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Q6UXX9

- RSPO2_HUMAN

UniProt

Q6UXX9 - RSPO2_HUMAN

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Protein

R-spondin-2

Gene

RSPO2

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

Functioni

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.3 Publications

GO - Molecular functioni

  1. heparin binding Source: UniProtKB-KW
  2. receptor binding Source: UniProtKB

GO - Biological processi

  1. bone mineralization Source: Ensembl
  2. embryonic forelimb morphogenesis Source: Ensembl
  3. embryonic hindlimb morphogenesis Source: Ensembl
  4. epithelial tube branching involved in lung morphogenesis Source: Ensembl
  5. lung growth Source: Ensembl
  6. osteoblast differentiation Source: Ensembl
  7. positive regulation of canonical Wnt signaling pathway Source: Ensembl
  8. trachea cartilage morphogenesis Source: Ensembl
  9. Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Sensory transduction, Wnt signaling pathway

Keywords - Ligandi

Heparin-binding

Enzyme and pathway databases

ReactomeiREACT_200716. regulation of FZD by ubiquitination.

Names & Taxonomyi

Protein namesi
Recommended name:
R-spondin-2
Alternative name(s):
Roof plate-specific spondin-2
Short name:
hRspo2
Gene namesi
Name:RSPO2
ORF Names:UNQ9384/PRO34209
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 8

Organism-specific databases

HGNCiHGNC:28583. RSPO2.

Subcellular locationi

Secreted By similarity

GO - Cellular componenti

  1. cell surface Source: Ensembl
  2. extracellular region Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA142670968.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence AnalysisAdd
BLAST
Chaini22 – 243222R-spondin-2PRO_0000234439Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi40 ↔ 46PROSITE-ProRule annotation
Disulfide bondi43 ↔ 52PROSITE-ProRule annotation
Disulfide bondi55 ↔ 74PROSITE-ProRule annotation
Disulfide bondi78 ↔ 93PROSITE-ProRule annotation
Disulfide bondi96 ↔ 104PROSITE-ProRule annotation
Disulfide bondi101 ↔ 110PROSITE-ProRule annotation
Disulfide bondi113 ↔ 124PROSITE-ProRule annotation
Disulfide bondi128 ↔ 141PROSITE-ProRule annotation
Disulfide bondi145 ↔ 187PROSITE-ProRule annotation
Disulfide bondi156 ↔ 163PROSITE-ProRule annotation
Glycosylationi160 – 1601N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi196 ↔ 203PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ6UXX9.
PRIDEiQ6UXX9.

PTM databases

PhosphoSiteiQ6UXX9.

Expressioni

Gene expression databases

BgeeiQ6UXX9.
CleanExiHS_RSPO2.
ExpressionAtlasiQ6UXX9. baseline and differential.
GenevestigatoriQ6UXX9.

Organism-specific databases

HPAiCAB025900.
HPA024764.

Interactioni

Subunit structurei

Interacts with WNT1. Binds heparin (By similarity). Interacts with LGR4, LGR5 and LGR6.By similarity3 Publications

Protein-protein interaction databases

BioGridi131049. 4 interactions.
IntActiQ6UXX9. 2 interactions.
MINTiMINT-8417715.
STRINGi9606.ENSP00000276659.

Structurei

3D structure databases

ProteinModelPortaliQ6UXX9.
SMRiQ6UXX9. Positions 39-143.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati90 – 13445FUAdd
BLAST
Domaini144 – 20461TSP type-1PROSITE-ProRule annotationAdd
BLAST

Domaini

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

Sequence similaritiesi

Belongs to the R-spondin family.Curated
Contains 1 FU (furin-like) repeat.Curated
Contains 1 TSP type-1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG285562.
GeneTreeiENSGT00390000011447.
HOGENOMiHOG000290668.
HOVERGENiHBG082751.
InParanoidiQ6UXX9.
OMAiDNGCIRC.
OrthoDBiEOG7X9G7G.
PhylomeDBiQ6UXX9.
TreeFamiTF331799.

Family and domain databases

InterProiIPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt_N_dom.
IPR000884. Thrombospondin_1_rpt.
[Graphical view]
SMARTiSM00261. FU. 2 hits.
SM00209. TSP1. 1 hit.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 1 hit.
SSF82895. SSF82895. 1 hit.
PROSITEiPS50092. TSP1. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q6UXX9-1) [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
MQFRLFSFAL IILNCMDYSH CQGNRWRRSK RASYVSNPIC KGCLSCSKDN
60 70 80 90 100
GCSRCQQKLF FFLRREGMRQ YGECLHSCPS GYYGHRAPDM NRCARCRIEN
110 120 130 140 150
CDSCFSKDFC TKCKVGFYLH RGRCFDECPD GFAPLEETME CVEGCEVGHW
160 170 180 190 200
SEWGTCSRNN RTCGFKWGLE TRTRQIVKKP VKDTILCPTI AESRRCKMTM
210 220 230 240
RHCPGGKRTP KAKEKRNKKK KRKLIERAQE QHSVFLATDR ANQ
Length:243
Mass (Da):28,315
Last modified:May 15, 2007 - v2
Checksum:i96F44F105B21BB52
GO
Isoform 2 (identifier: Q6UXX9-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-67: Missing.

Note: No experimental confirmation available.

Show »
Length:176
Mass (Da):20,426
Checksum:i0F9FD0E1AEE4CA85
GO
Isoform 3 (identifier: Q6UXX9-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     32-95: ASYVSNPICKGCLSCSKDNGCSRCQQKLFFFLRREGMRQYGECLHSCPSGYYGHRAPDMNRCAR → G
     143-143: Missing.

Note: No experimental confirmation available.

Show »
Length:179
Mass (Da):20,972
Checksum:i7C428C4A6C152798
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti186 – 1861L → P.4 Publications
Corresponds to variant rs601558 [ dbSNP | Ensembl ].
VAR_026247

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 6767Missing in isoform 2. 1 PublicationVSP_018321Add
BLAST
Alternative sequencei32 – 9564ASYVS…NRCAR → G in isoform 3. 1 PublicationVSP_018322Add
BLAST
Alternative sequencei143 – 1431Missing in isoform 3. 1 PublicationVSP_018323

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS6307.1. [Q6UXX9-1]
CCDS64953.1. [Q6UXX9-3]
RefSeqiNP_001269792.1. NM_001282863.1. [Q6UXX9-3]
NP_848660.3. NM_178565.4. [Q6UXX9-1]
XP_005250963.1. XM_005250906.1. [Q6UXX9-1]
UniGeneiHs.444834.

Genome annotation databases

EnsembliENST00000276659; ENSP00000276659; ENSG00000147655. [Q6UXX9-1]
ENST00000517781; ENSP00000427937; ENSG00000147655. [Q6UXX9-3]
ENST00000517939; ENSP00000428940; ENSG00000147655. [Q6UXX9-2]
GeneIDi340419.
KEGGihsa:340419.
UCSCiuc003ymq.3. human. [Q6UXX9-1]
uc003ymr.3. human. [Q6UXX9-3]

Polymorphism databases

DMDMi147744588.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS6307.1. [Q6UXX9-1 ]
CCDS64953.1. [Q6UXX9-3 ]
RefSeqi NP_001269792.1. NM_001282863.1. [Q6UXX9-3 ]
NP_848660.3. NM_178565.4. [Q6UXX9-1 ]
XP_005250963.1. XM_005250906.1. [Q6UXX9-1 ]
UniGenei Hs.444834.

3D structure databases

ProteinModelPortali Q6UXX9.
SMRi Q6UXX9. Positions 39-143.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 131049. 4 interactions.
IntActi Q6UXX9. 2 interactions.
MINTi MINT-8417715.
STRINGi 9606.ENSP00000276659.

PTM databases

PhosphoSitei Q6UXX9.

Polymorphism databases

DMDMi 147744588.

Proteomic databases

PaxDbi Q6UXX9.
PRIDEi Q6UXX9.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000276659 ; ENSP00000276659 ; ENSG00000147655 . [Q6UXX9-1 ]
ENST00000517781 ; ENSP00000427937 ; ENSG00000147655 . [Q6UXX9-3 ]
ENST00000517939 ; ENSP00000428940 ; ENSG00000147655 . [Q6UXX9-2 ]
GeneIDi 340419.
KEGGi hsa:340419.
UCSCi uc003ymq.3. human. [Q6UXX9-1 ]
uc003ymr.3. human. [Q6UXX9-3 ]

Organism-specific databases

CTDi 340419.
GeneCardsi GC08M108981.
H-InvDB HIX0007721.
HGNCi HGNC:28583. RSPO2.
HPAi CAB025900.
HPA024764.
MIMi 610575. gene.
neXtProti NX_Q6UXX9.
PharmGKBi PA142670968.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG285562.
GeneTreei ENSGT00390000011447.
HOGENOMi HOG000290668.
HOVERGENi HBG082751.
InParanoidi Q6UXX9.
OMAi DNGCIRC.
OrthoDBi EOG7X9G7G.
PhylomeDBi Q6UXX9.
TreeFami TF331799.

Enzyme and pathway databases

Reactomei REACT_200716. regulation of FZD by ubiquitination.

Miscellaneous databases

GeneWikii RSPO2.
GenomeRNAii 340419.
NextBioi 97857.
PROi Q6UXX9.
SOURCEi Search...

Gene expression databases

Bgeei Q6UXX9.
CleanExi HS_RSPO2.
ExpressionAtlasi Q6UXX9. baseline and differential.
Genevestigatori Q6UXX9.

Family and domain databases

InterProi IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt_N_dom.
IPR000884. Thrombospondin_1_rpt.
[Graphical view ]
SMARTi SM00261. FU. 2 hits.
SM00209. TSP1. 1 hit.
[Graphical view ]
SUPFAMi SSF57184. SSF57184. 1 hit.
SSF82895. SSF82895. 1 hit.
PROSITEi PS50092. TSP1. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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.
    , 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.
    , 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. 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. 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.

Entry informationi

Entry nameiRSPO2_HUMAN
AccessioniPrimary (citable) accession number: Q6UXX9
Secondary accession number(s): B3KVP0, Q4G0U4, Q8N6X6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: May 15, 2007
Last modified: October 29, 2014
This is version 87 of the entry and version 2 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

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 (PubMed:16357527).1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: 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