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Q6UXX9 (RSPO2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 84. 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·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
R-spondin-2
Alternative name(s):
Roof plate-specific spondin-2
Short name=hRspo2
Gene names
Name:RSPO2
ORF Names:UNQ9384/PRO34209
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length243 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Probably also acts as a ligand for frizzled and LRP receptors. Ref.7 Ref.8 Ref.9

Subunit structure

Interacts with WNT1. Binds heparin By similarity. Interacts with LGR4, LGR5 and LGR6. Ref.7 Ref.8 Ref.9

Subcellular location

Secreted By similarity.

Domain

The FU repeat is required for activation and stabilization of beta-catenin By similarity.

Miscellaneous

Upon injection into mice, it induces rapid onset of crypt cell proliferation involving beta-catenin stabilization. It also displays efficacy in a model of chemotherapy-induced intestinal mucositis (Ref.6).

Sequence similarities

Belongs to the R-spondin family.

Contains 1 FU (furin-like) repeat.

Contains 1 TSP type-1 domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6UXX9-1)

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: Q6UXX9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-67: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q6UXX9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     32-95: ASYVSNPICKGCLSCSKDNGCSRCQQKLFFFLRREGMRQYGECLHSCPSGYYGHRAPDMNRCAR → G
     143-143: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 243222R-spondin-2
PRO_0000234439

Regions

Repeat90 – 13445FU
Domain144 – 20461TSP type-1

Amino acid modifications

Glycosylation1601N-linked (GlcNAc...) Potential
Disulfide bond40 ↔ 46 By similarity
Disulfide bond43 ↔ 52 By similarity
Disulfide bond55 ↔ 74 By similarity
Disulfide bond78 ↔ 93 By similarity
Disulfide bond96 ↔ 104 By similarity
Disulfide bond101 ↔ 110 By similarity
Disulfide bond113 ↔ 124 By similarity
Disulfide bond128 ↔ 141 By similarity
Disulfide bond145 ↔ 187 By similarity
Disulfide bond156 ↔ 163 By similarity
Disulfide bond196 ↔ 203 By similarity

Natural variations

Alternative sequence1 – 6767Missing in isoform 2.
VSP_018321
Alternative sequence32 – 9564ASYVS…NRCAR → G in isoform 3.
VSP_018322
Alternative sequence1431Missing in isoform 3.
VSP_018323
Natural variant1861L → P. Ref.1 Ref.2 Ref.4 Ref.5
Corresponds to variant rs601558 [ dbSNP | Ensembl ].
VAR_026247

Sequences

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

Last modified May 15, 2007. Version 2.
Checksum: 96F44F105B21BB52

FASTA24328,315
        10         20         30         40         50         60 
MQFRLFSFAL IILNCMDYSH CQGNRWRRSK RASYVSNPIC KGCLSCSKDN GCSRCQQKLF 

        70         80         90        100        110        120 
FFLRREGMRQ YGECLHSCPS GYYGHRAPDM NRCARCRIEN CDSCFSKDFC TKCKVGFYLH 

       130        140        150        160        170        180 
RGRCFDECPD GFAPLEETME CVEGCEVGHW SEWGTCSRNN RTCGFKWGLE TRTRQIVKKP 

       190        200        210        220        230        240 
VKDTILCPTI AESRRCKMTM RHCPGGKRTP KAKEKRNKKK KRKLIERAQE QHSVFLATDR 


ANQ 

« Hide

Isoform 2 [UniParc].

Checksum: 0F9FD0E1AEE4CA85
Show »

FASTA17620,426
Isoform 3 [UniParc].

Checksum: 7C428C4A6C152798
Show »

FASTA17920,972

References

« Hide 'large scale' references
[1]"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 1), VARIANT PRO-186.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT PRO-186.
Tissue: Brain.
[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. expand/collapse author list , 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] [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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT PRO-186.
[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] (ISOFORMS 2 AND 3), VARIANT PRO-186.
Tissue: Lung and Testis.
[6]"R-spondin proteins: a novel link to beta-catenin activation."
Kim K.-A., Zhao J., Andarmani S., Kakitani M., Oshima T., Binnerts M.E., Abo A., Tomizuka K., Funk W.D.
Cell Cycle 5:23-26(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INJECTION INTO MICE.
[7]"LGR4 and LGR5 are R-spondin receptors mediating Wnt/beta-catenin and Wnt/PCP signalling."
Glinka A., Dolde C., Kirsch N., Huang Y.L., Kazanskaya O., Ingelfinger D., Boutros M., Cruciat C.M., Niehrs C.
EMBO Rep. 12:1055-1061(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH LGR4 AND LGR5.
[8]"Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling."
de Lau W., Barker N., Low T.Y., Koo B.K., Li V.S., Teunissen H., Kujala P., Haegebarth A., Peters P.J., van de Wetering M., Stange D.E., van Es J.E., Guardavaccaro D., Schasfoort R.B., Mohri Y., Nishimori K., Mohammed S., Heck A.J., Clevers H.
Nature 476:293-297(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH LGR4; LGR5 AND LGR6.
[9]"LGR6 is a high affinity receptor of R-spondins and potentially functions as a tumor suppressor."
Gong X., Carmon K.S., Lin Q., Thomas A., Yi J., Liu Q.
PLoS ONE 7:E37137-E37137(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH LGR6.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY358166 mRNA. Translation: AAQ88533.1.
AK123023 mRNA. Translation: BAG53852.1.
AC025508 Genomic DNA. No translation available.
AP003479 Genomic DNA. No translation available.
CH471060 Genomic DNA. Translation: EAW91916.1.
BC027938 mRNA. Translation: AAH27938.1.
BC036554 mRNA. Translation: AAH36554.1.
CCDSCCDS6307.1. [Q6UXX9-1]
CCDS64953.1. [Q6UXX9-3]
RefSeqNP_001269792.1. NM_001282863.1. [Q6UXX9-3]
NP_848660.3. NM_178565.4. [Q6UXX9-1]
XP_005250963.1. XM_005250906.1. [Q6UXX9-1]
UniGeneHs.444834.

3D structure databases

ProteinModelPortalQ6UXX9.
SMRQ6UXX9. Positions 39-143.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid131049. 4 interactions.
IntActQ6UXX9. 2 interactions.
MINTMINT-8417715.
STRING9606.ENSP00000276659.

PTM databases

PhosphoSiteQ6UXX9.

Polymorphism databases

DMDM147744588.

Proteomic databases

PaxDbQ6UXX9.
PRIDEQ6UXX9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000276659; ENSP00000276659; ENSG00000147655. [Q6UXX9-1]
ENST00000378439; ENSP00000367698; ENSG00000147655. [Q6UXX9-3]
ENST00000517781; ENSP00000427937; ENSG00000147655. [Q6UXX9-3]
ENST00000517939; ENSP00000428940; ENSG00000147655. [Q6UXX9-2]
GeneID340419.
KEGGhsa:340419.
UCSCuc003ymq.3. human. [Q6UXX9-1]
uc003ymr.3. human. [Q6UXX9-3]

Organism-specific databases

CTD340419.
GeneCardsGC08M108981.
H-InvDBHIX0007721.
HGNCHGNC:28583. RSPO2.
HPACAB025900.
HPA024764.
MIM610575. gene.
neXtProtNX_Q6UXX9.
PharmGKBPA142670968.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG285562.
HOGENOMHOG000290668.
HOVERGENHBG082751.
InParanoidQ6UXX9.
OMADNGCIRC.
OrthoDBEOG7X9G7G.
PhylomeDBQ6UXX9.
TreeFamTF331799.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressQ6UXX9.
BgeeQ6UXX9.
CleanExHS_RSPO2.
GenevestigatorQ6UXX9.

Family and domain databases

InterProIPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt_N_dom.
IPR000884. Thrombospondin_1_rpt.
[Graphical view]
SMARTSM00261. FU. 2 hits.
SM00209. TSP1. 1 hit.
[Graphical view]
SUPFAMSSF57184. SSF57184. 1 hit.
SSF82895. SSF82895. 1 hit.
PROSITEPS50092. TSP1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiRSPO2.
GenomeRNAi340419.
NextBio97857.
PROQ6UXX9.
SOURCESearch...

Entry information

Entry nameRSPO2_HUMAN
AccessionPrimary (citable) accession number: Q6UXX9
Secondary accession number(s): B3KVP0, Q4G0U4, Q8N6X6
Entry history
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: May 15, 2007
Last modified: July 9, 2014
This is version 84 of the entry and version 2 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 8

Human chromosome 8: entries, gene names and cross-references to MIM