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   24-JAN-2024, entry version 186.
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.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
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; 3.
DR   MINT; P57082; -.
DR   STRING; 9606.ENSP00000495986; -.
DR   iPTMnet; P57082; -.
DR   PhosphoSitePlus; P57082; -.
DR   BioMuta; TBX4; -.
DR   DMDM; 51338786; -.
DR   MassIVE; P57082; -.
DR   PaxDb; 9606-ENSP00000240335; -.
DR   PeptideAtlas; P57082; -.
DR   ProteomicsDB; 56994; -. [P57082-1]
DR   ProteomicsDB; 721; -.
DR   ABCD; P57082; 5 sequenced antibodies.
DR   Antibodypedia; 18589; 165 antibodies from 25 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   AGR; HGNC:11603; -.
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; QYHSGVG; -.
DR   OrthoDB; 5323209at2759; -.
DR   PhylomeDB; P57082; -.
DR   TreeFam; TF106341; -.
DR   PathwayCommons; P57082; -.
DR   SignaLink; P57082; -.
DR   BioGRID-ORCS; 9496; 16 hits in 1170 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 cell types or tissues.
DR   ExpressionAtlas; P57082; baseline and differential.
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 DNA-templated transcription; 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; cd20189; T-box_TBX4_5-like; 1.
DR   Gene3D; 2.60.40.820; Transcription factor, T-box; 1.
DR   InterPro; IPR008967; p53-like_TF_DNA-bd_sf.
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; T-BOX PROTEIN-RELATED; 1.
DR   PANTHER; PTHR11267:SF29; T-BOX TRANSCRIPTION FACTOR TBX4; 1.
DR   Pfam; PF00907; T-box; 1.
DR   PRINTS; PR00937; TBOX.
DR   SMART; SM00425; TBOX; 1.
DR   SUPFAM; SSF49417; p53-like transcription factors; 1.
DR   PROSITE; PS01283; TBOX_1; 1.
DR   PROSITE; PS01264; TBOX_2; 1.
DR   PROSITE; PS50252; TBOX_3; 1.
DR   Genevisible; P57082; HS.
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
//