UniProtKB - Q9C004 (SPY4_HUMAN)
Protein
Protein sprouty homolog 4
Gene
SPRY4
Organism
Homo sapiens (Human)
Status
Functioni
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).3 Publications
GO - Molecular functioni
- protein kinase inhibitor activity Source: UniProtKB
GO - Biological processi
- animal organ development Source: GO_Central
- negative regulation of ERK1 and ERK2 cascade Source: InterPro
- negative regulation of fibroblast growth factor receptor signaling pathway Source: GO_Central
- negative regulation of MAP kinase activity Source: GO_Central
- negative regulation of Ras protein signal transduction Source: GO_Central
- negative regulation of substrate adhesion-dependent cell spreading Source: UniProtKB
Keywordsi
Molecular function | Developmental protein |
Enzyme and pathway databases
PathwayCommonsi | Q9C004 |
SignaLinki | Q9C004 |
SIGNORi | Q9C004 |
Names & Taxonomyi
Protein namesi | Recommended name: Protein sprouty homolog 4Short name: Spry-4 |
Gene namesi | Name:SPRY4 |
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:15533, SPRY4 |
MIMi | 607984, gene |
neXtProti | NX_Q9C004 |
VEuPathDBi | HostDB:ENSG00000187678.8 |
Subcellular locationi
Plasma membrane
- ruffle membrane Curated; Peripheral membrane protein Curated; Cytoplasmic side Curated
Other locations
- Cytoplasm 2 Publications
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).By similarity1 Publication
Cytosol
- cytosol Source: GO_Central
Plasma Membrane
- ruffle membrane Source: UniProtKB-SubCell
Other locations
- cytoplasm Source: UniProtKB
- focal adhesion Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cell projection, Cytoplasm, MembranePathology & Biotechi
Involvement in diseasei
Hypogonadotropic hypogonadism 17 with or without anosmia (HH17)1 Publication
The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in SPRY4 also have a heterozygous mutation in another HH-associated gene including DUSP6 and FGFR1 (PubMed:23643382).1 Publication
Disease 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).
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_069929 | 77 | T → M in HH17; phenotype consistent with Kallmann syndrome. 1 PublicationCorresponds to variant dbSNP:rs774674946Ensembl. | 1 | |
Natural variantiVAR_069930 | 82 | D → N in HH17; without anosmia. 1 PublicationCorresponds to variant dbSNP:rs568363732Ensembl. | 1 | |
Natural variantiVAR_069931 | 154 | K → R in HH17; phenotype consistent with Kallmann syndrome. 1 PublicationCorresponds to variant dbSNP:rs78310959Ensembl. | 1 | |
Natural variantiVAR_069932 | 186 | C → Y in HH17; phenotype consistent with Kallmann syndrome. 1 PublicationCorresponds to variant dbSNP:rs148983803Ensembl. | 1 | |
Natural variantiVAR_069933 | 218 | S → Y in HH17; rare variant associated with susceptibility to disease; some patients have a second mutation in another HH-associated gene including DUSP6 and FGFR1. 1 PublicationCorresponds to variant dbSNP:rs139512218EnsemblClinVar. | 1 | |
Natural variantiVAR_069934 | 258 | V → M in HH17; without anosmia. 1 PublicationCorresponds to variant dbSNP:rs200364529Ensembl. | 1 | |
Natural variantiVAR_069935 | 281 | V → I in HH17; without anosmia. 1 PublicationCorresponds to variant dbSNP:rs142439525Ensembl. | 1 |
Keywords - Diseasei
Disease variant, Hypogonadotropic hypogonadism, Kallmann syndromeOrganism-specific databases
DisGeNETi | 81848 |
GeneReviewsi | SPRY4 |
MalaCardsi | SPRY4 |
MIMi | 615266, phenotype |
OpenTargetsi | ENSG00000187678 |
Orphaneti | 478, Kallmann syndrome 363494, Non-seminomatous germ cell tumor of testis 432, Normosmic congenital hypogonadotropic hypogonadism |
PharmGKBi | PA37975 |
Miscellaneous databases
Pharosi | Q9C004, Tbio |
Genetic variation databases
BioMutai | SPRY4 |
DMDMi | 14916719 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000076905 | 1 – 299 | Protein sprouty homolog 4Add BLAST | 299 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | |
Modified residuei | 125 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
CPTACi | CPTAC-1570 |
EPDi | Q9C004 |
jPOSTi | Q9C004 |
MassIVEi | Q9C004 |
MaxQBi | Q9C004 |
PaxDbi | Q9C004 |
PeptideAtlasi | Q9C004 |
PRIDEi | Q9C004 |
ProteomicsDBi | 79936 [Q9C004-1] 79937 [Q9C004-2] |
PTM databases
iPTMneti | Q9C004 |
PhosphoSitePlusi | Q9C004 |
SwissPalmi | Q9C004 |
Expressioni
Gene expression databases
Bgeei | ENSG00000187678, Expressed in left coronary artery and 173 other tissues |
ExpressionAtlasi | Q9C004, baseline and differential |
Organism-specific databases
HPAi | ENSG00000187678, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
Hide detailsQ9C004
Protein-protein interaction databases
BioGRIDi | 123599, 32 interactors |
IntActi | Q9C004, 49 interactors |
MINTi | Q9C004 |
STRINGi | 9606.ENSP00000344967 |
Miscellaneous databases
RNActi | Q9C004, protein |
Structurei
3D structure databases
SMRi | Q9C004 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9C004 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 166 – 273 | SPRPROSITE-ProRule annotationAdd BLAST | 108 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 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 spreading1 PublicationAdd BLAST | 119 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 97 – 107 | Poly-SerAdd BLAST | 11 | |
Compositional biasi | 159 – 283 | Cys-richAdd BLAST | 125 |
Domaini
The Cys-rich domain is responsible for the localization of the protein to the membrane ruffles.
Sequence similaritiesi
Belongs to the sprouty family.Curated
Phylogenomic databases
eggNOGi | ENOG502QQ4V, Eukaryota |
GeneTreei | ENSGT00950000183055 |
HOGENOMi | CLU_077696_0_0_1 |
InParanoidi | Q9C004 |
OrthoDBi | 1157681at2759 |
PhylomeDBi | Q9C004 |
TreeFami | TF325070 |
Family and domain databases
IDEALi | IID00585 |
InterProi | View protein in InterPro IPR007875, Sprouty IPR030790, SPRY4 |
PANTHERi | PTHR12365:SF6, PTHR12365:SF6, 1 hit |
Pfami | View protein in Pfam PF05210, Sprouty, 1 hit |
PROSITEi | View protein in PROSITE PS51227, SPR, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform A (identifier: Q9C004-1) [UniParc]FASTAAdd to basket
Also known as: Sprouty-4A
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MEPPIPQSAP LTPNSVMVQP LLDSRMSHSR LQHPLTILPI DQVKTSHVEN
60 70 80 90 100
DYIDNPSLAL TTGPKRTRGG APELAPTPAR CDQDVTHHWI SFSGRPSSVS
110 120 130 140 150
SSSSTSSDQR LLDHMAPPPV ADQASPRAVR IQPKVVHCQP LDLKGPAVPP
160 170 180 190 200
ELDKHFLLCE ACGKCKCKEC ASPRTLPSCW VCNQECLCSA QTLVNYGTCM
210 220 230 240 250
CLVQGIFYHC TNEDDEGSCA DHPCSCSRSN CCARWSFMGA LSVVLPCLLC
260 270 280 290
YLPATGCVKL AQRGYDRLRR PGCRCKHTNS VICKAASGDA KTSRPDKPF
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A0C4DFS6 | A0A0C4DFS6_HUMAN | Protein sprouty homolog 4 | SPRY4 | 322 | Annotation score: | ||
D6RB56 | D6RB56_HUMAN | Protein sprouty homolog 4 | SPRY4 | 50 | Annotation score: |
Sequence cautioni
The sequence AAK00652 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 102 | S → N in AAI25097 (PubMed:15489334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_069929 | 77 | T → M in HH17; phenotype consistent with Kallmann syndrome. 1 PublicationCorresponds to variant dbSNP:rs774674946Ensembl. | 1 | |
Natural variantiVAR_069930 | 82 | D → N in HH17; without anosmia. 1 PublicationCorresponds to variant dbSNP:rs568363732Ensembl. | 1 | |
Natural variantiVAR_069931 | 154 | K → R in HH17; phenotype consistent with Kallmann syndrome. 1 PublicationCorresponds to variant dbSNP:rs78310959Ensembl. | 1 | |
Natural variantiVAR_069932 | 186 | C → Y in HH17; phenotype consistent with Kallmann syndrome. 1 PublicationCorresponds to variant dbSNP:rs148983803Ensembl. | 1 | |
Natural variantiVAR_069933 | 218 | S → Y in HH17; rare variant associated with susceptibility to disease; some patients have a second mutation in another HH-associated gene including DUSP6 and FGFR1. 1 PublicationCorresponds to variant dbSNP:rs139512218EnsemblClinVar. | 1 | |
Natural variantiVAR_069934 | 258 | V → M in HH17; without anosmia. 1 PublicationCorresponds to variant dbSNP:rs200364529Ensembl. | 1 | |
Natural variantiVAR_069935 | 281 | V → I in HH17; without anosmia. 1 PublicationCorresponds to variant dbSNP:rs142439525Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_006219 | 97 – 106 | SSVSSSSSTS → CSATCLPPAA in isoform C. 1 Publication | 10 | |
Alternative sequenceiVSP_006220 | 107 – 299 | Missing in isoform C. 1 PublicationAdd BLAST | 193 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF227516 mRNA Translation: AAK00652.1 Different initiation. AF227517 mRNA Translation: AAK00653.1 AY538661 Genomic DNA Translation: AAS46253.1 AK096464 mRNA Translation: BAC04798.1 AC091825 Genomic DNA No translation available. BC125095 mRNA Translation: AAI25096.1 BC125096 mRNA Translation: AAI25097.1 |
CCDSi | CCDS47296.1 [Q9C004-1] |
RefSeqi | NP_001120968.1, NM_001127496.1 [Q9C004-1] NP_001280218.1, NM_001293289.1 [Q9C004-1] NP_001280219.1, NM_001293290.1 [Q9C004-1] NP_112226.2, NM_030964.3 XP_011535987.1, XM_011537685.2 XP_016865399.1, XM_017009910.1 [Q9C004-1] |
Genome annotation databases
Ensembli | ENST00000434127; ENSP00000399468; ENSG00000187678 [Q9C004-1] |
GeneIDi | 81848 |
KEGGi | hsa:81848 |
UCSCi | uc003lml.3, human [Q9C004-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF227516 mRNA Translation: AAK00652.1 Different initiation. AF227517 mRNA Translation: AAK00653.1 AY538661 Genomic DNA Translation: AAS46253.1 AK096464 mRNA Translation: BAC04798.1 AC091825 Genomic DNA No translation available. BC125095 mRNA Translation: AAI25096.1 BC125096 mRNA Translation: AAI25097.1 |
CCDSi | CCDS47296.1 [Q9C004-1] |
RefSeqi | NP_001120968.1, NM_001127496.1 [Q9C004-1] NP_001280218.1, NM_001293289.1 [Q9C004-1] NP_001280219.1, NM_001293290.1 [Q9C004-1] NP_112226.2, NM_030964.3 XP_011535987.1, XM_011537685.2 XP_016865399.1, XM_017009910.1 [Q9C004-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3BUN | X-ray | 2.00 | A | 46-58 | [»] | |
SMRi | Q9C004 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 123599, 32 interactors |
IntActi | Q9C004, 49 interactors |
MINTi | Q9C004 |
STRINGi | 9606.ENSP00000344967 |
PTM databases
iPTMneti | Q9C004 |
PhosphoSitePlusi | Q9C004 |
SwissPalmi | Q9C004 |
Genetic variation databases
BioMutai | SPRY4 |
DMDMi | 14916719 |
Proteomic databases
CPTACi | CPTAC-1570 |
EPDi | Q9C004 |
jPOSTi | Q9C004 |
MassIVEi | Q9C004 |
MaxQBi | Q9C004 |
PaxDbi | Q9C004 |
PeptideAtlasi | Q9C004 |
PRIDEi | Q9C004 |
ProteomicsDBi | 79936 [Q9C004-1] 79937 [Q9C004-2] |
Protocols and materials databases
Antibodypediai | 3761, 279 antibodies |
Genome annotation databases
Ensembli | ENST00000434127; ENSP00000399468; ENSG00000187678 [Q9C004-1] |
GeneIDi | 81848 |
KEGGi | hsa:81848 |
UCSCi | uc003lml.3, human [Q9C004-1] |
Organism-specific databases
CTDi | 81848 |
DisGeNETi | 81848 |
GeneCardsi | SPRY4 |
GeneReviewsi | SPRY4 |
HGNCi | HGNC:15533, SPRY4 |
HPAi | ENSG00000187678, Low tissue specificity |
MalaCardsi | SPRY4 |
MIMi | 607984, gene 615266, phenotype |
neXtProti | NX_Q9C004 |
OpenTargetsi | ENSG00000187678 |
Orphaneti | 478, Kallmann syndrome 363494, Non-seminomatous germ cell tumor of testis 432, Normosmic congenital hypogonadotropic hypogonadism |
PharmGKBi | PA37975 |
VEuPathDBi | HostDB:ENSG00000187678.8 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QQ4V, Eukaryota |
GeneTreei | ENSGT00950000183055 |
HOGENOMi | CLU_077696_0_0_1 |
InParanoidi | Q9C004 |
OrthoDBi | 1157681at2759 |
PhylomeDBi | Q9C004 |
TreeFami | TF325070 |
Enzyme and pathway databases
PathwayCommonsi | Q9C004 |
SignaLinki | Q9C004 |
SIGNORi | Q9C004 |
Miscellaneous databases
BioGRID-ORCSi | 81848, 5 hits in 876 CRISPR screens |
ChiTaRSi | SPRY4, human |
EvolutionaryTracei | Q9C004 |
GeneWikii | SPRY4 |
GenomeRNAii | 81848 |
Pharosi | Q9C004, Tbio |
PROi | PR:Q9C004 |
RNActi | Q9C004, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000187678, Expressed in left coronary artery and 173 other tissues |
ExpressionAtlasi | Q9C004, baseline and differential |
Family and domain databases
IDEALi | IID00585 |
InterProi | View protein in InterPro IPR007875, Sprouty IPR030790, SPRY4 |
PANTHERi | PTHR12365:SF6, PTHR12365:SF6, 1 hit |
Pfami | View protein in Pfam PF05210, Sprouty, 1 hit |
PROSITEi | View protein in PROSITE PS51227, SPR, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SPY4_HUMAN | |
Accessioni | Q9C004Primary (citable) accession number: Q9C004 Secondary accession number(s): A4FVB2 Q9C003 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 11, 2001 |
Last sequence update: | July 11, 2001 | |
Last modified: | February 10, 2021 | |
This is version 162 of the entry and version 2 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, Reference proteomeDocuments
- Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - 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 - Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM