O95936 (EOMES_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Eomesodermin homolog

Alternative name(s):
T-box brain protein 2
Short name=T-brain-2
Short name=TBR-2

Gene names

Name:	EOMES
Synonyms:	TBR2

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

General annotation (Comments)

Function	Functions as a transcriptional activator playing a crucial role during development. Functions in trophoblast differentiation and later in gastrulation, regulating both mesoderm delamination and endoderm specification. Plays a role in brain development being required for the specification and the proliferation of the intermediate progenitor cells and their progeny in the cerebral cortex. Also involved in the differentiation of CD8+ T-cells during immune response regulating the expression of lytic effector genes. Ref.6 Ref.7
Subcellular location	Nucleus Probable.
Tissue specificity	Expressed in CD8+ T-cells. Ref.6
Developmental stage	Detected at 7 weeks of development in the forebrain floorplate of the CNS. Expressed within the mantle layer and migrating neuroblasts of the telencephalon at 12.5 weeks of development. Ref.7
Induction	Up-regulated in CD8+ T-cells simultaneously stimulated with TGFB1 and IL4/interleukin-4. Ref.6
Involvement in disease	A translocation t(3;10)(p24;q23) located 215 kb 3' to the EOMES gene but leading to loss of its expression was identified in a large consanguineous family. Homozygous silencing produces microcephaly associated with corpus callosum agenesis, bilateral polymicrogyria, ventricular dilatation and a small cerebellum.
Sequence similarities	Contains 1 T-box DNA-binding domain.

Ontologies

Keywords
Biological process	Adaptive immunity Differentiation Gastrulation Immunity Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Ligand	DNA-binding
Molecular function	Activator Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	CD8-positive, alpha-beta T cell differentiation involved in immune response Inferred from mutant phenotype Ref.6. Source: UniProtKB brain development Inferred from mutant phenotype Ref.7. Source: UniProtKB cell differentiation involved in embryonic placenta development Inferred from sequence or structural similarity. Source: UniProtKB cerebral cortex neuron differentiation Inferred from electronic annotation. Source: Compara endoderm formation Inferred from sequence or structural similarity. Source: UniProtKB endodermal cell fate specification Inferred from electronic annotation. Source: Compara interferon-gamma production Inferred from electronic annotation. Source: Compara mesoderm formation Inferred from sequence or structural similarity. Source: UniProtKB mesodermal to mesenchymal transition involved in gastrulation Inferred from sequence or structural similarity. Source: UniProtKB olfactory bulb development Inferred from electronic annotation. Source: Compara positive regulation of cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 20713518. Source: MGI regulation of neuron differentiation Inferred from electronic annotation. Source: Compara stem cell maintenance Inferred from electronic annotation. Source: Compara trophectodermal cell differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	RNA polymerase II activating transcription factor binding Inferred from sequence or structural similarity. Source: BHF-UCL RNA polymerase II regulatory region sequence-specific DNA binding Inferred from electronic annotation. Source: Compara RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription Inferred from sequence or structural similarity. Source: BHF-UCL sequence-specific DNA binding Inferred from direct assay PubMed 20713518. Source: MGI sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95936-1)

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: O95936-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-286: Missing.
     460-460: S → SMYTASENDRLTPSPTDSPR

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 686	686	Eomesodermin homolog		PRO_0000184459
Regions
	DNA binding	276 – 456	181	T-box
	Region	571 – 686	116	Required for transcription activation By similarity
	Compositional bias	69 – 132	64	Ala-rich
	Compositional bias	194 – 264	71	Gly-rich
Natural variations
	Alternative sequence	1 – 286	286	Missing in isoform 2.		VSP_042161
	Alternative sequence	460	1	S → SMYTASENDRLTPSPTDSPR in isoform 2.		VSP_042162
	Natural variant	120	1	A → G. Corresponds to variant rs12715125 [ dbSNP | Ensembl ].		VAR_059827
	Natural variant	667	1	E → Q in a breast cancer sample; somatic mutation. Ref.9		VAR_036069
Experimental info
	Sequence conflict	49	1	D → G in BAA83417. Ref.1
	Sequence conflict	142	1	E → V in BAA83417. Ref.1
	Sequence conflict	200	1	V → A in BAA83417. Ref.1
	Sequence conflict	221 – 222	2	SS → IN in BAA83417. Ref.1
	Sequence conflict	262	1	G → S in BAA83417. Ref.1
	Sequence conflict	337	1	C → S in CAB37939. Ref.4
	Sequence conflict	411	1	E → EK in CAB37939. Ref.4
	Sequence conflict	415	1	E → D in CAB37939. Ref.4
	Sequence conflict	661	1	E → G in BAA83417. Ref.1
	Sequence conflict	685	1	T → S in BAA83417. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 5, 2009. Version 3. Checksum: 1A6BA0763C5A6681	FASTA	686	72,732
	10 20 30 40 50 60 MQLGEQLLVS SVNLPGAHFY PLESARGGSG GSAGHLPSAA PSPQKLDLDK ASKKFSGSLS 70 80 90 100 110 120 CEAVSGEPAA ASAGAPAAML SDTDAGDAFA SAAAVAKPGP PDGRKGSPCG EEELPSAAAA 130 140 150 160 170 180 AAAAAAAAAA TARYSMDSLS SERYYLQSPG PQGSELAAPC SLFPYQAAAG APHGPVYPAP 190 200 210 220 230 240 NGARYPYGSM LPPGGFPAAV CPPGRAQFGP GAGAGSGAGG SSGGGGGPGT YQYSQGAPLY 250 260 270 280 290 300 GPYPGAAAAG SCGGLGGLGV PGSGFRAHVY LCNRPLWLKF HRHQTEMIIT KQGRRMFPFL 310 320 330 340 350 360 SFNINGLNPT AHYNVFVEVV LADPNHWRFQ GGKWVTCGKA DNNMQGNKMY VHPESPNTGS 370 380 390 400 410 420 HWMRQEISFG KLKLTNNKGA NNNNTQMIVL QSLHKYQPRL HIVEVTEDGV EDLNEPSKTQ 430 440 450 460 470 480 TFTFSETQFI AVTAYQNTDI TQLKIDHNPF AKGFRDNYDS SHQIVPGGRY GVQSFFPEPF 490 500 510 520 530 540 VNTLPQARYY NGERTVPQTN GLLSPQQSEE VANPPQRWLV TPVQQPGTNK LDISSYESEY 550 560 570 580 590 600 TSSTLLPYGI KSLPLQTSHA LGYYPDPTFP AMAGWGGRGS YQRKMAAGLP WTSRTSPTVF 610 620 630 640 650 660 SEDQLSKEKV KEEIGSSWIE TPPSIKSLDS NDSGVYTSAC KRRRLSPSNS SNENSPSIKC 670 680 EDINAEEYSK DTSKGMGGYY AFYTTP
	Isoform 2 [UniParc]. Checksum: 897D0328730AD56A	FASTA	419	47,067
	10 20 30 40 50 60 MIITKQGRRM FPFLSFNING LNPTAHYNVF VEVVLADPNH WRFQGGKWVT CGKADNNMQG 70 80 90 100 110 120 NKMYVHPESP NTGSHWMRQE ISFGKLKLTN NKGANNNNTQ MIVLQSLHKY QPRLHIVEVT 130 140 150 160 170 180 EDGVEDLNEP SKTQTFTFSE TQFIAVTAYQ NTDITQLKID HNPFAKGFRD NYDSMYTASE 190 200 210 220 230 240 NDRLTPSPTD SPRSHQIVPG GRYGVQSFFP EPFVNTLPQA RYYNGERTVP QTNGLLSPQQ 250 260 270 280 290 300 SEEVANPPQR WLVTPVQQPG TNKLDISSYE SEYTSSTLLP YGIKSLPLQT SHALGYYPDP 310 320 330 340 350 360 TFPAMAGWGG RGSYQRKMAA GLPWTSRTSP TVFSEDQLSK EKVKEEIGSS WIETPPSIKS 370 380 390 400 410 LDSNDSGVYT SACKRRRLSP SNSSNENSPS IKCEDINAEE YSKDTSKGMG GYYAFYTTP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel mammalian T-box-containing gene, Tbr2, expressed in mouse developing brain." Kimura N., Nakashima K., Ueno M., Taga T. Brain Res. Dev. Brain Res. 115:183-193(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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. , 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] (ISOFORM 2). Tissue: Brain.
[3]	"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].
[4]	"Identification, mapping and phylogenomic analysis of four new human members of the T-box gene family: EOMES, TBX6, TBX18, and TBX19." Yi C.-H., Terrett J.A., Li Q.-Y., Ellington K., Packham E.A., Amstrong-Buisseret L., McClure P., Slingsby T., Brook J.D. Genomics 55:10-20(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 291-455 (ISOFORM 1).
[5]	"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] OF 297-686 (ISOFORM 1). Tissue: Brain.
[6]	"The T-box transcription factor eomesodermin controls CD8 T cell activity and lymph node metastasis in human colorectal cancer." Atreya I., Schimanski C.C., Becker C., Wirtz S., Dornhoff H., Schnuerer E., Berger M.R., Galle P.R., Herr W., Neurath M.F. Gut 56:1572-1578(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, INDUCTION.
[7]	"Homozygous silencing of T-box transcription factor EOMES leads to microcephaly with polymicrogyria and corpus callosum agenesis." Baala L., Briault S., Etchevers H.C., Laumonnier F., Natiq A., Amiel J., Boddaert N., Picard C., Sbiti A., Asermouh A., Attie-Bitach T., Encha-Razavi F., Munnich A., Sefiani A., Lyonnet S. Nat. Genet. 39:454-456(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN BRAIN DEVELOPMENT, DEVELOPMENTAL STAGE.
[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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[9]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-667.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB031038 mRNA. Translation: BAA83417.1. AK297389 mRNA. Translation: BAH12568.1. AC098614 Genomic DNA. No translation available. AJ010280 Genomic DNA. Translation: CAB37939.1. BC025363 mRNA. Translation: AAH25363.1.
IPI	IPI00296036. IPI00789239.
RefSeq	NP_005433.2. NM_005442.2.
UniGene	Hs.591663.
3D structure databases
ProteinModelPortal	O95936.
ModBase	Search...
Protein-protein interaction databases
IntAct	O95936. 2 interactions.
STRING	9606.ENSP00000295743.
PTM databases
PhosphoSite	O95936.
Proteomic databases
PaxDb	O95936.
PRIDE	O95936.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000295743; ENSP00000295743; ENSG00000163508.
GeneID	8320.
KEGG	hsa:8320.
UCSC	uc003cdx.3. human.
Organism-specific databases
CTD	8320.
GeneCards	GC03M027757.
H-InvDB	HIX0030693.
HGNC	HGNC:3372. EOMES.
HPA	HPA028896.
MIM	604615. gene.
neXtProt	NX_O95936.
Orphanet	171703. Microcephaly - polymicrogyria - corpus callosum agenesis.
PharmGKB	PA27806.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG245070.
HOGENOM	HOG000218633.
HOVERGEN	HBG000578.
InParanoid	O95936.
KO	K10173.
OrthoDB	EOG45QHD6.
PhylomeDB	O95936.
Enzyme and pathway databases
Pathway_Interaction_DB	cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells. il12_2pathway. IL12-mediated signaling events.
Gene expression databases
ArrayExpress	O95936.
Bgee	O95936.
CleanEx	HS_EOMES.
Genevestigator	O95936.
GermOnline	ENSG00000163508. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.820. 1 hit.
InterPro	IPR008967. p53-like_TF_DNA-bd. IPR001699. TF_T-box. IPR018186. TF_T-box_CS. [Graphical view]
PANTHER	PTHR11267. PTHR11267. 1 hit.
Pfam	PF00907. T-box. 1 hit. [Graphical view]
PRINTS	PR00937. TBOX.
SMART	SM00425. TBOX. 1 hit. [Graphical view]
SUPFAM	SSF49417. P53_like_DNA_bnd. 1 hit.
PROSITE	PS01283. TBOX_1. 1 hit. PS01264. TBOX_2. 1 hit. PS50252. TBOX_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	8320.
NextBio	31155.
SOURCE	Search...

Entry information

Entry name

EOMES_HUMAN

Accession

Primary (citable) accession number: O95936
Secondary accession number(s): B7Z4I2, Q8TAZ2, Q9UPM7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 5, 2009
Last modified:	May 1, 2013
This is version 112 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.