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Protein

Protein sprouty homolog 4

Gene

SPRY4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Suppresses the insulin receptor and EGFR-transduced MAPK signaling pathway, but does not inhibit MAPK activation by a constitutively active mutant Ras. Probably impairs the formation of GTP-Ras. Inhibits Ras-independent, but not Ras-dependent, activation of RAF1.1 Publication

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Enzyme and pathway databases

BioCyciZFISH:G66-33821-MONOMER.
SignaLinkiQ9C004.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein sprouty homolog 4
Short name:
Spry-4
Gene namesi
Name:SPRY4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:15533. SPRY4.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • focal adhesion Source: UniProtKB
  • Golgi apparatus Source: HPA
  • ruffle membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Hypogonadotropic hypogonadism 17 with or without anosmia (HH17)1 Publication
The disease is caused by mutations 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).
See also OMIM:615266
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06992977T → M in HH17; phenotype consistent with Kallmann syndrome. 1 PublicationCorresponds to variant rs774674946dbSNPEnsembl.1
Natural variantiVAR_06993082D → N in HH17; without anosmia. 1 PublicationCorresponds to variant rs568363732dbSNPEnsembl.1
Natural variantiVAR_069931154K → R in HH17; phenotype consistent with Kallmann syndrome. 1 PublicationCorresponds to variant rs78310959dbSNPEnsembl.1
Natural variantiVAR_069932186C → Y in HH17; phenotype consistent with Kallmann syndrome. 1 PublicationCorresponds to variant rs148983803dbSNPEnsembl.1
Natural variantiVAR_069933218S → 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 rs139512218dbSNPEnsembl.1
Natural variantiVAR_069934258V → M in HH17; without anosmia. 1 PublicationCorresponds to variant rs200364529dbSNPEnsembl.1
Natural variantiVAR_069935281V → I in HH17; without anosmia. 1 PublicationCorresponds to variant rs142439525dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism, Kallmann syndrome

Organism-specific databases

DisGeNETi81848.
MalaCardsiSPRY4.
MIMi615266. phenotype.
OpenTargetsiENSG00000187678.
Orphaneti478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
363494. Testicular non seminomatous germ cell tumor.
PharmGKBiPA37975.

Polymorphism and mutation databases

BioMutaiSPRY4.
DMDMi14916719.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000769051 – 299Protein sprouty homolog 4Add BLAST299

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei125PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9C004.
MaxQBiQ9C004.
PaxDbiQ9C004.
PeptideAtlasiQ9C004.
PRIDEiQ9C004.

PTM databases

iPTMnetiQ9C004.
PhosphoSitePlusiQ9C004.
SwissPalmiQ9C004.

Expressioni

Gene expression databases

BgeeiENSG00000187678.
CleanExiHS_SPRY4.
ExpressionAtlasiQ9C004. baseline and differential.

Organism-specific databases

HPAiCAB008086.

Interactioni

Subunit structurei

Interacts with the C-terminus of TESK1. Interacts with RAF1.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CBLP226819EBI-354861,EBI-518228
TESK1Q155694EBI-354861,EBI-354852
ZDHHC17Q8IUH52EBI-354861,EBI-524753

Protein-protein interaction databases

BioGridi123599. 11 interactors.
IntActiQ9C004. 6 interactors.
MINTiMINT-6538953.
STRINGi9606.ENSP00000344967.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BUNX-ray2.00A46-58[»]
ProteinModelPortaliQ9C004.
SMRiQ9C004.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9C004.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini166 – 273SPRPROSITE-ProRule annotationAdd BLAST108

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi97 – 107Poly-SerAdd BLAST11
Compositional biasi159 – 283Cys-richAdd BLAST125

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
Contains 1 SPR (sprouty) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IH70. Eukaryota.
ENOG410ZPNT. LUCA.
GeneTreeiENSGT00390000003535.
HOGENOMiHOG000233079.
HOVERGENiHBG003544.
InParanoidiQ9C004.
KOiK17385.
PhylomeDBiQ9C004.
TreeFamiTF325070.

Family and domain databases

InterProiIPR007875. Sprouty.
IPR030790. SPRY4.
[Graphical view]
PANTHERiPTHR12365:SF6. PTHR12365:SF6. 1 hit.
PfamiPF05210. Sprouty. 1 hit.
[Graphical view]
PROSITEiPS51227. SPR. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform A (identifier: Q9C004-1) [UniParc]FASTAAdd to basket
Also known as: Sprouty-4A

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.

« Hide

        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
Length:299
Mass (Da):32,541
Last modified:July 11, 2001 - v2
Checksum:i105F6F1BE9F7B6C3
GO
Isoform C (identifier: Q9C004-2) [UniParc]FASTAAdd to basket
Also known as: Sprouty-4C

The sequence of this isoform differs from the canonical sequence as follows:
     97-106: SSVSSSSSTS → CSATCLPPAA
     107-299: Missing.

Note: No experimental confirmation available.
Show »
Length:106
Mass (Da):11,482
Checksum:i6158571E3477A598
GO

Sequence cautioni

The sequence AAK00652 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti102S → N in AAI25097 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06992977T → M in HH17; phenotype consistent with Kallmann syndrome. 1 PublicationCorresponds to variant rs774674946dbSNPEnsembl.1
Natural variantiVAR_06993082D → N in HH17; without anosmia. 1 PublicationCorresponds to variant rs568363732dbSNPEnsembl.1
Natural variantiVAR_069931154K → R in HH17; phenotype consistent with Kallmann syndrome. 1 PublicationCorresponds to variant rs78310959dbSNPEnsembl.1
Natural variantiVAR_069932186C → Y in HH17; phenotype consistent with Kallmann syndrome. 1 PublicationCorresponds to variant rs148983803dbSNPEnsembl.1
Natural variantiVAR_069933218S → 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 rs139512218dbSNPEnsembl.1
Natural variantiVAR_069934258V → M in HH17; without anosmia. 1 PublicationCorresponds to variant rs200364529dbSNPEnsembl.1
Natural variantiVAR_069935281V → I in HH17; without anosmia. 1 PublicationCorresponds to variant rs142439525dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00621997 – 106SSVSSSSSTS → CSATCLPPAA in isoform C. 1 Publication10
Alternative sequenceiVSP_006220107 – 299Missing in isoform C. 1 PublicationAdd BLAST193

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.
CCDSiCCDS47296.1. [Q9C004-1]
RefSeqiNP_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]
UniGeneiHs.323308.

Genome annotation databases

EnsembliENST00000434127; ENSP00000399468; ENSG00000187678. [Q9C004-1]
GeneIDi81848.
KEGGihsa:81848.
UCSCiuc003lml.3. human. [Q9C004-1]

Keywords - Coding sequence diversityi

Alternative splicing

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.
CCDSiCCDS47296.1. [Q9C004-1]
RefSeqiNP_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]
UniGeneiHs.323308.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BUNX-ray2.00A46-58[»]
ProteinModelPortaliQ9C004.
SMRiQ9C004.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123599. 11 interactors.
IntActiQ9C004. 6 interactors.
MINTiMINT-6538953.
STRINGi9606.ENSP00000344967.

PTM databases

iPTMnetiQ9C004.
PhosphoSitePlusiQ9C004.
SwissPalmiQ9C004.

Polymorphism and mutation databases

BioMutaiSPRY4.
DMDMi14916719.

Proteomic databases

EPDiQ9C004.
MaxQBiQ9C004.
PaxDbiQ9C004.
PeptideAtlasiQ9C004.
PRIDEiQ9C004.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000434127; ENSP00000399468; ENSG00000187678. [Q9C004-1]
GeneIDi81848.
KEGGihsa:81848.
UCSCiuc003lml.3. human. [Q9C004-1]

Organism-specific databases

CTDi81848.
DisGeNETi81848.
GeneCardsiSPRY4.
HGNCiHGNC:15533. SPRY4.
HPAiCAB008086.
MalaCardsiSPRY4.
MIMi607984. gene.
615266. phenotype.
neXtProtiNX_Q9C004.
OpenTargetsiENSG00000187678.
Orphaneti478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
363494. Testicular non seminomatous germ cell tumor.
PharmGKBiPA37975.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IH70. Eukaryota.
ENOG410ZPNT. LUCA.
GeneTreeiENSGT00390000003535.
HOGENOMiHOG000233079.
HOVERGENiHBG003544.
InParanoidiQ9C004.
KOiK17385.
PhylomeDBiQ9C004.
TreeFamiTF325070.

Enzyme and pathway databases

BioCyciZFISH:G66-33821-MONOMER.
SignaLinkiQ9C004.

Miscellaneous databases

ChiTaRSiSPRY4. human.
EvolutionaryTraceiQ9C004.
GeneWikiiSPRY4.
GenomeRNAii81848.
PROiQ9C004.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000187678.
CleanExiHS_SPRY4.
ExpressionAtlasiQ9C004. baseline and differential.

Family and domain databases

InterProiIPR007875. Sprouty.
IPR030790. SPRY4.
[Graphical view]
PANTHERiPTHR12365:SF6. PTHR12365:SF6. 1 hit.
PfamiPF05210. Sprouty. 1 hit.
[Graphical view]
PROSITEiPS51227. SPR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSPY4_HUMAN
AccessioniPrimary (citable) accession number: Q9C004
Secondary accession number(s): A4FVB2
, A4FVB3, Q6QIX2, Q9C003
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2001
Last sequence update: July 11, 2001
Last modified: November 2, 2016
This is version 135 of the entry and version 2 of the sequence. [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. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar 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.