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 11-NOV-2015, entry version 158. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS SHOXA AND SHOXB), RP AND 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 RT growth 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., RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., RA 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., RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., RA 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., RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., RA 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., RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., RA Williams G., Williams L., Williamson A., Williamson H., Wilming L., RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., RA 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., RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., RA Gibbs R.A., Beck S., 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/jc.87.3.1390; 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 P35711:SOX5; NbExp=2; IntAct=EBI-3505698, EBI-3505701; CC P35712:SOX6; NbExp=3; IntAct=EBI-3505698, EBI-3505706; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE- CC ProRule:PRU00108, 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, CC placenta, pancreas, heart and bone marrow fibroblast and SHOXB is CC highly expressed in bone marrow fibroblast followed by kidney and CC skeletal muscle. SHOXB is not expressed in brain, kidney, liver CC and lung. Highly expressed in osteogenic cells. CC -!- INDUCTION: By retinoic acid and phorbol-12-myristate 13-acetate CC (PMA). CC -!- DISEASE: Leri-Weill dyschondrosteosis (LWD) [MIM:127300]: CC Dominantly inherited skeletal dysplasia characterized by moderate CC short stature predominantly because of short mesomelic limb CC segments. It is often associated with the Madelung deformity of CC the wrist, comprising bowing of the radius and dorsal dislocation CC of the distal ulna. {ECO:0000269|PubMed:11030412, CC ECO:0000269|PubMed:11403039}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Langer mesomelic dysplasia (LMD) [MIM:249700]: Autosomal CC recessive rare skeletal dysplasia characterized by severe short CC stature owing to shortening and maldevelopment of the mesomelic CC and rhizomelic segments of the limbs. Associated malformations are CC rarely reported and intellect is normal in all affected subjects CC reported to date. {ECO:0000269|PubMed:11889214}. Note=The disease CC is caused by mutations affecting the gene represented in this CC entry. CC -!- DISEASE: Short stature, idiopathic, X-linked (ISS) [MIM:300582]: A CC condition defined by a standing height more than 2 standard CC deviations below the mean (or below the 2.5 percentile) for sex CC and chronological age, compared with a well-nourished, genetically CC relevant population, in the absence of specific causative CC disorders. {ECO:0000269|PubMed:9140395}. Note=The disease is CC caused by mutations 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 CC subfamily. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 homeobox DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00108}. 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 UniGene; Hs.105932; -. DR ProteinModelPortal; O15266; -. DR SMR; O15266; 117-175. DR IntAct; O15266; 4. DR STRING; 9606.ENSP00000370990; -. DR PhosphoSite; O15266; -. DR BioMuta; SHOX; -. DR PaxDb; O15266; -. DR PRIDE; O15266; -. DR DNASU; 6473; -. DR Ensembl; ENST00000334060; ENSP00000335505; ENSG00000185960. [O15266-2] DR Ensembl; ENST00000381575; ENSP00000370987; ENSG00000185960. [O15266-2] DR Ensembl; ENST00000381578; ENSP00000370990; ENSG00000185960. [O15266-1] DR Ensembl; ENST00000554971; ENSP00000452016; ENSG00000185960. [O15266-1] DR GeneID; 6473; -. DR KEGG; hsa:6473; -. DR UCSC; uc004cph.1; human. [O15266-1] DR UCSC; uc004cpi.3; human. [O15266-2] DR CTD; 6473; -. DR GeneCards; SHOX; -. DR GeneReviews; SHOX; -. DR HGNC; HGNC:10853; 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 Orphanet; 2632; Langer mesomelic dysplasia. DR Orphanet; 240; Leri-Weill dyschondrosteosis. DR Orphanet; 314795; SHOX-related short stature. DR PharmGKB; PA134978644; -. DR eggNOG; KOG0490; Eukaryota. DR eggNOG; ENOG410YIJ3; LUCA. DR GeneTree; ENSGT00810000125347; -. DR HOGENOM; HOG000231518; -. DR HOVERGEN; HBG007233; -. DR InParanoid; O15266; -. DR KO; K09331; -. DR OMA; DHVESDK; -. DR PhylomeDB; O15266; -. DR TreeFam; TF350757; -. DR ChiTaRS; SHOX; human. DR GeneWiki; Short_stature_homeobox_gene; -. DR GenomeRNAi; 6473; -. DR NextBio; 25145; -. DR PRO; PR:O15266; -. DR Proteomes; UP000005640; Chromosome X. DR Bgee; O15266; -. DR CleanEx; HS_SHOX; -. DR ExpressionAtlas; O15266; baseline and differential. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; TAS:ProtInc. DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc. DR Gene3D; 1.10.10.60; -; 1. DR InterPro; IPR017970; Homeobox_CS. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR009057; Homeodomain-like. DR InterPro; IPR000047; HTH_motif. DR InterPro; IPR003654; OAR_dom. DR Pfam; PF00046; Homeobox; 1. DR Pfam; PF03826; OAR; 1. DR PRINTS; PR00031; HTHREPRESSR. DR SMART; SM00389; HOX; 1. DR SUPFAM; SSF46689; SSF46689; 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; Complete proteome; KW Developmental protein; Disease mutation; DNA-binding; Dwarfism; KW Homeobox; Nucleus; Reference proteome; Transcription; KW Transcription regulation. FT CHAIN 1 292 Short stature homeobox protein. FT /FTId=PRO_0000049291. FT DNA_BIND 117 176 Homeobox. {ECO:0000255|PROSITE- FT ProRule:PRU00108}. FT MOTIF 242 249 SH3-binding. {ECO:0000255}. FT MOTIF 274 287 OAR. {ECO:0000255|PROSITE- FT ProRule:PRU00138}. FT COMPBIAS 19 28 Poly-Gly. FT COMPBIAS 242 245 Poly-Pro. FT COMPBIAS 264 267 Poly-Ala. FT VAR_SEQ 212 292 VQAQLQLEGVAHAHPHLHPHLAAHAPYLMFPPPPFGLPIAS FT LAESASAAAVVAAAAKSNSKNSSIADLRLKARKHAEALGL FT -> MEFCSCRPGWSIMA (in isoform SHOXB). FT {ECO:0000303|PubMed:9140395}. FT /FTId=VSP_002287. FT VARIANT 132 132 L -> V (in LWD). FT {ECO:0000269|PubMed:11030412}. FT /FTId=VAR_019414. FT VARIANT 153 153 R -> L (in LWD). FT {ECO:0000269|PubMed:11030412}. FT /FTId=VAR_019415. FT VARIANT 168 168 R -> W (in LMD). FT {ECO:0000269|PubMed:11889214}. FT /FTId=VAR_019416. FT VARIANT 173 173 R -> C (in LWD). FT {ECO:0000269|PubMed:11403039}. FT /FTId=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 //