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O95389 (WISP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 115. 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·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
WNT1-inducible-signaling pathway protein 3

Short name=WISP-3
Alternative name(s):
CCN family member 6
Gene names
Name:WISP3
Synonyms:CCN6
ORF Names:UNQ462/PRO790/PRO956
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length354 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Appears to be required for normal postnatal skeletal growth and cartilage homeostasis.

Subcellular location

Secreted Probable.

Tissue specificity

Predominant expression in adult kidney and testis and fetal kidney. Weaker expression found in placenta, ovary, prostate and small intestine. Also expressed in skeletally-derived cells such as synoviocytes and articular cartilage chondrocytes.

Involvement in disease

Progressive pseudorheumatoid arthropathy of childhood (PPAC) [MIM:208230]: Autosomal recessive disorder characterized by stiffness and swelling of joints, motor weakness and joint contractures. Signs and symptoms of the disease develop typically between three and eight years of age. This progressive disease is a primary disorder of articular cartilage with continued cartilage loss and destructive bone changes with aging.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

Sequence similarities

Belongs to the CCN family.

Contains 1 CTCK (C-terminal cystine knot-like) domain.

Contains 1 IGFBP N-terminal domain.

Contains 1 TSP type-1 domain.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainSignal
   Molecular functionGrowth factor
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell-cell signaling

Traceable author statement Ref.1. Source: ProtInc

regulation of cell growth

Inferred from electronic annotation. Source: InterPro

signal transduction

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentextracellular space

Non-traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O95389-1)

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: O95389-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MNKRRLLYPSGWLHGPSDM

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Chain24 – 354331WNT1-inducible-signaling pathway protein 3
PRO_0000014412

Regions

Domain44 – 11774IGFBP N-terminal
Domain208 – 25346TSP type-1
Domain268 – 34275CTCK

Amino acid modifications

Glycosylation1781N-linked (GlcNAc...) Potential
Glycosylation3081N-linked (GlcNAc...) Potential
Disulfide bond268 ↔ 305 By similarity
Disulfide bond285 ↔ 319 By similarity
Disulfide bond296 ↔ 335 By similarity
Disulfide bond299 ↔ 337 By similarity
Disulfide bond304 ↔ 341 By similarity

Natural variations

Alternative sequence11M → MNKRRLLYPSGWLHGPSDM in isoform 2.
VSP_037803
Natural variant561Q → H Common polymorphism. Ref.6
Corresponds to variant rs1230345 [ dbSNP | Ensembl ].
VAR_016224
Natural variant601R → C.
Corresponds to variant rs17073260 [ dbSNP | Ensembl ].
VAR_049567
Natural variant781C → R in PPAC. Ref.6
VAR_016225

Experimental info

Sequence conflict2001N → D in AAQ88715. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: 67F48D0D5C2F5EE3

FASTA35439,293
        10         20         30         40         50         60 
MQGLLFSTLL LAGLAQFCCR VQGTGPLDTT PEGRPGEVSD APQRKQFCHW PCKCPQQKPR 

        70         80         90        100        110        120 
CPPGVSLVRD GCGCCKICAK QPGEICNEAD LCDPHKGLYC DYSVDRPRYE TGVCAYLVAV 

       130        140        150        160        170        180 
GCEFNQVHYH NGQVFQPNPL FSCLCVSGAI GCTPLFIPKL AGSHCSGAKG GKKSDQSNCS 

       190        200        210        220        230        240 
LEPLLQQLST SYKTMPAYRN LPLIWKKKCL VQATKWTPCS RTCGMGISNR VTNENSNCEM 

       250        260        270        280        290        300 
RKEKRLCYIQ PCDSNILKTI KIPKGKTCQP TFQLSKAEKF VFSGCSSTQS YKPTFCGICL 

       310        320        330        340        350 
DKRCCIPNKS KMITIQFDCP NEGSFKWKML WITSCVCQRN CREPGDIFSE LKIL 

« Hide

Isoform 2 [UniParc].

Checksum: 449A31188D480511
Show »

FASTA37241,402

References

« Hide 'large scale' references
[1]"WISP genes are members of the connective tissue growth factor family that are up-regulated in wnt-1-transformed cells and aberrantly expressed in human colon tumors."
Pennica D., Swanson T.A., Welsh J.W., Roy M.A., Lawrence D.A., Lee J., Brush J., Taneyhill L.A., Deuel B., Lew M., Watanabe C., Cohen R.L., Melham M.F., Finley G.G., Quirke P., Goddard A.D., Hillan K.J., Gurney A.L., Botstein D., Levine A.J.
Proc. Natl. Acad. Sci. U.S.A. 95:14717-14722(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Bone marrow and Fetal kidney.
[2]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[3]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[6]"Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia."
Hurvitz J.R., Suwairi W.M., Van Hul W., El-Shanti H., Superti-Furga A., Roudier J., Holderbaum D., Pauli R.M., Herd J.K., Van Hul E.V., Rezai-Delui H., Legius E., Le Merrer M., Al-Alami J., Bahabri S.A., Warman M.L.
Nat. Genet. 23:94-98(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PPAC ARG-78, VARIANT HIS-56.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF100781 mRNA. Translation: AAC96323.1.
AY358349 mRNA. Translation: AAQ88715.1.
AY358350 mRNA. Translation: AAQ88716.1.
Z99289, AL512299 Genomic DNA. Translation: CAI42331.1.
AL512299, Z99289 Genomic DNA. Translation: CAI19998.1.
CH471051 Genomic DNA. Translation: EAW48273.1.
CH471051 Genomic DNA. Translation: EAW48275.1.
BC105941 mRNA. Translation: AAI05942.1.
CCDSCCDS5097.1. [O95389-2]
CCDS5098.1. [O95389-1]
RefSeqNP_003871.1. NM_003880.3. [O95389-1]
NP_937882.1. NM_198239.1. [O95389-2]
UniGeneHs.558428.

3D structure databases

ProteinModelPortalO95389.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000354734.

PTM databases

PhosphoSiteO95389.

Proteomic databases

PaxDbO95389.
PRIDEO95389.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000230529; ENSP00000230529; ENSG00000112761. [O95389-1]
ENST00000361714; ENSP00000354734; ENSG00000112761. [O95389-2]
ENST00000368666; ENSP00000357655; ENSG00000112761. [O95389-1]
ENST00000581324; ENSP00000462890; ENSG00000266134. [O95389-2]
ENST00000582958; ENSP00000464005; ENSG00000266134. [O95389-1]
ENST00000604763; ENSP00000473777; ENSG00000112761. [O95389-1]
GeneID8838.
KEGGhsa:8838.
UCSCuc003pvm.3. human. [O95389-1]
uc003pvo.3. human. [O95389-2]

Organism-specific databases

CTD8838.
GeneCardsGC06P112375.
HGNCHGNC:12771. WISP3.
MIM208230. phenotype.
603400. gene.
neXtProtNX_O95389.
Orphanet1159. Progressive pseudorheumatoid arthropathy of childhood.
PharmGKBPA37374.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG73349.
HOGENOMHOG000231462.
HOVERGENHBG000635.
InParanoidO95389.
OMAICNEADL.
PhylomeDBO95389.
TreeFamTF326070.

Gene expression databases

ArrayExpressO95389.
BgeeO95389.
CleanExHS_WISP3.
GenevestigatorO95389.

Family and domain databases

InterProIPR006207. Cys_knot_C.
IPR006208. Glyco_hormone_CN.
IPR009030. Growth_fac_rcpt_N_dom.
IPR000867. IGFBP-like.
IPR012395. IGFBP_CNN.
IPR017891. Insulin_GF-bd_Cys-rich_CS.
IPR000884. Thrombospondin_1_rpt.
[Graphical view]
PfamPF00007. Cys_knot. 1 hit.
PF00219. IGFBP. 1 hit.
PF00090. TSP_1. 1 hit.
[Graphical view]
PIRSFPIRSF036495. IGFBP_rP_CNN. 1 hit.
SMARTSM00041. CT. 1 hit.
SM00121. IB. 1 hit.
SM00209. TSP1. 1 hit.
[Graphical view]
SUPFAMSSF57184. SSF57184. 1 hit.
SSF82895. SSF82895. 1 hit.
PROSITEPS01225. CTCK_2. 1 hit.
PS00222. IGFBP_N_1. 1 hit.
PS51323. IGFBP_N_2. 1 hit.
PS50092. TSP1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiWNT1-inducible-signaling_pathway_protein_3.
GenomeRNAi8838.
NextBio33172.
PROO95389.
SOURCESearch...

Entry information

Entry nameWISP3_HUMAN
AccessionPrimary (citable) accession number: O95389
Secondary accession number(s): Q3KR29, Q5H8W4, Q6UXH6
Entry history
Integrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: May 1, 1999
Last modified: July 9, 2014
This is version 115 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 6

Human chromosome 6: entries, gene names and cross-references to MIM