Q7Z698 · SPRE2_HUMAN
- ProteinSprouty-related, EVH1 domain-containing protein 2
- GeneSPRED2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids418 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Negatively regulates Ras signaling pathways and downstream activation of MAP kinases (PubMed:15683364, PubMed:34626534).
Recruits and translocates NF1 to the cell membrane, thereby enabling NF1-dependent hydrolysis of active GTP-bound Ras to inactive GDP-bound Ras (PubMed:34626534).
Inhibits fibroblast growth factor (FGF)-induced retinal lens fiber differentiation, probably by inhibiting FGF-mediated phosphorylation of ERK1/2 (By similarity).
Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens epithelial cells (By similarity).
Recruits and translocates NF1 to the cell membrane, thereby enabling NF1-dependent hydrolysis of active GTP-bound Ras to inactive GDP-bound Ras (PubMed:34626534).
Inhibits fibroblast growth factor (FGF)-induced retinal lens fiber differentiation, probably by inhibiting FGF-mediated phosphorylation of ERK1/2 (By similarity).
Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens epithelial cells (By similarity).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | plasma membrane | |
Cellular Component | transport vesicle membrane | |
Molecular Function | protein kinase binding | |
Molecular Function | protein serine/threonine kinase inhibitor activity | |
Molecular Function | stem cell factor receptor binding | |
Biological Process | negative regulation of epithelial to mesenchymal transition | |
Biological Process | negative regulation of ERK1 and ERK2 cascade | |
Biological Process | negative regulation of lens fiber cell differentiation | |
Biological Process | negative regulation of MAPK cascade | |
Biological Process | negative regulation of peptidyl-threonine phosphorylation | |
Biological Process | negative regulation of transforming growth factor beta receptor signaling pathway | |
Biological Process | positive regulation of DNA damage response, signal transduction by p53 class mediator | |
Biological Process | regulation of protein deacetylation |
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSprouty-related, EVH1 domain-containing protein 2
- Short namesSpred-2
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ7Z698
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Peripheral membrane protein
Cytoplasmic vesicle, secretory vesicle membrane ; Peripheral membrane protein
Note: Detected in the cytoplasm of the stratum spinosum cells, where it is associated with cytoplasmic vesicles that are supposed to be secretory granules.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Noonan syndrome 14 (NS14)
- Note
- DescriptionA form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. NS14 inheritance is autosomal recessive.
- See alsoMIM:619745
Natural variants in NS14
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_086929 | 63-418 | missing | in NS14; results in loss of MAPK down-regulation; increased protein degradation | |
VAR_086930 | 100 | L>P | in NS14; results in loss of MAPK down-regulation; increased protein degradation; properly targeted to the cell membrane; loss of interaction with NF1; dbSNP:rs2104216988 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_086929 | 63-418 | in NS14; results in loss of MAPK down-regulation; increased protein degradation | |||
Sequence: Missing | ||||||
Natural variant | VAR_086930 | 100 | in NS14; results in loss of MAPK down-regulation; increased protein degradation; properly targeted to the cell membrane; loss of interaction with NF1; dbSNP:rs2104216988 | |||
Sequence: L → P | ||||||
Mutagenesis | 228 | Reduces ubiquitination and CBL-induced phosphorylation; when associated with F-231. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 231 | Reduces ubiquitination and CBL-induced phosphorylation; when associated with F-228. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 240 | No effect on phosphorylation or ubiquitination. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 251 | No effect on phosphorylation or ubiquitination. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 264 | No effect on phosphorylation or ubiquitination; when associated with F-266. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 266 | No effect on phosphorylation or ubiquitination; when associated with F-264. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 268 | No effect on phosphorylation or ubiquitination. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 311 | No effect on phosphorylation or ubiquitination. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 351 | No effect on phosphorylation or ubiquitination. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 394 | No effect on phosphorylation or ubiquitination. | ||||
Sequence: Y → F |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 536 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000076910 | 1-418 | UniProt | Sprouty-related, EVH1 domain-containing protein 2 | |||
Sequence: MTEETHPDDDSYIVRVKAVVMTRDDSSGGWFPQEGGGISRVGVCKVMHPEGNGRSGFLIHGERQKDKLVVLECYVRKDLVYTKANPTFHHWKVDNRKFGLTFQSPADARAFDRGVRKAIEDLIEGSTTSSSTIHNEAELGDDDVFTTATDSSSNSSQKREQPTRTISSPTSCEHRRIYTLGHLHDSYPTDHYHLDQPMPRPYRQVSFPDDDEEIVRINPREKIWMTGYEDYRHAPVRGKYPDPSEDADSSYVRFAKGEVPKHDYNYPYVDSSDFGLGEDPKGRGGSVIKTQPSRGKSRRRKEDGERSRCVYCRDMFNHEENRRGHCQDAPDSVRTCIRRVSCMWCADSMLYHCMSDPEGDYTDPCSCDTSDEKFCLRWMALIALSFLAPCMCCYLPLRACYHCGVMCRCCGGKHKAAA | |||||||
Modified residue (large scale data) | 104 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 167 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 168 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 206 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 206 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 228 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 228 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 231 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 264 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 268 | PRIDE | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
Phosphorylated on serine and threonine residues (PubMed:15683364).
Phosphorylated on tyrosine. Phosphorylation of Tyr-228 and Tyr-231 are required for ubiquitination (PubMed:17094949).
Phosphorylated on tyrosine. Phosphorylation of Tyr-228 and Tyr-231 are required for ubiquitination (PubMed:17094949).
Ubiquitinated; leading to degradation by the proteasome.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in liver, skin, small intestine, salivary gland and prostate.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimer and heterodimer (PubMed:15683364).
Able to interact with SPRED1 to form heterodimers (PubMed:15683364).
Interacts with RAS (By similarity).
May interact with ZDHHC13 (via ANK repeats) and ZDHHC17 (via ANK repeats) (By similarity).
Interacts with TESK1 (By similarity).
Interacts with NF1 (PubMed:34626534).
Able to interact with SPRED1 to form heterodimers (PubMed:15683364).
Interacts with RAS (By similarity).
May interact with ZDHHC13 (via ANK repeats) and ZDHHC17 (via ANK repeats) (By similarity).
Interacts with TESK1 (By similarity).
Interacts with NF1 (PubMed:34626534).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 5-122 | WH1 | ||||
Sequence: THPDDDSYIVRVKAVVMTRDDSSGGWFPQEGGGISRVGVCKVMHPEGNGRSGFLIHGERQKDKLVVLECYVRKDLVYTKANPTFHHWKVDNRKFGLTFQSPADARAFDRGVRKAIEDL | ||||||
Region | 127-171 | Disordered | ||||
Sequence: TTSSSTIHNEAELGDDDVFTTATDSSSNSSQKREQPTRTISSPTS | ||||||
Compositional bias | 145-171 | Polar residues | ||||
Sequence: FTTATDSSSNSSQKREQPTRTISSPTS | ||||||
Domain | 201-257 | KBD | ||||
Sequence: PYRQVSFPDDDEEIVRINPREKIWMTGYEDYRHAPVRGKYPDPSEDADSSYVRFAKG | ||||||
Region | 275-302 | Disordered | ||||
Sequence: GLGEDPKGRGGSVIKTQPSRGKSRRRKE | ||||||
Domain | 308-416 | SPR | ||||
Sequence: RCVYCRDMFNHEENRRGHCQDAPDSVRTCIRRVSCMWCADSMLYHCMSDPEGDYTDPCSCDTSDEKFCLRWMALIALSFLAPCMCCYLPLRACYHCGVMCRCCGGKHKA |
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q7Z698-1
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.
- Name1
- Length418
- Mass (Da)47,558
- Last updated2006-07-25 v2
- ChecksumCA4FE80C45008851
Q7Z698-2
- Name2
- Differences from canonical
- 1-9: MTEETHPDD → MASPGS
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Features
Showing features for alternative sequence, sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_043755 | 1-9 | in isoform 2 | |||
Sequence: MTEETHPDD → MASPGS | ||||||
Sequence conflict | 33 | in Ref. 2; BAH12943 | ||||
Sequence: Q → R | ||||||
Compositional bias | 145-171 | Polar residues | ||||
Sequence: FTTATDSSSNSSQKREQPTRTISSPTS | ||||||
Sequence conflict | 202 | in Ref. 1; AAP59415 | ||||
Sequence: Y → C |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY299090 EMBL· GenBank· DDBJ | AAP59415.1 EMBL· GenBank· DDBJ | mRNA | ||
AK299079 EMBL· GenBank· DDBJ | BAH12943.1 EMBL· GenBank· DDBJ | mRNA | ||
AC012370 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC097503 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471053 EMBL· GenBank· DDBJ | EAW99905.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAW99906.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC111495 EMBL· GenBank· DDBJ | AAI11496.1 EMBL· GenBank· DDBJ | mRNA | ||
BC130292 EMBL· GenBank· DDBJ | AAI30293.1 EMBL· GenBank· DDBJ | mRNA | ||
BC136334 EMBL· GenBank· DDBJ | AAI36335.1 EMBL· GenBank· DDBJ | mRNA |