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Protein

Hypoxia-inducible factor 1

Gene

hif-1

Organism
Caenorhabditis elegans
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

A transcription factor which is a key regulator in various cellular processes; including environment stress resistance (oxygen levels, hydrogen sulfide and cyanide levels and heat), negative regulation of cell apoptosis in ASJ neurons by inhibition of cep-1 via transcriptional activation of tyr-2, resistance/susceptibility to pathogenic bacteria, lifespan and brood size (PubMed:11427734, PubMed:12006646, PubMed:12686697, PubMed:15781453, PubMed:18477695, PubMed:19461873, PubMed:21093262, PubMed:19889840, PubMed:20520707, PubMed:20400959). Involved in mediating susceptibility to enteropathogenic E.coli (PubMed:16091039). Increased levels of hif-1 activity confer resistance to P.aeruginosa-mediated death but also confer susceptibility to S.aureus infection (PubMed:20865124, PubMed:22792069). Required for aha-1 nuclear localization (PubMed:11427734). Following hypoxic stress, up-regulates serotonin levels through activation of tph-1 expression (PubMed:20400959). Role in life span extension is dependent of temperature (PubMed:21241450). Not required for survival in anoxic conditions (PubMed:11427734). Involved in iron homeostasis by repressing transcription of ferritin ftn-1 and ftn-2, and divalent metal transporter smf-3 (PubMed:22396654, PubMed:22194696). May be involved in manganese homeostasis by repressing divalent metal transporter smf-3 (PubMed:22194696).16 Publications

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cellular response to caloric restriction Source: UniProtKB
  • determination of adult lifespan Source: UniProtKB
  • heat acclimation Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • phosphorelay signal transduction system Source: UniProtKB-KW
  • positive regulation of transcription from RNA polymerase II promoter Source: WormBase
  • response to axon injury Source: WormBase
  • response to hypoxia Source: UniProtKB
  • transcription from RNA polymerase II promoter Source: WormBase
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

Apoptosis, Stress response, Transcription, Transcription regulation, Two-component regulatory system

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-CEL-1234158. Regulation of gene expression by Hypoxia-inducible Factor.
R-CEL-1234176. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
R-CEL-5689880. Ub-specific processing proteases.

Names & Taxonomyi

Protein namesi
Recommended name:
Hypoxia-inducible factor 12 Publications
Alternative name(s):
Hypoxia-induced factor 11 PublicationImported
Gene namesi
Name:hif-1Imported
ORF Names:F38A6.3
OrganismiCaenorhabditis elegans
Taxonomic identifieri6239 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
Proteomesi
  • UP000001940 Componenti: Chromosome V

Organism-specific databases

WormBaseiF38A6.3a; CE38182; WBGene00001851; hif-1.
F38A6.3b; CE42263; WBGene00001851; hif-1.
F38A6.3c; CE32019; WBGene00001851; hif-1.
F38A6.3d; CE38181; WBGene00001851; hif-1.
F38A6.3e; CE46300; WBGene00001851; hif-1.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation1 Publication

GO - Cellular componenti

  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

66% do not survive embryogenesis when cultured in hypoxic conditions of 1% oxygen. Able to survive anoxic conditions (PubMed:11427734, PubMed:12006646). Inefficient translocation of aha-1 to the nucleus (PubMed:11427734). Inability to acclimate to heat (PubMed:12686697). Partial resistance to paralysis and killing by enteropathogenic E.coli and P.aeruginosa (PubMed:16091039, PubMed:20865124). Extends lifespan in a temperature dependent manner but not when grown with a restricted diet (PubMed:19461873, PubMed:21093262). At lower temperatures impairs lifespan because of a vulval integrity defect (PubMed:21241450). Unable to survive in even relatively low concentrations of hydrogen sulfide (PubMed:19889840). Reduced body levels of Mn2+ and iron (PubMed:22194696). In low iron conditions, only 20% of animals reach the L4 larval stage (PubMed:22194696). RNAi-mediated knockdown causes an increase in ftn-1 and ftn-2 mRNA levels in normal conditions and prevents the repression of smf-3, ftn-1 and to a lesser extent ftn-2 mRNA transcription in response to low iron levels (PubMed:22194696).10 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi621P → G: Loss of egl-9-mediated hydroxylation resulting in the loss of interaction with vhl-1. Normal susceptibility to P.aeruginosa killing. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004169381 – 719Hypoxia-inducible factor 1Add BLAST719

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei6214-hydroxyproline; by egl-91 Publication1

Post-translational modificationi

Hydroxylation on Pro-621 by egl-9 during normoxia conditions is required for vhl-1-mediated proteasomal degradation.1 Publication

Keywords - PTMi

Hydroxylation

Proteomic databases

PaxDbiG5EGD2.

Expressioni

Tissue specificityi

Expressed in all somatic cells.2 Publications

Inductioni

By heat acclimation, hypoxia and addition of 50 ppm hydrogen sulfide (PubMed:11427734, PubMed:12686697, PubMed:19889840). By low iron levels (PubMed:22194696).4 Publications

Gene expression databases

BgeeiWBGene00001851.
ExpressionAtlasiG5EGD2. differential.

Interactioni

Subunit structurei

Binds to aha-1 (PubMed:11427734). Interacts (hydroxylated on Pro-621) with vhl-1; the interaction induces hif-1 degradation (PubMed:11595184).2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
aha-1O022193EBI-319821,EBI-2408984

GO - Molecular functioni

  • RNA polymerase II transcription factor binding Source: WormBase

Protein-protein interaction databases

BioGridi45316. 3 interactors.
IntActiG5EGD2. 52 interactors.
STRINGi6239.F38A6.3b.

Structurei

3D structure databases

ProteinModelPortaliG5EGD2.
SMRiG5EGD2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini11 – 65bHLHPROSITE-ProRule annotationAdd BLAST55
Domaini86 – 153PAS 1PROSITE-ProRule annotationAdd BLAST68
Domaini222 – 292PAS 2PROSITE-ProRule annotationAdd BLAST71
Domaini296 – 340PACSequence analysisAdd BLAST45

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi452 – 563Ser-richSequence analysisAdd BLAST112

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation
Contains 1 PAC (PAS-associated C-terminal) domain.Sequence analysis
Contains 2 PAS (PER-ARNT-SIM) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3558. Eukaryota.
ENOG410YK57. LUCA.
GeneTreeiENSGT00760000118788.
HOGENOMiHOG000017809.
InParanoidiG5EGD2.
KOiK08268.
OMAiEEPDLSC.
OrthoDBiEOG091G0CEQ.

Family and domain databases

InterProiIPR011598. bHLH_dom.
IPR000014. PAS.
IPR013767. PAS_fold.
[Graphical view]
PfamiPF00989. PAS. 1 hit.
[Graphical view]
SMARTiSM00091. PAS. 2 hits.
[Graphical view]
SUPFAMiSSF55785. SSF55785. 2 hits.
TIGRFAMsiTIGR00229. sensory_box. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
PS50112. PAS. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform a1 Publication (identifier: G5EGD2-1) [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
MEDNRKRNME RRRETSRHAA RDRRSKESDI FDDLKMCVPI VEEGTVTHLD
60 70 80 90 100
RIALLRVAAT ICRLRKTAGN VLENNLDNEI TNEVWTEDTI AECLDGFVMI
110 120 130 140 150
VDSDSSILYV TESVAMYLGL TQTDLTGRAL RDFLHPSDYD EFDKQSKMLH
160 170 180 190 200
KPRGEDTDTT GINMVLRMKT VISPRGRCLN LKSALYKSVS FLVHSKVSTG
210 220 230 240 250
GHVSFMQGIT IPAGQGTTNA NASAMTKYTE SPMGAFTTRH TCDMRITFVS
260 270 280 290 300
DKFNYILKSE LKTLMGTSFY ELVHPADMMI VSKSMKELFA KGHIRTPYYR
310 320 330 340 350
LIAANDTLAW IQTEATTITH TTKGQKGQYV ICVHYVLGIQ GAEESLVVCT
360 370 380 390 400
DSMPAGMQVD IKKEVDDTRD YIGRQPEIVE CVDFTPLIEP EDPFDTVIEP
410 420 430 440 450
VVGGEEPVKQ ADMGARKNSY DDVLQWLFRD QPSSPPPARY RSADRFRTTE
460 470 480 490 500
PSNFGSALAS PDFMDSSSRT SRPKTSYGRR AQSQGSRTTG SSSTSASATL
510 520 530 540 550
PHSANYSPLA EGISQCGLNS PPSIKSGQVV YGDARSMGRS CDPSDSSRRF
560 570 580 590 600
SALSPSDTLN VSSTRGINPV IGSNDVFSTM PFADSIAIAE RIDSSPTLTS
610 620 630 640 650
GEPILCDDLQ WEEPDLSCLA PFVDTYDMMQ MDEGLPPELQ ALYDLPDFTP
660 670 680 690 700
AVPQAPAARP VHIDRSPPAK RMHQSGPSDL DFMYTQHYQP FQQDETYWQG
710
QQQQNEQQPS SYSPFPMLS
Length:719
Mass (Da):79,934
Last modified:December 14, 2011 - v1
Checksum:iE6F5762100E179FE
GO
Isoform b1 Publication (identifier: G5EGD2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     523-523: S → SCS

Note: No experimental confirmation available.Curated
Show »
Length:721
Mass (Da):80,124
Checksum:i2FC85980E721128D
GO
Isoform c1 Publication (identifier: G5EGD2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-216: Missing.
     217-226: TTNANASAMT → MSRDSEYLDR

Note: No experimental confirmation available.Curated
Show »
Length:503
Mass (Da):55,860
Checksum:i497E7B6DD02FA597
GO
Isoform d1 Publication (identifier: G5EGD2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     415-719: ARKNSYDDVL...SSYSPFPMLS → IYSVTDEYEQ...LPKGSIRRQH

Note: No experimental confirmation available.Curated
Show »
Length:665
Mass (Da):75,201
Checksum:i7D1D94A215878ACB
GO
Isoform e1 Publication (identifier: G5EGD2-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-8: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:711
Mass (Da):78,890
Checksum:i78FEAD4A08B0D3BB
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0430051 – 216Missing in isoform c. 1 PublicationAdd BLAST216
Alternative sequenceiVSP_0430061 – 8Missing in isoform e. 1 Publication8
Alternative sequenceiVSP_043007217 – 226TTNANASAMT → MSRDSEYLDR in isoform c. 1 Publication10
Alternative sequenceiVSP_043008415 – 719ARKNS…FPMLS → IYSVTDEYEQRVYGQISAGN DIEDCDMDSDTESIEDSGLA PEFDVDLAPIYNEKMEVDGE DEDGGEEEHVRTATMTFCNG FFATSQALRRRHATGQRTAS GQPNRRISVPLWPRRTSWIR HLVPPDRRHHTDEEHKVREV EQLDRLPRQHRPHCHTVPTT RHLQRASHNVDLTVPRVSNL DKSCTETLDLWDVAAIRPIR HDAFPPFHHQILSMCRPLEA STQSSEAMMCSPLCLLPILS PLPKGSIRRQH in isoform d. 1 PublicationAdd BLAST305
Alternative sequenceiVSP_043009523S → SCS in isoform b. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF364604 mRNA. Translation: AAK62778.1.
Z92833, AL023842 Genomic DNA. Translation: CAB07380.2.
Z92833, AL023842 Genomic DNA. Translation: CAB07381.2.
AL023842 Genomic DNA. Translation: CAD54167.1.
Z92833, AL023842 Genomic DNA. Translation: CAD54141.2.
Z92833, AL023842 Genomic DNA. Translation: CCD31074.1.
RefSeqiNP_001023891.2. NM_001028720.3. [G5EGD2-2]
NP_001023892.1. NM_001028721.2. [G5EGD2-3]
NP_001023893.1. NM_001028722.3. [G5EGD2-4]
NP_001023894.2. NM_001028723.2. [G5EGD2-5]
NP_508008.4. NM_075607.5. [G5EGD2-1]
UniGeneiCel.17085.

Genome annotation databases

EnsemblMetazoaiF38A6.3a; F38A6.3a; WBGene00001851. [G5EGD2-1]
GeneIDi180359.
KEGGicel:CELE_F38A6.3.
UCSCiF38A6.3a. c. elegans.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF364604 mRNA. Translation: AAK62778.1.
Z92833, AL023842 Genomic DNA. Translation: CAB07380.2.
Z92833, AL023842 Genomic DNA. Translation: CAB07381.2.
AL023842 Genomic DNA. Translation: CAD54167.1.
Z92833, AL023842 Genomic DNA. Translation: CAD54141.2.
Z92833, AL023842 Genomic DNA. Translation: CCD31074.1.
RefSeqiNP_001023891.2. NM_001028720.3. [G5EGD2-2]
NP_001023892.1. NM_001028721.2. [G5EGD2-3]
NP_001023893.1. NM_001028722.3. [G5EGD2-4]
NP_001023894.2. NM_001028723.2. [G5EGD2-5]
NP_508008.4. NM_075607.5. [G5EGD2-1]
UniGeneiCel.17085.

3D structure databases

ProteinModelPortaliG5EGD2.
SMRiG5EGD2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi45316. 3 interactors.
IntActiG5EGD2. 52 interactors.
STRINGi6239.F38A6.3b.

Proteomic databases

PaxDbiG5EGD2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiF38A6.3a; F38A6.3a; WBGene00001851. [G5EGD2-1]
GeneIDi180359.
KEGGicel:CELE_F38A6.3.
UCSCiF38A6.3a. c. elegans.

Organism-specific databases

CTDi180359.
WormBaseiF38A6.3a; CE38182; WBGene00001851; hif-1.
F38A6.3b; CE42263; WBGene00001851; hif-1.
F38A6.3c; CE32019; WBGene00001851; hif-1.
F38A6.3d; CE38181; WBGene00001851; hif-1.
F38A6.3e; CE46300; WBGene00001851; hif-1.

Phylogenomic databases

eggNOGiKOG3558. Eukaryota.
ENOG410YK57. LUCA.
GeneTreeiENSGT00760000118788.
HOGENOMiHOG000017809.
InParanoidiG5EGD2.
KOiK08268.
OMAiEEPDLSC.
OrthoDBiEOG091G0CEQ.

Enzyme and pathway databases

ReactomeiR-CEL-1234158. Regulation of gene expression by Hypoxia-inducible Factor.
R-CEL-1234176. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
R-CEL-5689880. Ub-specific processing proteases.

Miscellaneous databases

PROiG5EGD2.

Gene expression databases

BgeeiWBGene00001851.
ExpressionAtlasiG5EGD2. differential.

Family and domain databases

InterProiIPR011598. bHLH_dom.
IPR000014. PAS.
IPR013767. PAS_fold.
[Graphical view]
PfamiPF00989. PAS. 1 hit.
[Graphical view]
SMARTiSM00091. PAS. 2 hits.
[Graphical view]
SUPFAMiSSF55785. SSF55785. 2 hits.
TIGRFAMsiTIGR00229. sensory_box. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
PS50112. PAS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHIF1_CAEEL
AccessioniPrimary (citable) accession number: G5EGD2
Secondary accession number(s): G5ECE6
, G5EDZ3, G5EE28, Q8I4D0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 18, 2012
Last sequence update: December 14, 2011
Last modified: November 30, 2016
This is version 48 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Caenorhabditis elegans
    Caenorhabditis elegans: entries, gene names and cross-references to WormBase
  2. 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.