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Q04725 (TLE2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. 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:
Transducin-like enhancer protein 2
Alternative name(s):
Enhancer of split groucho-like protein 2
Short name=ESG2
Gene names
Name:TLE2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length743 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional corepressor that binds to a number of transcription factors. Inhibits the transcriptional activation mediated by CTNNB1 and TCF family members in Wnt signaling. The effects of full-length TLE family members may be modulated by association with dominant-negative AES By similarity.

Subunit structure

Homooligomer and heterooligomer with other family members. Binds LEF1, TCF7, TCF7L1, TCF7L2, UTY, HES1 and HES5. Ref.5

Subcellular location

Nucleus.

Tissue specificity

In all tissues examined, mostly in heart, brain, and muscle.

Post-translational modification

Ubiquitinated by XIAP/BIRC4. Ref.10

Sequence similarities

Belongs to the WD repeat Groucho/TLE family.

Contains 6 WD repeats.

Sequence caution

The sequence AK308137 differs from that shown. Reason: Frameshift at position 537.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DDB1Q165312EBI-1176061,EBI-350322

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q04725-1)

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: Q04725-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-55: Missing.
     124-190: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q04725-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-8: MYPQGRHP → MVQSRLTATSASQDSPASGLQ
     124-124: Q → QQ
     683-743: GRWFVSTGKDNLLNAWRTPYGASIFQSKESSSVLSCDISRNNKYIVTGSGDKKATVYEVVY → VQGVVLSPEL
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 743743Transducin-like enhancer protein 2
PRO_0000051278

Regions

Repeat455 – 49339WD 1
Repeat501 – 54040WD 2
Repeat545 – 58440WD 3
Repeat587 – 62640WD 4
Repeat669 – 70840WD 5
Repeat710 – 74233WD 6
Region195 – 25662CCN domain
Motif214 – 2174Nuclear localization signal Potential
Compositional bias1 – 133133Gln-rich
Compositional bias134 – 19461Gly/Pro-rich
Compositional bias257 – 398142Pro/Ser-rich

Amino acid modifications

Modified residue2281Phosphoserine; by CK2 Potential
Modified residue2491Phosphoserine; by CDK1 Potential
Modified residue2531Phosphothreonine; by CDK1 Potential
Modified residue2811Phosphoserine Ref.8

Natural variations

Alternative sequence1 – 5555Missing in isoform 2.
VSP_045693
Alternative sequence1 – 88MYPQGRHP → MVQSRLTATSASQDSPASGL Q in isoform 3.
VSP_046162
Alternative sequence124 – 19067Missing in isoform 2.
VSP_045694
Alternative sequence1241Q → QQ in isoform 3.
VSP_046163
Alternative sequence683 – 74361GRWFV…YEVVY → VQGVVLSPEL in isoform 3.
VSP_046164
Natural variant3811S → G. Ref.2
Corresponds to variant rs199788562 [ dbSNP | Ensembl ].
VAR_069063

Experimental info

Sequence conflict2801G → R in AAA61193. Ref.1
Sequence conflict3281A → L in AAA61193. Ref.1
Sequence conflict4411G → D in AAA61193. Ref.1
Sequence conflict4951A → R in AAA61193. Ref.1
Sequence conflict636 – 6372LG → PC in AAA61193. Ref.1
Sequence conflict6601R → G in AAA61193. Ref.1
Sequence conflict6811S → P in AAA61193. Ref.1

Sequences

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

Last modified May 10, 2002. Version 2.
Checksum: 5E3DBFAB67278219

FASTA74379,841
        10         20         30         40         50         60 
MYPQGRHPTP LQSGQPFKFS ILEICDRIKE EFQFLQAQYH SLKLECEKLA SEKTEMQRHY 

        70         80         90        100        110        120 
VMYYEMSYGL NIEMHKQAEI VKRLSGICAQ IIPFLTQEHQ QQVLQAVERA KQVTVGELNS 

       130        140        150        160        170        180 
LIGQQLQPLS HHAPPVPLTP RPAGLVGGSA TGLLALSGAL AAQAQLAAAV KEDRAGVEAE 

       190        200        210        220        230        240 
GSRVERAPSR SASPSPPESL VEEERPSGPG GGGKQRADEK EPSGPYESDE DKSDYNLVVD 

       250        260        270        280        290        300 
EDQPSEPPSP ATTPCGKVPI CIPARRDLVD SPASLASSLG SPLPRAKELI LNDLPASTPA 

       310        320        330        340        350        360 
SKSCDSSPPQ DASTPGPSSA SHLCQLAAKP APSTDSVALR SPLTLSSPFT TSFSLGSHST 

       370        380        390        400        410        420 
LNGDLSVPSS YVSLHLSPQV SSSVVYGRSP VMAFESHPHL RGSSVSSSLP SIPGGKPAYS 

       430        440        450        460        470        480 
FHVSADGQMQ PVPFPSDALV GAGIPRHARQ LHTLAHGEVV CAVTISGSTQ HVYTGGKGCV 

       490        500        510        520        530        540 
KVWDVGQPGA KTPVAQLDCL NRDNYIRSCK LLPDGRSLIV GGEASTLSIW DLAAPTPRIK 

       550        560        570        580        590        600 
AELTSSAPAC YALAVSPDAK VCFSCCSDGN IVVWDLQNQT MVRQFQGHTD GASCIDISDY 

       610        620        630        640        650        660 
GTRLWTGGLD NTVRCWDLRE GRQLQQHDFS SQIFSLGHCP NQDWLAVGME SSNVEILHVR 

       670        680        690        700        710        720 
KPEKYQLHLH ESCVLSLKFA SCGRWFVSTG KDNLLNAWRT PYGASIFQSK ESSSVLSCDI 

       730        740 
SRNNKYIVTG SGDKKATVYE VVY 

« Hide

Isoform 2 [UniParc].

Checksum: F5100FF0B0FECFBA
Show »

FASTA62166,678
Isoform 3 [UniParc].

Checksum: 71A2BA068112A6AE
Show »

FASTA70675,364

References

« Hide 'large scale' references
[1]"Human homologs of a Drosophila enhancer of split gene product define a novel family of nuclear proteins."
Stifani S., Blaumueller C.M., Redhead N.J., Hill R.E., Artavanis-Tsakonas S.
Nat. Genet. 2:119-127(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fetal brain.
[2]"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 2 AND 3), VARIANT GLY-381.
Tissue: Brain and Urinary bladder.
[3]"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].
[4]"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).
Tissue: Placenta.
[5]"Transducin-like Enhancer of split 2, a mammalian homologue of Drosophila Groucho, acts as a transcriptional repressor, interacts with Hairy/Enhancer of split proteins, and is expressed during neuronal development."
Grbavec D., Lo R., Liu Y., Stifani S.
Eur. J. Biochem. 258:339-349(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: OLIGOMERIZATION, INTERACTION WITH HES1 AND HES5.
[6]"Groucho/transducin-like enhancer of split (TLE) family members interact with the yeast transcriptional co-repressor SSN6 and mammalian SSN6-related proteins: implications for evolutionary conservation of transcription repression mechanisms."
Grbavec D., Lo R., Liu Y., Greenfield A., Stifani S.
Biochem. J. 337:13-17(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UTY.
[7]"All Tcf HMG box transcription factors interact with Groucho-related co-repressors."
Brantjes H., Roose J., van De Wetering M., Clevers H.
Nucleic Acids Res. 29:1410-1419(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LEF1; TCF7; TCF7L1 AND TCF7L2.
[8]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-281, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[10]"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
M99436 mRNA. Translation: AAA61193.1.
AK293407 mRNA. Translation: BAG56914.1.
AK308137 mRNA. No translation available.
AC007766 Genomic DNA. Translation: AAD38075.1.
AC011549 Genomic DNA. No translation available.
AC093053 Genomic DNA. No translation available.
BC017364 mRNA. Translation: AAH17364.1.
CCDSCCDS45911.1. [Q04725-1]
CCDS45912.1. [Q04725-2]
CCDS45913.1. [Q04725-3]
PIRC56695.
RefSeqNP_001138233.1. NM_001144761.1. [Q04725-3]
NP_001138234.1. NM_001144762.1. [Q04725-2]
NP_003251.2. NM_003260.4. [Q04725-1]
UniGeneHs.332173.

3D structure databases

ProteinModelPortalQ04725.
SMRQ04725. Positions 414-743.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112944. 18 interactions.
IntActQ04725. 2 interactions.
STRING9606.ENSP00000262953.

PTM databases

PhosphoSiteQ04725.

Polymorphism databases

DMDM20532416.

Proteomic databases

MaxQBQ04725.
PaxDbQ04725.
PRIDEQ04725.

Protocols and materials databases

DNASU7089.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262953; ENSP00000262953; ENSG00000065717. [Q04725-1]
ENST00000426948; ENSP00000392869; ENSG00000065717. [Q04725-3]
ENST00000443826; ENSP00000392427; ENSG00000065717. [Q04725-2]
ENST00000455444; ENSP00000413107; ENSG00000065717. [Q04725-2]
ENST00000591529; ENSP00000468279; ENSG00000065717. [Q04725-3]
GeneID7089.
KEGGhsa:7089.
UCSCuc002lww.3. human. [Q04725-1]
uc010dti.3. human.
uc010xhc.2. human.

Organism-specific databases

CTD7089.
GeneCardsGC19M002997.
HGNCHGNC:11838. TLE2.
HPAHPA049103.
MIM601041. gene.
neXtProtNX_Q04725.
PharmGKBPA36540.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2319.
HOGENOMHOG000293211.
HOVERGENHBG004689.
InParanoidQ04725.
OrthoDBEOG7HQNC3.
PhylomeDBQ04725.
TreeFamTF314167.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
SignaLinkQ04725.

Gene expression databases

ArrayExpressQ04725.
BgeeQ04725.
CleanExHS_TLE2.
GenevestigatorQ04725.

Family and domain databases

Gene3D2.130.10.10. 1 hit.
InterProIPR005617. Groucho/TLE_N.
IPR009146. Groucho_enhance.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamPF03920. TLE_N. 1 hit.
PF00400. WD40. 5 hits.
[Graphical view]
PRINTSPR01850. GROUCHOFAMLY.
SMARTSM00320. WD40. 7 hits.
[Graphical view]
SUPFAMSSF50978. SSF50978. 1 hit.
PROSITEPS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 3 hits.
PS50294. WD_REPEATS_REGION. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiTLE2.
GenomeRNAi7089.
NextBio27727.
PROQ04725.
SOURCESearch...

Entry information

Entry nameTLE2_HUMAN
AccessionPrimary (citable) accession number: Q04725
Secondary accession number(s): B4DE03 expand/collapse secondary AC list , E9PEV7, F8WCH2, Q8WVY0, Q9Y6S0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: May 10, 2002
Last modified: July 9, 2014
This is version 138 of the entry and version 2 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