A9YTQ3 (AHRR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	701 AA.
Sequence status	Complete.
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.1 Ref.7 Ref.10
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 bHLH (basic helix-loop-helix) domain. Contains 1 PAS (PER-ARNT-SIM) domain.
Sequence caution	The sequence ABX89616.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAA86548.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of protein sumoylation Inferred from electronic annotation. Source: Compara transcription, DNA-dependent 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
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	28 – 81	54	bHLH
	Domain	112 – 182	71	PAS
	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. Ref.1 Corresponds to variant rs35008248 [ dbSNP | Ensembl ].		VAR_043308
	Natural variant	189	1	P → A. Ref.2 Ref.3 Ref.5 Ref.6 Corresponds to variant rs2292596 [ dbSNP | Ensembl ].		VAR_043309
	Natural variant	373	1	G → V. Corresponds to variant rs2303738 [ dbSNP | Ensembl ].		VAR_043310
	Natural variant	627	1	D → H. Corresponds to variant rs34453673 [ dbSNP | Ensembl ].		VAR_043311

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 2, 2010. Version 3. Checksum: 488F6D41298760E0	FASTA	701	76,265
	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 PPQVVFGQPP 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 [UniParc]. Checksum: BB88BB842E3C76FC	FASTA	719	78,307
	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 PPQVVFGQPP 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 [UniParc]. Checksum: 09A6288FDA63E7CA	FASTA	715	77,821
	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 VFGQPPPLET 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3), TISSUE SPECIFICITY, VARIANT PRO-114.
[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), VARIANT ALA-189.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ALA-189. 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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], VARIANT ALA-189.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ALA-189.
[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: POLYMORPHISM, ASSOCIATION WITH SUSCEPTIBILITY TO MALE INFERTILITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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_001229341.1. NM_001242412.1. NP_065782.2. NM_020731.4.
UniGene	Hs.50823.
3D structure databases
ProteinModelPortal	A9YTQ3.
SMR	A9YTQ3. Positions 34-265.
ModBase	Search...
PTM databases
PhosphoSite	A9YTQ3.
Proteomic databases
PaxDb	A9YTQ3.
PRIDE	A9YTQ3.
Protocols and materials databases
DNASU	57491.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000316418; ENSP00000323816; ENSG00000063438. ENST00000505113; ENSP00000424601; ENSG00000063438.
GeneID	57491.
KEGG	hsa:57491.
UCSC	uc003jav.3. human. uc003jaw.3. human.
Organism-specific databases
CTD	57491.
GeneCards	GC05P000291.
HGNC	HGNC:346. AHRR.
HPA	HPA019614. HPA021483.
MIM	606517. gene.
neXtProt	NX_A9YTQ3.
PharmGKB	PA24639.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG314160.
HOGENOM	HOG000033866.
HOVERGEN	HBG073122.
InParanoid	A9YTQ3.
KO	K09094.
OMA	AEGMIFY.
Gene expression databases
ArrayExpress	A9YTQ3.
Bgee	A9YTQ3.
Genevestigator	A9YTQ3.
Family and domain databases
Gene3D	4.10.280.10. 1 hit.
InterPro	IPR011598. bHLH_dom. 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. BHLH. 1 hit. PS50112. PAS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	57491.
NextBio	63778.
SOURCE	Search...

Entry information

Entry name

AHRR_HUMAN

Accession

Primary (citable) accession number: A9YTQ3
Secondary accession number(s): A7MBN5 , D6RAZ1, Q9HAZ3, Q9ULI6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 20, 2008
Last sequence update:	November 2, 2010
Last modified:	May 1, 2013
This is version 55 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.