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O43597 (SPY2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein sprouty homolog 2

Short name=Spry-2
Gene names
Name:SPRY2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length315 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May function as an antagonist of fibroblast growth factor (FGF) pathways and may negatively modulate respiratory organogenesis. Ref.6

Subunit structure

Interacts with RAF1. Ref.7

Subcellular location

Cytoplasmcytoskeleton. Cell projectionruffle membrane. Note: Associated with microtubules in unstimulated cells but is translocated to the membrane ruffles in cells stimulated ith EGF (epidermal growth factor). Ref.6

Induction

By FGF signaling.

Domain

The Cys-rich domain is responsible for the localization of the protein to the membrane ruffles. Ref.6

Sequence similarities

Belongs to the sprouty family.

Contains 1 SPR (sprouty) domain.

Ontologies

Keywords
   Cellular componentCell membrane
Cell projection
Cytoplasm
Cytoskeleton
Membrane
Microtubule
   Coding sequence diversityPolymorphism
   Molecular functionDevelopmental protein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbranching morphogenesis of an epithelial tube

Inferred from electronic annotation. Source: Ensembl

cell fate commitment

Inferred from electronic annotation. Source: Ensembl

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

inner ear morphogenesis

Inferred from electronic annotation. Source: Ensembl

lung growth

Inferred from electronic annotation. Source: Ensembl

lung morphogenesis

Inferred from electronic annotation. Source: Ensembl

negative regulation of ERK1 and ERK2 cascade

Inferred from electronic annotation. Source: Ensembl

negative regulation of MAP kinase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of Ras GTPase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of Ras protein signal transduction

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 18070883. Source: UniProtKB

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

negative regulation of fibroblast growth factor receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of neurotrophin TRK receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of peptidyl-threonine phosphorylation

Inferred from direct assay PubMed 20736167. Source: BHF-UCL

positive regulation of ERK1 and ERK2 cascade

Inferred from mutant phenotype PubMed 18070883. Source: UniProtKB

positive regulation of gene expression

Inferred from mutant phenotype PubMed 18070883. Source: UniProtKB

positive regulation of peptidyl-serine phosphorylation

Inferred from mutant phenotype PubMed 18070883. Source: UniProtKB

positive regulation of protein kinase B signaling

Inferred from mutant phenotype PubMed 18070883. Source: UniProtKB

positive regulation of protein serine/threonine kinase activity

Inferred from mutant phenotype PubMed 18070883. Source: GOC

sensory perception of sound

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

microtubule

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Traceable author statement. Source: Reactome

ruffle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 21784977. Source: UniProtKB

protein kinase binding

Inferred from physical interaction PubMed 20736167. Source: BHF-UCL

protein serine/threonine kinase activator activity

Inferred from mutant phenotype PubMed 18070883. Source: UniProtKB

protein serine/threonine kinase inhibitor activity

Inferred by curator PubMed 20736167. Source: BHF-UCL

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 315315Protein sprouty homolog 2
PRO_0000076901

Regions

Domain177 – 291115SPR
Compositional bias125 – 1317Poly-Ser
Compositional bias178 – 301124Cys-rich

Natural variations

Natural variant1061P → S.
Corresponds to variant rs504122 [ dbSNP | Ensembl ].
VAR_024647

Experimental info

Sequence conflict481A → V in BAG36546. Ref.2

Sequences

Sequence LengthMass (Da)Tools
O43597 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: 8CC6256929D91A7E

FASTA31534,688
        10         20         30         40         50         60 
MEARAQSGNG SQPLLQTPRD GGRQRGEPDP RDALTQQVHV LSLDQIRAIR NTNEYTEGPT 

        70         80         90        100        110        120 
VVPRPGLKPA PRPSTQHKHE RLHGLPEHRQ PPRLQHSQVH SSARAPLSRS ISTVSSGSRS 

       130        140        150        160        170        180 
STRTSTSSSS SEQRLLGSSF SSGPVADGII RVQPKSELKP GELKPLSKED LGLHAYRCED 

       190        200        210        220        230        240 
CGKCKCKECT YPRPLPSDWI CDKQCLCSAQ NVIDYGTCVC CVKGLFYHCS NDDEDNCADN 

       250        260        270        280        290        300 
PCSCSQSHCC TRWSAMGVMS LFLPCLWCYL PAKGCLKLCQ GCYDRVNRPG CRCKNSNTVC 

       310 
CKVPTVPPRN FEKPT 

« Hide

References

« Hide 'large scale' references
[1]"Sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways."
Hacohen N., Kramer S., Sutherland D., Hiromi Y., Krasnow M.A.
Cell 92:253-263(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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. expand/collapse author list , 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].
Tissue: Substantia nigra.
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[4]"The DNA sequence and analysis of human chromosome 13."
Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.
Nature 428:522-528(2004) [PubMed] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skin.
[6]"Sprouty proteins are targeted to membrane ruffles upon growth factor receptor tyrosine kinase activation. Identification of a novel translocation domain."
Lim J., Wong E.S.M., Ong S.H., Yusoff P., Low B.C., Guy G.R.
J. Biol. Chem. 275:32837-32845(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, DOMAIN.
[7]"Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1."
Sasaki A., Taketomi T., Kato R., Saeki K., Nonami A., Sasaki M., Kuriyama M., Saito N., Shibuya M., Yoshimura A.
Nat. Cell Biol. 5:427-432(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAF1.
[8]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF039843 mRNA. Translation: AAC04258.1.
AL713749 mRNA. Translation: CAD28524.1.
AK313810 mRNA. Translation: BAG36546.1.
AL354668 Genomic DNA. Translation: CAI14911.1.
BC015745 mRNA. Translation: AAH15745.1.
CCDSCCDS9463.1.
RefSeqNP_005833.1. NM_005842.2.
XP_005266274.1. XM_005266217.1.
XP_006719815.1. XM_006719752.1.
XP_006719816.1. XM_006719753.1.
UniGeneHs.18676.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3BUMX-ray2.00A49-61[»]
3OB1X-ray2.20A49-60[»]
ProteinModelPortalO43597.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115547. 52 interactions.
IntActO43597. 28 interactions.
MINTMINT-2999467.
STRING9606.ENSP00000366306.

PTM databases

PhosphoSiteO43597.

Proteomic databases

PaxDbO43597.
PRIDEO43597.

Protocols and materials databases

DNASU10253.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000377102; ENSP00000366306; ENSG00000136158.
ENST00000377104; ENSP00000366308; ENSG00000136158.
ENST00000540649; ENSP00000439027; ENSG00000136158.
GeneID10253.
KEGGhsa:10253.
UCSCuc001vli.3. human.

Organism-specific databases

CTD10253.
GeneCardsGC13M080910.
HGNCHGNC:11270. SPRY2.
HPACAB037205.
MIM602466. gene.
neXtProtNX_O43597.
PharmGKBPA36099.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG83905.
HOVERGENHBG003544.
InParanoidO43597.
KOK17383.
OMAPHGEPDL.
OrthoDBEOG7G4QDV.
PhylomeDBO43597.
TreeFamTF325070.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
SignaLinkO43597.

Gene expression databases

BgeeO43597.
CleanExHS_SPRY2.
GenevestigatorO43597.

Family and domain databases

InterProIPR007875. Sprouty.
[Graphical view]
PfamPF05210. Sprouty. 1 hit.
[Graphical view]
PROSITEPS51227. SPR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO43597.
GeneWikiSPRY2.
GenomeRNAi10253.
NextBio35467891.
PROO43597.
SOURCESearch...

Entry information

Entry nameSPY2_HUMAN
AccessionPrimary (citable) accession number: O43597
Secondary accession number(s): B2R9J9, Q5T6Z7
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: June 1, 1998
Last modified: July 9, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 13

Human chromosome 13: entries, gene names and cross-references to MIM