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Q6UXX9

- RSPO2_HUMAN

UniProt

Q6UXX9 - RSPO2_HUMAN

Protein

R-spondin-2

Gene

RSPO2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 86 (01 Oct 2014)
      Sequence version 2 (15 May 2007)
      Previous versions | rss
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    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

    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-SubCell

    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

    ArrayExpressiQ6UXX9.
    BgeeiQ6UXX9.
    CleanExiHS_RSPO2.
    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.
    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

    MQFRLFSFAL IILNCMDYSH CQGNRWRRSK RASYVSNPIC KGCLSCSKDN    50
    GCSRCQQKLF FFLRREGMRQ YGECLHSCPS GYYGHRAPDM NRCARCRIEN 100
    CDSCFSKDFC TKCKVGFYLH RGRCFDECPD GFAPLEETME CVEGCEVGHW 150
    SEWGTCSRNN RTCGFKWGLE TRTRQIVKKP VKDTILCPTI AESRRCKMTM 200
    RHCPGGKRTP KAKEKRNKKK KRKLIERAQE QHSVFLATDR ANQ 243
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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.
    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

    ArrayExpressi Q6UXX9.
    Bgeei Q6UXX9.
    CleanExi HS_RSPO2.
    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

    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 1, 2014
    This is version 86 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