Q04727 (TLE4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transducin-like enhancer protein 4

Gene names

Name:	TLE4
Synonyms:	KIAA1261

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	773 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional corepressor that binds to a number of transcription factors. Inhibits the transcriptional activation mediated by PAX5, and 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 PAX5, LEF1, TCF7, TCF7L1 and TCF7L2. Interacts with ZNF703; TLE4 may mediate ZNF703 transcriptional repression By similarity.
Subcellular location	Nucleus.
Tissue specificity	In all tissues examined, mostly in brain, and muscle.
Post-translational modification	Phosphorylated. PAX5 binding increases phosphorylation By similarity. Ubiquitinated by XIAP/BIRC4. Ref.11
Sequence similarities	Belongs to the WD repeat Groucho/TLE family. Contains 7 WD repeats.
Sequence caution	The sequence BAA86575.1 differs from that shown. Reason: Erroneous initiation. The sequence CAC22598.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAC22599.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI13644.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI13734.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI41315.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Wnt signaling pathway
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat WD repeat
Molecular function	Repressor
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch signaling pathway Traceable author statement. Source: Reactome Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara chromatin binding Inferred from electronic annotation. Source: Compara transcription corepressor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q04727-1)

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: Q04727-2)

The sequence of this isoform differs from the canonical sequence as follows:
     244-312: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q04727-3)

The sequence of this isoform differs from the canonical sequence as follows:
     312-312: L → LKRDMGKLSETRLSEDEQCTLGLQRWFCRLWFM

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 773	773	Transducin-like enhancer protein 4		PRO_0000051283
Regions
	Repeat	485 – 523	39	WD 1
	Repeat	531 – 570	40	WD 2
	Repeat	575 – 614	40	WD 3
	Repeat	617 – 656	40	WD 4
	Repeat	658 – 697	40	WD 5
	Repeat	699 – 738	40	WD 6
	Repeat	740 – 773	34	WD 7
	Region	207 – 274	68	CCN domain
	Compositional bias	1 – 137	137	Gln-rich (Q domain)
	Compositional bias	138 – 205	68	Gly/Pro-rich (GP domain)
	Compositional bias	405 – 415	11	Poly-Ala
Amino acid modifications
	Modified residue	237	1	N6-acetyllysine Ref.9
	Modified residue	250	1	Phosphoserine Ref.6
	Modified residue	269	1	Phosphoserine Ref.6
	Modified residue	281	1	N6-acetyllysine Ref.9
	Modified residue	292	1	Phosphoserine Ref.8 Ref.10
Natural variations
	Alternative sequence	244 – 312	69	Missing in isoform 2.		VSP_030497
	Alternative sequence	312	1	L → LKRDMGKLSETRLSEDEQCT LGLQRWFCRLWFM in isoform 3.		VSP_030498
Experimental info
	Sequence conflict	131	1	Q → QQ in CAB82397. Ref.4
	Sequence conflict	468	1	A → P in AAA61195. Ref.5
	Sequence conflict	509	1	C → A in AAA61195. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 11, 2007. Version 3. Checksum: DA138F1DA29E81B6	FASTA	773	83,755
	10 20 30 40 50 60 MIRDLSKMYP QTRHPAPHQP AQPFKFTISE SCDRIKEEFQ FLQAQYHSLK LECEKLASEK 70 80 90 100 110 120 TEMQRHYVMY YEMSYGLNIE MHKQAEIVKR LNAICAQVIP FLSQEHQQQV VQAVERAKQV 130 140 150 160 170 180 TMAELNAIIG QQLQAQHLSH GHGLPVPLTP HPSGLQPPAI PPIGSSAGLL ALSSALGGQS 190 200 210 220 230 240 HLPIKDEKKH HDNDHQRDRD SIKSSSVSPS ASFRGAEKHR NSADYSSESK KQKTEEKEIA 250 260 270 280 290 300 ARYDSDGEKS DDNLVVDVSN EDPSSPRGSP AHSPRENGLD KTRLLKKDAP ISPASIASSS 310 320 330 340 350 360 STPSSKSKEL SLNEKSTTPV SKSNTPTPRT DAPTPGSNST PGLRPVPGKP PGVDPLASSL 370 380 390 400 410 420 RTPMAVPCPY PTPFGIVPHA GMNGELTSPG AAYAGLHNIS PQMSAAAAAA AAAAAYGRSP 430 440 450 460 470 480 VVGFDPHHHM RVPAIPPNLT GIPGGKPAYS FHVSADGQMQ PVPFPPDALI GPGIPRHARQ 490 500 510 520 530 540 INTLNHGEVV CAVTISNPTR HVYTGGKGCV KVWDISHPGN KSPVSQLDCL NRDNYIRSCR 550 560 570 580 590 600 LLPDGRTLIV GGEASTLSIW DLAAPTPRIK AELTSSAPAC YALAISPDSK VCFSCCSDGN 610 620 630 640 650 660 IAVWDLHNQT LVRQFQGHTD GASCIDISND GTKLWTGGLD NTVRSWDLRE GRQLQQHDFT 670 680 690 700 710 720 SQIFSLGYCP TGEWLAVGME NSNVEVLHVT KPDKYQLHLH ESCVLSLKFA HCGKWFVSTG 730 740 750 760 770 KDNLLNAWRT PYGASIFQSK ESSSVLSCDI SVDDKYIVTG SGDKKATVYE VIY
	Isoform 2 [UniParc]. Checksum: EF8F211B53D9CD3C	FASTA	704	76,581
	10 20 30 40 50 60 MIRDLSKMYP QTRHPAPHQP AQPFKFTISE SCDRIKEEFQ FLQAQYHSLK LECEKLASEK 70 80 90 100 110 120 TEMQRHYVMY YEMSYGLNIE MHKQAEIVKR LNAICAQVIP FLSQEHQQQV VQAVERAKQV 130 140 150 160 170 180 TMAELNAIIG QQLQAQHLSH GHGLPVPLTP HPSGLQPPAI PPIGSSAGLL ALSSALGGQS 190 200 210 220 230 240 HLPIKDEKKH HDNDHQRDRD SIKSSSVSPS ASFRGAEKHR NSADYSSESK KQKTEEKEIA 250 260 270 280 290 300 ARYNEKSTTP VSKSNTPTPR TDAPTPGSNS TPGLRPVPGK PPGVDPLASS LRTPMAVPCP 310 320 330 340 350 360 YPTPFGIVPH AGMNGELTSP GAAYAGLHNI SPQMSAAAAA AAAAAAYGRS PVVGFDPHHH 370 380 390 400 410 420 MRVPAIPPNL TGIPGGKPAY SFHVSADGQM QPVPFPPDAL IGPGIPRHAR QINTLNHGEV 430 440 450 460 470 480 VCAVTISNPT RHVYTGGKGC VKVWDISHPG NKSPVSQLDC LNRDNYIRSC RLLPDGRTLI 490 500 510 520 530 540 VGGEASTLSI WDLAAPTPRI KAELTSSAPA CYALAISPDS KVCFSCCSDG NIAVWDLHNQ 550 560 570 580 590 600 TLVRQFQGHT DGASCIDISN DGTKLWTGGL DNTVRSWDLR EGRQLQQHDF TSQIFSLGYC 610 620 630 640 650 660 PTGEWLAVGM ENSNVEVLHV TKPDKYQLHL HESCVLSLKF AHCGKWFVST GKDNLLNAWR 670 680 690 700 TPYGASIFQS KESSSVLSCD ISVDDKYIVT GSGDKKATVY EVIY
	Isoform 3 [UniParc]. Checksum: 7301C1C49E992219	FASTA	805	87,702
	10 20 30 40 50 60 MIRDLSKMYP QTRHPAPHQP AQPFKFTISE SCDRIKEEFQ FLQAQYHSLK LECEKLASEK 70 80 90 100 110 120 TEMQRHYVMY YEMSYGLNIE MHKQAEIVKR LNAICAQVIP FLSQEHQQQV VQAVERAKQV 130 140 150 160 170 180 TMAELNAIIG QQLQAQHLSH GHGLPVPLTP HPSGLQPPAI PPIGSSAGLL ALSSALGGQS 190 200 210 220 230 240 HLPIKDEKKH HDNDHQRDRD SIKSSSVSPS ASFRGAEKHR NSADYSSESK KQKTEEKEIA 250 260 270 280 290 300 ARYDSDGEKS DDNLVVDVSN EDPSSPRGSP AHSPRENGLD KTRLLKKDAP ISPASIASSS 310 320 330 340 350 360 STPSSKSKEL SLKRDMGKLS ETRLSEDEQC TLGLQRWFCR LWFMNEKSTT PVSKSNTPTP 370 380 390 400 410 420 RTDAPTPGSN STPGLRPVPG KPPGVDPLAS SLRTPMAVPC PYPTPFGIVP HAGMNGELTS 430 440 450 460 470 480 PGAAYAGLHN ISPQMSAAAA AAAAAAAYGR SPVVGFDPHH HMRVPAIPPN LTGIPGGKPA 490 500 510 520 530 540 YSFHVSADGQ MQPVPFPPDA LIGPGIPRHA RQINTLNHGE VVCAVTISNP TRHVYTGGKG 550 560 570 580 590 600 CVKVWDISHP GNKSPVSQLD CLNRDNYIRS CRLLPDGRTL IVGGEASTLS IWDLAAPTPR 610 620 630 640 650 660 IKAELTSSAP ACYALAISPD SKVCFSCCSD GNIAVWDLHN QTLVRQFQGH TDGASCIDIS 670 680 690 700 710 720 NDGTKLWTGG LDNTVRSWDL REGRQLQQHD FTSQIFSLGY CPTGEWLAVG MENSNVEVLH 730 740 750 760 770 780 VTKPDKYQLH LHESCVLSLK FAHCGKWFVS TGKDNLLNAW RTPYGASIFQ SKESSSVLSC 790 800 DISVDDKYIV TGSGDKKATV YEVIY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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 1). Tissue: Brain.
[2]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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] (ISOFORMS 2 AND 3). Tissue: Testis.
[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., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 51-773 (ISOFORM 1). Tissue: Brain.
[5]	"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] OF 326-773. Tissue: Fetal brain.
[6]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-250 AND SER-269, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[8]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-292, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-237 AND LYS-281, MASS SPECTROMETRY.
[10]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-292, MASS SPECTROMETRY.
[11]	"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	AB033087 mRNA. Translation: BAA86575.1. Different initiation. AL358975 Genomic DNA. Translation: CAC22598.1. Sequence problems. AL358975 Genomic DNA. Translation: CAC22599.1. Sequence problems. AL445252, AL353813, AL358975 Genomic DNA. Translation: CAI13644.1. Sequence problems. AL353813, AL445252, AL358975 Genomic DNA. Translation: CAI41315.1. Sequence problems. AL358975, AL445252, AL353813 Genomic DNA. Translation: CAI13734.1. Sequence problems. BC045650 mRNA. Translation: AAH45650.1. BC059405 mRNA. Translation: AAH59405.2. AL162059 mRNA. Translation: CAB82397.1. M99439 mRNA. Translation: AAA61195.1.
IPI	IPI00446767. IPI00749371. IPI00877770.
PIR	T47149.
RefSeq	NP_008936.2. NM_007005.3.
UniGene	Hs.444213.
3D structure databases
ProteinModelPortal	Q04727.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q04727. 3 interactions.
PTM databases
PhosphoSite	Q04727.
Polymorphism databases
DMDM	158518541.
Proteomic databases
PaxDb	Q04727.
PRIDE	Q04727.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000376537; ENSP00000365720; ENSG00000106829. ENST00000376552; ENSP00000365735; ENSG00000106829. ENST00000461758; ENSP00000417906; ENSG00000106829.
GeneID	7091.
KEGG	hsa:7091.
UCSC	uc004alc.3. human. uc004ald.3. human. uc010mps.3. human.
Organism-specific databases
CTD	7091.
GeneCards	GC09P082186.
HGNC	HGNC:11840. TLE4.
MIM	605132. gene.
neXtProt	NX_Q04727.
PharmGKB	PA36542.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2319.
HOVERGEN	HBG004689.
OMA	GLQRWFC.
OrthoDB	EOG4MGS6V.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q04727.
Bgee	Q04727.
Genevestigator	Q04727.
GermOnline	ENSG00000106829. Homo sapiens.
Family and domain databases
Gene3D	2.130.10.10. 1 hit.
InterPro	IPR005617. 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]
Pfam	PF03920. TLE_N. 1 hit. PF00400. WD40. 6 hits. [Graphical view]
PRINTS	PR01850. GROUCHOFAMLY.
SMART	SM00320. WD40. 7 hits. [Graphical view]
SUPFAM	SSF50978. WD40_like. 1 hit.
PROSITE	PS00678. WD_REPEATS_1. 2 hits. PS50082. WD_REPEATS_2. 3 hits. PS50294. WD_REPEATS_REGION. 2 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	7091.
NextBio	27739.
SOURCE	Search...

Entry information

Entry name

TLE4_HUMAN

Accession

Primary (citable) accession number: Q04727
Secondary accession number(s): Q3ZCS1 , Q5T1Y2, Q6PCB3, Q9BZ07, Q9BZ08, Q9BZ09, Q9NSL3, Q9ULF9

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	September 11, 2007
Last modified:	May 1, 2013
This is version 138 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.