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Protein

Hypoxia-inducible factor 1-alpha

Gene

Hif1a

Organism
Mus musculus (Mouse)
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

Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (PubMed:26245371). Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia (By similarity).By similarity4 Publications

<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, DNA-binding
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-MMU-1234158 Regulation of gene expression by Hypoxia-inducible Factor
R-MMU-1234162 Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha
R-MMU-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-MMU-5689880 Ub-specific processing proteases
R-MMU-8857538 PTK6 promotes HIF1A stabilization
R-MMU-8951664 Neddylation

<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:
Hypoxia-inducible factor 1-alpha
Short name:
HIF-1-alpha
Short name:
HIF1-alpha
Alternative name(s):
ARNT-interacting protein
<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:Hif1a
<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>OrganismiMus musculus (Mouse)
<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 identifieri10090 [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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
<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
  • UP000000589 <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 12

Organism-specific databases

Mouse genome database (MGD) from Mouse Genome Informatics (MGI)

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MGIi
MGI:106918 Hif1a

<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; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, 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

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>Mutagenesisi170R → A: Decreases heterodimer formation with ARNT. Impairs heterodimer formation with ARNT; when associated with D-191. 1 Publication1
Mutagenesisi191V → D: Decreases heterodimer formation with ARNT. Impairs heterodimer formation with ARNT; when associated with A-170. 1 Publication1

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL6046

<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_00001272211 – 836Hypoxia-inducible factor 1-alphaAdd BLAST836

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 residuei247Phosphoserine; by CK1By similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki391Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei4024-hydroxyprolineBy similarity1
Cross-linki476Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei545N6-acetyllysine; alternateBy similarity1
Cross-linki545Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarityCurated
Cross-linki551Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarityCurated
Cross-linki560Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarityCurated
Modified residuei564Phosphoserine; by GSK3-betaBy similarity1
Modified residuei568Phosphothreonine; by GSK3-betaBy similarity1
Modified residuei5774-hydroxyprolineBy similarity1
Modified residuei589Phosphoserine; by PLK3By similarity1
Modified residuei602Phosphoserine; by GSK3-betaBy similarity1
Modified residuei668Phosphoserine; by PLK3By similarity1
Modified residuei719N6-acetyllysineBy similarity1
Modified residuei810S-nitrosocysteineBy similarity1
Modified residuei813(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

S-nitrosylation of Cys-810 may be responsible for increased recruitment of p300 coactivator necessary for transcriptional activity of HIF-1 complex.By similarity
Requires phosphorylation for DNA-binding. Phosphorylation at Ser-247 by CSNK1D/CK1 represses kinase activity and impairs ARNT binding (By similarity). Phosphorylation by GSK3-beta and PLK3 promote degradation by the proteasome.By similarity1 Publication
Sumoylated; with SUMO1 under hypoxia. Sumoylation is enhanced through interaction with RWDD3. Both sumoylation and desumoylation seem to be involved in the regulation of its stability during hypoxia. Sumoylation can promote either its stabilization or its VHL-dependent degradation by promoting hydroxyproline-independent HIF1A-VHL complex binding, thus leading to HIF1A ubiquitination and proteasomal degradation. Desumoylation by SENP1 increases its stability amd transcriptional activity. There is a disaccord between various publications on the effect of sumoylation and desumoylation on its stability and transcriptional activity.2 Publications
Acetylation of Lys-545 by ARD1 increases interaction with VHL and stimulates subsequent proteasomal degradation. Deacetylation of Lys-719 by SIRT2 increases its interaction with and hydroxylation by EGLN1 thereby inactivating HIF1A activity by inducing its proteasomal degradation (By similarity).By similarity
Ubiquitinated; in normoxia, following hydroxylation and interaction with VHL. Lys-545 appears to be the principal site of ubiquitination. Clioquinol, the Cu/Zn-chelator, inhibits ubiquitination through preventing hydroxylation at Asn-813 (By similarity).By similarity
The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains.By similarity
In normoxia, is hydroxylated on Pro-402 and Pro-577 in the oxygen-dependent degradation domain (ODD) by EGLN1/PHD2 and EGLN2/PHD1. EGLN3/PHD3 has also been shown to hydroxylate Pro-577. The hydroxylated prolines promote interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation. Deubiquitinated by USP20. Under hypoxia, proline hydroxylation is impaired and ubiquitination is attenuated, resulting in stabilization (By similarity). In normoxia, is hydroxylated on Asn-813 by HIF1AN, thus abrogating interaction with CREBBP and EP300 and preventing transcriptional activation. Repressed by iron ion, via Fe2+ prolyl hydroxylase (PHD) enzymes-mediated hydroxylation and subsequent proteasomal degradation.By similarity

Keywords - PTMi

Acetylation, Hydroxylation, Isopeptide bond, Phosphoprotein, S-nitrosylation, Ubl conjugation

Proteomic databases

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

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PaxDbi
Q61221

PRoteomics IDEntifications database

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PRIDEi
Q61221

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
Q61221

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

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PhosphoSitePlusi
Q61221

<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

Ubiquitous.

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSMUSG00000021109 Expressed in 332 organ(s), highest expression level in retina

CleanEx database of gene expression profiles

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CleanExi
MM_HIF1A

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q61221 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q61221 MM

<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 isoform 2 (PubMed:21546903). Interacts with the ARNT; forms a heterodimer that binds core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (PubMed:26245371). Interacts with Interacts with NCOA1, NCOA2, APEX and HSP90. Interacts (hydroxylated within the ODD domain) with VHLL (via beta domain); the interaction, leads to polyubiquitination and subsequent HIF1A proteasomal degradation. During hypoxia, sumoylated HIF1A also binds VHL; the interaction promotes the ubiquitination of HIF1A. Interacts with SENP1; the interaction desumoylates HIF1A resulting in stabilization and activation of transcription. Interacts (Via the ODD domain) with ARD1A; the interaction appears not to acetylate HIF1A nor have any affect on protein stability, during hypoxia. Interacts with RWDD3; the interaction enhances HIF1A sumoylation. Interacts with RORA (via the DNA binding domain); the interaction enhances HIF1A transcription under hypoxia through increasing protein stability. Interaction with PSMA7 inhibits the transactivation activity of HIF1A under both normoxic and hypoxia-mimicking conditions. Interacts with USP20. Interacts with RACK1; promotes HIF1A ubiquitination and proteasome-mediated degradation. Interacts with EP300 (via TAZ-type 1 domain); the interaction is stimulated in response to hypoxia and inhibited by CITED2. Interacts with CREBBP (via TAZ-type 1 domain). Interacts with SIRT2. Interacts (deacetylated form) with EGLN1 (By similarity). Interacts with TSGA10. Interacts (via N-terminus) with USP19. Interacts with COPS5; the interaction increases the transcriptional activity of HIF1A through increased stability. Interacts with CBFA2T3. Interacts with HSP90AA1 and HSP90AB1 (By similarity).By similarity4 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
200304, 20 interactors

Database of interacting proteins

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DIPi
DIP-31083N

Protein interaction database and analysis system

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IntActi
Q61221, 15 interactors

Molecular INTeraction database

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MINTi
Q61221

STRING: functional protein association networks

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STRINGi
10090.ENSMUSP00000021530

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q61221

<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

3D structure databases

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
Q61221

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

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SMRi
Q61221

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

<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>Domaini17 – 70bHLHPROSITE-ProRule annotationAdd BLAST54
Domaini80 – 155PAS 1PROSITE-ProRule annotationAdd BLAST76
Domaini228 – 298PAS 2PROSITE-ProRule annotationAdd BLAST71
Domaini302 – 345PACAdd 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>Regioni1 – 401Interaction with TSGA101 PublicationAdd BLAST401
Regioni21 – 30DNA-binding1 Publication10
Regioni170 – 191Required for heterodimer formation with ARNT1 PublicationAdd BLAST22
Regioni380 – 417N-terminal VHL recognition siteBy similarityAdd BLAST38
Regioni401 – 613ODDAdd BLAST213
Regioni544 – 588NTADAdd BLAST45
Regioni569 – 585C-terminal VHL recognition siteBy similarityAdd BLAST17
Regioni589 – 795IDAdd BLAST207
Regioni796 – 836CTADAdd BLAST41

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi728 – 731Nuclear localization signalSequence analysis4

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

Contains two independent C-terminal transactivation domains, NTAD and CTAD, which function synergistically. Their transcriptional activity is repressed by an intervening inhibitory domain (ID) (By similarity).By similarity

Keywords - Domaini

Repeat

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG3558 Eukaryota
ENOG410YK57 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000156774

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG060456

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q61221

KEGG Orthology (KO)

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KOi
K08268

Database of Orthologous Groups

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OrthoDBi
EOG091G0486

Database for complete collections of gene phylogenies

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PhylomeDBi
Q61221

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
IPR001321 HIF-1_alpha
IPR014887 HIF-1_TAD_C
IPR021537 HIF_alpha_subunit
IPR036638 HLH_DNA-bd_sf
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

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PRINTSi
PR01080 HYPOXIAIF1A

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

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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>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)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 describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q61221-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MEGAGGENEK KKMSSERRKE KSRDAARSRR SKESEVFYEL AHQLPLPHNV
60 70 80 90 100
SSHLDKASVM RLTISYLRVR KLLDAGGLDS EDEMKAQMDC FYLKALDGFV
110 120 130 140 150
MVLTDDGDMV YISDNVNKYM GLTQFELTGH SVFDFTHPCD HEEMREMLTH
160 170 180 190 200
RNGPVRKGKE LNTQRSFFLR MKCTLTSRGR TMNIKSATWK VLHCTGHIHV
210 220 230 240 250
YDTNSNQPQC GYKKPPMTCL VLICEPIPHP SNIEIPLDSK TFLSRHSLDM
260 270 280 290 300
KFSYCDERIT ELMGYEPEEL LGRSIYEYYH ALDSDHLTKT HHDMFTKGQV
310 320 330 340 350
TTGQYRMLAK RGGYVWVETQ ATVIYNTKNS QPQCIVCVNY VVSGIIQHDL
360 370 380 390 400
IFSLQQTESV LKPVESSDMK MTQLFTKVES EDTSCLFDKL KKEPDALTLL
410 420 430 440 450
APAAGDTIIS LDFGSDDTET EDQQLEDVPL YNDVMFPSSN EKLNINLAMS
460 470 480 490 500
PLPSSETPKP LRSSADPALN QEVALKLESS PESLGLSFTM PQIQDQPASP
510 520 530 540 550
SDGSTRQSSP ERLLQENVNT PNFSQPNSPS EYCFDVDSDM VNVFKLELVE
560 570 580 590 600
KLFAEDTEAK NPFSTQDTDL DLEMLAPYIP MDDDFQLRSF DQLSPLESNS
610 620 630 640 650
PSPPSMSTVT GFQQTQLQKP TITATATTTA TTDESKTETK DNKEDIKILI
660 670 680 690 700
ASPSSTQVPQ ETTTAKASAY SGTHSRTASP DRAGKRVIEQ TDKAHPRSLN
710 720 730 740 750
LSATLNQRNT VPEEELNPKT IASQNAQRKR KMEHDGSLFQ AAGIGTLLQQ
760 770 780 790 800
PGDCAPTMSL SWKRVKGFIS SEQNGTEQKT IILIPSDLAC RLLGQSMDES
810 820 830
GLPQLTSYDC EVNAPIQGSR NLLQGEELLR ALDQVN
Length:836
Mass (Da):93,516
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:i84D64ECAC2CC753B
GO
Isoform 2 (identifier: Q61221-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     512-525: Missing.

Show »
Length:822
Mass (Da):91,874
Checksum:i8DC6E7C1772AF1BF
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 are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0R4J1E9A0A0R4J1E9_MOUSE
Hypoxia-inducible factor 1-alpha
Hif1a
810Annotation 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>
A0A0R4J1F0A0A0R4J1F0_MOUSE
Hypoxia-inducible factor 1-alpha
Hif1a
258Annotation 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 conflicti12K → NR in BAC28578 (PubMed:16141072).Curated1
Sequence conflicti31S → T in AAC52730 (PubMed:8702901).Curated1
Sequence conflicti128T → A in AAC52730 (PubMed:8702901).Curated1
Sequence conflicti128T → A in CAA64833 (PubMed:8660378).Curated1
Sequence conflicti351I → L in AAC52730 (PubMed:8702901).Curated1
Sequence conflicti369M → K in AAH26139 (PubMed:15489334).Curated1
Sequence conflicti382D → A in AAH26139 (PubMed:15489334).Curated1
Sequence conflicti397L → H in BAC28578 (PubMed:16141072).Curated1
Sequence conflicti569D → G in BAC28578 (PubMed:16141072).Curated1
Sequence conflicti660Q → K in BAC28305 (PubMed:16141072).Curated1
Sequence conflicti700N → K in AAC52730 (PubMed:8702901).Curated1
Sequence conflicti700N → K in AAC53455 (PubMed:9368100).Curated1
Sequence conflicti700N → K in AAC53461 (PubMed:9368100).Curated1
Sequence conflicti799E → V in CAA64833 (PubMed:8660378).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_007739512 – 525Missing in isoform 2. 1 PublicationAdd BLAST14

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

More...
DDBJi
Links Updated
U59496 Genomic DNA Translation: AAC52730.1
AF003695 mRNA Translation: AAC53455.1
AF004155
, AF004141, AF004142, AF004143, AF004144, AF004145, AF004146, AF004147, AF004148, AF004149, AF004150, AF004151, AF004152, AF004153, AF004154 Genomic DNA Translation: AAC53461.1
Y09085 Genomic DNA Translation: CAA70305.1
Y09085, Y13656 Genomic DNA Translation: CAA70306.1
AK034087 mRNA Translation: BAC28578.1
AK076395 mRNA Translation: BAC36320.1
AK033471 mRNA Translation: BAC28305.1
AK017853 mRNA Translation: BAB30975.1
BC026139 mRNA Translation: AAH26139.1
X95580 mRNA Translation: CAA64833.1
X95002 mRNA Translation: CAA64458.1

The Consensus CDS (CCDS) project

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CCDSi
CCDS25977.1 [Q61221-1]

Protein sequence database of the Protein Information Resource

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PIRi
JC4837

NCBI Reference Sequences

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RefSeqi
NP_001300848.1, NM_001313919.1
NP_001300849.1, NM_001313920.1
NP_034561.2, NM_010431.2 [Q61221-1]
XP_017170450.1, XM_017314961.1 [Q61221-2]

UniGene gene-oriented nucleotide sequence clusters

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UniGenei
Mm.3879
Mm.446610

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENSMUST00000021530; ENSMUSP00000021530; ENSMUSG00000021109 [Q61221-1]

Database of genes from NCBI RefSeq genomes

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GeneIDi
15251

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
mmu:15251

UCSC genome browser

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UCSCi
uc007nwo.2 mouse [Q61221-2]
uc007nwq.2 mouse [Q61221-1]

Keywords - Coding sequence diversityi

Alternative splicing

<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
U59496 Genomic DNA Translation: AAC52730.1
AF003695 mRNA Translation: AAC53455.1
AF004155
, AF004141, AF004142, AF004143, AF004144, AF004145, AF004146, AF004147, AF004148, AF004149, AF004150, AF004151, AF004152, AF004153, AF004154 Genomic DNA Translation: AAC53461.1
Y09085 Genomic DNA Translation: CAA70305.1
Y09085, Y13656 Genomic DNA Translation: CAA70306.1
AK034087 mRNA Translation: BAC28578.1
AK076395 mRNA Translation: BAC36320.1
AK033471 mRNA Translation: BAC28305.1
AK017853 mRNA Translation: BAB30975.1
BC026139 mRNA Translation: AAH26139.1
X95580 mRNA Translation: CAA64833.1
X95002 mRNA Translation: CAA64458.1
CCDSiCCDS25977.1 [Q61221-1]
PIRiJC4837
RefSeqiNP_001300848.1, NM_001313919.1
NP_001300849.1, NM_001313920.1
NP_034561.2, NM_010431.2 [Q61221-1]
XP_017170450.1, XM_017314961.1 [Q61221-2]
UniGeneiMm.3879
Mm.446610

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
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
4ZPRX-ray3.90B13-357[»]
ProteinModelPortaliQ61221
SMRiQ61221
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200304, 20 interactors
DIPiDIP-31083N
IntActiQ61221, 15 interactors
MINTiQ61221
STRINGi10090.ENSMUSP00000021530

Chemistry databases

BindingDBiQ61221
ChEMBLiCHEMBL6046

PTM databases

iPTMnetiQ61221
PhosphoSitePlusiQ61221

Proteomic databases

PaxDbiQ61221
PRIDEiQ61221

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021530; ENSMUSP00000021530; ENSMUSG00000021109 [Q61221-1]
GeneIDi15251
KEGGimmu:15251
UCSCiuc007nwo.2 mouse [Q61221-2]
uc007nwq.2 mouse [Q61221-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
3091
MGIiMGI:106918 Hif1a

Phylogenomic databases

eggNOGiKOG3558 Eukaryota
ENOG410YK57 LUCA
GeneTreeiENSGT00940000156774
HOVERGENiHBG060456
InParanoidiQ61221
KOiK08268
OrthoDBiEOG091G0486
PhylomeDBiQ61221
TreeFamiTF317772

Enzyme and pathway databases

ReactomeiR-MMU-1234158 Regulation of gene expression by Hypoxia-inducible Factor
R-MMU-1234162 Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha
R-MMU-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-MMU-5689880 Ub-specific processing proteases
R-MMU-8857538 PTK6 promotes HIF1A stabilization
R-MMU-8951664 Neddylation

Miscellaneous databases

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

More...
ChiTaRSi
Hif1a mouse

Protein Ontology

More...
PROi
PR:Q61221

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSMUSG00000021109 Expressed in 332 organ(s), highest expression level in retina
CleanExiMM_HIF1A
ExpressionAtlasiQ61221 baseline and differential
GenevisibleiQ61221 MM

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
IPR001321 HIF-1_alpha
IPR014887 HIF-1_TAD_C
IPR021537 HIF_alpha_subunit
IPR036638 HLH_DNA-bd_sf
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
PRINTSiPR01080 HYPOXIAIF1A
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

More...
ProtoNeti
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 nameiHIF1A_MOUSE
<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: Q61221
Secondary accession number(s): O08741
, O08993, Q61664, Q61665, Q8C681, Q8CC19, Q8CCB6, Q8R385, Q9CYA8
<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: November 1, 1997
Last sequence update: July 3, 2003
Last modified: December 5, 2018
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

<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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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