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Reviewed, UniProtKB/Swiss-Prot P27540 (ARNT_HUMAN)

Last modified June 16, 2009. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Aryl hydrocarbon receptor nuclear translocator
      Short name=ARNT protein
Alternative name(s):
    Class E basic helix-loop-helix protein 2
      Short name=bHLHe2
    Dioxin receptor, nuclear translocator
    Hypoxia-inducible factor 1 beta
      Short name=HIF-1 beta
Gene names
Name: ARNT
Synonyms: BHLHE2
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length789 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Required for activity of the Ah (dioxin) receptor. This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex then initiates transcription of genes involved in the activation of PAH procarcinogens. The heterodimer with HIF1A or EPAS1/HIF2A functions as a transcriptional regulator of the adaptive response to hypoxia.

Subunit structure

Efficient DNA binding requires dimerization with another bHLH protein. Forms a heterodimer with AHR, AHRR, HIF1A and EPAS1/HIF2A as well as with other bHLH proteins. Interacts with TACC3 By similarity. Interacts with NOCA7.

Subcellular location

Nucleus.

Sequence similarities

Contains 1 basic helix-loop-helix (bHLH) domain.

Contains 1 PAC (PAS-associated C-terminal) domain.

Contains 2 PAS (PER-ARNT-SIM) domains.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandDNA-binding
   Molecular functionActivator
   PTMPhosphoprotein
   Technical term3D-structure
Direct protein sequencing
Gene Ontology (GO)
   Biological processmRNA transcription from RNA polymerase II promoter Ref.8

Inferred by curator. Source: UniProtKB

positive regulation of endothelial cell proliferation

Inferred by curator. Source: UniProtKB

positive regulation of erythrocyte differentiation

Inferred by curator. Source: UniProtKB

positive regulation of gene-specific transcription

Inferred from direct assay. Source: UniProtKB

positive regulation of glycolysis

Inferred by curator. Source: UniProtKB

positive regulation of hormone biosynthetic process

Inferred from direct assay. Source: UniProtKB

positive regulation of vascular endothelial growth factor receptor signaling pathway

Inferred by curator. Source: UniProtKB

positive regulation vascular endothelial growth factor production

Inferred from direct assay. Source: UniProtKB

regulation of transcription from RNA polymerase II promoter in response to oxidative stress

Inferred from direct assay. Source: UniProtKB

response to hypoxia

Inferred from direct assay. Source: UniProtKB

signal transduction

Inferred from electronic annotation. Source: InterPro

   Cellular componentnucleus Ref.9

Inferred from direct assay. Source: UniProtKB

   Molecular functionaryl hydrocarbon receptor binding

Inferred from physical interaction. Source: UniProtKB

protein heterodimerization activity

Inferred from physical interaction. Source: UniProtKB

signal transducer activity

Inferred from electronic annotation. Source: InterPro

transcription coactivator activity Ref.9

Traceable author statement. Source: ProtInc

transcription factor activity Ref.9

Traceable author statement. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

NCOA7Q8NI081EBI-80809,EBI-80799
NCOR2Q9Y6181EBI-80809,EBI-80830

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P27540-1)

Also known as: Long;

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: P27540-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     77-91: Missing.
Isoform 3 (identifier: P27540-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: Missing.
     319-323: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 789789Aryl hydrocarbon receptor nuclear translocator
PRO_0000127118

Regions

Domain103 – 14341Helix-loop-helix motif
Domain161 – 23575PAS 1
Domain349 – 41971PAS 2
Domain424 – 46744PAC
DNA binding90 – 10213Basic motif
Compositional bias99 – 1024Poly-Arg
Compositional bias503 – 5075Poly-Gln
Compositional bias710 – 76960Gln-rich
Compositional bias738 – 7414Poly-Ser

Amino acid modifications

Modified residue771Phosphoserine Ref.11

Natural variations

Alternative sequence1 – 99Missing in isoform 3.
VSP_036532
Alternative sequence77 – 9115Missing in isoform 2.
VSP_002092
Alternative sequence319 – 3235Missing in isoform 3.
VSP_036533
Natural variant4301R → Q: dbSNP rs2229175.
VAR_024280
Natural variant4351E → K: dbSNP rs2229176.
VAR_049537
Natural variant5111D → N: dbSNP rs1805133.
VAR_014819
Natural variant5171D → E: dbSNP rs10305741. Ref.5
VAR_018906
Natural variant7061P → L: dbSNP rs2275237.
VAR_020189

Secondary structure

......................... 789
Helix Strand Turn

Details...

Sequences

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

Last modified August 1, 1992. Version 1.
Checksum: 2E278F8E62BFBF6D

FASTA78986,636
        10         20         30         40         50         60 
MAATTANPEM TSDVPSLGPA IASGNSGPGI QGGGAIVQRA IKRRPGLDFD DDGEGNSKFL 

        70         80         90        100        110        120 
RCDDDQMSND KERFARSDDE QSSADKERLA RENHSEIERR RRNKMTAYIT ELSDMVPTCS 

       130        140        150        160        170        180 
ALARKPDKLT ILRMAVSHMK SLRGTGNTST DGSYKPSFLT DQELKHLILE AADGFLFIVS 

       190        200        210        220        230        240 
CETGRVVYVS DSVTPVLNQP QSEWFGSTLY DQVHPDDVDK LREQLSTSEN ALTGRILDLK 

       250        260        270        280        290        300 
TGTVKKEGQQ SSMRMCMGSR RSFICRMRCG SSSVDPVSVN RLSFVRNRCR NGLGSVKDGE 

       310        320        330        340        350        360 
PHFVVVHCTG YIKAWPPAGV SLPDDDPEAG QGSKFCLVAI GRLQVTSSPN CTDMSNVCQP 

       370        380        390        400        410        420 
TEFISRHNIE GIFTFVDHRC VATVGYQPQE LLGKNIVEFC HPEDQQLLRD SFQQVVKLKG 

       430        440        450        460        470        480 
QVLSVMFRFR SKNQEWLWMR TSSFTFQNPY SDEIEYIICT NTNVKNSSQE PRPTLSNTIQ 

       490        500        510        520        530        540 
RPQLGPTANL PLEMGSGQLA PRQQQQQTEL DMVPGRDGLA SYNHSQVVQP VTTTGPEHSK 

       550        560        570        580        590        600 
PLEKSDGLFA QDRDPRFSEI YHNINADQSK GISSSTVPAT QQLFSQGNTF PPTPRPAENF 

       610        620        630        640        650        660 
RNSGLAPPVT IVQPSASAGQ MLAQISRHSN PTQGATPTWT PTTRSGFSAQ QVATQATAKT 

       670        680        690        700        710        720 
RTSQFGVGSF QTPSSFSSMS LPGAPTASPG AAAYPSLTNR GSNFAPETGQ TAGQFQTRTA 

       730        740        750        760        770        780 
EGVGVWPQWQ GQQPHHRSSS SEQHVQQPPA QQPGQPEVFQ EMLSMLGDQS NSYNNEEFPD 


LTMFPPFSE 

« Hide

Isoform 2 (Short).

Checksum: 0653070528296044
Show »

FASTA77484,948
Isoform 3.

Checksum: 74839AACC350CB6B
Show »

FASTA77585,296

References

« Hide 'large scale' references
[1]"Cloning of a factor required for activity of the Ah (dioxin) receptor."
Hoffman E.C., Reyes H., Chu F.-F., Sander F., Conley L.H., Brooks B.A., Hankinson O.
Science 252:954-958(1991) [PubMed: 1852076] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[2]Scheel J.
Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Thalamus and Uterus.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Brain.
[5]NIEHS SNPs program
Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-517.
[6]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed: 16710414] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension."
Wang G.L., Jiang B.-H., Rue E.A., Semenza G.L.
Proc. Natl. Acad. Sci. U.S.A. 92:5510-5514(1995) [PubMed: 7539918] [Abstract]
Cited for: PROTEIN SEQUENCE OF 186-203 AND 662-694.
[9]"Identification of the Ah receptor nuclear translocator protein (Arnt) as a component of the DNA binding form of the Ah receptor."
Reyes H., Reisz-Porszasz S., Hankinson O.
Science 256:1193-1195(1992) [PubMed: 1317062] [Abstract]
Cited for: CHARACTERIZATION.
[10]"Interactions of nuclear receptor coactivator/corepressor proteins with the aryl hydrocarbon receptor complex."
Nguyen T.A., Hoivik D., Lee J.-E., Safe S.
Arch. Biochem. Biophys. 367:250-257(1999) [PubMed: 10395741] [Abstract]
Cited for: INTERACTION WITH NOCA7.
[11]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77, MASS SPECTROMETRY.
+Additional computationally mapped references.

Cross-references

Sequence databases

M69238 mRNA. Translation: AAA51777.1.
Y18859 expand/collapse EMBL AC list , AJ404853, AJ404852, AJ404851, AJ404854, AJ251863 Genomic DNA. Translation: CAC21446.1.
AK290177 mRNA. Translation: BAF82866.1.
AK293027 mRNA. Translation: BAF85716.1.
AL834279 mRNA. Translation: CAD38953.1. Different initiation.
AY430083 Genomic DNA. Translation: AAQ96598.1.
AL355860 Genomic DNA. Translation: CAI12797.1.
CH471121 Genomic DNA. Translation: EAW53510.1.
IPIIPI00218287.
IPI00514749.
IPI00922490.
PIRI59550.
RefSeqNP_001659.1.
NP_848514.1.
UniGeneHs.632446

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1D7Gmodel-C87-145[»]
1X0ONMR-A356-470[»]
2A24NMR-B358-465[»]
2ARNmodel-A335-462[»]
2B02X-ray1.50A354-470[»]
2HV1NMR-A/B356-470[»]
2K7SNMR-A356-470[»]
3F1NX-ray1.48B356-470[»]
3F1OX-ray1.60B356-470[»]
3F1PX-ray1.17B356-470[»]
SMRQ5QP39. Positions 354-464.
ModBaseSearch...

Protein-protein interaction databases

IntActP27540. 9 interactions.

PTM databases

PhosphoSiteP27540.

Proteomic databases

PRIDEP27540.

Genome annotation databases

EnsemblENSG00000143437. Homo sapiens. [Contig view]
GeneID405.
KEGGhsa:405.

Organism-specific databases

GeneCardsGC01M149048.
H-InvDBHIX0001037.
HGNCHGNC:700. ARNT.
HPACAB004318.
HPA001759.
MIM126110. gene.
PharmGKBPA24994.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP27540.

Enzyme and pathway databases

Pathway_Interaction_DBhif1_tfpathway. HIF-1-alpha transcription factor network.
hif1apathway. Hypoxic and oxygen homeostasis regulation of HIF-1-alpha.
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.

Gene expression databases

ArrayExpressP27540.
BgeeP27540.
CleanExHS_ARNT.
GermOnlineENSG00000143437. Homo sapiens.

Family and domain databases

InterProIPR001092. HLH_basic.
IPR011598. HLH_DNA_bd.
IPR001067. Nuc_translocat.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
IPR013655. PAS_fold_3.
[Graphical view]
Gene3DG3DSA:4.10.280.10. HLH_DNA_bd. 1 hit.
PfamPF00010. HLH. 1 hit.
PF00989. PAS. 1 hit.
PF08447. PAS_3. 1 hit.
[Graphical view]
PRINTSPR00785. NCTRNSLOCATR.
SMARTSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
TIGRFAMsTIGR00229. sensory_box. 1 hit.
PROSITEPS50888. HLH. 1 hit.
PS50113. PAC. False negative.
PS50112. PAS. 2 hits.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio1693.
SOURCESearch...

Entry information

Entry nameARNT_HUMAN
AccessionPrimary (citable) accession number: P27540
Secondary accession number(s): Q5QP39, Q8NDC7
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: June 16, 2009
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents