ID   BRAC_HUMAN              Reviewed;         435 AA.
AC   O15178;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   25-JAN-2012, entry version 95.
DE   RecName: Full=Brachyury protein;
DE   AltName: Full=Protein T;
GN   Name=T;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=96402060; PubMed=8963900;
RA   Edwards Y.H., Putt W., Lekoape K.M., Stott D., Fox M., Hopkinson D.A.,
RA   Sowden J.;
RT   "The human homolog T of the mouse T(Brachyury) gene; gene structure,
RT   cDNA sequence, and assignment to chromosome 6q27.";
RL   Genome Res. 6:226-233(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   MEDLINE=22935763; PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA   Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA   Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA   Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA   Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA   Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA   Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA   Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA   Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA   Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA   Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA   Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA   Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA   Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA   Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA   McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA   Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA   Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA   Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA   Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA   Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA   Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA   Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA   Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA   Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA   Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [3]
RP   INVOLVEMENT IN SUSCEPTIBILITY TO NTD.
RX   PubMed=15449172; DOI=10.1007/s00439-004-1185-8;
RA   Jensen L.E., Barbaux S., Hoess K., Fraterman S., Whitehead A.S.,
RA   Mitchell L.E.;
RT   "The human T locus and spina bifida risk.";
RL   Hum. Genet. 115:475-482(2004).
RN   [4]
RP   INVOLVEMENT IN SUSCEPTIBILITY TO THE DEVELOPMENT OF CHORDOMA.
RX   PubMed=19801981; DOI=10.1038/ng.454;
RA   Yang X.R., Ng D., Alcorta D.A., Liebsch N.J., Sheridan E., Li S.,
RA   Goldstein A.M., Parry D.M., Kelley M.J.;
RT   "T (brachyury) gene duplication confers major susceptibility to
RT   familial chordoma.";
RL   Nat. Genet. 41:1176-1178(2009).
CC   -!- FUNCTION: Involved in the transcriptional regulation of genes
CC       required for mesoderm formation and differentiation. Binds to a
CC       palindromic site (called T site) and activates gene transcription
CC       when bound to such a site.
CC   -!- SUBUNIT: Monomer (By similarity).
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- DISEASE: Genetic variations in T are associated with
CC       susceptibility to neural tube defects (NTD) [MIM:182940]. NTD are
CC       common congenital malformations. Spina bifida, which results from
CC       malformations in the caudal region of the neural tube, is
CC       compatible with life but associated with significant morbidity,
CC       including lower limb paralysis.
CC   -!- DISEASE: T is involved in susceptibility to the development of
CC       chordoma (CHDM) [MIM:215400]. Chordomas are rare, clinically
CC       malignant tumors derived from notochordal remnants. They occur
CC       along the length of the spinal axis, predominantly in the
CC       sphenooccipital, vertebral and sacrococcygeal regions. They are
CC       characterized by slow growth, local destruction of bone, extension
CC       into adjacent soft tissues and rarely, distant metastatic spread.
CC       Note=Susceptibility to development of chordomas is due to a T gene
CC       duplication.
CC   -!- SIMILARITY: Contains 1 T-box DNA-binding domain.
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DR   EMBL; AJ001699; CAA04938.1; -; mRNA.
DR   EMBL; AL627443; CAI14269.1; -; Genomic_DNA.
DR   IPI; IPI00005203; -.
DR   RefSeq; NP_003172.1; NM_003181.2.
DR   UniGene; Hs.389457; -.
DR   ProteinModelPortal; O15178; -.
DR   SMR; O15178; 41-223.
DR   STRING; O15178; -.
DR   PhosphoSite; O15178; -.
DR   PRIDE; O15178; -.
DR   Ensembl; ENST00000296946; ENSP00000296946; ENSG00000164458.
DR   Ensembl; ENST00000366876; ENSP00000355841; ENSG00000164458.
DR   GeneID; 6862; -.
DR   KEGG; hsa:6862; -.
DR   UCSC; uc003qut.1; human.
DR   CTD; 6862; -.
DR   GeneCards; GC06M166541; -.
DR   H-InvDB; HIX0032807; -.
DR   HGNC; HGNC:11515; T.
DR   HPA; HPA003322; -.
DR   MIM; 182940; phenotype.
DR   MIM; 215400; phenotype.
DR   MIM; 601397; gene.
DR   neXtProt; NX_O15178; -.
DR   Orphanet; 3027; Caudal regression sequence.
DR   Orphanet; 823; Isolated spina bifida.
DR   PharmGKB; PA36296; -.
DR   eggNOG; prNOG08473; -.
DR   GeneTree; ENSGT00590000082772; -.
DR   HOGENOM; HBG402911; -.
DR   HOVERGEN; HBG004599; -.
DR   InParanoid; O15178; -.
DR   OMA; PTYSDNS; -.
DR   OrthoDB; EOG4FXR7S; -.
DR   PhylomeDB; O15178; -.
DR   NextBio; 26779; -.
DR   ArrayExpress; O15178; -.
DR   Bgee; O15178; -.
DR   CleanEx; HS_T; -.
DR   Genevestigator; O15178; -.
DR   GermOnline; ENSG00000164458; Homo sapiens.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; NAS:ProtInc.
DR   GO; GO:0008595; P:anterior/posterior axis specification, embryo; TAS:ProtInc.
DR   GO; GO:0007498; P:mesoderm development; TAS:ProtInc.
DR   GO; GO:0090009; P:primitive streak formation; NAS:BHF-UCL.
DR   GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR   InterPro; IPR008967; p53-like_TF_DNA-bd.
DR   InterPro; IPR002070; TF_Brachyury.
DR   InterPro; IPR001699; TF_T-box.
DR   InterPro; IPR018186; TF_T-box_CS.
DR   Gene3D; G3DSA:2.60.40.820; TF_T-box; 1.
DR   KO; K10172; -.
DR   PANTHER; PTHR11267; TF_T-box; 1.
DR   Pfam; PF00907; T-box; 1.
DR   PRINTS; PR00938; BRACHYURY.
DR   PRINTS; PR00937; TBOX.
DR   SMART; SM00425; TBOX; 1.
DR   SUPFAM; SSF49417; P53_like_DNA_bnd; 1.
DR   PROSITE; PS01283; TBOX_1; 1.
DR   PROSITE; PS01264; TBOX_2; 1.
DR   PROSITE; PS50252; TBOX_3; 1.
PE   2: Evidence at transcript level;
KW   Activator; Complete proteome; Developmental protein; DNA-binding;
KW   Nucleus; Polymorphism; Reference proteome; Transcription;
KW   Transcription regulation.
FT   CHAIN         1    435       Brachyury protein.
FT                                /FTId=PRO_0000184414.
FT   DNA_BIND     51    219       T-box.
FT   VARIANT     177    177       G -> D (in dbSNP:rs2305089).
FT                                /FTId=VAR_021982.
FT   VARIANT     356    356       G -> S (in dbSNP:rs3127328).
FT                                /FTId=VAR_024656.
FT   VARIANT     358    358       V -> I (in dbSNP:rs77703807).
FT                                /FTId=VAR_063239.
FT   VARIANT     367    367       V -> M (in dbSNP:rs35292451).
FT                                /FTId=VAR_032457.
FT   VARIANT     369    369       N -> S (in dbSNP:rs3816300).
FT                                /FTId=VAR_020250.
FT   VARIANT     402    402       E -> K (in dbSNP:rs34517945).
FT                                /FTId=VAR_032458.
SQ   SEQUENCE   435 AA;  47443 MW;  9D470088C8602631 CRC64;
     MSSPGTESAG KSLQYRVDHL LSAVENELQA GSEKGDPTER ELRVGLEESE LWLRFKELTN
     EMIVTKNGRR MFPVLKVNVS GLDPNAMYSF LLDFVAADNH RWKYVNGEWV PGGKPEPQAP
     SCVYIHPDSP NFGAHWMKAP VSFSKVKLTN KLNGGGQIML NSLHKYEPRI HIVRVGGPQR
     MITSHCFPET QFIAVTAYQN EEITALKIKY NPFAKAFLDA KERSDHKEMM EEPGDSQQPG
     YSQWGWLLPG TSTLCPPANP HPQFGGALSL PSTHSCDRYP TLRSHRSSPY PSPYAHRNNS
     PTYSDNSPAC LSMLQSHDNW SSLGMPAHPS MLPVSHNASP PTSSSQYPSL WSVSNGAVTP
     GSQAAAVSNG LGAQFFRGSP AHYTPLTHPV SAPSSSGSPL YEGAAAATDI VDSQYDAAAQ
     GRLIASWTPV SPPSM
//