O43597 (SPY2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein sprouty homolog 2
Short name=Spry-2

Gene names

Name:

SPRY2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	315 AA.
Sequence status	Complete.
Protein existence	Evidence 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.5
Subunit structure	Interacts with RAF1. Ref.6
Subcellular location	Cytoplasm › cytoskeleton. Cell projection › ruffle membrane. Note: Associated with microtubules in unstimulated cells but is translocated to the membrane ruffles in cells stimulated ith EGF (epidermal growth factor). Ref.5
Induction	By FGF signaling.
Domain	The Cys-rich domain is responsible for the localization of the protein to the membrane ruffles. Ref.5
Sequence similarities	Belongs to the sprouty family. Contains 1 SPR (sprouty) domain.

Ontologies

Keywords
Cellular component	Cell membrane Cell projection Cytoplasm Cytoskeleton Membrane Microtubule
Coding sequence diversity	Polymorphism
Molecular function	Developmental protein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	branching morphogenesis of an epithelial tube Inferred from electronic annotation. Source: Compara cell fate commitment Inferred from electronic annotation. Source: Compara 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: Compara lung growth Inferred from electronic annotation. Source: Compara lung morphogenesis Inferred from electronic annotation. Source: Compara negative regulation of ERK1 and ERK2 cascade Inferred from electronic annotation. Source: Compara negative regulation of MAP kinase activity Inferred from electronic annotation. Source: Compara negative regulation of Ras GTPase activity Inferred from electronic annotation. Source: Compara negative regulation of Ras protein signal transduction Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from mutant phenotype PubMed 18070883. Source: UniProtKB negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara 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: Compara negative regulation of nerve growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara 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 cascade Inferred from mutant phenotype PubMed 18070883. Source: UniProtKB sensory perception of sound Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol 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_function	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...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 315	315	Protein sprouty homolog 2		PRO_0000076901
Regions
	Domain	177 – 291	115	SPR
	Compositional bias	125 – 131	7	Poly-Ser
	Compositional bias	178 – 301	124	Cys-rich
Natural variations
	Natural variant	106	1	P → S. Corresponds to variant rs504122 [ dbSNP | Ensembl ].		VAR_024647

Sequences

	Sequence		Length	Mass (Da)
	O43597 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 8CC6256929D91A7E	FASTA	315	34,688
	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

References

	« Hide 'large scale' referencesShow '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]	"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.
[3]	"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. , 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].
[4]	"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.
[5]	"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.
[6]	"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.
[7]	"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.
AL354668 Genomic DNA. Translation: CAI14911.1.
BC015745 mRNA. Translation: AAH15745.1.

IPI

IPI01014320.

RefSeq

NP_005833.1. NM_005842.2.

UniGene

Hs.18676.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3BUM	X-ray	2.00	A	49-61	[»]
3OB1	X-ray	2.20	A	49-60	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O43597. 7 interactions.

MINT

MINT-2999467.

STRING

9606.ENSP00000366306.

PTM databases

PhosphoSite

O43597.

Proteomic databases

PaxDb

O43597.

PRIDE

O43597.

Protocols and materials databases

DNASU

10253.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000377102; ENSP00000366306; ENSG00000136158.
ENST00000377104; ENSP00000366308; ENSG00000136158.
ENST00000540649; ENSP00000439027; ENSG00000136158.

GeneID

10253.

KEGG

hsa:10253.

UCSC

uc001vli.3. human.

Organism-specific databases

CTD

10253.

GeneCards

GC13M080910.

HGNC

HGNC:11270. SPRY2.

HPA

CAB037205.

MIM

602466. gene.

neXtProt

NX_O43597.

PharmGKB

PA36099.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG83905.

HOVERGEN

HBG003544.

InParanoid

O43597.

KO

K04704.

OrthoDB

EOG43TZW1.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_116125. Disease.

Gene expression databases

Bgee

O43597.

CleanEx

HS_SPRY2.

Genevestigator

O43597.

GermOnline

ENSG00000136158. Homo sapiens.

Family and domain databases

InterPro

IPR007875. Sprouty.
[Graphical view]

Pfam

PF05210. Sprouty. 1 hit.
[Graphical view]

PROSITE

PS51227. SPR. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O43597.

GenomeRNAi

10253.

NextBio

38852.

SOURCE

Search...

Entry information

Entry name

SPY2_HUMAN

Accession

Primary (citable) accession number: O43597
Secondary accession number(s): Q5T6Z7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	June 1, 1998
Last modified:	May 1, 2013
This is version 112 of the entry and version 1 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.