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Entry version 208 (16 Oct 2019)
Sequence version 3 (03 Jul 2003)
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Protein

Endothelial PAS domain-containing protein 1

Gene

EPAS1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Transcription factor involved in the induction of oxygen regulated genes. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). 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 requires recruitment of transcriptional coactivators such as CREBBP and probably EP300. Interaction with redox regulatory protein APEX seems to activate CTAD (By similarity).By similarity

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding
Biological processAngiogenesis, Differentiation, Transcription, Transcription regulation

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-1234158 Regulation of gene expression by Hypoxia-inducible Factor
R-HSA-1234174 Cellular response to hypoxia
R-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-452723 Transcriptional regulation of pluripotent stem cells
R-HSA-8849473 PTK6 Expression
R-HSA-8951664 Neddylation

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...
SignaLinki
Q99814

SIGNOR Signaling Network Open Resource

More...
SIGNORi
Q99814

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Endothelial PAS domain-containing protein 1
Short name:
EPAS-1
Alternative name(s):
Basic-helix-loop-helix-PAS protein MOP2
Class E basic helix-loop-helix protein 73
Short name:
bHLHe73
HIF-1-alpha-like factor
Short name:
HLF
Hypoxia-inducible factor 2-alpha
Short name:
HIF-2-alpha
Short name:
HIF2-alpha
Member of PAS protein 2
PAS domain-containing protein 2
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:EPAS1
Synonyms:BHLHE73, HIF2A, MOP2, PASD2
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 2

Organism-specific databases

Human Gene Nomenclature Database

More...
HGNCi
HGNC:3374 EPAS1

Online Mendelian Inheritance in Man (OMIM)

More...
MIMi
603349 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_Q99814

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Erythrocytosis, familial, 4 (ECYT4)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disorder characterized by elevated serum hemoglobin and hematocrit, and normal platelet and leukocyte counts.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_067358534P → L in ECYT4; impairs interaction with EGLN1 and VHL. 1 Publication1
Natural variantiVAR_067359535M → T in ECYT4. 1 Publication1
Natural variantiVAR_067360535M → V in ECYT4; impairs interaction with EGLN1. 2 PublicationsCorresponds to variant dbSNP:rs137853037EnsemblClinVar.1
Natural variantiVAR_067361537G → R in ECYT4; impairs interaction with EGLN1 and VHL. 2 PublicationsCorresponds to variant dbSNP:rs137853036EnsemblClinVar.1
Natural variantiVAR_042443537G → W in ECYT4; gain of function; affects hydroxylation. 1 PublicationCorresponds to variant dbSNP:rs137853036EnsemblClinVar.1
Natural variantiVAR_067362540F → L in ECYT4; affects the interaction with EGLN1 and VHL. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi844C → S: Abolishes hypoxia-inducible transcriptional activation of ctaD. 1 Publication1

Keywords - Diseasei

Congenital erythrocytosis, Disease mutation

Organism-specific databases

DisGeNET

More...
DisGeNETi
2034

MalaCards human disease database

More...
MalaCardsi
EPAS1
MIMi611783 phenotype

Open Targets

More...
OpenTargetsi
ENSG00000116016

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
247511 Autosomal dominant secondary polycythemia
324299 Multiple paragangliomas associated with polycythemia
276624 Sporadic pheochromocytoma
276627 Sporadic secreting paraganglioma

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...
PharmGKBi
PA27809

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...
Pharosi
Q99814

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL1744522

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
EPAS1

Domain mapping of disease mutations (DMDM)

More...
DMDMi
32470617

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001274191 – 870Endothelial PAS domain-containing protein 1Add BLAST870

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei4054-hydroxyprolineBy similarity1
Modified residuei5314-hydroxyprolineBy similarity1
Modified residuei840PhosphothreonineBy similarity1
Modified residuei847(3S)-3-hydroxyasparagineBy similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

In normoxia, is probably hydroxylated on Pro-405 and Pro-531 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-847 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

jPOST - Japan Proteome Standard Repository/Database

More...
jPOSTi
Q99814

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
Q99814

MaxQB - The MaxQuant DataBase

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MaxQBi
Q99814

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
Q99814

PeptideAtlas

More...
PeptideAtlasi
Q99814

PRoteomics IDEntifications database

More...
PRIDEi
Q99814

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
78489

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q99814

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
Q99814

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed in most tissues, with highest levels in placenta, lung and heart. Selectively expressed in endothelial cells.

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000116016 Expressed in 234 organ(s), highest expression level in visceral pleura

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q99814 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q99814 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
HPA031200
HPA069697

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts with HIF3A (By similarity). Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (PubMed:16181639).

Interacts with CREBBP (By similarity).

Interacts with EGLN1.

Interacts with VHL (PubMed:19208626).

By similarity3 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
108348, 127 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
Q99814

Database of interacting proteins

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DIPi
DIP-32857N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
Q99814

Protein interaction database and analysis system

More...
IntActi
Q99814, 39 interactors

Molecular INTeraction database

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MINTi
Q99814

STRING: functional protein association networks

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STRINGi
9606.ENSP00000263734

Chemistry databases

BindingDB database of measured binding affinities

More...
BindingDBi
Q99814

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1870
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q99814

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

More...
PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...
EvolutionaryTracei
Q99814

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini14 – 67bHLHPROSITE-ProRule annotationAdd BLAST54
Domaini84 – 154PAS 1PROSITE-ProRule annotationAdd BLAST71
Domaini230 – 300PAS 2PROSITE-ProRule annotationAdd BLAST71
Domaini304 – 347PACAdd BLAST44

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni26 – 53DNA-bindingBy similarityAdd BLAST28
Regioni171 – 192Required for heterodimer formation with ARNTBy similarityAdd BLAST22
Regioni496 – 542NTADAdd BLAST47
Regioni830 – 870CTADAdd BLAST41

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi474 – 480Poly-Ser7

Keywords - Domaini

Repeat

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG3558 Eukaryota
ENOG410YK57 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000155930

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000234306

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q99814

KEGG Orthology (KO)

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KOi
K09095

Identification of Orthologs from Complete Genome Data

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OMAi
MNSIFDN

Database of Orthologous Groups

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OrthoDBi
547545at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
Q99814

TreeFam database of animal gene trees

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TreeFami
TF317772

Family and domain databases

Conserved Domains Database

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CDDi
cd00083 HLH, 1 hit
cd00130 PAS, 2 hits

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
4.10.280.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR011598 bHLH_dom
IPR014887 HIF-1_TAD_C
IPR021537 HIF_alpha_subunit
IPR036638 HLH_DNA-bd_sf
IPR001067 Nuc_translocat
IPR001610 PAC
IPR000014 PAS
IPR035965 PAS-like_dom_sf
IPR013767 PAS_fold
IPR013655 PAS_fold_3

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF11413 HIF-1, 1 hit
PF08778 HIF-1a_CTAD, 1 hit
PF00989 PAS, 1 hit
PF08447 PAS_3, 1 hit

Protein Motif fingerprint database; a protein domain database

More...
PRINTSi
PR00785 NCTRNSLOCATR

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00353 HLH, 1 hit
SM00086 PAC, 1 hit
SM00091 PAS, 2 hits

Superfamily database of structural and functional annotation

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SUPFAMi
SSF47459 SSF47459, 1 hit
SSF55785 SSF55785, 2 hits

TIGRFAMs; a protein family database

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TIGRFAMsi
TIGR00229 sensory_box, 2 hits

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS50888 BHLH, 1 hit
PS50112 PAS, 2 hits

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q99814-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTADKEKKRS SSERRKEKSR DAARCRRSKE TEVFYELAHE LPLPHSVSSH
60 70 80 90 100
LDKASIMRLA ISFLRTHKLL SSVCSENESE AEADQQMDNL YLKALEGFIA
110 120 130 140 150
VVTQDGDMIF LSENISKFMG LTQVELTGHS IFDFTHPCDH EEIRENLSLK
160 170 180 190 200
NGSGFGKKSK DMSTERDFFM RMKCTVTNRG RTVNLKSATW KVLHCTGQVK
210 220 230 240 250
VYNNCPPHNS LCGYKEPLLS CLIIMCEPIQ HPSHMDIPLD SKTFLSRHSM
260 270 280 290 300
DMKFTYCDDR ITELIGYHPE ELLGRSAYEF YHALDSENMT KSHQNLCTKG
310 320 330 340 350
QVVSGQYRML AKHGGYVWLE TQGTVIYNPR NLQPQCIMCV NYVLSEIEKN
360 370 380 390 400
DVVFSMDQTE SLFKPHLMAM NSIFDSSGKG AVSEKSNFLF TKLKEEPEEL
410 420 430 440 450
AQLAPTPGDA IISLDFGNQN FEESSAYGKA ILPPSQPWAT ELRSHSTQSE
460 470 480 490 500
AGSLPAFTVP QAAAPGSTTP SATSSSSSCS TPNSPEDYYT SLDNDLKIEV
510 520 530 540 550
IEKLFAMDTE AKDQCSTQTD FNELDLETLA PYIPMDGEDF QLSPICPEER
560 570 580 590 600
LLAENPQSTP QHCFSAMTNI FQPLAPVAPH SPFLLDKFQQ QLESKKTEPE
610 620 630 640 650
HRPMSSIFFD AGSKASLPPC CGQASTPLSS MGGRSNTQWP PDPPLHFGPT
660 670 680 690 700
KWAVGDQRTE FLGAAPLGPP VSPPHVSTFK TRSAKGFGAR GPDVLSPAMV
710 720 730 740 750
ALSNKLKLKR QLEYEEQAFQ DLSGGDPPGG STSHLMWKRM KNLRGGSCPL
760 770 780 790 800
MPDKPLSANV PNDKFTQNPM RGLGHPLRHL PLPQPPSAIS PGENSKSRFP
810 820 830 840 850
PQCYATQYQD YSLSSAHKVS GMASRLLGPS FESYLLPELT RYDCEVNVPV
860 870
LGSSTLLQGG DLLRALDQAT
Length:870
Mass (Da):96,459
Last modified:July 3, 2003 - v3
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i4838989598234FC1
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9J9N2C9J9N2_HUMAN
Endothelial PAS domain-containing p...
EPAS1
259Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti60A → E in AAB41495 (PubMed:9000051).Curated1
Sequence conflicti539D → G in AAC51212 (PubMed:9079689).Curated1
Sequence conflicti601H → R in AAC51212 (PubMed:9079689).Curated1
Sequence conflicti693D → N in AAC51212 (PubMed:9079689).Curated1
Sequence conflicti716E → K in AAC51212 (PubMed:9079689).Curated1
Sequence conflicti722L → P in AAC51212 (PubMed:9079689).Curated1
Sequence conflicti765F → L in AAC51212 (PubMed:9079689).Curated1
Sequence conflicti769P → S in AAC51212 (PubMed:9079689).Curated1
Sequence conflicti844C → R in AAC51212 (PubMed:9079689).Curated1
Sequence conflicti847N → K in AAC51212 (PubMed:9079689).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067358534P → L in ECYT4; impairs interaction with EGLN1 and VHL. 1 Publication1
Natural variantiVAR_067359535M → T in ECYT4. 1 Publication1
Natural variantiVAR_067360535M → V in ECYT4; impairs interaction with EGLN1. 2 PublicationsCorresponds to variant dbSNP:rs137853037EnsemblClinVar.1
Natural variantiVAR_067361537G → R in ECYT4; impairs interaction with EGLN1 and VHL. 2 PublicationsCorresponds to variant dbSNP:rs137853036EnsemblClinVar.1
Natural variantiVAR_042443537G → W in ECYT4; gain of function; affects hydroxylation. 1 PublicationCorresponds to variant dbSNP:rs137853036EnsemblClinVar.1
Natural variantiVAR_067362540F → L in ECYT4; affects the interaction with EGLN1 and VHL. 1 Publication1
Natural variantiVAR_061261766T → P. Corresponds to variant dbSNP:rs59901247EnsemblClinVar.1
Natural variantiVAR_061262785P → T. Corresponds to variant dbSNP:rs61518065EnsemblClinVar.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
U81984 mRNA Translation: AAB41495.1
U51626 mRNA Translation: AAC51212.1
BC051338 mRNA Translation: AAH51338.1

The Consensus CDS (CCDS) project

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CCDSi
CCDS1825.1

NCBI Reference Sequences

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RefSeqi
NP_001421.2, NM_001430.4

Genome annotation databases

Ensembl eukaryotic genome annotation project

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Ensembli
ENST00000263734; ENSP00000263734; ENSG00000116016

Database of genes from NCBI RefSeq genomes

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GeneIDi
2034

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:2034

UCSC genome browser

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UCSCi
uc002ruv.3 human

Keywords - Coding sequence diversityi

Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U81984 mRNA Translation: AAB41495.1
U51626 mRNA Translation: AAC51212.1
BC051338 mRNA Translation: AAH51338.1
CCDSiCCDS1825.1
RefSeqiNP_001421.2, NM_001430.4

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1P97NMR-A240-350[»]
2A24NMR-A242-348[»]
3F1NX-ray1.48A239-350[»]
3F1OX-ray1.60A239-350[»]
3F1PX-ray1.17A239-350[»]
3H7WX-ray1.65A239-350[»]
3H82X-ray1.50A239-350[»]
4GHIX-ray1.50A239-350[»]
4GS9X-ray1.72A239-350[»]
4PKYX-ray3.20G239-350[»]
4XT2X-ray1.70A/C239-350[»]
5KIZNMR-A239-349[»]
5TBMX-ray1.85A239-348[»]
5UFPX-ray1.90A239-348[»]
6BVBX-ray2.00H523-540[»]
6CZWX-ray1.60A239-350[»]
6D09X-ray1.85A239-350[»]
6D0BX-ray1.60A239-350[»]
6D0CX-ray1.50A239-350[»]
SMRiQ99814
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGridi108348, 127 interactors
CORUMiQ99814
DIPiDIP-32857N
ELMiQ99814
IntActiQ99814, 39 interactors
MINTiQ99814
STRINGi9606.ENSP00000263734

Chemistry databases

BindingDBiQ99814
ChEMBLiCHEMBL1744522

PTM databases

iPTMnetiQ99814
PhosphoSitePlusiQ99814

Polymorphism and mutation databases

BioMutaiEPAS1
DMDMi32470617

Proteomic databases

jPOSTiQ99814
MassIVEiQ99814
MaxQBiQ99814
PaxDbiQ99814
PeptideAtlasiQ99814
PRIDEiQ99814
ProteomicsDBi78489

Genome annotation databases

EnsembliENST00000263734; ENSP00000263734; ENSG00000116016
GeneIDi2034
KEGGihsa:2034
UCSCiuc002ruv.3 human

Organism-specific databases

Comparative Toxicogenomics Database

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CTDi
2034
DisGeNETi2034

GeneCards: human genes, protein and diseases

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GeneCardsi
EPAS1
HGNCiHGNC:3374 EPAS1
HPAiHPA031200
HPA069697
MalaCardsiEPAS1
MIMi603349 gene
611783 phenotype
neXtProtiNX_Q99814
OpenTargetsiENSG00000116016
Orphaneti247511 Autosomal dominant secondary polycythemia
324299 Multiple paragangliomas associated with polycythemia
276624 Sporadic pheochromocytoma
276627 Sporadic secreting paraganglioma
PharmGKBiPA27809

GenAtlas: human gene database

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GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG3558 Eukaryota
ENOG410YK57 LUCA
GeneTreeiENSGT00940000155930
HOGENOMiHOG000234306
InParanoidiQ99814
KOiK09095
OMAiMNSIFDN
OrthoDBi547545at2759
PhylomeDBiQ99814
TreeFamiTF317772

Enzyme and pathway databases

ReactomeiR-HSA-1234158 Regulation of gene expression by Hypoxia-inducible Factor
R-HSA-1234174 Cellular response to hypoxia
R-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-452723 Transcriptional regulation of pluripotent stem cells
R-HSA-8849473 PTK6 Expression
R-HSA-8951664 Neddylation
SignaLinkiQ99814
SIGNORiQ99814

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

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ChiTaRSi
EPAS1 human
EvolutionaryTraceiQ99814

The Gene Wiki collection of pages on human genes and proteins

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GeneWikii
EPAS1

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

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GenomeRNAii
2034
PharosiQ99814

Protein Ontology

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PROi
PR:Q99814

The Stanford Online Universal Resource for Clones and ESTs

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SOURCEi
Search...

Gene expression databases

BgeeiENSG00000116016 Expressed in 234 organ(s), highest expression level in visceral pleura
ExpressionAtlasiQ99814 baseline and differential
GenevisibleiQ99814 HS

Family and domain databases

CDDicd00083 HLH, 1 hit
cd00130 PAS, 2 hits
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR014887 HIF-1_TAD_C
IPR021537 HIF_alpha_subunit
IPR036638 HLH_DNA-bd_sf
IPR001067 Nuc_translocat
IPR001610 PAC
IPR000014 PAS
IPR035965 PAS-like_dom_sf
IPR013767 PAS_fold
IPR013655 PAS_fold_3
PfamiView protein in Pfam
PF11413 HIF-1, 1 hit
PF08778 HIF-1a_CTAD, 1 hit
PF00989 PAS, 1 hit
PF08447 PAS_3, 1 hit
PRINTSiPR00785 NCTRNSLOCATR
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SM00086 PAC, 1 hit
SM00091 PAS, 2 hits
SUPFAMiSSF47459 SSF47459, 1 hit
SSF55785 SSF55785, 2 hits
TIGRFAMsiTIGR00229 sensory_box, 2 hits
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit
PS50112 PAS, 2 hits

ProtoNet; Automatic hierarchical classification of proteins

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ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiEPAS1_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q99814
Secondary accession number(s): Q86VA2, Q99630
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: July 3, 2003
Last modified: October 16, 2019
This is version 208 of the entry and version 3 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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