Q6UXX9 (RSPO2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
R-spondin-2

Alternative name(s):
Roof plate-specific spondin-2
Short name=hRspo2

Gene names

Name:	RSPO2
ORF Names:	UNQ9384/PRO34209

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	243 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein 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. Probably also acts as a ligand for frizzled and LRP receptors By similarity.
Subunit structure	Interacts with WNT1. Binds heparin By similarity.
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.
Sequence similarities	Belongs to the R-spondin family. Contains 1 FU (furin-like) repeat. Contains 1 TSP type-1 domain.

Ontologies

Keywords
Biological process	Sensory transduction Wnt signaling pathway
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Ligand	Heparin-binding
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	heparin binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 243	222	R-spondin-2		PRO_0000234439
Regions
	Repeat	90 – 134	45	FU
	Domain	144 – 204	61	TSP type-1
Amino acid modifications
	Glycosylation	160	1	N-linked (GlcNAc...) Potential
	Disulfide bond	145 ↔ 187		By similarity
	Disulfide bond	156 ↔ 163		By similarity
	Disulfide bond	196 ↔ 203		By similarity
Natural variations
	Alternative sequence	1 – 67	67	Missing in isoform 2.		VSP_018321
	Alternative sequence	32 – 95	64	ASYVS…NRCAR → G in isoform 3.		VSP_018322
	Alternative sequence	143	1	Missing in isoform 3.		VSP_018323
	Natural variant	186	1	L → P. Ref.1 Ref.2 Ref.4 Ref.5 Corresponds to variant rs601558 [ dbSNP | Ensembl ].		VAR_026247

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 15, 2007. Version 2. Checksum: 96F44F105B21BB52	FASTA	243	28,315
	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
	Isoform 2 [UniParc]. Checksum: 0F9FD0E1AEE4CA85	FASTA	176	20,426
	10 20 30 40 50 60 MRQYGECLHS CPSGYYGHRA PDMNRCARCR IENCDSCFSK DFCTKCKVGF YLHRGRCFDE 70 80 90 100 110 120 CPDGFAPLEE TMECVEGCEV GHWSEWGTCS RNNRTCGFKW GLETRTRQIV KKPVKDTILC 130 140 150 160 170 PTIAESRRCK MTMRHCPGGK RTPKAKEKRN KKKKRKLIER AQEQHSVFLA TDRANQ
	Isoform 3 [UniParc]. Checksum: 7C428C4A6C152798	FASTA	179	20,972
	10 20 30 40 50 60 MQFRLFSFAL IILNCMDYSH CQGNRWRRSK RGCRIENCDS CFSKDFCTKC KVGFYLHRGR 70 80 90 100 110 120 CFDECPDGFA PLEETMECVG CEVGHWSEWG TCSRNNRTCG FKWGLETRTR QIVKKPVKDT 130 140 150 160 170 ILCPTIAESR RCKMTMRHCP GGKRTPKAKE KRNKKKKRKL IERAQEQHSV FLATDRANQ

References

	« Hide 'large scale' referencesShow '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. , 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: 12975309] [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. , 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 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: 16421571] [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. , 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: 15489334] [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: 16357527] [Abstract] Cited for: INJECTION INTO MICE.
+	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.
IPI	IPI00167122. IPI00640775. IPI00747330.
RefSeq	NP_848660.3. NM_178565.4.
UniGene	Hs.444834.
3D structure databases
ProteinModelPortal	Q6UXX9.
SMR	Q6UXX9. Positions 39-205.
ModBase	Search...
Protein-protein interaction databases
STRING	Q6UXX9.
Polymorphism databases
DMDM	147744588.
Proteomic databases
PRIDE	Q6UXX9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000276659; ENSP00000276659; ENSG00000147655.
GeneID	340419.
KEGG	hsa:340419.
NMPDR	fig|9606.3.peg.30648.
UCSC	uc003ymq.1. human. uc003ymr.1. human.
Organism-specific databases
CTD	340419.
GeneCards	GC08M108981.
H-InvDB	HIX0007721.
HGNC	HGNC:28583. RSPO2.
HPA	CAB025900. HPA024764.
MIM	610575. gene.
neXtProt	NX_Q6UXX9.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18969.
GeneTree	ENSGT00390000011447.
HOGENOM	HBG715962.
HOVERGEN	HBG082751.
InParanoid	Q6UXX9.
OMA	HCPGGKR.
PhylomeDB	Q6UXX9.
Gene expression databases
ArrayExpress	Q6UXX9.
Bgee	Q6UXX9.
CleanEx	HS_RSPO2.
Genevestigator	Q6UXX9.
GermOnline	ENSG00000147655. Homo sapiens.
Family and domain databases
InterPro	IPR006212. Furin_repeat. IPR009030. Growth_fac_rcpt. IPR000884. Thrombospondin_1_rpt. [Graphical view]
SMART	SM00261. FU. 2 hits. SM00209. TSP1. 1 hit. [Graphical view]
SUPFAM	SSF57184. Grow_fac_recept. 1 hit. SSF82895. TSP1. 1 hit.
PROSITE	PS50092. TSP1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	97857.
SOURCE	Search...

Entry information

Entry name

RSPO2_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 61 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.