NKX32_HUMAN
ID NKX32_HUMAN Reviewed; 333 AA.
AC P78367; Q2M2I7;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Homeobox protein Nkx-3.2;
DE AltName: Full=Bagpipe homeobox protein homolog 1;
DE AltName: Full=Homeobox protein NK-3 homolog B;
GN Name=NKX3-2; Synonyms=BAPX1, NKX3B;
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 [GENOMIC DNA].
RX PubMed=9426254; DOI=10.1016/s0378-1119(97)00520-9;
RA Tribioli C., Lufkin T.;
RT "Molecular cloning, chromosomal mapping and developmental expression of
RT BAPX1, a novel human homeobox-containing gene homologous to Drosophila
RT bagpipe.";
RL Gene 203:225-233(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=9344671; DOI=10.1006/geno.1997.4926;
RA Yoshiura K., Murray J.C.;
RT "Sequence and chromosomal assignment of human BAPX1, a bagpipe-related
RT gene, to 4p16.1: a candidate gene for skeletal dysplasia.";
RL Genomics 45:425-428(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 206-265.
RX PubMed=9256352; DOI=10.1016/s0925-4773(97)00067-1;
RA Tribioli C., Frasch M., Lufkin T.;
RT "Bapx1: an evolutionary conserved homologue of the Drosophila bagpipe
RT homeobox gene is expressed in splanchnic mesoderm and the embryonic
RT skeleton.";
RL Mech. Dev. 65:145-162(1997).
RN [5]
RP INVOLVEMENT IN SMMD, AND TISSUE SPECIFICITY.
RX PubMed=20004766; DOI=10.1016/j.ajhg.2009.11.005;
RA Hellemans J., Simon M., Dheedene A., Alanay Y., Mihci E., Rifai L.,
RA Sefiani A., van Bever Y., Meradji M., Superti-Furga A., Mortier G.;
RT "Homozygous inactivating mutations in the NKX3-2 gene result in spondylo-
RT megaepiphyseal-metaphyseal dysplasia.";
RL Am. J. Hum. Genet. 85:916-922(2009).
CC -!- FUNCTION: Transcriptional repressor that acts as a negative regulator
CC of chondrocyte maturation. PLays a role in distal stomach development;
CC required for proper antral-pyloric morphogenesis and development of
CC antral-type epithelium. In concert with GSC, defines the structural
CC components of the middle ear; required for tympanic ring and gonium
CC development and in the regulation of the width of the malleus (By
CC similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P78367; P78424: POU6F2; NbExp=3; IntAct=EBI-12077522, EBI-12029004;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed at highest levels in cartilage, bone
CC (osteosarcoma) and gut (small intestine and colon), whereas moderate
CC expression is seen in trachea and brain. Expressed in visceral mesoderm
CC and embryonic skeleton. {ECO:0000269|PubMed:20004766}.
CC -!- DISEASE: Spondylo-megaepiphyseal-metaphyseal dysplasia (SMMD)
CC [MIM:613330]: A skeletal dysplasia characterized by disproportionate
CC short stature with a short and stiff neck and trunk, relatively long
CC limbs that may show flexion contractures of the distal joints, delayed
CC and impaired ossification of the vertebral bodies, the presence of
CC large epiphyseal ossification centers and wide growth plates in the
CC long tubular bones, and numerous pseudoepiphyses of the short tubular
CC bones in hands and feet. {ECO:0000269|PubMed:20004766}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the NK-3 homeobox family. {ECO:0000305}.
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DR EMBL; AF005260; AAC39536.1; -; Genomic_DNA.
DR EMBL; AF009801; AAB82783.1; -; mRNA.
DR EMBL; AF009802; AAB82784.1; -; Genomic_DNA.
DR EMBL; BC111966; AAI11967.1; -; mRNA.
DR EMBL; U89845; AAB49696.1; -; Genomic_DNA.
DR CCDS; CCDS3410.1; -.
DR RefSeq; NP_001180.1; NM_001189.3.
DR AlphaFoldDB; P78367; -.
DR SMR; P78367; -.
DR BioGRID; 107055; 8.
DR IntAct; P78367; 1.
DR STRING; 9606.ENSP00000371875; -.
DR iPTMnet; P78367; -.
DR PhosphoSitePlus; P78367; -.
DR BioMuta; NKX3-2; -.
DR DMDM; 6016210; -.
DR EPD; P78367; -.
DR jPOST; P78367; -.
DR MassIVE; P78367; -.
DR PaxDb; P78367; -.
DR PeptideAtlas; P78367; -.
DR PRIDE; P78367; -.
DR ProteomicsDB; 57595; -.
DR Antibodypedia; 22925; 208 antibodies from 30 providers.
DR DNASU; 579; -.
DR Ensembl; ENST00000382438.6; ENSP00000371875.5; ENSG00000109705.8.
DR GeneID; 579; -.
DR KEGG; hsa:579; -.
DR MANE-Select; ENST00000382438.6; ENSP00000371875.5; NM_001189.4; NP_001180.1.
DR UCSC; uc003gmx.3; human.
DR CTD; 579; -.
DR DisGeNET; 579; -.
DR GeneCards; NKX3-2; -.
DR HGNC; HGNC:951; NKX3-2.
DR HPA; ENSG00000109705; Tissue enriched (intestine).
DR MalaCards; NKX3-2; -.
DR MIM; 602183; gene.
DR MIM; 613330; phenotype.
DR neXtProt; NX_P78367; -.
DR OpenTargets; ENSG00000109705; -.
DR Orphanet; 228387; Spondylo-megaepiphyseal-metaphyseal dysplasia.
DR PharmGKB; PA162397617; -.
DR VEuPathDB; HostDB:ENSG00000109705; -.
DR eggNOG; KOG0842; Eukaryota.
DR GeneTree; ENSGT00940000161843; -.
DR HOGENOM; CLU_049543_2_0_1; -.
DR InParanoid; P78367; -.
DR OMA; SEACEPT; -.
DR OrthoDB; 1303626at2759; -.
DR PhylomeDB; P78367; -.
DR TreeFam; TF351204; -.
DR PathwayCommons; P78367; -.
DR Reactome; R-HSA-8939902; Regulation of RUNX2 expression and activity.
DR SignaLink; P78367; -.
DR BioGRID-ORCS; 579; 8 hits in 1073 CRISPR screens.
DR GenomeRNAi; 579; -.
DR Pharos; P78367; Tbio.
DR PRO; PR:P78367; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P78367; protein.
DR Bgee; ENSG00000109705; Expressed in tibia and 59 other tissues.
DR Genevisible; P78367; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0048645; P:animal organ formation; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0007368; P:determination of left/right symmetry; IEA:Ensembl.
DR GO; GO:0048706; P:embryonic skeletal system development; IEA:Ensembl.
DR GO; GO:0060576; P:intestinal epithelial cell development; IEA:Ensembl.
DR GO; GO:0042474; P:middle ear morphogenesis; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0031016; P:pancreas development; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR GO; GO:0048705; P:skeletal system morphogenesis; IEA:Ensembl.
DR GO; GO:0048536; P:spleen development; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; TAS:ProtInc.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR020479; Homeobox_metazoa.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00024; HOMEOBOX.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW DNA-binding; Dwarfism; Homeobox; Nucleus; Reference proteome; Repressor;
KW Transcription; Transcription regulation.
FT CHAIN 1..333
FT /note="Homeobox protein Nkx-3.2"
FT /id="PRO_0000048947"
FT DNA_BIND 206..265
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 65..113
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 138..212
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 333 AA; 34814 MW; 8C406E188D27780B CRC64;
MAVRGANTLT SFSIQAILNK KEERGGLAAP EGRPAPGGTA ASVAAAPAVC CWRLFGERDA
GALGGAEDSL LASPAGTRTA AGRTAESPEG WDSDSALSEE NESRRRCADA RGASGAGLAG
GSLSLGQPVC ELAASKDLEE EAAGRSDSEM SASVSGDRSP RTEDDGVGPR GAHVSALCSG
AGGGGGSGPA GVAEEEEEPA APKPRKKRSR AAFSHAQVFE LERRFNHQRY LSGPERADLA
ASLKLTETQV KIWFQNRRYK TKRRQMAADL LASAPAAKKV AVKVLVRDDQ RQYLPGEVLR
PPSLLPLQPS YYYPYYCLPG WALSTCAAAA GTQ
