Reviewed, UniProtKB/Swiss-Prot Q2MKA7 (RSPO1_HUMAN)

Names and origin

Protein names

Recommended name:
    R-spondin-1
Alternative name(s):
    Roof plate-specific spondin-1
      Short name=hRspo1

Gene names

Name:

RSPO1

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 stimulus Inferred 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

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 7, 2006. Version 1. Checksum: 43794A881B1C0278	FASTA	263	28,959
	10 20 30 40 50 60 MRLGLCVVAL VLSWTHLTIS SRGIKGKRQR RISAEGSQAC AKGCELCSEV NGCLKCSPKL 70 80 90 100 110 120 FILLERNDIR QVGVCLPSCP PGYFDARNPD MNKCIKCKIE HCEACFSHNF CTKCKEGLYL 130 140 150 160 170 180 HKGRCYPACP EGSSAANGTM ECSSPAQCEM SEWSPWGPCS KKQQLCGFRR GSEERTRRVL 190 200 210 220 230 240 HAPVGDHAAC SDTKETRRCT VRRVPCPEGQ KRRKGGQGRR ENANRNLARK ESKEAGAGSR 250 260 RRKGQQQQQQ QGTVGPLTSA GPA
	Isoform 2. Checksum: 8D08802127EC5668	FASTA	236	25,975
	10 20 30 40 50 60 MIFRVSAEGS QACAKGCELC SEVNGCLKCS PKLFILLERN DIRQVGVCLP SCPPGYFDAR 70 80 90 100 110 120 NPDMNKCIKC KIEHCEACFS HNFCTKCKEG LYLHKGRCYP ACPEGSSAAN GTMECSSPAQ 130 140 150 160 170 180 CEMSEWSPWG PCSKKQQLCG FRRGSEERTR RVLHAPVGDH AACSDTKETR RCTVRRVPCP 190 200 210 220 230 EGQKRRKGGQ GRRENANRNL ARKESKEAGA GSRRRKGQQQ QQQQGTVGPL TSAGPA

References

	« Hide 'large scale' referencesShow '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. , 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: 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. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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 , Q14C72, Q5T0F2, Q8N7L5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 16, 2006
Last sequence update:	February 7, 2006
Last modified:	January 19, 2010
This is version 40 of the entry and version 1 of the sequence. [Complete 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.