TBX4_HUMAN
ID TBX4_HUMAN Reviewed; 545 AA.
AC P57082; A5PKU7; B2RMT1; B7ZLV3;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=T-box transcription factor TBX4;
DE Short=T-box protein 4;
GN Name=TBX4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10945475; DOI=10.1006/geno.2000.6222;
RA Yi C.H., Russ A., Brook J.D.;
RT "Virtual cloning and physical mapping of a human T-box gene, TBX4.";
RL Genomics 67:92-95(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ALA-6.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP VARIANTS ICPPS VAL-248 AND ARG-531, AND VARIANTS ALA-6 AND VAL-35.
RX PubMed=15106123; DOI=10.1086/421331;
RA Bongers E.M.H.F., Duijf P.H.G., van Beersum S.E.M., Schoots J.,
RA van Kampen A., Burckhardt A., Hamel B.C.J., Losan F., Hoefsloot L.H.,
RA Yntema H.G., Knoers N.V.A.M., van Bokhoven H.;
RT "Mutations in the human TBX4 gene cause small patella syndrome.";
RL Am. J. Hum. Genet. 74:1239-1248(2004).
RN [5]
RP VARIANT THR-282.
RX PubMed=24038782; DOI=10.1002/ajmg.a.36134;
RA Matsushita M., Kitoh H., Kaneko H., Mishima K., Kadono I., Ishiguro N.,
RA Nishimura G.;
RT "A novel SOX9 H169Q mutation in a family with overlapping phenotype of mild
RT campomelic dysplasia and small patella syndrome.";
RL Am. J. Med. Genet. A 161A:2528-2534(2013).
RN [6]
RP VARIANT PAPPAS 113-TYR--GLY-545 DEL, CHARACTERIZATION OF VARIANT PAPPAS
RP 113-TYR--GLY-545 DEL, INVOLVEMENT IN PAPPAS, AND FUNCTION.
RX PubMed=31761294; DOI=10.1016/j.ajhg.2019.10.013;
RA Kariminejad A., Szenker-Ravi E., Lekszas C., Tajsharghi H., Moslemi A.R.,
RA Naert T., Tran H.T., Ahangari F., Rajaei M., Nasseri M., Haaf T., Azad A.,
RA Superti-Furga A., Maroofian R., Ghaderi-Sohi S., Najmabadi H.,
RA Abbaszadegan M.R., Vleminckx K., Nikuei P., Reversade B.;
RT "Homozygous null TBX4 mutations lead to posterior amelia with pelvic and
RT pulmonary hypoplasia.";
RL Am. J. Hum. Genet. 105:1294-1301(2019).
CC -!- FUNCTION: Transcriptional regulator that has an essential role in the
CC organogenesis of lungs, pelvis, and hindlimbs.
CC {ECO:0000269|PubMed:31761294}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00201}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P57082-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P57082-2; Sequence=VSP_054002;
CC -!- DISEASE: Ischiocoxopodopatellar syndrome with or without pulmonary
CC arterial hypertension (ICPPS) [MIM:147891]: An autosomal dominant bone
CC disease characterized by patellar aplasia or hypoplasia and by
CC anomalies of the pelvis and feet, including disrupted ossification of
CC the ischia and inferior pubic rami. {ECO:0000269|PubMed:15106123}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Amelia, posterior, with pelvic and pulmonary hypoplasia
CC syndrome (PAPPAS) [MIM:601360]: An autosomal recessive, lethal
CC embryonic syndrome characterized by absent hindlimbs, pulmonary
CC hypoplasia, severely hypoplastic or absent pelvic bones, hypoplasia of
CC the sacrum, and ambiguous genitalia. {ECO:0000269|PubMed:31761294}.
CC Note=The disease may be caused by variants affecting the gene
CC represented in this entry.
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DR EMBL; AF188703; AAF68854.1; -; mRNA.
DR EMBL; AC005901; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC136403; AAI36404.1; -; mRNA.
DR EMBL; BC142620; AAI42621.1; -; mRNA.
DR EMBL; BC144062; AAI44063.1; -; mRNA.
DR CCDS; CCDS11629.1; -. [P57082-1]
DR CCDS; CCDS82180.1; -. [P57082-2]
DR RefSeq; NP_001308049.1; NM_001321120.1. [P57082-2]
DR RefSeq; NP_060958.2; NM_018488.3. [P57082-1]
DR AlphaFoldDB; P57082; -.
DR SMR; P57082; -.
DR BioGRID; 114875; 5.
DR IntAct; P57082; 4.
DR MINT; P57082; -.
DR STRING; 9606.ENSP00000240335; -.
DR iPTMnet; P57082; -.
DR PhosphoSitePlus; P57082; -.
DR BioMuta; TBX4; -.
DR DMDM; 51338786; -.
DR MassIVE; P57082; -.
DR PaxDb; P57082; -.
DR PeptideAtlas; P57082; -.
DR PRIDE; P57082; -.
DR ProteomicsDB; 56994; -. [P57082-1]
DR ProteomicsDB; 721; -.
DR ABCD; P57082; 5 sequenced antibodies.
DR Antibodypedia; 18589; 152 antibodies from 24 providers.
DR DNASU; 9496; -.
DR Ensembl; ENST00000240335.1; ENSP00000240335.1; ENSG00000121075.11. [P57082-1]
DR Ensembl; ENST00000642491.1; ENSP00000495714.1; ENSG00000121075.11. [P57082-2]
DR Ensembl; ENST00000644296.1; ENSP00000495986.1; ENSG00000121075.11. [P57082-2]
DR GeneID; 9496; -.
DR KEGG; hsa:9496; -.
DR MANE-Select; ENST00000644296.1; ENSP00000495986.1; NM_001321120.2; NP_001308049.1. [P57082-2]
DR UCSC; uc002izi.3; human. [P57082-1]
DR CTD; 9496; -.
DR DisGeNET; 9496; -.
DR GeneCards; TBX4; -.
DR HGNC; HGNC:11603; TBX4.
DR HPA; ENSG00000121075; Tissue enhanced (lung, placenta, prostate).
DR MalaCards; TBX4; -.
DR MIM; 147891; phenotype.
DR MIM; 601360; phenotype.
DR MIM; 601719; gene.
DR neXtProt; NX_P57082; -.
DR OpenTargets; ENSG00000121075; -.
DR Orphanet; 261279; 17q23.1q23.2 microdeletion syndrome.
DR Orphanet; 1509; Coxopodopatellar syndrome.
DR Orphanet; 238578; Familial clubfoot due to 17q23.1q23.2 microduplication.
DR Orphanet; 275777; Heritable pulmonary arterial hypertension.
DR PharmGKB; PA36366; -.
DR VEuPathDB; HostDB:ENSG00000121075; -.
DR eggNOG; KOG3585; Eukaryota.
DR GeneTree; ENSGT00940000158882; -.
DR HOGENOM; CLU_037025_1_0_1; -.
DR InParanoid; P57082; -.
DR OMA; GNHQTLQ; -.
DR OrthoDB; 344556at2759; -.
DR PhylomeDB; P57082; -.
DR TreeFam; TF106341; -.
DR PathwayCommons; P57082; -.
DR SignaLink; P57082; -.
DR BioGRID-ORCS; 9496; 14 hits in 1092 CRISPR screens.
DR ChiTaRS; TBX4; human.
DR GenomeRNAi; 9496; -.
DR Pharos; P57082; Tbio.
DR PRO; PR:P57082; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P57082; protein.
DR Bgee; ENSG00000121075; Expressed in right lung and 87 other tissues.
DR ExpressionAtlas; P57082; baseline and differential.
DR Genevisible; P57082; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; NAS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IBA:GO_Central.
DR GO; GO:0001708; P:cell fate specification; IBA:GO_Central.
DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IMP:UniProtKB.
DR GO; GO:1990401; P:embryonic lung development; IMP:UniProtKB.
DR GO; GO:0035108; P:limb morphogenesis; IMP:UniProtKB.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0002009; P:morphogenesis of an epithelium; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0048705; P:skeletal system morphogenesis; IMP:UniProtKB.
DR CDD; cd00182; TBOX; 1.
DR Gene3D; 2.60.40.820; -; 1.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
DR InterPro; IPR046360; T-box_DNA-bd.
DR InterPro; IPR036960; T-box_sf.
DR InterPro; IPR001699; TF_T-box.
DR InterPro; IPR018186; TF_T-box_CS.
DR PANTHER; PTHR11267; PTHR11267; 1.
DR Pfam; PF00907; T-box; 1.
DR PRINTS; PR00937; TBOX.
DR SMART; SM00425; TBOX; 1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR PROSITE; PS01283; TBOX_1; 1.
DR PROSITE; PS01264; TBOX_2; 1.
DR PROSITE; PS50252; TBOX_3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; Disease variant; DNA-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..545
FT /note="T-box transcription factor TBX4"
FT /id="PRO_0000184433"
FT DNA_BIND 71..251
FT /note="T-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00201"
FT REGION 479..509
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 507
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70325"
FT VAR_SEQ 340
FT /note="R -> RA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054002"
FT VARIANT 6
FT /note="G -> A (in dbSNP:rs3744448)"
FT /evidence="ECO:0000269|PubMed:15106123,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_020251"
FT VARIANT 35
FT /note="A -> V (in dbSNP:rs148424252)"
FT /evidence="ECO:0000269|PubMed:15106123"
FT /id="VAR_026772"
FT VARIANT 113..545
FT /note="Missing (in PAPPAS; also responsible for
FT ischiocoxopodopatellar syndrome in heterozygous carriers;
FT no detectable protein expression in homozygous patient
FT cells)"
FT /evidence="ECO:0000269|PubMed:31761294"
FT /id="VAR_083526"
FT VARIANT 248
FT /note="G -> V (in ICPPS; dbSNP:rs28938474)"
FT /evidence="ECO:0000269|PubMed:15106123"
FT /id="VAR_026745"
FT VARIANT 282
FT /note="P -> T"
FT /evidence="ECO:0000269|PubMed:24038782"
FT /id="VAR_078493"
FT VARIANT 314
FT /note="A -> V (in dbSNP:rs3744438)"
FT /id="VAR_021983"
FT VARIANT 531
FT /note="Q -> R (in ICPPS; dbSNP:rs28936696)"
FT /evidence="ECO:0000269|PubMed:15106123"
FT /id="VAR_026746"
SQ SEQUENCE 545 AA; 60204 MW; B822FD05EE98C8CD CRC64;
MLQDKGLSES EEAFRAPGPA LGEASAANAP EPALAAPGLS GAALGSPPGP GADVVAAAAA
EQTIENIKVG LHEKELWKKF HEAGTEMIIT KAGRRMFPSY KVKVTGMNPK TKYILLIDIV
PADDHRYKFC DNKWMVAGKA EPAMPGRLYV HPDSPATGAH WMRQLVSFQK LKLTNNHLDP
FGHIILNSMH KYQPRLHIVK ADENNAFGSK NTAFCTHVFP ETSFISVTSY QNHKITQLKI
ENNPFAKGFR GSDDSDLRVA RLQSKEYPVI SKSIMRQRLI SPQLSATPDV GPLLGTHQAL
QHYQHENGAH SQLAEPQDLP LSTFPTQRDS SLFYHCLKRR DGTRHLDLPC KRSYLEAPSS
VGEDHYFRSP PPYDQQMLSP SYCSEVTPRE ACMYSGSGPE IAGVSGVDDL PPPPLSCNMW
TSVSPYTSYS VQTMETVPYQ PFPTHFTATT MMPRLPTLSA QSSQPPGNAH FSVYNQLSQS
QVRERGPSAS FPRERGLPQG CERKPPSPHL NAANEFLYSQ TFSLSRESSL QYHSGMGTVE
NWTDG
