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UniProtKB - Q9C004 (SPY4_HUMAN)

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Protein

Protein sprouty homolog 4

Gene

SPRY4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionDevelopmental protein

Enzyme and pathway databases

SignaLinkiQ9C004
SIGNORiQ9C004

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000187678.8
HGNCiHGNC:15533 SPRY4
MIMi607984 gene
neXtProtiNX_Q9C004

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, 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 dbSNP:rs774674946Ensembl.1
Natural variantiVAR_06993082D → N in HH17; without anosmia. 1 PublicationCorresponds to variant dbSNP:rs568363732Ensembl.1
Natural variantiVAR_069931154K → R in HH17; phenotype consistent with Kallmann syndrome. 1 PublicationCorresponds to variant dbSNP:rs78310959Ensembl.1
Natural variantiVAR_069932186C → Y in HH17; phenotype consistent with Kallmann syndrome. 1 PublicationCorresponds to variant dbSNP:rs148983803Ensembl.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 dbSNP:rs139512218Ensembl.1
Natural variantiVAR_069934258V → M in HH17; without anosmia. 1 PublicationCorresponds to variant dbSNP:rs200364529Ensembl.1
Natural variantiVAR_069935281V → I in HH17; without anosmia. 1 PublicationCorresponds to variant dbSNP:rs142439525Ensembl.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
ProteomicsDBi79936
79937 [Q9C004-2]

PTM databases

iPTMnetiQ9C004
PhosphoSitePlusiQ9C004
SwissPalmiQ9C004

Expressioni

Gene expression databases

BgeeiENSG00000187678
CleanExiHS_SPRY4
ExpressionAtlasiQ9C004 baseline and differential

Organism-specific databases

HPAiCAB008086
HPA072661

Interactioni

Subunit structurei

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

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi123599, 11 interactors
IntActiQ9C004, 22 interactors
MINTiQ9C004
STRINGi9606.ENSP00000344967

Structurei

3D structure databases

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

Phylogenomic databases

eggNOGiENOG410IH70 Eukaryota
ENOG410ZPNT LUCA
GeneTreeiENSGT00390000003535
HOGENOMiHOG000233079
HOVERGENiHBG003544
InParanoidiQ9C004
KOiK17385
PhylomeDBiQ9C004
TreeFamiTF325070

Family and domain databases

InterProiView protein in InterPro
IPR007875 Sprouty
IPR030790 SPRY4
PANTHERiPTHR12365:SF6 PTHR12365:SF6, 1 hit
PfamiView protein in Pfam
PF05210 Sprouty, 1 hit
PROSITEiView protein in PROSITE
PS51227 SPR, 1 hit

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 dbSNP:rs774674946Ensembl.1
Natural variantiVAR_06993082D → N in HH17; without anosmia. 1 PublicationCorresponds to variant dbSNP:rs568363732Ensembl.1
Natural variantiVAR_069931154K → R in HH17; phenotype consistent with Kallmann syndrome. 1 PublicationCorresponds to variant dbSNP:rs78310959Ensembl.1
Natural variantiVAR_069932186C → Y in HH17; phenotype consistent with Kallmann syndrome. 1 PublicationCorresponds to variant dbSNP:rs148983803Ensembl.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 dbSNP:rs139512218Ensembl.1
Natural variantiVAR_069934258V → M in HH17; without anosmia. 1 PublicationCorresponds to variant dbSNP:rs200364529Ensembl.1
Natural variantiVAR_069935281V → I in HH17; without anosmia. 1 PublicationCorresponds to variant dbSNP:rs142439525Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiSPY4_HUMAN
AccessioniPrimary (citable) accession number: Q9C004
Secondary accession number(s): A4FVB2
, A4FVB3, Q6QIX2, Q9C003
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 11, 2001
Last sequence update: July 11, 2001
Last modified: July 18, 2018
This is version 145 of the entry and version 2 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. 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

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