ID SHOX_HUMAN Reviewed; 292 AA. AC O15266; O00412; O00413; O15267; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 27-MAR-2024, entry version 212. DE RecName: Full=Short stature homeobox protein; DE AltName: Full=Pseudoautosomal homeobox-containing osteogenic protein; DE AltName: Full=Short stature homeobox-containing protein; GN Name=SHOX; Synonyms=PHOG; 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 / MRNA] (ISOFORMS SHOXA AND SHOXB), AND RP INVOLVEMENT IN ISS. RC TISSUE=Skeletal muscle; RX PubMed=9140395; DOI=10.1038/ng0597-54; RA Rao E., Weiss B., Fukami M., Rump A., Niesler B., Mertz A., Muroya K., RA Binder G., Kirsch S., Winkelmann M., Nordsiek G., Heinrich U., RA Breuning M.H., Ranke M.B., Rosenthal A., Ogata T., Rappold G.A.; RT "Pseudoautosomal deletions encompassing a novel homeobox gene cause growth RT failure in idiopathic short stature and Turner syndrome."; RL Nat. Genet. 16:54-63(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHOXA). RX PubMed=9259282; DOI=10.1093/hmg/6.8.1341; RA Ellison J.W., Wardak Z., Young M.F., Gehron Robey P., Laig-Webster M., RA Chiong W.; RT "PHOG, a candidate gene for involvement in the short stature of Turner RT syndrome."; RL Hum. Mol. Genet. 6:1341-1347(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [4] RP VARIANTS LWD VAL-132 AND LEU-153. RX PubMed=11030412; DOI=10.1007/s004390000352; RA Grigelioniene G., Ekloef O., Ivarsson S.A., Westphal O., Neumeyer L., RA Kedra D., Dumanski J., Hagenaes L.; RT "Mutations in short stature homeobox containing gene (SHOX) in RT dyschondrosteosis but not in hypochondroplasia."; RL Hum. Genet. 107:145-149(2000). RN [5] RP DISEASE. RX PubMed=11891678; DOI=10.1002/ajmg.10228; RA Cormier-Daire V., Huber C., Munnich A.; RT "Allelic and nonallelic heterogeneity in dyschondrosteosis (Leri-Weill RT syndrome)."; RL Am. J. Med. Genet. 106:272-274(2001). RN [6] RP VARIANT LWD CYS-173. RX PubMed=11403039; DOI=10.1136/jmg.38.5.323; RA Huber C., Cusin V., Le Merrer M., Mathieu M., Sulmont V., Dagoneau N., RA Munnich A., Cormier-Daire V.; RT "SHOX point mutations in dyschondrosteosis."; RL J. Med. Genet. 38:323-323(2001). RN [7] RP VARIANT LMD TRP-168. RX PubMed=11889214; DOI=10.1210/jcem.87.3.8348; RA Ogata T., Muroya K., Sasaki G., Nishimura G., Kitoh H., Hattori T.; RT "SHOX nullizygosity and haploinsufficiency in a Japanese family: RT implication for the development of Turner skeletal features."; RL J. Clin. Endocrinol. Metab. 87:1390-1394(2002). CC -!- FUNCTION: Controls fundamental aspects of growth and development. CC -!- INTERACTION: CC O15266; P35711: SOX5; NbExp=2; IntAct=EBI-3505698, EBI-3505701; CC O15266; P35712: SOX6; NbExp=3; IntAct=EBI-3505698, EBI-3505706; CC O15266-2; Q9BZE0: GLIS2; NbExp=3; IntAct=EBI-12825957, EBI-7251368; CC O15266-2; Q9Y5R4: HEMK1; NbExp=3; IntAct=EBI-12825957, EBI-10329202; CC O15266-2; P78318: IGBP1; NbExp=3; IntAct=EBI-12825957, EBI-1055954; CC O15266-2; P52952: NKX2-5; NbExp=3; IntAct=EBI-12825957, EBI-936601; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108, CC ECO:0000255|PROSITE-ProRule:PRU00138}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=SHOXA; CC IsoId=O15266-1; Sequence=Displayed; CC Name=SHOXB; CC IsoId=O15266-2; Sequence=VSP_002287; CC -!- TISSUE SPECIFICITY: SHOXA is expressed in skeletal muscle, placenta, CC pancreas, heart and bone marrow fibroblast and SHOXB is highly CC expressed in bone marrow fibroblast followed by kidney and skeletal CC muscle. SHOXB is not expressed in brain, kidney, liver and lung. Highly CC expressed in osteogenic cells. CC -!- INDUCTION: By retinoic acid and phorbol-12-myristate 13-acetate (PMA). CC -!- DISEASE: Leri-Weill dyschondrosteosis (LWD) [MIM:127300]: Dominantly CC inherited skeletal dysplasia characterized by moderate short stature CC predominantly because of short mesomelic limb segments. It is often CC associated with the Madelung deformity of the wrist, comprising bowing CC of the radius and dorsal dislocation of the distal ulna. CC {ECO:0000269|PubMed:11030412, ECO:0000269|PubMed:11403039}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Langer mesomelic dysplasia (LMD) [MIM:249700]: Autosomal CC recessive rare skeletal dysplasia characterized by severe short stature CC owing to shortening and maldevelopment of the mesomelic and rhizomelic CC segments of the limbs. Associated malformations are rarely reported and CC intellect is normal in all affected subjects reported to date. CC {ECO:0000269|PubMed:11889214}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Short stature, idiopathic, X-linked (ISS) [MIM:300582]: A CC condition defined by a standing height more than 2 standard deviations CC below the mean (or below the 2.5 percentile) for sex and chronological CC age, compared with a well-nourished, genetically relevant population, CC in the absence of specific causative disorders. CC {ECO:0000269|PubMed:9140395}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: The gene coding for this protein is located in the CC pseudoautosomal region 1 (PAR1) of X and Y chromosomes. CC -!- SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily. CC {ECO:0000305}. 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; Y11536; CAA72299.1; -; mRNA. DR EMBL; Y11535; CAA72298.1; -; mRNA. DR EMBL; U82668; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; U89331; AAC18820.1; -; mRNA. DR EMBL; BX004827; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS14106.1; -. [O15266-2] DR CCDS; CCDS14107.1; -. [O15266-1] DR RefSeq; NP_000442.1; NM_000451.3. [O15266-1] DR RefSeq; NP_006874.1; NM_006883.2. [O15266-2] DR AlphaFoldDB; O15266; -. DR SMR; O15266; -. DR BioGRID; 112369; 13. DR IntAct; O15266; 8. DR STRING; 9606.ENSP00000370990; -. DR iPTMnet; O15266; -. DR PhosphoSitePlus; O15266; -. DR BioMuta; SHOX; -. DR jPOST; O15266; -. DR MassIVE; O15266; -. DR PaxDb; 9606-ENSP00000370990; -. DR PeptideAtlas; O15266; -. DR ProteomicsDB; 48555; -. [O15266-1] DR ProteomicsDB; 48556; -. [O15266-2] DR Antibodypedia; 23329; 148 antibodies from 25 providers. DR DNASU; 6473; -. DR Ensembl; ENST00000334060.8; ENSP00000335505.3; ENSG00000185960.15. [O15266-2] DR Ensembl; ENST00000381575.6; ENSP00000370987.1; ENSG00000185960.15. [O15266-2] DR Ensembl; ENST00000381578.6; ENSP00000370990.1; ENSG00000185960.15. [O15266-1] DR Ensembl; ENST00000686671.1; ENSP00000508521.1; ENSG00000185960.15. [O15266-1] DR Ensembl; ENST00000711141.1; ENSP00000518639.1; ENSG00000292354.1. [O15266-2] DR Ensembl; ENST00000711142.1; ENSP00000518640.1; ENSG00000292354.1. [O15266-1] DR Ensembl; ENST00000711143.1; ENSP00000518641.1; ENSG00000292354.1. [O15266-2] DR Ensembl; ENST00000711145.1; ENSP00000518642.1; ENSG00000292354.1. [O15266-1] DR GeneID; 6473; -. DR KEGG; hsa:6473; -. DR MANE-Select; ENST00000686671.1; ENSP00000508521.1; NM_000451.4; NP_000442.1. DR UCSC; uc004cph.1; human. [O15266-1] DR AGR; HGNC:10853; -. DR CTD; 6473; -. DR DisGeNET; 6473; -. DR GeneCards; SHOX; -. DR GeneReviews; SHOX; -. DR HGNC; HGNC:10853; SHOX. DR HPA; ENSG00000185960; Low tissue specificity. DR MalaCards; SHOX; -. DR MIM; 127300; phenotype. DR MIM; 249700; phenotype. DR MIM; 300582; phenotype. DR MIM; 312865; gene. DR MIM; 400020; gene. DR neXtProt; NX_O15266; -. DR OpenTargets; ENSG00000185960; -. DR Orphanet; 2632; Langer mesomelic dysplasia. DR Orphanet; 240; Leri-Weill dyschondrosteosis. DR Orphanet; 314795; SHOX-related short stature. DR PharmGKB; PA134978644; -. DR VEuPathDB; HostDB:ENSG00000185960; -. DR eggNOG; KOG0490; Eukaryota. DR GeneTree; ENSGT00940000154287; -. DR HOGENOM; CLU_047013_5_0_1; -. DR InParanoid; O15266; -. DR OMA; YDCKEKR; -. DR OrthoDB; 2897127at2759; -. DR PhylomeDB; O15266; -. DR TreeFam; TF350757; -. DR PathwayCommons; O15266; -. DR SignaLink; O15266; -. DR SIGNOR; O15266; -. DR BioGRID-ORCS; 6473; 8 hits in 632 CRISPR screens. DR ChiTaRS; SHOX; human. DR GeneWiki; Short_stature_homeobox_gene; -. DR GenomeRNAi; 6473; -. DR Pharos; O15266; Tbio. DR PRO; PR:O15266; -. DR Proteomes; UP000005640; Chromosome X. DR Proteomes; UP000005640; Chromosome Y. DR RNAct; O15266; Protein. DR Bgee; ENSG00000185960; Expressed in calcaneal tendon and 22 other cell types or tissues. DR ExpressionAtlas; O15266; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:NTNU_SB. 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 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; IPR000047; HTH_motif. DR InterPro; IPR003654; OAR_dom. DR PANTHER; PTHR46255; SHORT STATURE HOMEOBOX; 1. DR PANTHER; PTHR46255:SF2; SHORT STATURE HOMEOBOX PROTEIN; 1. DR Pfam; PF00046; Homeodomain; 1. DR Pfam; PF03826; OAR; 1. DR PRINTS; PR00031; HTHREPRESSR. DR SMART; SM00389; HOX; 1. DR SUPFAM; SSF46689; Homeodomain-like; 1. DR PROSITE; PS00027; HOMEOBOX_1; 1. DR PROSITE; PS50071; HOMEOBOX_2; 1. DR PROSITE; PS50803; OAR; 1. PE 1: Evidence at protein level; KW Activator; Alternative splicing; Developmental protein; Disease variant; KW DNA-binding; Dwarfism; Homeobox; Nucleus; Reference proteome; KW Transcription; Transcription regulation. FT CHAIN 1..292 FT /note="Short stature homeobox protein" FT /id="PRO_0000049291" FT DNA_BIND 117..176 FT /note="Homeobox" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108" FT REGION 1..34 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 100..119 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 242..249 FT /note="SH3-binding" FT /evidence="ECO:0000255" FT MOTIF 274..287 FT /note="OAR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00138" FT VAR_SEQ 212..292 FT /note="VQAQLQLEGVAHAHPHLHPHLAAHAPYLMFPPPPFGLPIASLAESASAAAVV FT AAAAKSNSKNSSIADLRLKARKHAEALGL -> MEFCSCRPGWSIMA (in isoform FT SHOXB)" FT /evidence="ECO:0000303|PubMed:9140395" FT /id="VSP_002287" FT VARIANT 132 FT /note="L -> V (in LWD; dbSNP:rs137852554)" FT /evidence="ECO:0000269|PubMed:11030412" FT /id="VAR_019414" FT VARIANT 153 FT /note="R -> L (in LWD; dbSNP:rs137852555)" FT /evidence="ECO:0000269|PubMed:11030412" FT /id="VAR_019415" FT VARIANT 168 FT /note="R -> W (in LMD; dbSNP:rs137852557)" FT /evidence="ECO:0000269|PubMed:11889214" FT /id="VAR_019416" FT VARIANT 173 FT /note="R -> C (in LWD; dbSNP:rs137852556)" FT /evidence="ECO:0000269|PubMed:11403039" FT /id="VAR_012346" SQ SEQUENCE 292 AA; 32236 MW; 0F2A61A3051CB360 CRC64; MEELTAFVSK SFDQKSKDGN GGGGGGGGKK DSITYREVLE SGLARSRELG TSDSSLQDIT EGGGHCPVHL FKDHVDNDKE KLKEFGTARV AEGIYECKEK REDVKSEDED GQTKLKQRRS RTNFTLEQLN ELERLFDETH YPDAFMREEL SQRLGLSEAR VQVWFQNRRA KCRKQENQMH KGVILGTANH LDACRVAPYV NMGALRMPFQ QVQAQLQLEG VAHAHPHLHP HLAAHAPYLM FPPPPFGLPI ASLAESASAA AVVAAAAKSN SKNSSIADLR LKARKHAEAL GL //