SHOX_HUMAN
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 03-AUG-2022, entry version 203.
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}.
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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; O15266; -.
DR PeptideAtlas; O15266; -.
DR PRIDE; O15266; -.
DR ProteomicsDB; 48555; -. [O15266-1]
DR ProteomicsDB; 48556; -. [O15266-2]
DR Antibodypedia; 23329; 126 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 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 CTD; 6473; -.
DR DisGeNET; 6473; -.
DR GeneCards; SHOX; -.
DR GeneReviews; SHOX; -.
DR HGNC; HGNC:10853; SHOX.
DR HPA; ENSG00000185960; Tissue enriched (brain).
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; YECKDKR; -.
DR PhylomeDB; O15266; -.
DR TreeFam; TF350757; -.
DR PathwayCommons; O15266; -.
DR SignaLink; O15266; -.
DR SIGNOR; O15266; -.
DR BioGRID-ORCS; 6473; 6 hits in 586 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 RNAct; O15266; protein.
DR Bgee; ENSG00000185960; Expressed in calcaneal tendon and 22 other 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 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 Pfam; PF00046; Homeodomain; 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; 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
