UniProtKB - O43597 (SPY2_HUMAN)
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Protein
Protein sprouty homolog 2
Gene
SPRY2
Organism
Homo sapiens (Human)
Status
Functioni
May function as an antagonist of fibroblast growth factor (FGF) pathways and may negatively modulate respiratory organogenesis.1 Publication
GO - Molecular functioni
- protein kinase binding Source: BHF-UCL
- protein serine/threonine kinase activator activity Source: UniProtKB
- protein serine/threonine kinase inhibitor activity Source: BHF-UCL
GO - Biological processi
- bud elongation involved in lung branching Source: Ensembl
- cell fate commitment Source: Ensembl
- establishment of mitotic spindle orientation Source: Ensembl
- inner ear morphogenesis Source: Ensembl
- lung growth Source: Ensembl
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of cell projection organization Source: BHF-UCL
- negative regulation of cell proliferation Source: Ensembl
- negative regulation of epidermal growth factor receptor signaling pathway Source: Reactome
- negative regulation of ERK1 and ERK2 cascade Source: BHF-UCL
- negative regulation of fibroblast growth factor receptor signaling pathway Source: Ensembl
- negative regulation of GTPase activity Source: Ensembl
- negative regulation of MAP kinase activity Source: Ensembl
- negative regulation of neurotrophin TRK receptor signaling pathway Source: Ensembl
- negative regulation of peptidyl-threonine phosphorylation Source: BHF-UCL
- negative regulation of Ras protein signal transduction Source: Ensembl
- positive regulation of cell migration Source: BHF-UCL
- positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
- positive regulation of gene expression Source: UniProtKB
- positive regulation of peptidyl-serine phosphorylation Source: UniProtKB
- positive regulation of protein kinase B signaling Source: UniProtKB
- regulation of cell differentiation Source: InterPro
- sensory perception of sound Source: Ensembl
Keywordsi
| Molecular function | Developmental protein |
Enzyme and pathway databases
| Reactomei | R-HSA-1295596. Spry regulation of FGF signaling. R-HSA-182971. EGFR downregulation. |
| SignaLinki | O43597. |
| SIGNORi | O43597. |
Names & Taxonomyi
| Protein namesi | Recommended name: Protein sprouty homolog 2Short name: Spry-2 |
| Gene namesi | Name:SPRY2 |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| HGNCi | HGNC:11270. SPRY2. |
Subcellular locationi
- Cytoplasm › cytoskeleton 1 Publication
- Cell projection › ruffle membrane 1 Publication
Note: Associated with microtubules in unstimulated cells but is translocated to the membrane ruffles in cells stimulated ith EGF (epidermal growth factor).
GO - Cellular componenti
- cytoskeleton Source: BHF-UCL
- cytosol Source: BHF-UCL
- membrane Source: BHF-UCL
- microtubule Source: UniProtKB-KW
- microtubule cytoskeleton Source: HPA
- nucleus Source: BHF-UCL
- plasma membrane Source: Reactome
- ruffle membrane Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, MicrotubulePathology & Biotechi
Involvement in diseasei
IgA nephropathy 3 (IGAN3)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA form of IgA nephropathy, a common primary glomerulonephritis characterized by glomerular sclerosis, interstitial fibrosis, and mesangial glomerular deposits of immunoglobulin A and immunoglobulin G visible on renal biopsies. IgA nephropathy is associated with renal insufficiency that can progress to end-stage renal disease. Proteinuria and hematuria are characteristic clinical presentations.
See also OMIM:616818| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_076288 | 119 | R → W in IGAN3; no effect on protein expression; negatively regulates ERK1 and ERK2 cascade. 1 PublicationCorresponds to variant dbSNP:rs869025336Ensembl. | 1 |
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 144 | P → L: Inhibits cleavage by the prolyl endopeptidase FAP. 1 Publication | 1 |
Keywords - Diseasei
Disease mutationOrganism-specific databases
| DisGeNETi | 10253. |
| MalaCardsi | SPRY2. |
| MIMi | 616818. phenotype. |
| OpenTargetsi | ENSG00000136158. |
| PharmGKBi | PA36099. |
Polymorphism and mutation databases
| BioMutai | SPRY2. |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000076901 | 1 – 315 | Protein sprouty homolog 2Add BLAST | 315 |
Post-translational modificationi
Cleaved at Pro-144 by the prolyl endopeptidase FAP (seprase) activity (in vitro).1 Publication
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sitei | 144 – 145 | Cleavage; by FAP1 Publication | 2 |
Proteomic databases
| EPDi | O43597. |
| PaxDbi | O43597. |
| PeptideAtlasi | O43597. |
| PRIDEi | O43597. |
PTM databases
| iPTMneti | O43597. |
| PhosphoSitePlusi | O43597. |
| SwissPalmi | O43597. |
Expressioni
Inductioni
By FGF signaling.
Gene expression databases
| Bgeei | ENSG00000136158. |
| CleanExi | HS_SPRY2. |
| Genevisiblei | O43597. HS. |
Organism-specific databases
| HPAi | CAB037205. HPA042198. |
Interactioni
Subunit structurei
Interacts with RAF1.1 Publication
Binary interactionsi
GO - Molecular functioni
- protein kinase binding Source: BHF-UCL
Protein-protein interaction databases
| BioGridi | 115547. 119 interactors. |
| IntActi | O43597. 82 interactors. |
| MINTi | MINT-2999467. |
| STRINGi | 9606.ENSP00000366306. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Turni | 43 – 45 | Combined sources | 3 |
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 3BUM | X-ray | 2.00 | A | 49-61 | [»] | |
| 3OB1 | X-ray | 2.20 | A | 49-60 | [»] | |
| 5HKY | X-ray | 1.80 | B | 36-60 | [»] | |
| 5HKZ | X-ray | 1.80 | B | 36-60 | [»] | |
| 5HL0 | X-ray | 2.20 | B | 54-60 | [»] | |
| ProteinModelPortali | O43597. | |||||
| SMRi | O43597. | |||||
| ModBasei | Search... | |||||
| MobiDBi | Search... | |||||
Miscellaneous databases
| EvolutionaryTracei | O43597. |
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 177 – 291 | SPRPROSITE-ProRule annotationAdd BLAST | 115 |
Compositional bias
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Compositional biasi | 125 – 131 | Poly-Ser | 7 | |
| Compositional biasi | 178 – 301 | Cys-richAdd BLAST | 124 |
Domaini
The Cys-rich domain is responsible for the localization of the protein to the membrane ruffles.1 Publication
Sequence similaritiesi
Belongs to the sprouty family.Curated
Phylogenomic databases
| eggNOGi | ENOG410IHQY. Eukaryota. ENOG4111S05. LUCA. |
| GeneTreei | ENSGT00390000003535. |
| HOVERGENi | HBG003544. |
| InParanoidi | O43597. |
| KOi | K17383. |
| OMAi | ECTYPRT. |
| PhylomeDBi | O43597. |
| TreeFami | TF325070. |
Family and domain databases
| InterProi | View protein in InterPro IPR007875. Sprouty. IPR030780. SPRY2. |
| PANTHERi | PTHR12365:SF14. PTHR12365:SF14. 1 hit. |
| Pfami | View protein in Pfam PF05210. Sprouty. 1 hit. |
| PROSITEi | View protein in PROSITE PS51227. SPR. 1 hit. |
Sequencei
Sequence statusi: Complete.
O43597-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MEARAQSGNG SQPLLQTPRD GGRQRGEPDP RDALTQQVHV LSLDQIRAIR
60 70 80 90 100
NTNEYTEGPT VVPRPGLKPA PRPSTQHKHE RLHGLPEHRQ PPRLQHSQVH
110 120 130 140 150
SSARAPLSRS ISTVSSGSRS STRTSTSSSS SEQRLLGSSF SSGPVADGII
160 170 180 190 200
RVQPKSELKP GELKPLSKED LGLHAYRCED CGKCKCKECT YPRPLPSDWI
210 220 230 240 250
CDKQCLCSAQ NVIDYGTCVC CVKGLFYHCS NDDEDNCADN PCSCSQSHCC
260 270 280 290 300
TRWSAMGVMS LFLPCLWCYL PAKGCLKLCQ GCYDRVNRPG CRCKNSNTVC
310
CKVPTVPPRN FEKPT
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 48 | A → V in BAG36546 (PubMed:14702039).Curated | 1 |
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_024647 | 106 | P → S. Corresponds to variant dbSNP:rs504122Ensembl. | 1 | |
| Natural variantiVAR_076288 | 119 | R → W in IGAN3; no effect on protein expression; negatively regulates ERK1 and ERK2 cascade. 1 PublicationCorresponds to variant dbSNP:rs869025336Ensembl. | 1 |
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF039843 mRNA. Translation: AAC04258.1. AL713749 mRNA. Translation: CAD28524.1. AK313810 mRNA. Translation: BAG36546.1. AL354668 Genomic DNA. No translation available. BC015745 mRNA. Translation: AAH15745.1. |
| CCDSi | CCDS9463.1. |
| RefSeqi | NP_001305465.1. NM_001318536.1. NP_001305466.1. NM_001318537.1. NP_001305467.1. NM_001318538.1. NP_005833.1. NM_005842.3. |
| UniGenei | Hs.18676. |
Genome annotation databases
| Ensembli | ENST00000377102; ENSP00000366306; ENSG00000136158. ENST00000377104; ENSP00000366308; ENSG00000136158. |
| GeneIDi | 10253. |
| KEGGi | hsa:10253. |
| UCSCi | uc001vli.4. human. |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:| 100% | UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry. |
| 90% | UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence). |
| 50% | UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster. |
Entry informationi
| Entry namei | SPY2_HUMAN | |
| Accessioni | O43597Primary (citable) accession number: O43597 Secondary accession number(s): B2R9J9, Q5T6Z7 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 21, 2001 |
| Last sequence update: | June 1, 1998 | |
| Last modified: | July 5, 2017 | |
| This is version 155 of the entry and version 1 of the sequence. See complete history. | ||
| Entry statusi | 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. | |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Reference proteomeDocuments
- Human chromosome 13
Human chromosome 13: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families
