JHS1.

Family and domain databases

InterProiIPR011598. bHLH_dom.
IPR014887. HIF-1_TAD_C.
IPR021537. HIF_alpha_subunit.
IPR001067. Nuc_translocat.
IPR001610. PAC.
IPR000014. PAS.
IPR013655. PAS_fold_3.
[Graphical view]
PfamiPF11413. HIF-1. 1 hit.
PF08778. HIF-1a_CTAD. 1 hit.
PF08447. PAS_3. 1 hit.
PF13426. PAS_9. 1 hit.
[Graphical view]
PRINTSiPR00785. NCTRNSLOCATR.
SMARTiSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 2 hits.
TIGRFAMsiTIGR00229. sensory_box. 2 hits.
PROSITEiPS50888. BHLH. 1 hit.
PS50112. PAS. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Perivenous expression of the mRNA of the three hypoxia-inducible factor a-subunits HIF-1a, HIF2a and HIF3a in rat liver."
    Kietzmann T., Cornesse Y., Brechtel K., Modaressi S., Jungermann K.
    Biochem. J. 354:531-537(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Liver.

Entry informationi

Entry nameiEPAS1_RAT
AccessioniPrimary (citable) accession number: Q9JHS1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 3, 2003
Last sequence update: October 1, 2000
Last modified: May 11, 2016
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.