Skip Header

Contribute Send feedback
Read comments (?) or add your own

O15266 (SHOX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified December 14, 2011. Version 121. 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·Web links·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·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)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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

Defects in SHOX are the cause of Leri-Weill dyschondrosteosis (LWD) [MIM:127300]. LWD is a 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. Ref.4 Ref.5 Ref.6

Defects in SHOX are a cause of Langer mesomelic dysplasia (LMD) [MIM:249700]. LMD is an 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. Ref.5 Ref.7

Defects in SHOX are a cause of idiopathic short stature (ISS) [MIM:300582]. Idiopathic short stature is usually defined as a height below the third percentile for chronological age or minus 2 standard deviations of national height standards in the absence of specific causative disorders. Ref.1 Ref.5

Miscellaneous

The gene encoding 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

With

Entry

#Exp.

IntAct

Notes

SOX5P357112EBI-3505698,EBI-3505701
SOX6P357123EBI-3505698,EBI-3505706

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: 9140395] [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: 9259282] [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: 15772651] [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: 11030412] [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: 11891678] [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: 11403039] [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: 11889214] [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.
IPIIPI00005744.
IPI00411417.
RefSeqNP_000442.1. NM_000451.3.
NP_006874.1. NM_006883.2.
UniGeneHs.105932.

3D structure databases

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

Protein-protein interaction databases

IntActO15266. 6 interactions.
STRINGO15266.

PTM databases

PhosphoSiteO15266.

Proteomic databases

PRIDEO15266.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000381578; ENSP00000370990; ENSG00000185960.
GeneID6473.
KEGGhsa:6473.
UCSCuc004cph.1. human.
uc004cpi.1. human.

Organism-specific databases

CTD6473.
GeneCardsGC0XP000585.
HGNCHGNC:10853. SHOX.
MIM127300. phenotype.
249700. phenotype.
300582. phenotype.
312865. gene.
400020. gene.
neXtProtNX_O15266.
Orphanet137693. Idiopathic short stature.
2632. Langer mesomelic dysplasia.
240. Leri-Weill dyschondrosteosis.
PharmGKBPA134978644.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG05026.
HOGENOMHBG717473.
HOVERGENHBG007233.
InParanoidO15266.
OMASKESITY.
OrthoDBEOG41C6X2.
PhylomeDBO15266.

Gene expression databases

ArrayExpressO15266.
CleanExHS_SHOX.
GenevestigatorO15266.

Family and domain databases

InterProIPR003654. Homeo_OAR.
IPR001356. Homeobox.
IPR017970. Homeobox_CS.
IPR009057. Homeodomain-like.
IPR012287. Homeodomain-rel.
IPR000047. HTH_motif.
[Graphical view]
Gene3DG3DSA:1.10.10.60. Homeodomain-rel. 1 hit.
KOK09331.
PfamPF00046. Homeobox. 1 hit.
PF03826. OAR. 1 hit.
[Graphical view]
PRINTSPR00031. HTHREPRESSR.
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. Homeodomain_like. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
PS50803. OAR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio25145.
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: December 14, 2011
This is version 121 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

Human chromosome X

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents