Reviewed, UniProtKB/Swiss-Prot Q9BQB4 (SOST_HUMAN)

Names and origin

Protein names

Recommended name:
    Sclerostin

Gene names

Name:	SOST
ORF Names:	UNQ2976/PRO7455/PRO7476

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	213 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Seems to play a role in bone homeostasis.
Subcellular location	Secreted Potential.
Tissue specificity	Widely expressed at low levels with highest levels in bone, cartilage, kidney, liver, bone marrow and primary osteeoblasts differentiated for 21 days.
Involvement in disease	Defects in SOST are the cause of sclerosteosis (SOST) [MIM:269500]; also known as cortical hyperostosis with syndactyly. SOST is an autosomal recessive sclerosing bone dysplasia characterized by a generalized hyperostosis and sclerosis leading to a markedly thickened skull, with mandible, ribs, clavicles and all long bones also being affected. Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur. Sclerosteosis is clinically and radiologically very similar to van Buchem disease, mainly differentiated by hand malformations and a large stature in sclerosteosis patients. Ref.1 Ref.2 A 52 kb deletion downstream of SOST results in SOST transcription suppression and is a cause of van Buchem disease (VBCH) [MIM:239100]; also known as hyperostosis corticalis generalisata. VBCH is an autosomal recessive sclerosing bone dysplasia characterized by endosteal hyperostosis of the mandible, skull, ribs, clavicles, and diaphyses of the long bones. Affected patients present a symmetrically increased thickness of bones, most frequently found as an enlarged jawbone, but also an enlargement of the skull, ribs, diaphysis of long bones, as well as tubular bones of hands and feet. The clinical consequence of increased thickness of the skull include facial nerve palsy causing hearing loss, visual problems, neurological pain, and, very rarely, blindness as a consequence of optic atrophy. Serum alkaline phosphatase levels are elevated. Ref.6
Sequence similarities	Belongs to the sclerostin family. Contains 1 CTCK (C-terminal cystine knot-like) domain.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
PTM	Glycoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	negative regulation of BMP signaling pathway Inferred from direct assay. Source: MGI negative regulation of ossification Ref.1 Non-traceable author statement. Source: UniProtKB
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9BQB4-1)

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 2 (identifier: Q9BQB4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     64-73: RPPHHPFETK → WPGGRPPSRAPLST

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Ref.5
	Chain	24 – 213	190	Sclerostin		PRO_0000033177
Regions
	Domain	82 – 172	91	CTCK
Amino acid modifications
	Glycosylation	53	1	N-linked (GlcNAc...) Potential
	Glycosylation	175	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	64 – 73	10	RPPHHPFETK → WPGGRPPSRAPLST in isoform 2.		VSP_010189

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 30DBD55CE73D5BB2	FASTA	213	24,031
	10 20 30 40 50 60 MQLPLALCLV CLLVHTAFRV VEGQGWQAFK NDATEIIPEL GEYPEPPPEL ENNKTMNRAE 70 80 90 100 110 120 NGGRPPHHPF ETKDVSEYSC RELHFTRYVT DGPCRSAKPV TELVCSGQCG PARLLPNAIG 130 140 150 160 170 180 RGKWWRPSGP DFRCIPDRYR AQRVQLLCPG GEAPRARKVR LVASCKCKRL TRFHNQSELK 190 200 210 DFGTEAARPQ KGRKPRPRAR SAKANQAELE NAY
	Isoform 2. Checksum: 652294D9DE5DB402	FASTA	217	24,264
	10 20 30 40 50 60 MQLPLALCLV CLLVHTAFRV VEGQGWQAFK NDATEIIPEL GEYPEPPPEL ENNKTMNRAE 70 80 90 100 110 120 NGGWPGGRPP SRAPLSTDVS EYSCRELHFT RYVTDGPCRS AKPVTELVCS GQCGPARLLP 130 140 150 160 170 180 NAIGRGKWWR PSGPDFRCIP DRYRAQRVQL LCPGGEAPRA RKVRLVASCK CKRLTRFHNQ 190 200 210 SELKDFGTEA ARPQKGRKPR PRARSAKANQ AELENAY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST)." Balemans W., Ebeling M., Patel N., van Hul E., Olson P., Dioszegi M., Lacza C., Wuyts W., van den Ende J., Willems P., Paes-Alves A.F., Hill S., Bueno M., Ramos F.J., Tacconi P., Dikkers F.G., Stratakis C., Lindpaintner K. , Vickery B., Foernzler D., Van Hul W. Hum. Mol. Genet. 10:537-543(2001) [PubMed: 11181578] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN SOST.
[2]	"Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein." Brunkow M.E., Gardner J.C., Van Ness J., Paeper B.W., Kovacevich B.R., Proll S., Skonier J.E., Zhao L., Sabo P.J., Fu Y.H., Alisch R.S., Gillett L., Colbert T., Tacconi P., Galas D., Hamersma H., Beighton P., Mulligan J.T. Am. J. Hum. Genet. 68:577-589(2001) [PubMed: 11179006] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), INVOLVEMENT IN SOST.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-38.
[6]	"Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease." Balemans W., Patel N., Ebeling M., Van Hul E., Wuyts W., Lacza C., Dioszegi M., Dikkers F.G., Hildering P., Willems P.J., Verheij J.B., Lindpaintner K., Vickery B., Foernzler D., Van Hul W. J. Med. Genet. 39:91-97(2002) [PubMed: 11836356] [Abstract] Cited for: INVOLVEMENT IN VBCH.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF331844 mRNA. Translation: AAK16158.1.
AF326736 Genomic DNA. Translation: AAK13451.1.
AF326739 mRNA. Translation: AAK13454.1.
AY358203 mRNA. Translation: AAQ88570.1.
AY358627 mRNA. Translation: AAQ88990.1.
BC101086 mRNA. Translation: AAI01087.1.
BC101087 mRNA. Translation: AAI01088.1.
BC101088 mRNA. Translation: AAI01089.1.
BC101089 mRNA. Translation: AAI01090.1.

IPI

IPI00019272.
IPI00410101.

RefSeq

NP_079513.1.

UniGene

Hs.349204

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2K8P	NMR	-	A	25-213	[»]

ModBase

Search...

Proteomic databases

PRIDE

Q9BQB4.

Genome annotation databases

Ensembl

ENSG00000167941. Homo sapiens. [Contig view]

GeneID

50964.

KEGG

hsa:50964.

Organism-specific databases

GeneCards

GC17M039186.

H-InvDB

HIX0039071.

HGNC

HGNC:13771. SOST.

MIM

239100. phenotype.
269500. phenotype.
605740. gene.

Orphanet

3152. Sclerosteosis.

PharmGKB

PA37809.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q9BQB4.

HOVERGEN

Q9BQB4.

OMA

Q9BQB4. SCKCKRL.

Gene expression databases

ArrayExpress

Q9BQB4.

Bgee

Q9BQB4.

CleanEx

HS_SOST.

GermOnline

ENSG00000167941. Homo sapiens.

Family and domain databases

InterPro

IPR006207. Cys_knot_C.
IPR008835. Sclerostin.
IPR015665. SOST.
[Graphical view]

PANTHER

PTHR14903. Sclerostin. 1 hit.
PTHR14903:SF2. SOST. 1 hit.

Pfam

PF05463. Sclerostin. 1 hit.
[Graphical view]

PROSITE

PS01185. CTCK_1. False negative.
PS01225. CTCK_2. False negative.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

53429.

SOURCE

Search...

Entry information

Entry name

SOST_HUMAN

Accession

Primary (citable) accession number: Q9BQB4
Secondary accession number(s): Q495N9

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 5, 2002
Last sequence update:	June 1, 2001
Last modified:	June 16, 2009
This is version 71 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)