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   27-MAR-2024, entry version 176.
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; 9.
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; 9606-ENSP00000371875; -.
DR   PeptideAtlas; P78367; -.
DR   ProteomicsDB; 57595; -.
DR   Antibodypedia; 22925; 227 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   AGR; HGNC:951; -.
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; RRCADVP; -.
DR   OrthoDB; 461623at2759; -.
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 1151 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 60 other cell types or tissues.
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   Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR   InterPro; IPR009057; Homeobox-like_sf.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR001356; Homeobox_dom.
DR   InterPro; IPR020479; Homeobox_metazoa.
DR   PANTHER; PTHR24340; HOMEOBOX PROTEIN NKX; 1.
DR   PANTHER; PTHR24340:SF34; HOMEOBOX PROTEIN NKX-3.2; 1.
DR   Pfam; PF00046; Homeodomain; 1.
DR   PRINTS; PR00024; HOMEOBOX.
DR   SMART; SM00389; HOX; 1.
DR   SUPFAM; SSF46689; Homeodomain-like; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
DR   Genevisible; P78367; HS.
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
//