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Protein

Hypoxia-inducible factor 1-alpha inhibitor

Gene

Hif1an

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hydroxylates HIF-1 alpha at 'Asp-799' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation (By similarity). Positively regulates ASB4 activity, promoting vascular differentiation.By similarity1 Publication

Catalytic activityi

Hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 = hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2.
Ankyrin-repeat-L-histidine + 2-oxoglutarate + O2 = ankyrin-repeat-(3S)-3-hydroxy-L-histidine + succinate + CO2.

Cofactori

Fe2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei1452-oxoglutarateBy similarity1
Binding sitei152SubstrateBy similarity1
Binding sitei1962-oxoglutarateBy similarity1
Metal bindingi199Iron; via tele nitrogen; catalyticBy similarity1
Metal bindingi201Iron; catalyticBy similarity1
Binding sitei2052-oxoglutarateBy similarity1
Binding sitei2142-oxoglutarateBy similarity1
Metal bindingi279Iron; via tele nitrogen; catalyticBy similarity1
Binding sitei2942-oxoglutarateBy similarity1
Binding sitei300Substrate; via amide nitrogenBy similarity1
Binding sitei321SubstrateBy similarity1
Sitei340Important for dimer formationBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-1234162. Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha.

Names & Taxonomyi

Protein namesi
Recommended name:
Hypoxia-inducible factor 1-alpha inhibitor (EC:1.14.11.30, EC:1.14.11.n4)
Alternative name(s):
Hypoxia-inducible factor asparagine hydroxylase
Gene namesi
Name:Hif1an
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:2442345. Hif1an.

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm By similarity
  • Cytoplasmperinuclear region By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000839752 – 349Hypoxia-inducible factor 1-alpha inhibitorAdd BLAST348

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ8BLR9.
PaxDbiQ8BLR9.
PeptideAtlasiQ8BLR9.
PRIDEiQ8BLR9.

PTM databases

PhosphoSitePlusiQ8BLR9.

Expressioni

Gene expression databases

BgeeiENSMUSG00000036450.
GenevisibleiQ8BLR9. MM.

Interactioni

Subunit structurei

Homodimer; homodimerization is essential for catalytic activity. Interacts with VHL and HIF1A. Part of a complex with VHL, HIF1A and HDAC1 or HDAC2 or HDAC3. Interacts with NFKB1 and NFKBIA. Interacts with NOTCH1, NOTCH2 and NOTCH3 but not with NOTCH4. Interacts with ABPA3. Interacts with TNKS2. Interacts with PPP1R12A (By similarity). Interacts with UBE3A (By similarity). Interacts with ASB4. Interacts with ANKS3 (PubMed:25671767).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi235386. 2 interactors.
STRINGi10090.ENSMUSP00000035326.

Structurei

3D structure databases

ProteinModelPortaliQ8BLR9.
SMRiQ8BLR9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini142 – 307JmjCPROSITE-ProRule annotationAdd BLAST166

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 125Interaction with VHLBy similarityAdd BLAST124
Regioni181 – 183Substrate bindingBy similarity3
Regioni201 – 203Substrate bindingBy similarity3
Regioni238 – 239Substrate bindingBy similarity2

Sequence similaritiesi

Contains 1 JmjC domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2132. Eukaryota.
ENOG410XQDR. LUCA.
GeneTreeiENSGT00530000062914.
HOGENOMiHOG000008146.
HOVERGENiHBG051903.
InParanoidiQ8BLR9.
KOiK18055.
OMAiMIKGRYD.
OrthoDBiEOG091G0C8E.
PhylomeDBiQ8BLR9.
TreeFamiTF329609.

Family and domain databases

Gene3Di1.10.287.1010. 1 hit.
InterProiIPR027445. FIH-1.
IPR027452. FIH-1_domII.
IPR003347. JmjC_dom.
[Graphical view]
PANTHERiPTHR12461:SF51. PTHR12461:SF51. 1 hit.
SMARTiSM00558. JmjC. 1 hit.
[Graphical view]
PROSITEiPS51184. JMJC. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8BLR9-1) [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
MAATAAEVAA SGSGEAREEA EAPGPAWDES QLRSYSFPTR PIPRLSQSDP
60 70 80 90 100
RAEELIENEE PVVLTDTNLV YPALKWDLEY LQENIGNGDF SVYSASTHKF
110 120 130 140 150
LYYDEKKMGN FQNFKPRSNR EEIKFHEFVE KLQAIQQRGG EERLYLQQTL
160 170 180 190 200
NDTVGRKIVM DFLGFNWNWI NKQQGKRGWG QLTSNLLLIG MEGNVTPAHY
210 220 230 240 250
DEQQNFFAQI KGHKRCILFP PDQFECLYPY PVHHPCDRQS QVDFDNPDYE
260 270 280 290 300
RFPNFRNVVG YETVVGPGDV LYIPMYWWHH IESLLNGGIT ITVNFWYKGA
310 320 330 340
PTPKRIEYPL KAHQKVAIMR NIEKMLGEAL GNPQEVGPLL NTMIKGRYN
Length:349
Mass (Da):40,241
Last modified:March 7, 2006 - v2
Checksum:iED5C2B875EBCE76E
GO
Isoform 2 (identifier: Q8BLR9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     241-263: QVDFDNPDYERFPNFRNVVGYET → GVKRRDQAKRETIAKEKYTKQNK
     264-349: Missing.

Note: No experimental confirmation available.
Show »
Length:263
Mass (Da):30,424
Checksum:iF7386262A6C77954
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti177R → L in AAI30014 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_017537241 – 263QVDFD…VGYET → GVKRRDQAKRETIAKEKYTK QNK in isoform 2. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_017538264 – 349Missing in isoform 2. 1 PublicationAdd BLAST86

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK043636 mRNA. Translation: BAC31602.1.
AK154774 mRNA. Translation: BAE32822.1.
BC130013 mRNA. Translation: AAI30014.1.
CCDSiCCDS29852.1. [Q8BLR9-1]
RefSeqiNP_795932.2. NM_176958.3. [Q8BLR9-1]
UniGeneiMm.145278.

Genome annotation databases

EnsembliENSMUST00000040455; ENSMUSP00000035326; ENSMUSG00000036450. [Q8BLR9-1]
GeneIDi319594.
KEGGimmu:319594.
UCSCiuc008hpx.1. mouse. [Q8BLR9-2]
uc008hpy.1. mouse. [Q8BLR9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK043636 mRNA. Translation: BAC31602.1.
AK154774 mRNA. Translation: BAE32822.1.
BC130013 mRNA. Translation: AAI30014.1.
CCDSiCCDS29852.1. [Q8BLR9-1]
RefSeqiNP_795932.2. NM_176958.3. [Q8BLR9-1]
UniGeneiMm.145278.

3D structure databases

ProteinModelPortaliQ8BLR9.
SMRiQ8BLR9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi235386. 2 interactors.
STRINGi10090.ENSMUSP00000035326.

PTM databases

PhosphoSitePlusiQ8BLR9.

Proteomic databases

EPDiQ8BLR9.
PaxDbiQ8BLR9.
PeptideAtlasiQ8BLR9.
PRIDEiQ8BLR9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000040455; ENSMUSP00000035326; ENSMUSG00000036450. [Q8BLR9-1]
GeneIDi319594.
KEGGimmu:319594.
UCSCiuc008hpx.1. mouse. [Q8BLR9-2]
uc008hpy.1. mouse. [Q8BLR9-1]

Organism-specific databases

CTDi55662.
MGIiMGI:2442345. Hif1an.

Phylogenomic databases

eggNOGiKOG2132. Eukaryota.
ENOG410XQDR. LUCA.
GeneTreeiENSGT00530000062914.
HOGENOMiHOG000008146.
HOVERGENiHBG051903.
InParanoidiQ8BLR9.
KOiK18055.
OMAiMIKGRYD.
OrthoDBiEOG091G0C8E.
PhylomeDBiQ8BLR9.
TreeFamiTF329609.

Enzyme and pathway databases

ReactomeiR-MMU-1234162. Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha.

Miscellaneous databases

ChiTaRSiHif1an. mouse.
PROiQ8BLR9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000036450.
GenevisibleiQ8BLR9. MM.

Family and domain databases

Gene3Di1.10.287.1010. 1 hit.
InterProiIPR027445. FIH-1.
IPR027452. FIH-1_domII.
IPR003347. JmjC_dom.
[Graphical view]
PANTHERiPTHR12461:SF51. PTHR12461:SF51. 1 hit.
SMARTiSM00558. JmjC. 1 hit.
[Graphical view]
PROSITEiPS51184. JMJC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHIF1N_MOUSE
AccessioniPrimary (citable) accession number: Q8BLR9
Secondary accession number(s): A1L3B7, Q3U3G4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 16, 2003
Last sequence update: March 7, 2006
Last modified: November 30, 2016
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  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.