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Q8BLR9 (HIF1N_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Hif1an
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length349 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3

Catalytic activity

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.

Cofactor

Fe2+ ion By similarity.

Subunit structure

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. Ref.3

Subcellular location

Nucleus By similarity. Cytoplasm By similarity. Cytoplasmperinuclear region By similarity.

Sequence similarities

Contains 1 JmjC domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   LigandIron
Metal-binding
   Molecular functionDioxygenase
Oxidoreductase
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processnegative regulation of Notch signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter in response to hypoxia

Inferred from sequence or structural similarity. Source: UniProtKB

oxidation-reduction process

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-asparagine hydroxylation

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-aspartic acid hydroxylation

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-histidine hydroxylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of myoblast differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionNotch binding

Inferred from sequence or structural similarity. Source: UniProtKB

ankyrin repeat binding

Inferred from sequence or structural similarity. Source: UniProtKB

carboxylic acid binding

Inferred from electronic annotation. Source: Ensembl

cofactor binding

Inferred from electronic annotation. Source: Ensembl

iron ion binding

Inferred from electronic annotation. Source: Ensembl

peptidyl-asparagine 3-dioxygenase activity

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-histidine dioxygenase activity

Inferred from sequence or structural similarity. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8BLR9-1)

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.
Isoform 2 (identifier: Q8BLR9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     241-263: QVDFDNPDYERFPNFRNVVGYET → GVKRRDQAKRETIAKEKYTKQNK
     264-349: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 349348Hypoxia-inducible factor 1-alpha inhibitor
PRO_0000083975

Regions

Domain142 – 307166JmjC
Region2 – 125124Interaction with VHL By similarity
Region181 – 1833Substrate binding By similarity
Region201 – 2033Substrate binding By similarity
Region238 – 2392Substrate binding By similarity

Sites

Metal binding1991Iron; via tele nitrogen; catalytic By similarity
Metal binding2011Iron; via tele nitrogen; catalytic By similarity
Metal binding2791Iron; via tele nitrogen; catalytic By similarity
Binding site14512-oxoglutarate By similarity
Binding site1521Substrate By similarity
Binding site19612-oxoglutarate By similarity
Binding site20512-oxoglutarate By similarity
Binding site21412-oxoglutarate By similarity
Binding site29412-oxoglutarate By similarity
Binding site3001Substrate; via amide nitrogen By similarity
Binding site3211Substrate By similarity
Site3401Important for dimer formation By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity

Natural variations

Alternative sequence241 – 26323QVDFD…VGYET → GVKRRDQAKRETIAKEKYTK QNK in isoform 2.
VSP_017537
Alternative sequence264 – 34986Missing in isoform 2.
VSP_017538

Experimental info

Sequence conflict1771R → L in AAI30014. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 7, 2006. Version 2.
Checksum: ED5C2B875EBCE76E

FASTA34940,241
        10         20         30         40         50         60 
MAATAAEVAA SGSGEAREEA EAPGPAWDES QLRSYSFPTR PIPRLSQSDP RAEELIENEE 

        70         80         90        100        110        120 
PVVLTDTNLV YPALKWDLEY LQENIGNGDF SVYSASTHKF LYYDEKKMGN FQNFKPRSNR 

       130        140        150        160        170        180 
EEIKFHEFVE KLQAIQQRGG EERLYLQQTL NDTVGRKIVM DFLGFNWNWI NKQQGKRGWG 

       190        200        210        220        230        240 
QLTSNLLLIG MEGNVTPAHY DEQQNFFAQI KGHKRCILFP PDQFECLYPY PVHHPCDRQS 

       250        260        270        280        290        300 
QVDFDNPDYE RFPNFRNVVG YETVVGPGDV LYIPMYWWHH IESLLNGGIT ITVNFWYKGA 

       310        320        330        340 
PTPKRIEYPL KAHQKVAIMR NIEKMLGEAL GNPQEVGPLL NTMIKGRYN 

« Hide

Isoform 2 [UniParc].

Checksum: F7386262A6C77954
Show »

FASTA26330,424

References

« Hide 'large scale' references
[1]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Strain: C57BL/6J and NOD.
Tissue: Brain cortex.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]"ASB4 is a hydroxylation substrate of FIH and promotes vascular differentiation via an oxygen-dependent mechanism."
Ferguson J.E. III, Wu Y., Smith K., Charles P., Powers K., Wang H., Patterson C.
Mol. Cell. Biol. 27:6407-6419(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ASB4.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK043636 mRNA. Translation: BAC31602.1.
AK154774 mRNA. Translation: BAE32822.1.
BC130013 mRNA. Translation: AAI30014.1.
CCDSCCDS29852.1. [Q8BLR9-1]
RefSeqNP_795932.2. NM_176958.3. [Q8BLR9-1]
UniGeneMm.145278.

3D structure databases

ProteinModelPortalQ8BLR9.
SMRQ8BLR9. Positions 22-349.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid235386. 2 interactions.

PTM databases

PhosphoSiteQ8BLR9.

Proteomic databases

PaxDbQ8BLR9.
PRIDEQ8BLR9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000040455; ENSMUSP00000035326; ENSMUSG00000036450. [Q8BLR9-1]
GeneID319594.
KEGGmmu:319594.
UCSCuc008hpx.1. mouse. [Q8BLR9-2]
uc008hpy.1. mouse. [Q8BLR9-1]

Organism-specific databases

CTD55662.
MGIMGI:2442345. Hif1an.

Phylogenomic databases

eggNOGNOG71927.
GeneTreeENSGT00530000062914.
HOGENOMHOG000008146.
HOVERGENHBG051903.
InParanoidQ8BLR9.
KOK18055.
OMAMIKGRYD.
OrthoDBEOG72NRQ4.
PhylomeDBQ8BLR9.
TreeFamTF329609.

Gene expression databases

BgeeQ8BLR9.
GenevestigatorQ8BLR9.

Family and domain databases

Gene3D1.10.287.1010. 1 hit.
InterProIPR027445. FIH-1.
IPR027452. FIH-1_domII.
IPR003347. JmjC_dom.
[Graphical view]
PANTHERPTHR12461:SF19. PTHR12461:SF19. 1 hit.
SMARTSM00558. JmjC. 1 hit.
[Graphical view]
PROSITEPS51184. JMJC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio395052.
PROQ8BLR9.
SOURCESearch...

Entry information

Entry nameHIF1N_MOUSE
AccessionPrimary (citable) accession number: Q8BLR9
Secondary accession number(s): A1L3B7, Q3U3G4
Entry history
Integrated into UniProtKB/Swiss-Prot: June 16, 2003
Last sequence update: March 7, 2006
Last modified: July 9, 2014
This is version 97 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

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