Reviewed,
UniProtKB/Swiss-Prot Q2MKA7 (RSPO1_HUMAN)
Last modified
January 19, 2010.
Version 40.
History...
Clusters with 100%,
90%,
50% identity |
Documents (3) |
Third-party data |
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Names and origin
| Protein names | Recommended name: R-spondin-1 Alternative name(s): Roof plate-specific spondin-1 Short name=hRspo1 | ||
| Gene names |
| ||
| 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 | 263 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at transcript level. |
General annotation (Comments)
| Function | Activator of the beta-catenin signaling cascade, leading to TCF-dependent gene activation. Acts both in the canonical Wnt/beta-catenin-dependent pathway, possibly via a direct interaction with Wnt proteins, and in a Wnt-independent beta catenin pathway through a receptor signaling pathway that may not use frizzled/LRP receptors. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway. Has a essential roles in ovary determination. Ref.1 |
| Subunit structure | Interacts with the extracelular domain of FZD8 and LRP6. It however does not form a ternary complex with FZD8 and LRP6. Interacts with WNT1. Binds heparin By similarity. |
| Subcellular location | Secreted By similarity. |
| Tissue specificity | Abundantly expressed in adrenal glands, ovary, testis, thyroid and trachea but not in bonre marrow, spinal cord, stomach, leukocytes colon, small intestine, prostate, thymus and spleen. Ref.2 |
| Domain | The FU repeats are required for activation and stabilization of beta-catenin By similarity. |
| Involvement in disease | Defects in RSPO1 are the cause of palmoplantar keratoderma with squamous cell carcinoma of skin and sex reversal (PKKSCC) [MIM:610644]. This recessive syndrome is characterized by XX (female to male) SRY-independent sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin. |
| 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 suggesting possible therapeutic application in gastrointestinal diseases. |
| Sequence similarities | Belongs to the R-spondin family. Contains 2 FU (furin-like) repeats. Contains 1 TSP type-1 domain. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Sensory transduction Wnt signaling pathway |
| Cellular component | Secreted |
| Coding sequence diversity | Alternative splicing |
| Disease | Palmoplantar keratoderma |
| Domain | Repeat Signal |
| Ligand | Heparin-binding |
| PTM | Disulfide bond Glycoprotein |
| Technical term | Complete proteome |
| Gene Ontology (GO) | |
| Biological process | Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW response to stimulusInferred from electronic annotation. Source: UniProtKB-KW |
| Molecular function | heparin binding Inferred from electronic annotation. Source: UniProtKB-KW |
| Complete GO annotation... | |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q2MKA7-1) 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: Q2MKA7-2) The sequence of this isoform differs from the canonical sequence as follows: 1-32: MRLGLCVVALVLSWTHLTISSRGIKGKRQRRI → MIFRV | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 20 | 20 | Potential | ||||||||
| Chain | 21 – 263 | 243 | R-spondin-1 | PRO_0000234436 | |||||||
Regions | |||||||||||
| Repeat | 34 – 85 | 52 | FU 1 | ||||||||
| Repeat | 91 – 135 | 45 | FU 2 | ||||||||
| Domain | 147 – 207 | 61 | TSP type-1 | ||||||||
Amino acid modifications | |||||||||||
| Glycosylation | 137 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Disulfide bond | 148 ↔ 190 | By similarity | |||||||||
| Disulfide bond | 159 ↔ 166 | By similarity | |||||||||
| Disulfide bond | 199 ↔ 206 | By similarity | |||||||||
Natural variations | |||||||||||
| Alternative sequence | 1 – 32 | 32 | MRLGL…RQRRI → MIFRV in isoform 2. | VSP_018320 | |||||||
Experimental info | |||||||||||
| Sequence conflict | 150 | 1 | M → V in BAC05263. Ref.3 | ||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Mitogenic influence of human R-spondin1 on the intestinal epithelium." Kim K.-A., Kakitani M., Zhao J., Oshima T., Tang T., Binnerts M., Liu Y., Boyle B., Park E., Emtage P., Funk W.D., Tomizuka K. Science 309:1256-1259(2005) [PubMed: 16109882] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION. |
| [2] | "R-spondin1 is essential in sex determination, skin differentiation and malignancy." Parma P., Radi O., Vidal V., Chaboissier M.C., Dellambra E., Valentini S., Guerra L., Schedl A., Camerino G. Nat. Genet. 38:1304-1309(2006) [PubMed: 17041600] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INVOLVEMENT IN PALMOPLANTAR HYPERKERATOSIS WITH SQUAMOUS CELL CARCINOMA OF SKIN AND SEX REVERSAL. |
| [3] | "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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Uterus. |
| [4] | "The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. Bentley D.R.Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] 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 1). |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | DQ318235 mRNA. Translation: ABC54570.1. DQ165084 mRNA. Translation: ABA54597.1. AK098225 mRNA. Translation: BAC05263.1. AL513220 Genomic DNA. Translation: CAM12883.1. AL513220 Genomic DNA. Translation: CAI15785.1. BC114966 mRNA. Translation: AAI14967.1. |
| IPI | IPI00719160. IPI00748481. |
| RefSeq | NP_001033722.1. |
| UniGene | Hs.135015 |
3D structure databases | |
| SMR | Q2MKA7. Positions 146-208. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | Q2MKA7. |
Proteomic databases | |
| PRIDE | Q2MKA7. |
Genome annotation databases | |
| Ensembl | ENST00000356545; ENSP00000348944; ENSG00000169218; Homo sapiens. [Genome view] ENST00000401068; ENSP00000383846; ENSG00000169218; Homo sapiens. [Genome view] ENST00000401069; ENSP00000383847; ENSG00000169218; Homo sapiens. [Genome view] ENST00000445126; ENSP00000388194; ENSG00000169218; Homo sapiens. [Genome view] |
| GeneID | 284654. |
| KEGG | hsa:284654. |
| UCSC | uc001cbl.1. human. uc009vvf.1. human. |
Organism-specific databases | |
| CTD | 284654. |
| GeneCards | GC01M037849. |
| H-InvDB | HIX0000436. |
| HGNC | HGNC:21679. RSPO1. |
| MIM | 609595. gene. 610644. phenotype. |
| Orphanet | 85112. Palmoplantar keratoderma - XX sex reversal - predisposition to squamous cell carcinoma. |
| PharmGKB | PA142670967. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG06681. |
| HOGENOM | HBG715962. |
| HOVERGEN | Q2MKA7. |
| InParanoid | Q2MKA7. |
| OMA | RLGLCVV. |
| OrthoDB | EOG9SJ807. |
Gene expression databases | |
| ArrayExpress | Q2MKA7. |
| Bgee | Q2MKA7. |
| CleanEx | HS_RSPO1. |
| Genevestigator | Q2MKA7. |
| GermOnline | ENSG00000169218. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR006212. Furin_repeat. IPR009030. Growth_fac_rcpt. IPR000884. Thrombospondin_1_rpt. [Graphical view] |
| Pfam | PF00090. TSP_1. 1 hit. [Graphical view] |
| SMART | SM00261. FU. 2 hits. SM00209. TSP1. 1 hit. [Graphical view] |
| PROSITE | PS50092. TSP1. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 95027. |
| SOURCE | Search... |
Entry information
| Entry name | RSPO1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q2MKA7 Secondary accession number(s): A2A420 Q8N7L5 | ||||||||
| Entry 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. | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

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