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O15266 (SHOX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Short stature homeobox protein
Alternative name(s):
Pseudoautosomal homeobox-containing osteogenic protein
Short stature homeobox-containing protein
Gene names
Name:SHOX
Synonyms:PHOG
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length292 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Controls fundamental aspects of growth and development.

Subcellular location

Nucleus By similarity.

Tissue specificity

SHOXA is expressed in skeletal muscle, placenta, pancreas, heart and bone marrow fibroblast and SHOXB is highly expressed in bone marrow fibroblast followed by kidney and skeletal muscle. SHOXB is not expressed in brain, kidney, liver and lung. Highly expressed in osteogenic cells.

Induction

By retinoic acid and phorbol-12-myristate 13-acetate (PMA).

Involvement in disease

Leri-Weill dyschondrosteosis (LWD) [MIM:127300]: Dominantly inherited skeletal dysplasia characterized by moderate short stature predominantly because of short mesomelic limb segments. It is often associated with the Madelung deformity of the wrist, comprising bowing of the radius and dorsal dislocation of the distal ulna.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.5 Ref.6

Langer mesomelic dysplasia (LMD) [MIM:249700]: Autosomal recessive rare skeletal dysplasia characterized by severe short stature owing to shortening and maldevelopment of the mesomelic and rhizomelic segments of the limbs. Associated malformations are rarely reported and intellect is normal in all affected subjects reported to date.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.7

Short stature, idiopathic, X-linked (ISS) [MIM:300582]: A condition defined by a standing height more than 2 standard deviations below the mean (or below the 2.5 percentile) for sex and chronological age, compared with a well-nourished, genetically relevant population, in the absence of specific causative disorders.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.5

Miscellaneous

The gene coding for this protein is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes.

Sequence similarities

Belongs to the paired homeobox family. Bicoid subfamily.

Contains 1 homeobox DNA-binding domain.

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform SHOXA (identifier: O15266-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform SHOXB (identifier: O15266-2)

The sequence of this isoform differs from the canonical sequence as follows:
     212-292: VQAQLQLEGV...ARKHAEALGL → MEFCSCRPGWSIMA

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 292292Short stature homeobox protein
PRO_0000049291

Regions

DNA binding117 – 17660Homeobox
Motif242 – 2498SH3-binding Potential
Motif274 – 28714OAR
Compositional bias19 – 2810Poly-Gly
Compositional bias242 – 2454Poly-Pro
Compositional bias264 – 2674Poly-Ala

Natural variations

Alternative sequence212 – 29281VQAQL…EALGL → MEFCSCRPGWSIMA in isoform SHOXB.
VSP_002287
Natural variant1321L → V in LWD. Ref.4
VAR_019414
Natural variant1531R → L in LWD. Ref.4
VAR_019415
Natural variant1681R → W in LMD. Ref.7
VAR_019416
Natural variant1731R → C in LWD. Ref.6
VAR_012346

Sequences

Sequence LengthMass (Da)Tools
Isoform SHOXA [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 0F2A61A3051CB360

FASTA29232,236
        10         20         30         40         50         60 
MEELTAFVSK SFDQKSKDGN GGGGGGGGKK DSITYREVLE SGLARSRELG TSDSSLQDIT 

        70         80         90        100        110        120 
EGGGHCPVHL FKDHVDNDKE KLKEFGTARV AEGIYECKEK REDVKSEDED GQTKLKQRRS 

       130        140        150        160        170        180 
RTNFTLEQLN ELERLFDETH YPDAFMREEL SQRLGLSEAR VQVWFQNRRA KCRKQENQMH 

       190        200        210        220        230        240 
KGVILGTANH LDACRVAPYV NMGALRMPFQ QVQAQLQLEG VAHAHPHLHP HLAAHAPYLM 

       250        260        270        280        290 
FPPPPFGLPI ASLAESASAA AVVAAAAKSN SKNSSIADLR LKARKHAEAL GL 

« Hide

Isoform SHOXB [UniParc].

Checksum: 653FEB8D90C6107C
Show »

FASTA22525,501

References

« Hide 'large scale' references
[1]"Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome."
Rao E., Weiss B., Fukami M., Rump A., Niesler B., Mertz A., Muroya K., Binder G., Kirsch S., Winkelmann M., Nordsiek G., Heinrich U., Breuning M.H., Ranke M.B., Rosenthal A., Ogata T., Rappold G.A.
Nat. Genet. 16:54-63(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS SHOXA AND SHOXB), INVOLVEMENT IN ISS.
Tissue: Skeletal muscle.
[2]"PHOG, a candidate gene for involvement in the short stature of Turner syndrome."
Ellison J.W., Wardak Z., Young M.F., Gehron Robey P., Laig-Webster M., Chiong W.
Hum. Mol. Genet. 6:1341-1347(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHOXA).
[3]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Mutations in short stature homeobox containing gene (SHOX) in dyschondrosteosis but not in hypochondroplasia."
Grigelioniene G., Ekloef O., Ivarsson S.A., Westphal O., Neumeyer L., Kedra D., Dumanski J., Hagenaes L.
Hum. Genet. 107:145-149(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LWD VAL-132 AND LEU-153.
[5]"Allelic and nonallelic heterogeneity in dyschondrosteosis (Leri-Weill syndrome)."
Cormier-Daire V., Huber C., Munnich A.
Am. J. Med. Genet. 106:272-274(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: DISEASE.
[6]"SHOX point mutations in dyschondrosteosis."
Huber C., Cusin V., Le Merrer M., Mathieu M., Sulmont V., Dagoneau N., Munnich A., Cormier-Daire V.
J. Med. Genet. 38:323-323(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LWD CYS-173.
[7]"SHOX nullizygosity and haploinsufficiency in a Japanese family: implication for the development of Turner skeletal features."
Ogata T., Muroya K., Sasaki G., Nishimura G., Kitoh H., Hattori T.
J. Clin. Endocrinol. Metab. 87:1390-1394(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LMD TRP-168.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y11536 mRNA. Translation: CAA72299.1.
Y11535 mRNA. Translation: CAA72298.1.
U82668 Genomic DNA. No translation available.
U89331 mRNA. Translation: AAC18820.1.
BX004827 Genomic DNA. No translation available.
CCDSCCDS14106.1. [O15266-2]
CCDS14107.1. [O15266-1]
RefSeqNP_000442.1. NM_000451.3. [O15266-1]
NP_006874.1. NM_006883.2. [O15266-2]
UniGeneHs.105932.

3D structure databases

ProteinModelPortalO15266.
SMRO15266. Positions 117-175.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO15266. 4 interactions.
STRING9606.ENSP00000370990.

PTM databases

PhosphoSiteO15266.

Proteomic databases

PaxDbO15266.
PRIDEO15266.

Protocols and materials databases

DNASU6473.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000334060; ENSP00000335505; ENSG00000185960. [O15266-2]
ENST00000381575; ENSP00000370987; ENSG00000185960. [O15266-2]
ENST00000381578; ENSP00000370990; ENSG00000185960. [O15266-1]
ENST00000554971; ENSP00000452016; ENSG00000185960. [O15266-1]
GeneID6473.
KEGGhsa:6473.
UCSCuc004cph.1. human. [O15266-1]
uc004cpi.3. human. [O15266-2]

Organism-specific databases

CTD6473.
GeneCardsGC0XP000585.
GeneReviewsSHOX.
HGNCHGNC:10853. SHOX.
MIM127300. phenotype.
249700. phenotype.
300582. phenotype.
312865. gene.
400020. gene.
neXtProtNX_O15266.
Orphanet2632. Langer mesomelic dysplasia.
240. Lori-Weill dyschondrosteosis.
314795. Shox-related short stature.
PharmGKBPA134978644.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG113578.
HOGENOMHOG000231518.
HOVERGENHBG007233.
InParanoidO15266.
KOK09331.
OMASNHCPVH.
PhylomeDBO15266.
TreeFamTF350757.

Gene expression databases

ArrayExpressO15266.
BgeeO15266.
CleanExHS_SHOX.
GenevestigatorO15266.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR000047. HTH_motif.
IPR003654. OAR_dom.
[Graphical view]
PfamPF00046. Homeobox. 1 hit.
PF03826. OAR. 1 hit.
[Graphical view]
PRINTSPR00031. HTHREPRESSR.
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
PS50803. OAR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiShort_stature_homeobox_gene.
GenomeRNAi6473.
NextBio25145.
PROO15266.
SOURCESearch...

Entry information

Entry nameSHOX_HUMAN
AccessionPrimary (citable) accession number: O15266
Secondary accession number(s): O00412, O00413, O15267
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: July 9, 2014
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM