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Protein

Protein sprouty homolog 2

Gene

SPRY2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

Keywordsi

Molecular functionDevelopmental protein

Enzyme and pathway databases

ReactomeiR-HSA-1295596 Spry regulation of FGF signaling
R-HSA-182971 EGFR downregulation
SignaLinkiO43597
SIGNORiO43597

Names & Taxonomyi

Protein namesi
Recommended name:
Protein sprouty homolog 2
Short name:
Spry-2
Gene namesi
Name:SPRY2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

EuPathDBiHostDB:ENSG00000136158.10
HGNCiHGNC:11270 SPRY2
MIMi602466 gene
neXtProtiNX_O43597

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Microtubule

Pathology & 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 keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_076288119R → W in IGAN3; no effect on protein expression; negatively regulates ERK1 and ERK2 cascade. 1 PublicationCorresponds to variant dbSNP:rs869025336EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi144P → L: Inhibits cleavage by the prolyl endopeptidase FAP. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi10253
MalaCardsiSPRY2
MIMi616818 phenotype
OpenTargetsiENSG00000136158
PharmGKBiPA36099

Polymorphism and mutation databases

BioMutaiSPRY2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000769011 – 315Protein sprouty homolog 2Add BLAST315

Post-translational modificationi

Cleaved at Pro-144 by the prolyl endopeptidase FAP (seprase) activity (in vitro).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei144 – 145Cleavage; by FAP1 Publication2

Proteomic databases

EPDiO43597
PaxDbiO43597
PeptideAtlasiO43597
PRIDEiO43597
ProteomicsDBi49069

PTM databases

iPTMnetiO43597
PhosphoSitePlusiO43597
SwissPalmiO43597

Expressioni

Inductioni

By FGF signaling.

Gene expression databases

BgeeiENSG00000136158 Expressed in 224 organ(s), highest expression level in cerebellum
CleanExiHS_SPRY2
GenevisibleiO43597 HS

Organism-specific databases

HPAiCAB037205
HPA042198

Interactioni

Subunit structurei

Interacts with RAF1 (PubMed:12717443). Part of a tripartite complex containing GAB1, METTL13 and SPRY2 (PubMed:29408807). Interacts with METTL13 (PubMed:29408807).2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Q5JPT63EBI-742487,EBI-10244213
AQP1P299723EBI-742487,EBI-745213
ATRIPQ8WXE13EBI-742487,EBI-747353
CATSPER1Q8NEC53EBI-742487,EBI-744545
CBLP2268117EBI-742487,EBI-518228
CHRDQ9H2X03EBI-742487,EBI-947551
CHRNGP07510-23EBI-742487,EBI-11979451
CREB5Q02930-33EBI-742487,EBI-10192698
EIF4E2O605733EBI-742487,EBI-398610
FAIMQ9NVQ43EBI-742487,EBI-10314711
FRS3O435593EBI-742487,EBI-725515
GNEQ9Y2233EBI-742487,EBI-4291090
GP9P147703EBI-742487,EBI-1754109
GRAP2O757913EBI-742487,EBI-740418
GRB2P629933EBI-742487,EBI-401755
GRNP287993EBI-742487,EBI-747754
HEXIM2Q96MH23EBI-742487,EBI-5460660
HSD3B7Q9H2F33EBI-742487,EBI-3918847
KRTAP10-11P604123EBI-742487,EBI-10217483
KRTAP10-5P603703EBI-742487,EBI-10172150
KRTAP10-8P604103EBI-742487,EBI-10171774
KRTAP10-9P604113EBI-742487,EBI-10172052
KRTAP4-11Q9BYQ63EBI-742487,EBI-10302392
KRTAP4-12Q9BQ664EBI-742487,EBI-739863
KRTAP4-7Q9BYR03EBI-742487,EBI-10302547
KRTAP5-6Q6L8G93EBI-742487,EBI-10250562
KRTAP5-9P263713EBI-742487,EBI-3958099
KRTAP9-2Q9BYQ43EBI-742487,EBI-1044640
KRTAP9-4Q9BYQ23EBI-742487,EBI-10185730
LASP1Q148473EBI-742487,EBI-742828
LCE1BQ5T7P33EBI-742487,EBI-10245913
LCE2DQ5TA823EBI-742487,EBI-10246750
LCE3CQ5T5A83EBI-742487,EBI-10245291
LCE3EQ5T5B03EBI-742487,EBI-10245456
LCE4AQ5TA783EBI-742487,EBI-10246358
LONRF1Q17RB83EBI-742487,EBI-2341787
MAPKBP1O603363EBI-742487,EBI-947402
MDFIQ997503EBI-742487,EBI-724076
MEOX2P502223EBI-742487,EBI-748397
MID2Q9UJV3-23EBI-742487,EBI-10172526
MLLT6Q6P2C63EBI-742487,EBI-5773143
NCK2O436393EBI-742487,EBI-713635
OTX1P322424EBI-742487,EBI-740446
PACSIN3Q9UKS63EBI-742487,EBI-77926
PRKAB2O437413EBI-742487,EBI-1053424
PTGER3P43115-123EBI-742487,EBI-10234038
RUNX1T1Q06455-43EBI-742487,EBI-10224192
RYDENQ9NUL53EBI-742487,EBI-10313866
SH3KBP1Q96B972EBI-742487,EBI-346595
SPRY1O436093EBI-742487,EBI-3866665
STK16O757163EBI-742487,EBI-749295
TCAF1Q9Y4C23EBI-742487,EBI-750484
TXNDC5Q86UY03EBI-742487,EBI-2825190
UBASH3AP570754EBI-742487,EBI-2105393
UBASH3BQ8TF423EBI-742487,EBI-1380492
USP20Q9Y2K63EBI-742487,EBI-2511991
ZDHHC17Q8IUH53EBI-742487,EBI-524753
ZNF417Q8TAU33EBI-742487,EBI-740727
ZNF587Q96SQ53EBI-742487,EBI-6427977

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115547, 129 interactors
IntActiO43597, 82 interactors
MINTiO43597
STRINGi9606.ENSP00000366306

Structurei

Secondary structure

1315
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO43597
SMRiO43597
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43597

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini177 – 291SPRPROSITE-ProRule annotationAdd BLAST115

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi125 – 131Poly-Ser7
Compositional biasi178 – 301Cys-richAdd BLAST124

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

eggNOGiENOG410IHQY Eukaryota
ENOG4111S05 LUCA
GeneTreeiENSGT00390000003535
HOVERGENiHBG003544
InParanoidiO43597
KOiK17383
OMAiECTYPRT
PhylomeDBiO43597
TreeFamiTF325070

Family and domain databases

InterProiView protein in InterPro
IPR007875 Sprouty
IPR030780 SPRY2
PANTHERiPTHR12365:SF8 PTHR12365:SF8, 1 hit
PfamiView protein in Pfam
PF05210 Sprouty, 1 hit
PROSITEiView protein in PROSITE
PS51227 SPR, 1 hit

Sequencei

Sequence statusi: Complete.

O43597-1 [UniParc]FASTAAdd to basket
« Hide
        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
Length:315
Mass (Da):34,688
Last modified:June 1, 1998 - v1
Checksum:i8CC6256929D91A7E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti48A → V in BAG36546 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_024647106P → S. Corresponds to variant dbSNP:rs504122Ensembl.1
Natural variantiVAR_076288119R → W in IGAN3; no effect on protein expression; negatively regulates ERK1 and ERK2 cascade. 1 PublicationCorresponds to variant dbSNP:rs869025336EnsemblClinVar.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
CCDSiCCDS9463.1
RefSeqiNP_001305465.1, NM_001318536.1
NP_001305466.1, NM_001318537.1
NP_001305467.1, NM_001318538.1
NP_005833.1, NM_005842.3
UniGeneiHs.18676

Genome annotation databases

EnsembliENST00000377102; ENSP00000366306; ENSG00000136158
ENST00000377104; ENSP00000366308; ENSG00000136158
GeneIDi10253
KEGGihsa:10253
UCSCiuc001vli.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

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
CCDSiCCDS9463.1
RefSeqiNP_001305465.1, NM_001318536.1
NP_001305466.1, NM_001318537.1
NP_001305467.1, NM_001318538.1
NP_005833.1, NM_005842.3
UniGeneiHs.18676

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BUMX-ray2.00A49-61[»]
3OB1X-ray2.20A49-60[»]
5HKYX-ray1.80B36-60[»]
5HKZX-ray1.80B36-60[»]
5HL0X-ray2.20B54-60[»]
ProteinModelPortaliO43597
SMRiO43597
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115547, 129 interactors
IntActiO43597, 82 interactors
MINTiO43597
STRINGi9606.ENSP00000366306

PTM databases

iPTMnetiO43597
PhosphoSitePlusiO43597
SwissPalmiO43597

Polymorphism and mutation databases

BioMutaiSPRY2

Proteomic databases

EPDiO43597
PaxDbiO43597
PeptideAtlasiO43597
PRIDEiO43597
ProteomicsDBi49069

Protocols and materials databases

DNASUi10253
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000377102; ENSP00000366306; ENSG00000136158
ENST00000377104; ENSP00000366308; ENSG00000136158
GeneIDi10253
KEGGihsa:10253
UCSCiuc001vli.4 human

Organism-specific databases

CTDi10253
DisGeNETi10253
EuPathDBiHostDB:ENSG00000136158.10
GeneCardsiSPRY2
HGNCiHGNC:11270 SPRY2
HPAiCAB037205
HPA042198
MalaCardsiSPRY2
MIMi602466 gene
616818 phenotype
neXtProtiNX_O43597
OpenTargetsiENSG00000136158
PharmGKBiPA36099
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IHQY Eukaryota
ENOG4111S05 LUCA
GeneTreeiENSGT00390000003535
HOVERGENiHBG003544
InParanoidiO43597
KOiK17383
OMAiECTYPRT
PhylomeDBiO43597
TreeFamiTF325070

Enzyme and pathway databases

ReactomeiR-HSA-1295596 Spry regulation of FGF signaling
R-HSA-182971 EGFR downregulation
SignaLinkiO43597
SIGNORiO43597

Miscellaneous databases

ChiTaRSiSPRY2 human
EvolutionaryTraceiO43597
GeneWikiiSPRY2
GenomeRNAii10253
PROiPR:O43597
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136158 Expressed in 224 organ(s), highest expression level in cerebellum
CleanExiHS_SPRY2
GenevisibleiO43597 HS

Family and domain databases

InterProiView protein in InterPro
IPR007875 Sprouty
IPR030780 SPRY2
PANTHERiPTHR12365:SF8 PTHR12365:SF8, 1 hit
PfamiView protein in Pfam
PF05210 Sprouty, 1 hit
PROSITEiView protein in PROSITE
PS51227 SPR, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSPY2_HUMAN
AccessioniPrimary (citable) accession number: O43597
Secondary accession number(s): B2R9J9, Q5T6Z7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: June 1, 1998
Last modified: November 7, 2018
This is version 167 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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