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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei145 – 14512-oxoglutarateBy similarity
Binding sitei152 – 1521SubstrateBy similarity
Binding sitei196 – 19612-oxoglutarateBy similarity
Metal bindingi199 – 1991Iron; via tele nitrogen; catalyticBy similarity
Metal bindingi201 – 2011Iron; via tele nitrogen; catalyticBy similarity
Binding sitei205 – 20512-oxoglutarateBy similarity
Binding sitei214 – 21412-oxoglutarateBy similarity
Metal bindingi279 – 2791Iron; via tele nitrogen; catalyticBy similarity
Binding sitei294 – 29412-oxoglutarateBy similarity
Binding sitei300 – 3001Substrate; via amide nitrogenBy similarity
Binding sitei321 – 3211SubstrateBy similarity
Sitei340 – 3401Important for dimer formationBy similarity

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

ReactomeiREACT_283028. 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
ProteomesiUP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:2442345. Hif1an.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 349348Hypoxia-inducible factor 1-alpha inhibitorPRO_0000083975Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ8BLR9.
PaxDbiQ8BLR9.
PRIDEiQ8BLR9.

PTM databases

PhosphoSiteiQ8BLR9.

Expressioni

Gene expression databases

BgeeiQ8BLR9.
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

Protein-protein interaction databases

BioGridi235386. 2 interactions.
STRINGi10090.ENSMUSP00000035326.

Structurei

3D structure databases

ProteinModelPortaliQ8BLR9.
SMRiQ8BLR9. Positions 22-349.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini142 – 307166JmjCPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 125124Interaction with VHLBy similarityAdd
BLAST
Regioni181 – 1833Substrate bindingBy similarity
Regioni201 – 2033Substrate bindingBy similarity
Regioni238 – 2392Substrate bindingBy similarity

Sequence similaritiesi

Contains 1 JmjC domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG71927.
GeneTreeiENSGT00530000062914.
HOGENOMiHOG000008146.
HOVERGENiHBG051903.
InParanoidiQ8BLR9.
KOiK18055.
OMAiMIKGRYD.
OrthoDBiEOG72NRQ4.
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:SF19. PTHR12461:SF19. 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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti177 – 1771R → L in AAI30014 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei241 – 26323QVDFD…VGYET → GVKRRDQAKRETIAKEKYTK QNK in isoform 2. 1 PublicationVSP_017537Add
BLAST
Alternative sequencei264 – 34986Missing in isoform 2. 1 PublicationVSP_017538Add
BLAST

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. Positions 22-349.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi235386. 2 interactions.
STRINGi10090.ENSMUSP00000035326.

PTM databases

PhosphoSiteiQ8BLR9.

Proteomic databases

MaxQBiQ8BLR9.
PaxDbiQ8BLR9.
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

eggNOGiNOG71927.
GeneTreeiENSGT00530000062914.
HOGENOMiHOG000008146.
HOVERGENiHBG051903.
InParanoidiQ8BLR9.
KOiK18055.
OMAiMIKGRYD.
OrthoDBiEOG72NRQ4.
PhylomeDBiQ8BLR9.
TreeFamiTF329609.

Enzyme and pathway databases

ReactomeiREACT_283028. Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha.

Miscellaneous databases

ChiTaRSiHif1an. mouse.
NextBioi395052.
PROiQ8BLR9.
SOURCEiSearch...

Gene expression databases

BgeeiQ8BLR9.
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:SF19. PTHR12461:SF19. 1 hit.
SMARTiSM00558. JmjC. 1 hit.
[Graphical view]
PROSITEiPS51184. JMJC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.
  4. "Anks3 interacts with nephronophthisis proteins and is required for normal renal development."
    Yakulov T.A., Yasunaga T., Ramachandran H., Engel C., Mueller B., Hoff S., Dengjel J., Lienkamp S.S., Walz G.
    Kidney Int. 0:0-0(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ANKS3.

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: June 24, 2015
This is version 107 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

External Data

Dasty 3

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 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.