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Protein

WNT1-inducible-signaling pathway protein 3

Gene

WISP3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

GO - Molecular functioni

  1. heparin binding Source: GO_Central
  2. integrin binding Source: GO_Central

GO - Biological processi

  1. cell adhesion Source: GO_Central
  2. cell-cell signaling Source: ProtInc
  3. negative regulation of cell death Source: GO_Central
  4. regulation of cell growth Source: InterPro
  5. signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Names & Taxonomyi

Protein namesi
Recommended name:
WNT1-inducible-signaling pathway protein 3
Short name:
WISP-3
Alternative name(s):
CCN family member 6
Gene namesi
Name:WISP3
Synonyms:CCN6
ORF Names:UNQ462/PRO790/PRO956
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 6

Organism-specific databases

HGNCiHGNC:12771. WISP3.

Subcellular locationi

Secreted Curated

GO - Cellular componenti

  1. extracellular space Source: UniProtKB
  2. proteinaceous extracellular matrix Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Progressive pseudorheumatoid arthropathy of childhood1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAutosomal 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.

See also OMIM:208230
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti78 – 781C → R in PPAC. 1 Publication
VAR_016225

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi208230. phenotype.
Orphaneti1159. Progressive pseudorheumatoid arthropathy of childhood.
PharmGKBiPA37374.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence AnalysisAdd
BLAST
Chaini24 – 354331WNT1-inducible-signaling pathway protein 3PRO_0000014412Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi178 – 1781N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi268 ↔ 305By similarity
Disulfide bondi285 ↔ 319By similarity
Disulfide bondi296 ↔ 335By similarity
Disulfide bondi299 ↔ 337By similarity
Disulfide bondi304 ↔ 341By similarity
Glycosylationi308 – 3081N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO95389.
PRIDEiO95389.

PTM databases

PhosphoSiteiO95389.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiO95389.
CleanExiHS_WISP3.
ExpressionAtlasiO95389. baseline and differential.
GenevestigatoriO95389.

Interactioni

Protein-protein interaction databases

BioGridi114365. 5 interactions.
STRINGi9606.ENSP00000354734.

Structurei

3D structure databases

ProteinModelPortaliO95389.
SMRiO95389. Positions 58-155.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini44 – 11774IGFBP N-terminalPROSITE-ProRule annotationAdd
BLAST
Domaini208 – 25346TSP type-1PROSITE-ProRule annotationAdd
BLAST
Domaini268 – 34275CTCKPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the CCN family.Curated
Contains 1 CTCK (C-terminal cystine knot-like) domain.PROSITE-ProRule annotation
Contains 1 IGFBP N-terminal domain.PROSITE-ProRule annotation
Contains 1 TSP type-1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG73349.
GeneTreeiENSGT00760000119225.
HOGENOMiHOG000231462.
HOVERGENiHBG000635.
InParanoidiO95389.
OMAiICNEADL.
PhylomeDBiO95389.
TreeFamiTF326070.

Family and domain databases

InterProiIPR006207. 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]
PfamiPF00007. Cys_knot. 1 hit.
PF00219. IGFBP. 1 hit.
PF00090. TSP_1. 1 hit.
[Graphical view]
PIRSFiPIRSF036495. IGFBP_rP_CNN. 1 hit.
SMARTiSM00041. CT. 1 hit.
SM00121. IB. 1 hit.
SM00209. TSP1. 1 hit.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 1 hit.
SSF82895. SSF82895. 1 hit.
PROSITEiPS01225. CTCK_2. 1 hit.
PS00222. IGFBP_N_1. 1 hit.
PS51323. IGFBP_N_2. 1 hit.
PS50092. TSP1. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: O95389-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MQGLLFSTLL LAGLAQFCCR VQGTGPLDTT PEGRPGEVSD APQRKQFCHW
60 70 80 90 100
PCKCPQQKPR CPPGVSLVRD GCGCCKICAK QPGEICNEAD LCDPHKGLYC
110 120 130 140 150
DYSVDRPRYE TGVCAYLVAV GCEFNQVHYH NGQVFQPNPL FSCLCVSGAI
160 170 180 190 200
GCTPLFIPKL AGSHCSGAKG GKKSDQSNCS LEPLLQQLST SYKTMPAYRN
210 220 230 240 250
LPLIWKKKCL VQATKWTPCS RTCGMGISNR VTNENSNCEM RKEKRLCYIQ
260 270 280 290 300
PCDSNILKTI KIPKGKTCQP TFQLSKAEKF VFSGCSSTQS YKPTFCGICL
310 320 330 340 350
DKRCCIPNKS KMITIQFDCP NEGSFKWKML WITSCVCQRN CREPGDIFSE

LKIL
Length:354
Mass (Da):39,293
Last modified:May 1, 1999 - v1
Checksum:i67F48D0D5C2F5EE3
GO
Isoform 2 (identifier: O95389-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:372
Mass (Da):41,402
Checksum:i449A31188D480511
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti200 – 2001N → D in AAQ88715. (PubMed:12975309)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti56 – 561Q → H Common polymorphism. 1 Publication
Corresponds to variant rs1230345 [ dbSNP | Ensembl ].
VAR_016224
Natural varianti60 – 601R → C.
Corresponds to variant rs17073260 [ dbSNP | Ensembl ].
VAR_049567
Natural varianti78 – 781C → R in PPAC. 1 Publication
VAR_016225

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 11M → MNKRRLLYPSGWLHGPSDM in isoform 2. 2 PublicationsVSP_037803

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5097.1. [O95389-2]
CCDS5098.1. [O95389-1]
RefSeqiNP_003871.1. NM_003880.3. [O95389-1]
NP_937882.1. NM_198239.1. [O95389-2]
UniGeneiHs.558428.

Genome annotation databases

EnsembliENST00000230529; ENSP00000230529; ENSG00000112761. [O95389-1]
ENST00000361714; ENSP00000354734; ENSG00000112761. [O95389-1]
ENST00000368666; ENSP00000357655; ENSG00000112761. [O95389-2]
ENST00000604763; ENSP00000473777; ENSG00000112761. [O95389-1]
GeneIDi8838.
KEGGihsa:8838.
UCSCiuc003pvm.3. human. [O95389-1]
uc003pvo.3. human. [O95389-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5097.1. [O95389-2]
CCDS5098.1. [O95389-1]
RefSeqiNP_003871.1. NM_003880.3. [O95389-1]
NP_937882.1. NM_198239.1. [O95389-2]
UniGeneiHs.558428.

3D structure databases

ProteinModelPortaliO95389.
SMRiO95389. Positions 58-155.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114365. 5 interactions.
STRINGi9606.ENSP00000354734.

PTM databases

PhosphoSiteiO95389.

Proteomic databases

PaxDbiO95389.
PRIDEiO95389.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000230529; ENSP00000230529; ENSG00000112761. [O95389-1]
ENST00000361714; ENSP00000354734; ENSG00000112761. [O95389-1]
ENST00000368666; ENSP00000357655; ENSG00000112761. [O95389-2]
ENST00000604763; ENSP00000473777; ENSG00000112761. [O95389-1]
GeneIDi8838.
KEGGihsa:8838.
UCSCiuc003pvm.3. human. [O95389-1]
uc003pvo.3. human. [O95389-2]

Organism-specific databases

CTDi8838.
GeneCardsiGC06P112375.
HGNCiHGNC:12771. WISP3.
MIMi208230. phenotype.
603400. gene.
neXtProtiNX_O95389.
Orphaneti1159. Progressive pseudorheumatoid arthropathy of childhood.
PharmGKBiPA37374.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG73349.
GeneTreeiENSGT00760000119225.
HOGENOMiHOG000231462.
HOVERGENiHBG000635.
InParanoidiO95389.
OMAiICNEADL.
PhylomeDBiO95389.
TreeFamiTF326070.

Miscellaneous databases

GeneWikiiWNT1-inducible-signaling_pathway_protein_3.
GenomeRNAii8838.
NextBioi33172.
PROiO95389.
SOURCEiSearch...

Gene expression databases

BgeeiO95389.
CleanExiHS_WISP3.
ExpressionAtlasiO95389. baseline and differential.
GenevestigatoriO95389.

Family and domain databases

InterProiIPR006207. 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]
PfamiPF00007. Cys_knot. 1 hit.
PF00219. IGFBP. 1 hit.
PF00090. TSP_1. 1 hit.
[Graphical view]
PIRSFiPIRSF036495. IGFBP_rP_CNN. 1 hit.
SMARTiSM00041. CT. 1 hit.
SM00121. IB. 1 hit.
SM00209. TSP1. 1 hit.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 1 hit.
SSF82895. SSF82895. 1 hit.
PROSITEiPS01225. CTCK_2. 1 hit.
PS00222. IGFBP_N_1. 1 hit.
PS51323. IGFBP_N_2. 1 hit.
PS50092. TSP1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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.
    , 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. 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. Cited for: VARIANT PPAC ARG-78, VARIANT HIS-56.

Entry informationi

Entry nameiWISP3_HUMAN
AccessioniPrimary (citable) accession number: O95389
Secondary accession number(s): Q3KR29, Q5H8W4, Q6UXH6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: May 1, 1999
Last modified: February 4, 2015
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.