Q9C004 · SPY4_HUMAN
- ProteinProtein sprouty homolog 4
- GeneSPRY4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids299 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Suppresses the insulin receptor and EGFR-transduced MAPK signaling pathway, but does not inhibit MAPK activation by a constitutively active mutant Ras (PubMed:12027893).
Probably impairs the formation of GTP-Ras (PubMed:12027893).
Inhibits Ras-independent, but not Ras-dependent, activation of RAF1 (PubMed:12717443).
Represses integrin-mediated cell spreading via inhibition of TESK1-mediated phosphorylation of cofilin (PubMed:15584898).
Probably impairs the formation of GTP-Ras (PubMed:12027893).
Inhibits Ras-independent, but not Ras-dependent, activation of RAF1 (PubMed:12717443).
Represses integrin-mediated cell spreading via inhibition of TESK1-mediated phosphorylation of cofilin (PubMed:15584898).
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 | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | focal adhesion | |
Cellular Component | ruffle membrane | |
Molecular Function | protein kinase inhibitor activity | |
Biological Process | animal organ development | |
Biological Process | cellular response to leukemia inhibitory factor | |
Biological Process | negative regulation of fibroblast growth factor receptor signaling pathway | |
Biological Process | negative regulation of Ras protein signal transduction | |
Biological Process | negative regulation of substrate adhesion-dependent cell spreading |
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein sprouty homolog 4
- Short namesSpry-4
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9C004
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell projection, ruffle membrane ; Peripheral membrane protein
Note: Found in the cytoplasm in unstimulated cells but is translocated to the membrane ruffles in cells stimulated with EGF (epidermal growth factor) (By similarity).
Colocalizes with TESK1 in vesicular spots in the cytoplasm (PubMed:15584898).
Colocalizes with TESK1 in vesicular spots in the cytoplasm (PubMed:15584898).
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Hypogonadotropic hypogonadism 17 with or without anosmia (HH17)
- Note
- DescriptionA disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
- See alsoMIM:615266
Natural variants in HH17
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_069929 | 77 | T>M | in HH17; phenotype consistent with Kallmann syndrome; dbSNP:rs774674946 | |
VAR_069930 | 82 | D>N | in HH17; without anosmia; dbSNP:rs568363732 | |
VAR_069931 | 154 | K>R | in HH17; phenotype consistent with Kallmann syndrome; dbSNP:rs78310959 | |
VAR_069932 | 186 | C>Y | in HH17; phenotype consistent with Kallmann syndrome; dbSNP:rs148983803 | |
VAR_069933 | 218 | S>Y | in HH17; some patients have a second mutation in another HH-associated gene including DUSP6 and FGFR1; dbSNP:rs139512218 | |
VAR_069934 | 258 | V>M | in HH17; without anosmia; dbSNP:rs200364529 | |
VAR_069935 | 281 | V>I | in HH17; without anosmia; dbSNP:rs142439525 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_069929 | 77 | in HH17; phenotype consistent with Kallmann syndrome; dbSNP:rs774674946 | |||
Sequence: T → M | ||||||
Natural variant | VAR_069930 | 82 | in HH17; without anosmia; dbSNP:rs568363732 | |||
Sequence: D → N | ||||||
Natural variant | VAR_069931 | 154 | in HH17; phenotype consistent with Kallmann syndrome; dbSNP:rs78310959 | |||
Sequence: K → R | ||||||
Natural variant | VAR_069932 | 186 | in HH17; phenotype consistent with Kallmann syndrome; dbSNP:rs148983803 | |||
Sequence: C → Y | ||||||
Natural variant | VAR_069933 | 218 | in HH17; some patients have a second mutation in another HH-associated gene including DUSP6 and FGFR1; dbSNP:rs139512218 | |||
Sequence: S → Y | ||||||
Natural variant | VAR_069934 | 258 | in HH17; without anosmia; dbSNP:rs200364529 | |||
Sequence: V → M | ||||||
Natural variant | VAR_069935 | 281 | in HH17; without anosmia; dbSNP:rs142439525 | |||
Sequence: V → I |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 412 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 modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Modified residue | 1 | UniProt | N-acetylmethionine | ||||
Sequence: M | |||||||
Chain | PRO_0000076905 | 1-299 | UniProt | Protein sprouty homolog 4 | |||
Sequence: MEPPIPQSAPLTPNSVMVQPLLDSRMSHSRLQHPLTILPIDQVKTSHVENDYIDNPSLALTTGPKRTRGGAPELAPTPARCDQDVTHHWISFSGRPSSVSSSSSTSSDQRLLDHMAPPPVADQASPRAVRIQPKVVHCQPLDLKGPAVPPELDKHFLLCEACGKCKCKECASPRTLPSCWVCNQECLCSAQTLVNYGTCMCLVQGIFYHCTNEDDEGSCADHPCSCSRSNCCARWSFMGALSVVLPCLLCYLPATGCVKLAQRGYDRLRRPGCRCKHTNSVICKAASGDAKTSRPDKPF | |||||||
Modified residue (large scale data) | 8 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 12 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 15 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 52 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 77 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 97 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 98 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 125 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 125 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Interacts (via C-terminus) with TESK1 (via both C- and N-termini); the interaction inhibits TESK1 kinase activity (PubMed:12027893, PubMed:15584898).
Interacts with RAF1 (PubMed:12717443).
Interacts with CAV1 (via C-terminus) (By similarity).
Interacts with RAF1 (PubMed:12717443).
Interacts with CAV1 (via C-terminus) (By similarity).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 55-79 | Disordered | ||||
Sequence: NPSLALTTGPKRTRGGAPELAPTPA | ||||||
Compositional bias | 92-111 | Polar residues | ||||
Sequence: FSGRPSSVSSSSSTSSDQRL | ||||||
Region | 92-126 | Disordered | ||||
Sequence: FSGRPSSVSSSSSTSSDQRLLDHMAPPPVADQASP | ||||||
Domain | 166-273 | SPR | ||||
Sequence: KCKECASPRTLPSCWVCNQECLCSAQTLVNYGTCMCLVQGIFYHCTNEDDEGSCADHPCSCSRSNCCARWSFMGALSVVLPCLLCYLPATGCVKLAQRGYDRLRRPGC | ||||||
Region | 181-299 | Required for interaction with TESK1. Required for colocalization with TESK1 at vesicular spots in the cytoplasm and inhibition of TESK1 kinase activity, resulting in inhibition of cell spreading | ||||
Sequence: VCNQECLCSAQTLVNYGTCMCLVQGIFYHCTNEDDEGSCADHPCSCSRSNCCARWSFMGALSVVLPCLLCYLPATGCVKLAQRGYDRLRRPGCRCKHTNSVICKAASGDAKTSRPDKPF |
Domain
The Cys-rich domain is responsible for the localization of the protein to the membrane ruffles.
Sequence similarities
Belongs to the sprouty family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q9C004-1
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.
- NameA
- SynonymsSprouty-4A
- Length299
- Mass (Da)32,541
- Last updated2001-07-11 v2
- Checksum105F6F1BE9F7B6C3
Q9C004-2
- NameC
- SynonymsSprouty-4C
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
D6RB56 | D6RB56_HUMAN | SPRY4 | 50 | ||
A0A0C4DFS6 | A0A0C4DFS6_HUMAN | SPRY4 | 322 |
Sequence caution
Features
Showing features for compositional bias, alternative sequence, sequence conflict.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF227516 EMBL· GenBank· DDBJ | AAK00652.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AF227517 EMBL· GenBank· DDBJ | AAK00653.1 EMBL· GenBank· DDBJ | mRNA | ||
AY538661 EMBL· GenBank· DDBJ | AAS46253.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AK096464 EMBL· GenBank· DDBJ | BAC04798.1 EMBL· GenBank· DDBJ | mRNA | ||
AC091825 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC125095 EMBL· GenBank· DDBJ | AAI25096.1 EMBL· GenBank· DDBJ | mRNA | ||
BC125096 EMBL· GenBank· DDBJ | AAI25097.1 EMBL· GenBank· DDBJ | mRNA |