Reviewed, UniProtKB/Swiss-Prot A9YTQ3 (AHRR_HUMAN)

Names and origin

Protein names

Recommended name:
    Aryl hydrocarbon receptor repressor
      Short name=AhR repressor
      Short name=AhRR
Alternative name(s):
    Class E basic helix-loop-helix protein 77
      Short name=bHLHe77

Gene names

Name:	AHRR
Synonyms:	BHLHE77, KIAA1234

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	701 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Mediates dioxin toxicity and is involved in regulation of cell growth and differentiation. Represses the transcription activity of AHR by competing with this transcription factor for heterodimer formation with the ARNT and subsequently binding to the xenobiotic response element (XRE) sequence present in the promoter regulatory region of variety of genes. Represses CYP1A1 by binding the XRE sequence and recruiting ANKRA2, HDAC4 and/or HDAC5. Autoregulates its expression by associating with its own XRE site. Ref.9 Ref.10
Subunit structure	Interacts with ARNT, ANKRA2, HDAC4 and HDAC5 By similarity.
Subcellular location	Cytoplasm. Nucleus. Note: Predominantly in the nuclear compartment. First cytoplasmic, translocates into the nuclear compartment upon interaction with ARNT in the cytoplasmic compartment. Ref.8
Tissue specificity	Highly expressed in testis, lung, ovary, spleen and pancreas. Highly expressed in mononuclear cells (MNCs) from umbilical cord blood. Isoform 3 is highly expressed in lung, kidney, spleen and thymus. Down-regulated malignant tissue from different anatomical origins, including colon, breast, lung, stomach, cervix, and ovary. Ref.10 Ref.1 Ref.7
Induction	By 3-methylcholanthrene (3-MC) in MNCs from adults. By the heterodimer AHR/ARNT. Ref.7
Polymorphism	The Ala-189 allele may be a susceptibility factor for dioxin-related male infertility. Homozygosity for Ala-189 is observed in azoospermic individuals at higher frequency than in normozoospermic individuals. Might also be associated with susceptibility to and severity of endometriosis.
Sequence similarities	Contains 1 basic helix-loop-helix (bHLH) domain. Contains 1 PAS (PER-ARNT-SIM) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro signal transduction Inferred from electronic annotation. Source: InterPro transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW signal transducer activity Inferred from electronic annotation. Source: InterPro transcription regulator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: A9YTQ3-1)

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: A9YTQ3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     240-240: L → LARGSQAWQLRLCCPEPLM

Isoform 3 (identifier: A9YTQ3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: Missing.
     240-240: L → LARGSQAWQLRLCCPEPLM

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 701	701	Aryl hydrocarbon receptor repressor		PRO_0000333857
Regions
	Domain	17 – 82	66	Helix-loop-helix motif
	Domain	112 – 182	71	PAS
	DNA binding	16 – 41	26	Basic motif By similarity
	Region	551 – 701	151	Needed for transcriptional repression By similarity
Natural variations
	Alternative sequence	1 – 4	4	Missing in isoform 3.		VSP_033563
	Alternative sequence	240	1	L → LARGSQAWQLRLCCPEPLM in isoform 2 and isoform 3.		VSP_033564
	Natural variant	114	1	L → P: dbSNP rs35008248. Ref.1		VAR_043308
	Natural variant	189	1	A → P: dbSNP rs2292596. Ref.1 Ref.4		VAR_043309
	Natural variant	373	1	G → V: dbSNP rs2303738.		VAR_043310
	Natural variant	627	1	D → H: dbSNP rs34453673.		VAR_043311

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 20, 2008. Version 2. Checksum: 4C21DDF1298760E0	FASTA	701	76,239
	10 20 30 40 50 60 MPRTMIPPGE CTYAGRKRRR PLQKQRPAVG AEKSNPSKRH RDRLNAELDH LASLLPFPPD 70 80 90 100 110 120 IISKLDKLSV LRLSVSYLRV KSFFQVVQEQ SSRQPAAGAP SPGDSCPLAG SAVLEGRLLL 130 140 150 160 170 180 ESLNGFALVV SAEGTIFYAS ATIVDYLGFH QTDVMHQNIY DYIHVDDRQD FCRQLHWAMD 190 200 210 220 230 240 PPQVVFGQAP PLETGDDAIL GRLLRAQEWG TGTPTEYSAF LTRCFICRVR CLLDSTSGFL 250 260 270 280 290 300 TMQFQGKLKF LFGQKKKAPS GAMLPPRLSL FCIAAPVLLP SAAEMKMRSA LLRAKPRADT 310 320 330 340 350 360 AATADAKVKA TTSLCESELH GKPNYSAGRS SRESGVLVLR EQTDAGRWAQ VPARAPCLCL 370 380 390 400 410 420 RGGPDLVLDP KGGSGDREEE QHRMLSRASG VTGRRETPGP TKPLPWTAGK HSEDGARPRL 430 440 450 460 470 480 QPSKNDPPSL RPMPRGSCLP CPCVQGTFRN SPISHPPSPS PSAYSSRTSR PMRDVGEDQV 490 500 510 520 530 540 HPPLCHFPQR SLQHQLPQPG AQRFATRGYP MEDMKLQGVP MPPGDLCGPT LLLDVSIKME 550 560 570 580 590 600 KDSGCEGAAD GCVPSQVWLG ASDRSHPATF PTRMHLKTEP DSRQQVYISH LGHGVRGAQP 610 620 630 640 650 660 HGRATAGRSR ELTPFHPAHC ACLEPTDGLP QSEPPHQLCA RGRGEQSCTC RAAEAAPVVK 670 680 690 700 REPLDSPQWA THSQGMVPGM LPKSALATLV PPQASGCTFL P
	Isoform 2. Checksum: BB88BE1726D206FC	FASTA	719	78,281
	10 20 30 40 50 60 MPRTMIPPGE CTYAGRKRRR PLQKQRPAVG AEKSNPSKRH RDRLNAELDH LASLLPFPPD 70 80 90 100 110 120 IISKLDKLSV LRLSVSYLRV KSFFQVVQEQ SSRQPAAGAP SPGDSCPLAG SAVLEGRLLL 130 140 150 160 170 180 ESLNGFALVV SAEGTIFYAS ATIVDYLGFH QTDVMHQNIY DYIHVDDRQD FCRQLHWAMD 190 200 210 220 230 240 PPQVVFGQAP PLETGDDAIL GRLLRAQEWG TGTPTEYSAF LTRCFICRVR CLLDSTSGFL 250 260 270 280 290 300 ARGSQAWQLR LCCPEPLMTM QFQGKLKFLF GQKKKAPSGA MLPPRLSLFC IAAPVLLPSA 310 320 330 340 350 360 AEMKMRSALL RAKPRADTAA TADAKVKATT SLCESELHGK PNYSAGRSSR ESGVLVLREQ 370 380 390 400 410 420 TDAGRWAQVP ARAPCLCLRG GPDLVLDPKG GSGDREEEQH RMLSRASGVT GRRETPGPTK 430 440 450 460 470 480 PLPWTAGKHS EDGARPRLQP SKNDPPSLRP MPRGSCLPCP CVQGTFRNSP ISHPPSPSPS 490 500 510 520 530 540 AYSSRTSRPM RDVGEDQVHP PLCHFPQRSL QHQLPQPGAQ RFATRGYPME DMKLQGVPMP 550 560 570 580 590 600 PGDLCGPTLL LDVSIKMEKD SGCEGAADGC VPSQVWLGAS DRSHPATFPT RMHLKTEPDS 610 620 630 640 650 660 RQQVYISHLG HGVRGAQPHG RATAGRSREL TPFHPAHCAC LEPTDGLPQS EPPHQLCARG 670 680 690 700 710 RGEQSCTCRA AEAAPVVKRE PLDSPQWATH SQGMVPGMLP KSALATLVPP QASGCTFLP
	Isoform 3. Checksum: 09A62D1CD28D97CA	FASTA	715	77,795
	10 20 30 40 50 60 MIPPGECTYA GRKRRRPLQK QRPAVGAEKS NPSKRHRDRL NAELDHLASL LPFPPDIISK 70 80 90 100 110 120 LDKLSVLRLS VSYLRVKSFF QVVQEQSSRQ PAAGAPSPGD SCPLAGSAVL EGRLLLESLN 130 140 150 160 170 180 GFALVVSAEG TIFYASATIV DYLGFHQTDV MHQNIYDYIH VDDRQDFCRQ LHWAMDPPQV 190 200 210 220 230 240 VFGQAPPLET GDDAILGRLL RAQEWGTGTP TEYSAFLTRC FICRVRCLLD STSGFLARGS 250 260 270 280 290 300 QAWQLRLCCP EPLMTMQFQG KLKFLFGQKK KAPSGAMLPP RLSLFCIAAP VLLPSAAEMK 310 320 330 340 350 360 MRSALLRAKP RADTAATADA KVKATTSLCE SELHGKPNYS AGRSSRESGV LVLREQTDAG 370 380 390 400 410 420 RWAQVPARAP CLCLRGGPDL VLDPKGGSGD REEEQHRMLS RASGVTGRRE TPGPTKPLPW 430 440 450 460 470 480 TAGKHSEDGA RPRLQPSKND PPSLRPMPRG SCLPCPCVQG TFRNSPISHP PSPSPSAYSS 490 500 510 520 530 540 RTSRPMRDVG EDQVHPPLCH FPQRSLQHQL PQPGAQRFAT RGYPMEDMKL QGVPMPPGDL 550 560 570 580 590 600 CGPTLLLDVS IKMEKDSGCE GAADGCVPSQ VWLGASDRSH PATFPTRMHL KTEPDSRQQV 610 620 630 640 650 660 YISHLGHGVR GAQPHGRATA GRSRELTPFH PAHCACLEPT DGLPQSEPPH QLCARGRGEQ 670 680 690 700 710 SCTCRAAEAA PVVKREPLDS PQWATHSQGM VPGMLPKSAL ATLVPPQASG CTFLP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of the aryl hydrocarbon receptor repressor gene and association of its Pro185Ala polymorphism with micropenis." Fujita H., Kosaki R., Yoshihashi H., Ogata T., Tomita M., Hasegawa T., Takahashi T., Matsuo N., Kosaki K. Teratology 65:10-18(2002) [PubMed: 11835227] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3), TISSUE SPECIFICITY, VARIANTS PRO-114 AND PRO-189.
[2]	"Identification and functional analysis of a human AHR repressor." Karchner S.I., Evans B., Jenny M.J., Hahn M.E. Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O. DNA Res. 6:337-345(1999) [PubMed: 10574462] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[4]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed: 15372022] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT PRO-189.
[5]	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. , 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[7]	"Characteristic expression of aryl hydrocarbon receptor repressor gene in human tissues: organ-specific distribution and variable induction patterns in mononuclear cells." Yamamoto J., Ihara K., Nakayama H., Hikino S., Satoh K., Kubo N., Iida T., Fujii Y., Hara T. Life Sci. 74:1039-1049(2004) [PubMed: 14672759] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION.
[8]	"Identification of intracellular localization signals and of mechanisms underlining the nucleocytoplasmic shuttling of human aryl hydrocarbon receptor repressor." Kanno Y., Miyama Y., Takane Y., Nakahama T., Inouye Y. Biochem. Biophys. Res. Commun. 364:1026-1031(2007) [PubMed: 17980155] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"Analysis of the transcriptional regulation and molecular function of the aryl hydrocarbon receptor repressor in human cell lines." Haarmann-Stemmann T., Bothe H., Kohli A., Sydlik U., Abel J., Fritsche E. Drug Metab. Dispos. 35:2262-2269(2007) [PubMed: 17890447] [Abstract] Cited for: FUNCTION.
[10]	"The aryl hydrocarbon receptor repressor is a putative tumor suppressor gene in multiple human cancers." Zudaire E., Cuesta N., Murty V., Woodson K., Adams L., Gonzalez N., Martinez A., Narayan G., Kirsch I., Franklin W., Hirsch F., Birrer M., Cuttitta F. J. Clin. Invest. 118:640-650(2008) [PubMed: 18172554] [Abstract] Cited for: TISSUE SPECIFICITY, FUNCTION.
[11]	"Association of male infertility with Pro185Ala polymorphism in the aryl hydrocarbon receptor repressor gene: implication for the susceptibility to dioxins." Watanabe M., Sueoka K., Sasagawa I., Nakabayashi A., Yoshimura Y., Ogata T. Fertil. Steril. 82:1067-1071(2004) [PubMed: 15474075] [Abstract] Cited for: POLYMORPHISM, ASSOCIATION WITH SUSCEPTIBILITY TO MALE INFERTILITY.
[12]	"Analysis of the AhR, ARNT, and AhRR gene polymorphisms: genetic contribution to endometriosis susceptibility and severity." Tsuchiya M., Katoh T., Motoyama H., Sasaki H., Tsugane S., Ikenoue T. Fertil. Steril. 84:454-458(2005) [PubMed: 16084889] [Abstract] Cited for: POLYMORPHISM, ASSOCIATION WITH SUSCEPTIBILITY TO ENDOMETRIOSIS.
[13]	"The contribution of genetic variations of aryl hydrocarbon receptor pathway genes to male factor infertility." Merisalu A., Punab M., Altmaee S., Haller K., Tiido T., Peters M., Salumets A. Fertil. Steril. 88:854-859(2007) [PubMed: 17559847] [Abstract] Cited for: POLYMORPHISM, ASSOCIATION WITH SUSCEPTIBILITY TO MALE INFERTILITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF293639 , AF293629, AF293630, AF293631, AF293632, AF293633, AF293634, AF293635, AF293636, AF293637, AF293638 Genomic DNA. Translation: AAG33381.1. EU293605 mRNA. Translation: ABX89616.1. Different initiation. AB033060 mRNA. Translation: BAA86548.1. Different initiation. AC010442 Genomic DNA. No translation available. AC118458 Genomic DNA. No translation available. CH471235 Genomic DNA. Translation: EAW50992.1. BC151852 mRNA. Translation: AAI51853.1. BC152406 mRNA. Translation: AAI52407.1.
IPI	IPI00718806. IPI00893051. IPI00893349.
RefSeq	NP_065782.2.
UniGene	Hs.50823
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	A9YTQ3.
PTM databases
PhosphoSite	A9YTQ3.
Genome annotation databases
Ensembl	ENST00000448949; ENSP00000408278; ENSG00000063438; Homo sapiens. [Genome view]
GeneID	57491.
KEGG	hsa:57491.
UCSC	uc003jav.1. human. uc003jaw.1. human.
Organism-specific databases
CTD	57491.
GeneCards	GC05P000327.
HGNC	HGNC:346. AHRR.
HPA	HPA019614. HPA021483.
MIM	606517. gene.
PharmGKB	PA24639.
HUGE	Search...
GenAtlas	Search...
Gene expression databases
Bgee	A9YTQ3.
Genevestigator	A9YTQ3.
Family and domain databases
InterPro	IPR001092. HLH_basic. IPR000014. PAS. IPR013767. PAS_fold. [Graphical view]
Pfam	PF00010. HLH. 1 hit. PF00989. PAS. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. SM00091. PAS. 1 hit. [Graphical view]
PROSITE	PS50888. HLH. 1 hit. PS50112. PAS. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	63778.
SOURCE	Search...

Entry information

Entry name

AHRR_HUMAN

Accession

Primary (citable) accession number: A9YTQ3
Secondary accession number(s): A7MBN5, Q9HAZ3, Q9ULI6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 20, 2008
Last sequence update:	May 20, 2008
Last modified:	November 24, 2009
This is version 20 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.