Reviewed, UniProtKB/Swiss-Prot O95389 (WISP3_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	354 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	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	Defects in WISP3 are the cause of progressive pseudorheumatoid arthropathy of childhood (PPAC) [MIM:208230]. PPAC is an 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. 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 component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Signal
Molecular function	Growth factor
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	cell-cell signaling Ref.1 Traceable author statement. Source: ProtInc regulation of cell growth Inferred from electronic annotation. Source: InterPro signal transduction Ref.1 Traceable author statement. Source: ProtInc
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell soluble fraction Ref.1 Traceable author statement. Source: ProtInc
Molecular function	growth factor activity Inferred from electronic annotation. Source: UniProtKB-KW insulin-like growth factor binding Inferred from electronic annotation. Source: InterPro
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 354	331	WNT1-inducible-signaling pathway protein 3		PRO_0000014412
Regions
	Domain	44 – 117	74	IGFBP N-terminal
	Domain	208 – 253	46	TSP type-1
	Domain	268 – 342	75	CTCK
Amino acid modifications
	Glycosylation	178	1	N-linked (GlcNAc...) Potential
	Glycosylation	308	1	N-linked (GlcNAc...) Potential
	Disulfide bond	268 ↔ 305		By similarity
	Disulfide bond	285 ↔ 319		By similarity
	Disulfide bond	296 ↔ 335		By similarity
	Disulfide bond	299 ↔ 337		By similarity
	Disulfide bond	304 ↔ 341		By similarity
Natural variations
	Alternative sequence	1	1	M → MNKRRLLYPSGWLHGPSDM in isoform 2.		VSP_037803
	Natural variant	56	1	Q → H Common polymorphism. dbSNP rs1230345. Ref.6		VAR_016224
	Natural variant	60	1	R → C: dbSNP rs17073260.		VAR_049567
	Natural variant	78	1	C → R in PPAC. Ref.6		VAR_016225
Experimental info
	Sequence conflict	200	1	N → D in AAQ88715. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 67F48D0D5C2F5EE3	FASTA	354	39,293
	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
	Isoform 2. Checksum: 449A31188D480511	FASTA	372	41,402
	10 20 30 40 50 60 MNKRRLLYPS GWLHGPSDMQ GLLFSTLLLA GLAQFCCRVQ GTGPLDTTPE GRPGEVSDAP 70 80 90 100 110 120 QRKQFCHWPC KCPQQKPRCP PGVSLVRDGC GCCKICAKQP GEICNEADLC DPHKGLYCDY 130 140 150 160 170 180 SVDRPRYETG VCAYLVAVGC EFNQVHYHNG QVFQPNPLFS CLCVSGAIGC TPLFIPKLAG 190 200 210 220 230 240 SHCSGAKGGK KSDQSNCSLE PLLQQLSTSY KTMPAYRNLP LIWKKKCLVQ ATKWTPCSRT 250 260 270 280 290 300 CGMGISNRVT NENSNCEMRK EKRLCYIQPC DSNILKTIKI PKGKTCQPTF QLSKAEKFVF 310 320 330 340 350 360 SGCSSTQSYK PTFCGICLDK RCCIPNKSKM ITIQFDCPNE GSFKWKMLWI TSCVCQRNCR 370 EPGDIFSELK IL

References

	« Hide 'large scale' referencesShow '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: 9843955] [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. , 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] (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: 14574404] [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. , 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: 15489334] [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: 10471507] [Abstract] Cited for: VARIANT PPAC ARG-78, VARIANT HIS-56.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

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.
IPI	IPI00022051. IPI00419732.
RefSeq	NP_003871.1. NP_937882.1.
UniGene	Hs.558428
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	O95389.
Proteomic databases
PRIDE	O95389.
Genome annotation databases
Ensembl	ENST00000230529; ENSP00000230529; ENSG00000112761; Homo sapiens. [Genome view] ENST00000361714; ENSP00000354734; ENSG00000112761; Homo sapiens. [Genome view] ENST00000368666; ENSP00000357655; ENSG00000112761; Homo sapiens. [Genome view]
GeneID	8838.
KEGG	hsa:8838.
UCSC	uc003pvm.1. human.
Organism-specific databases
CTD	8838.
GeneCards	GC06P112481.
HGNC	HGNC:12771. WISP3.
MIM	208230. phenotype. 603400. gene.
Orphanet	1159. Arthropathy progressive pseudorheumatoid of childhood. 252. Spondyloepimetaphyseal dysplasia.
PharmGKB	PA37374.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG04716.
HOVERGEN	O95389.
InParanoid	O95389.
OMA	DRPRYET.
Gene expression databases
ArrayExpress	O95389.
Bgee	O95389.
CleanEx	HS_WISP3.
Genevestigator	O95389.
GermOnline	ENSG00000112761. Homo sapiens.
Family and domain databases
InterPro	IPR006208. Cys_knot. IPR006207. Cys_knot_C. IPR000867. IGFBP-like. IPR012395. IGFBP_CNN. IPR017891. Insulin_GF-bd_Cys-rich_CS. IPR000884. Thrombospondin_1_rpt. [Graphical view]
Pfam	PF00007. Cys_knot. 1 hit. PF00219. IGFBP. 1 hit. PF00090. TSP_1. 1 hit. [Graphical view]
PIRSF	PIRSF036495. IGFBP_rP_CNN. 1 hit.
SMART	SM00041. CT. 1 hit. SM00121. IB. 1 hit. SM00209. TSP1. 1 hit. [Graphical view]
PROSITE	PS01185. CTCK_1. False negative. PS01225. CTCK_2. 1 hit. PS00222. IGFBP_N_1. 1 hit. PS51323. IGFBP_N_2. 1 hit. PS50092. TSP1. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	33172.
SOURCE	Search...

Entry information

Entry name

WISP3_HUMAN

Accession

Primary (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:	February 9, 2010
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.