Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q08117 (AES_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Amino-terminal enhancer of split

Short name=Amino enhancer of split
Alternative name(s):
Gp130-associated protein GAM
Protein ESP1
Protein GRG
Gene names
Name:AES
Synonyms:GRG
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length197 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts as dominant repressor towards other family members. Inhibits NF-kappa-B-regulated gene expression. May be required for the initiation and maintenance of the differentiated state. Ref.9 Ref.10

Subunit structure

Homooligomer and heterooligomer with other family members. Binds TCF7 By similarity. Binds the NF-kappa-B subunit RELA. Interacts with PHF12. Ref.9 Ref.10 Ref.11

Subcellular location

Nucleus By similarity.

Tissue specificity

Found predominantly in muscle, heart and Placenta. In fetal tissues, abundantly expressed in the heart, lung, kidney, brain and liver.

Domain

Lacks the C-terminal WD repeats.

Post-translational modification

Ubiquitinated by XIAP/BIRC4. Ref.13

Sequence similarities

Belongs to the WD repeat Groucho/TLE family.

Sequence caution

The sequence AAC35517.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
Wnt signaling pathway
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   Molecular functionRepressor
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to extracellular stimulus

Inferred from electronic annotation. Source: Ensembl

multicellular organismal development

Traceable author statement Ref.8. Source: ProtInc

negative regulation of canonical Wnt signaling pathway

Inferred from direct assay PubMed 19460168. Source: UniProtKB

negative regulation of gene expression

Inferred from mutant phenotype PubMed 15006356. Source: UniProtKB

negative regulation of protein binding

Inferred from direct assay PubMed 15489227. Source: BHF-UCL

negative regulation of response to cytokine stimulus

Inferred from mutant phenotype PubMed 15489227. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype Ref.9. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 19460168. Source: UniProtKB

organ morphogenesis

Traceable author statement Ref.2. Source: ProtInc

positive regulation of anoikis

Inferred from mutant phenotype PubMed 15006356. Source: UniProtKB

regulation of growth

Inferred from electronic annotation. Source: Ensembl

response to interleukin-1

Inferred from direct assay PubMed 15489227. Source: BHF-UCL

skeletal system development

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnucleus

Inferred from direct assay PubMed 22952044. Source: UniProtKB

   Molecular_functionprotein binding

Inferred from physical interaction Ref.11. Source: UniProtKB

transcription corepressor activity

Inferred from direct assay PubMed 19460168. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q08117-1)

Also known as: AES-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: Q08117-2)

Also known as: AES-2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: MMFPQSRHS → MCHKNGFPQE...WGNRGPAGCR

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 197197Amino-terminal enhancer of split
PRO_0000050834

Regions

Region166 – 19732CCN domain
Compositional bias1 – 131131Gln-rich (Q domain)
Compositional bias132 – 16534Gly/Pro-rich (GP domain)

Amino acid modifications

Modified residue1961Phosphoserine Ref.12

Natural variations

Alternative sequence1 – 99MMFPQSRHS → MCHKNGFPQEGGITAAFLQK RKLRLSKNHRPARAKVTEHV RGTRPGRATAGPAASTRAAG SLFFDRWGNRGPAGCR in isoform 2.
VSP_043527
Natural variant1681A → E.
Corresponds to variant rs1802578 [ dbSNP | Ensembl ].
VAR_011958

Experimental info

Sequence conflict301K → T Ref.2
Sequence conflict301K → T Ref.5

Sequences

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

Last modified September 19, 2002. Version 4.
Checksum: 3851663AA6921A9F

FASTA19721,970
        10         20         30         40         50         60 
MMFPQSRHSG SSHLPQQLKF TTSDSCDRIK DEFQLLQAQY HSLKLECDKL ASEKSEMQRH 

        70         80         90        100        110        120 
YVMYYEMSYG LNIEMHKQAE IVKRLNGICA QVLPYLSQEH QQQVLGAIER AKQVTAPELN 

       130        140        150        160        170        180 
SIIRQQLQAH QLSQLQALAL PLTPLPVGLQ PPSLPAVSAG TGLLSLSALG SQAHLSKEDK 

       190 
NGHDGDTHQE DDGEKSD 

« Hide

Isoform 2 (AES-2) [UniParc].

Checksum: 8E6CD80583D0B82D
Show »

FASTA26429,091

References

« Hide 'large scale' references
[1]"Molecular cloning, sequence analysis and characterization of a human homolog of Drosophila enhancer of split m9/m10."
Scala L.A., Piparo K.E., Tirumalai P.S., Howells R.D.
Submitted (DEC-1993) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Neuroblastoma.
[2]"Genomic organization and chromosome localization to band 19p13.3 of the human AES gene: gene product exhibits strong similarity to the N-terminal domain of Drosophila enhancer of split Groucho protein."
Hou E.W., Li S.S.-L.
DNA Cell Biol. 17:911-913(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Lymphocyte and Umbilical cord.
[3]"Cloning and eukaryotic expressing of a novel gp130 associated molecule."
Liu Y., Jin B.Q., Liu F.
Zhonghua Wei Sheng Wu Xue He Mian Yi Xue Za Zhi 18:106-110(1998)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Placenta.
[4]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Amygdala and Cerebellum.
[5]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]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].
[7]"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).
Tissue: Brain.
[8]"Molecular cloning and expression of mouse and human cDNA encoding AES and ESG proteins with strong similarity to Drosophila enhancer of split groucho protein."
Miyasaka H., Choudhury B.K., Hou E.W., Li S.S.-L.
Eur. J. Biochem. 216:343-352(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 13-197 (ISOFORMS 1 AND 2).
Tissue: Testis.
[9]"Inhibition of nuclear factor-kappaB-mediated transcription by association with the amino-terminal enhancer of split, a Groucho-related protein lacking WD40 repeats."
Tetsuka T., Uranishi H., Imai H., Ono T., Sonta S., Takahashi N., Asamitsu K., Okamoto T.
J. Biol. Chem. 275:4383-4390(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RELA.
[10]"Transducin-like enhancer of split proteins, the human homologs of Drosophila groucho, interact with hepatic nuclear factor 3beta."
Wang J.-C., Waltner-Law M., Yamada K., Osawa H., Stifani S., Granner D.K.
J. Biol. Chem. 275:18418-18423(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, OLIGOMERIZATION.
[11]"Pf1, a novel PHD zinc finger protein that links the TLE corepressor to the mSin3A-histone deacetylase complex."
Yochum G.S., Ayer D.E.
Mol. Cell. Biol. 21:4110-4118(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PHF12.
[12]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-196, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt signaling."
Hanson A.J., Wallace H.A., Freeman T.J., Beauchamp R.D., Lee L.A., Lee E.
Mol. Cell 45:619-628(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY XIAP/BIRC4.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U04241 mRNA. Translation: AAA16223.1.
U88832, U88831 Genomic DNA. Translation: AAD00654.1.
AF072902 mRNA. Translation: AAC35517.1. Different initiation.
AK094591 mRNA. Translation: BAG52894.1.
AK314713 mRNA. Translation: BAG37257.1.
AC005944 Genomic DNA. Translation: AAC72103.1.
CH471139 Genomic DNA. Translation: EAW69345.1.
CH471139 Genomic DNA. Translation: EAW69347.1.
BC113735 mRNA. Translation: AAI13736.1.
BC113737 mRNA. Translation: AAI13738.1.
X73358 mRNA. Translation: CAA51768.1.
CCDSCCDS12101.1. [Q08117-2]
CCDS12102.1. [Q08117-1]
PIRG01236.
S35678.
S35679.
RefSeqNP_001121.2. NM_001130.5. [Q08117-1]
NP_945320.1. NM_198969.1. [Q08117-2]
NP_945321.1. NM_198970.1.
UniGeneHs.515053.

3D structure databases

ProteinModelPortalQ08117.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106675. 25 interactions.
IntActQ08117. 33 interactions.
MINTMINT-1382079.
STRING9606.ENSP00000221561.

PTM databases

PhosphoSiteQ08117.

Polymorphism databases

DMDM23503062.

Proteomic databases

MaxQBQ08117.
PaxDbQ08117.
PRIDEQ08117.

Protocols and materials databases

DNASU166.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000221561; ENSP00000221561; ENSG00000104964. [Q08117-2]
ENST00000327141; ENSP00000317537; ENSG00000104964. [Q08117-1]
GeneID166.
KEGGhsa:166.
UCSCuc002lwy.1. human. [Q08117-1]
uc002lxb.1. human. [Q08117-2]

Organism-specific databases

CTD166.
GeneCardsGC19M003003.
HGNCHGNC:307. AES.
HPAHPA049499.
MIM600188. gene.
neXtProtNX_Q08117.
PharmGKBPA24606.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG258600.
HOGENOMHOG000033830.
HOVERGENHBG000205.
OMAHRDEDAD.
OrthoDBEOG7HQNC3.
PhylomeDBQ08117.

Gene expression databases

ArrayExpressQ08117.
BgeeQ08117.
CleanExHS_AES.
GenevestigatorQ08117.

Family and domain databases

InterProIPR005617. Groucho/TLE_N.
[Graphical view]
PfamPF03920. TLE_N. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSAES. human.
GenomeRNAi166.
NextBio669.
PROQ08117.
SOURCESearch...

Entry information

Entry nameAES_HUMAN
AccessionPrimary (citable) accession number: Q08117
Secondary accession number(s): B2RBL0 expand/collapse secondary AC list , Q12808, Q14CJ1, Q96TG9, Q9UDY9
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: September 19, 2002
Last modified: July 9, 2014
This is version 130 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM