O15266 (SHOX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Short stature homeobox protein

Alternative name(s):
Pseudoautosomal homeobox-containing osteogenic protein
Short stature homeobox-containing protein

Gene names

Name:	SHOX
Synonyms:	PHOG

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	292 AA.
Sequence status	Complete.
Protein existence	Evidence 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 Idiopathic short stature (ISS) [MIM:300582]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. 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.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Dwarfism
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Activator Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	skeletal system development Traceable author statement PubMed 9590292. Source: ProtInc transcription from RNA polymerase II promoter Traceable author statement Ref.2. Source: ProtInc
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	sequence-specific DNA binding transcription factor activity Traceable author statement Ref.2. Source: ProtInc transcription regulatory region sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SOX5	P35711	2	EBI-3505698,EBI-3505701
SOX6	P35712	3	EBI-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 292	292	Short stature homeobox protein		PRO_0000049291
Regions
	DNA binding	117 – 176	60	Homeobox
	Motif	242 – 249	8	SH3-binding Potential
	Motif	274 – 287	14	OAR
	Compositional bias	19 – 28	10	Poly-Gly
	Compositional bias	242 – 245	4	Poly-Pro
	Compositional bias	264 – 267	4	Poly-Ala
Natural variations
	Alternative sequence	212 – 292	81	VQAQL…EALGL → MEFCSCRPGWSIMA in isoform SHOXB.		VSP_002287
	Natural variant	132	1	L → V in LWD. Ref.4		VAR_019414
	Natural variant	153	1	R → L in LWD. Ref.4		VAR_019415
	Natural variant	168	1	R → W in LMD. Ref.7		VAR_019416
	Natural variant	173	1	R → C in LWD. Ref.6		VAR_012346

Sequences

	Sequence		Length	Mass (Da)
	Isoform SHOXA [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 0F2A61A3051CB360	FASTA	292	32,236
	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
	Isoform SHOXB [UniParc]. Checksum: 653FEB8D90C6107C	FASTA	225	25,501
	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 KGVILGTANH LDACRVAPYV NMGALRMPFQ QMEFCSCRPG WSIMA

References

	« Hide 'large scale' referencesShow '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. , 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.

Web resources

GeneReviews

GeneReviews

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.
IPI	IPI00005744. IPI00411417.
RefSeq	NP_000442.1. NM_000451.3. NP_006874.1. NM_006883.2.
UniGene	Hs.105932.
3D structure databases
ProteinModelPortal	O15266.
ModBase	Search...
Protein-protein interaction databases
IntAct	O15266. 4 interactions.
STRING	9606.ENSP00000370990.
PTM databases
PhosphoSite	O15266.
Proteomic databases
PaxDb	O15266.
PRIDE	O15266.
Protocols and materials databases
DNASU	6473.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000334060; ENSP00000335505; ENSG00000185960. ENST00000381575; ENSP00000370987; ENSG00000185960. ENST00000381578; ENSP00000370990; ENSG00000185960. ENST00000554971; ENSP00000452016; ENSG00000185960.
GeneID	6473.
KEGG	hsa:6473.
UCSC	uc004cph.1. human. uc004cpi.3. human.
Organism-specific databases
CTD	6473.
GeneCards	GC0XP000585.
HGNC	HGNC:10853. SHOX.
MIM	127300. phenotype. 249700. phenotype. 300582. phenotype. 312865. gene. 400020. gene.
neXtProt	NX_O15266.
Orphanet	137693. Idiopathic short stature. 2632. Langer mesomelic dysplasia. 240. Leri-Weill dyschondrosteosis.
PharmGKB	PA134978644.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG113578.
HOGENOM	HOG000231518.
HOVERGEN	HBG007233.
InParanoid	O15266.
KO	K09331.
OMA	SNHCPVH.
OrthoDB	EOG41C6X2.
PhylomeDB	O15266.
Gene expression databases
ArrayExpress	O15266.
Bgee	O15266.
CleanEx	HS_SHOX.
Genevestigator	O15266.
Family and domain databases
Gene3D	1.10.10.60. 1 hit.
InterPro	IPR017970. Homeobox_CS. IPR001356. Homeodomain. IPR009057. Homeodomain-like. IPR000047. HTH_motif. IPR003654. OAR_dom. [Graphical view]
Pfam	PF00046. Homeobox. 1 hit. PF03826. OAR. 1 hit. [Graphical view]
PRINTS	PR00031. HTHREPRESSR.
SMART	SM00389. HOX. 1 hit. [Graphical view]
SUPFAM	SSF46689. Homeodomain_like. 1 hit.
PROSITE	PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. PS50803. OAR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	6473.
NextBio	25145.
SOURCE	Search...

Entry information

Entry name

SHOX_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 134 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.