Reviewed, UniProtKB/Swiss-Prot O95388 (WISP1_HUMAN)

Names and origin

Protein names

Recommended name:
    WNT1-inducible-signaling pathway protein 1
      Short name=WISP-1
Alternative name(s):
    Wnt-1-induced secreted protein

Gene names

Name:	WISP1
Synonyms:	CCN4

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	367 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	Downstream regulator in the Wnt/Frizzled-signaling pathway. Associated with cell survival. Attenuates p53-mediated apoptosis in response to DNA damage through activation of AKT kinase. Up-regulates the anti-apoptotic Bcl-X(L) protein. Adheres to skin and melanoma fibroblasts. In vitro binding to skin fibroblasts occurs through the proteoglycans, decorin and biglycan. Ref.5 Ref.6
Subcellular location	Secreted.
Tissue specificity	Expressed in heart, kidney, lung, pancreas, placenta, ovary, small intestine and spleen. Isoform 2 is expressed predominantly in scirrhous gastric carcinoma and, weakly in placenta. Overexpression is associated with several cancers including breast cancer and colon tumors. Isoform 2 is overexpressed in scirrhous gastric carcinoma.
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. Contains 1 VWFC domain.

Ontologies

Keywords
Biological process	Cell adhesion Wnt signaling pathway
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Disease	Proto-oncogene
Domain	Signal
PTM	Glycoprotein
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW cell-cell signaling Ref.1 Traceable author statement. Source: ProtInc regulation of cell growth Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: InterPro soluble fraction Ref.1 Traceable author statement. Source: ProtInc
Molecular function	insulin-like growth factor binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
UGCGL1	Q9NYU2	1	EBI-1050638,EBI-1056389

Alternative products

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

Isoform 1 (identifier: O95388-1)

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: O95388-2)

Also known as: WISP1v;

The sequence of this isoform differs from the canonical sequence as follows:
     117-117: Q → H
     118-204: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 367	345	WNT1-inducible-signaling pathway protein 1		PRO_0000014406
Regions
	Domain	40 – 118	79	IGFBP N-terminal
	Domain	121 – 186	66	VWFC
	Domain	215 – 260	46	TSP type-1
	Domain	273 – 347	75	CTCK
Amino acid modifications
	Glycosylation	86	1	N-linked (GlcNAc...) Potential
	Glycosylation	143	1	N-linked (GlcNAc...) Potential
	Glycosylation	284	1	N-linked (GlcNAc...) Potential
	Glycosylation	343	1	N-linked (GlcNAc...) Potential
	Disulfide bond	273 ↔ 310		By similarity
	Disulfide bond	290 ↔ 324		By similarity
	Disulfide bond	301 ↔ 340		By similarity
	Disulfide bond	304 ↔ 342		By similarity
	Disulfide bond	309 ↔ 346		By similarity
Natural variations
	Alternative sequence	117	1	Q → H in isoform 2.		VSP_008008
	Alternative sequence	118 – 204	87	Missing in isoform 2.		VSP_008009

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 9F29CA94D69C0502	FASTA	367	40,331
	10 20 30 40 50 60 MRWFLPWTLA AVTAAAASTV LATALSPAPT TMDFTPAPLE DTSSRPQFCK WPCECPPSPP 70 80 90 100 110 120 RCPLGVSLIT DGCECCKMCA QQLGDNCTEA AICDPHRGLY CDYSGDRPRY AIGVCAQVVG 130 140 150 160 170 180 VGCVLDGVRY NNGQSFQPNC KYNCTCIDGA VGCTPLCLRV RPPRLWCPHP RRVSIPGHCC 190 200 210 220 230 240 EQWVCEDDAK RPRKTAPRDT GAFDAVGEVE AWHRNCIAYT SPWSPCSTSC GLGVSTRISN 250 260 270 280 290 300 VNAQCWPEQE SRLCNLRPCD VDIHTLIKAG KKCLAVYQPE ASMNFTLAGC ISTRSYQPKY 310 320 330 340 350 360 CGVCMDNRCC IPYKSKTIDV SFQCPDGLGF SRQVLWINAC FCNLSCRNPN DIFADLESYP DFSEIAN
	Isoform 2 (WISP1v). Checksum: 26B254D4A060738E		280	30,697
	10 20 30 40 50 60 MRWFLPWTLA AVTAAAASTV LATALSPAPT TMDFTPAPLE DTSSRPQFCK WPCECPPSPP 70 80 90 100 110 120 RCPLGVSLIT DGCECCKMCA QQLGDNCTEA AICDPHRGLY CDYSGDRPRY AIGVCAHAVG 130 140 150 160 170 180 EVEAWHRNCI AYTSPWSPCS TSCGLGVSTR ISNVNAQCWP EQESRLCNLR PCDVDIHTLI 190 200 210 220 230 240 KAGKKCLAVY QPEASMNFTL AGCISTRSYQ PKYCGVCMDN RCCIPYKSKT IDVSFQCPDG 250 260 270 280 LGFSRQVLWI NACFCNLSCR NPNDIFADLE SYPDFSEIAN

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: Fetal kidney and Lung.
[2]	"A novel variant of WISP1 lacking a Von Willebrand type C module overexpressed in scirrhous gastric carcinoma." Tanaka S., Sugimachi K., Saeki H., Kinoshita J., Ohga T., Shimada M., Maehara Y., Sugimachi K. Oncogene 20:5525-5532(2001) [PubMed: 11571650] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Gastric carcinoma.
[3]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed: 16421571] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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). Tissue: Lung.
[5]	"WISP-1 is a Wnt-1- and beta-catenin-responsive oncogene." Xu L., Corcoran R.B., Welsh J.W., Pennica D., Levine A.J. Genes Dev. 14:585-595(2000) [PubMed: 10716946] [Abstract] Cited for: FUNCTION IN WNT1 SIGNALING.
[6]	"WISP-1 attenuates p53-mediated apoptosis in response to DNA damage through activation of the Akt kinase." Su F., Overholtzer M., Besser D., Levine A.J. Genes Dev. 16:46-57(2002) [PubMed: 11782444] [Abstract] Cited for: FUNCTION IN P53-MEDIATED APOPTOSIS.
[7]	"WISP-1 binds to decorin and biglycan." Desnoyers L., Arnott D., Pennica D. J. Biol. Chem. 276:47599-47607(2001) [PubMed: 11598131] [Abstract] Cited for: INTERACTION WITH DECORIN AND BIGLYCAN.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF100779 mRNA. Translation: AAC96321.1. AB034725 mRNA. Translation: BAB17849.1. AF192304 Genomic DNA. No translation available. BC074840 mRNA. Translation: AAH74840.1. BC074841 mRNA. Translation: AAH74841.1.
RefSeq	NP_003873.1. NP_543028.1.
UniGene	Hs.492974
3D structure databases
HSSP	HSSP built from PDB template 1LSL based on UniProtKB P07996.
ModBase	Search...
Protein-protein interaction databases
IntAct	O95388. 1 interaction.
Genome annotation databases
Ensembl	ENSG00000104415. Homo sapiens. [Contig view]
GeneID	8840.
KEGG	hsa:8840.
Organism-specific databases
GeneCards	GC08P134272.
H-InvDB	HIX0034236.
HGNC	HGNC:12769. WISP1.
HPA	CAB012205. HPA007121.
MIM	603398. gene.
PharmGKB	PA37372.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O95388.
HOVERGEN	O95388.
Gene expression databases
ArrayExpress	O95388.
CleanEx	HS_WISP1.
GermOnline	ENSG00000104415. Homo sapiens.
Family and domain databases
InterPro	IPR006208. Cys_knot. IPR006207. Cys_knot_C. IPR012395. IGFBP_CNN. IPR000867. IGFBP_like. IPR000884. TSP1. IPR001007. VWF_C. [Graphical view]
Pfam	PF00007. Cys_knot. 1 hit. PF00219. IGFBP. 1 hit. PF00090. TSP_1. 1 hit. PF00093. VWC. 1 hit. [Graphical view]
PIRSF	PIRSF036495. IGFBP_rP_CNN. 1 hit.
SMART	SM00041. CT. 1 hit. SM00121. IB. 1 hit. SM00209. TSP1. 1 hit. SM00214. VWC. 1 hit. [Graphical view]
PROSITE	PS01185. CTCK_1. 1 hit. PS01225. CTCK_2. 1 hit. PS00222. IGFBP_N_1. 1 hit. PS51323. IGFBP_N_2. 1 hit. PS50092. TSP1. 1 hit. PS01208. VWFC_1. 1 hit. PS50184. VWFC_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	33184.
SOURCE	Search...

Entry information

Entry name

WISP1_HUMAN

Accession

Primary (citable) accession number: O95388
Secondary accession number(s): Q9HCS3

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 15, 2003
Last sequence update:	May 1, 1999
Last modified:	December 16, 2008
This is version 68 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)