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Q7Z699 (SPRE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sprouty-related, EVH1 domain-containing protein 1

Short name=Spred-1
Short name=hSpred1
Gene names
Name:SPRED1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length444 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Tyrosine kinase substrate that inhibits growth-factor-mediated activation of MAP kinase. Negatively regulates hematopoiesis of bone marrow By similarity.

Subunit structure

Interacts with Ras. Interacts with TAOK2 and TESK1 By similarity. Homodimer and heterodimer. Interacts with CAV1. Able to interact with SPRED2 to form heterodimers. Ref.1 Ref.6

Subcellular location

Cell membrane; Peripheral membrane protein. Membranecaveola; Peripheral membrane protein. Nucleus. Note: Localized in cholesterol-rich membrane raft/caveola fractions. Ref.6

Tissue specificity

Weakly expressed in embryonic cell line HEK293. Ref.5

Post-translational modification

Phosphorylated on tyrosine By similarity.

Involvement in disease

Neurofibromatosis 1-like syndrome (NFLS) [MIM:611431]: A disorder characterized mainly by cafe au lait macules without neurofibromas or other tumor manifestations of neurofibromatosis type 1, axillary freckling, and macrocephaly. Additional clinical manifestations include Noonan-like facial dysmorphism, lipomas, learning disabilities and attention deficit-hyperactivity.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.9 Ref.10 Ref.11

Sequence similarities

Contains 1 KBD domain.

Contains 1 SPR (sprouty) domain.

Contains 1 WH1 domain.

Sequence caution

The sequence AAH18015.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
Nucleus
   DiseaseDisease mutation
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processinactivation of MAPK activity

Inferred from sequence or structural similarity. Source: UniProtKB

multicellular organismal development

Inferred from electronic annotation. Source: InterPro

negative regulation of peptidyl-threonine phosphorylation

Inferred from mutant phenotype PubMed 20736167. Source: BHF-UCL

negative regulation of phosphatase activity

Inferred from direct assay PubMed 19389623. Source: UniProtKB

positive regulation of DNA damage response, signal transduction by p53 class mediator

Inferred from sequence or structural similarity PubMed 20736167. Source: BHF-UCL

regulation of protein deacetylation

Inferred from sequence or structural similarity PubMed 20736167. Source: BHF-UCL

   Cellular_componentcaveola

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay. Source: HPA

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionphosphatase binding

Inferred from direct assay PubMed 19389623. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 15231748PubMed 19389623PubMed 22321011PubMed 24705354. Source: IntAct

protein kinase binding

Inferred from physical interaction PubMed 20736167. Source: BHF-UCL

protein serine/threonine kinase inhibitor activity

Inferred from sequence or structural similarity PubMed 20736167. Source: BHF-UCL

stem cell factor receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PPP1CAP621364EBI-5235340,EBI-357253
ZDHHC17Q8IUH53EBI-5235340,EBI-524753

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.8
Chain2 – 444443Sprouty-related, EVH1 domain-containing protein 1
PRO_0000076907

Regions

Domain6 – 123118WH1
Domain233 – 28553KBD
Domain334 – 442109SPR
Compositional bias147 – 1504Poly-Ser

Amino acid modifications

Modified residue21N-acetylserine Ref.8
Modified residue2381Phosphoserine By similarity

Natural variations

Natural variant311W → C in NFLS. Ref.11
VAR_064827
Natural variant441V → D in NFLS. Ref.9 Ref.10
VAR_064828

Experimental info

Sequence conflict6 – 72AT → GL in AAP59414. Ref.1

Secondary structure

...................... 444
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q7Z699 [UniParc].

Last modified January 4, 2005. Version 2.
Checksum: 6FFDECCE590DB311

FASTA44450,477
        10         20         30         40         50         60 
MSEETATSDN DNSYARVRAV VMTRDDSSGG WLPLGGSGLS SVTVFKVPHQ EENGCADFFI 

        70         80         90        100        110        120 
RGERLRDKMV VLECMLKKDL IYNKVTPTFH HWKIDDKKFG LTFQSPADAR AFDRGIRRAI 

       130        140        150        160        170        180 
EDISQGCPES KNEAEGADDL QANEEDSSSS LVKDHLFQQE TVVTSEPYRS SNIRPSPFED 

       190        200        210        220        230        240 
LNARRVYMQS QANQITFGQP GLDIQSRSME YVQRQISKEC GSLKSQNRVP LKSIRHVSFQ 

       250        260        270        280        290        300 
DEDEIVRINP RDILIRRYAD YRHPDMWKND LERDDADSSI QFSKPDSKKS DYLYSCGDET 

       310        320        330        340        350        360 
KLSSPKDSVV FKTQPSSLKI KKSKRRKEDG ERSRCVYCQE RFNHEENVRG KCQDAPDPIK 

       370        380        390        400        410        420 
RCIYQVSCML CAESMLYHCM SDSEGDFSDP CSCDTSDDKF CLRWLALVAL SFIVPCMCCY 

       430        440 
VPLRMCHRCG EACGCCGGKH KAAG 

« Hide

References

« Hide 'large scale' references
[1]"Distinct requirements for the Sprouty domain for functional activity of Spred proteins."
King J.A.J., Straffon A.F.L., D'Abaco G.M., Poon C.L.C., I S.T.T., Smith C.M., Buchert M., Corcoran N.M., Hall N.E., Callus B.A., Sarcevic B., Martin D., Lock P., Hovens C.M.
Biochem. J. 388:445-454(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH SPRED2.
Tissue: Glioblastoma.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Tongue.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]"Expression and subcellular localization of Spred proteins in mouse and human tissues."
Engelhardt C.M., Bundschu K., Messerschmitt M., Renne T., Walter U., Reinhard M., Schuh K.
Histochem. Cell Biol. 122:527-538(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[6]"The Sprouty-related protein, Spred-1, localizes in a lipid raft/caveola and inhibits ERK activation in collaboration with caveolin-1."
Nonami A., Taketomi T., Kimura A., Saeki K., Takaki H., Sanada T., Taniguchi K., Harada M., Kato R., Yoshimura A.
Genes Cells 10:887-895(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CAV1, SUBCELLULAR LOCATION.
[7]"Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype."
Brems H., Chmara M., Sahbatou M., Denayer E., Taniguchi K., Kato R., Somers R., Messiaen L., De Schepper S., Fryns J.-P., Cools J., Marynen P., Thomas G., Yoshimura A., Legius E.
Nat. Genet. 39:1120-1126(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN NFLS.
[8]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[9]"SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype."
Spurlock G., Bennett E., Chuzhanova N., Thomas N., Jim H.P., Side L., Davies S., Haan E., Kerr B., Huson S.M., Upadhyaya M.
J. Med. Genet. 46:431-437(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NFLS ASP-44.
[10]"Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome."
Jim H.P., Upadhyaya M.
Hum. Genet. 127:112-112(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NFLS ASP-44.
[11]"Legius syndrome in fourteen families."
Denayer E., Chmara M., Brems H., Kievit A.M., van Bever Y., Van den Ouweland A.M., Van Minkelen R., de Goede-Bolder A., Oostenbrink R., Lakeman P., Beert E., Ishizaki T., Mori T., Keymolen K., Van den Ende J., Mangold E., Peltonen S., Brice G. expand/collapse author list , Rankin J., Van Spaendonck-Zwarts K.Y., Yoshimura A., Legius E.
Hum. Mutat. 32:E1985-E1998(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NFLS CYS-31.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY299089 mRNA. Translation: AAP59414.1.
AK091222 mRNA. Translation: BAC03614.1.
CH471125 Genomic DNA. Translation: EAW92368.1.
BC018015 mRNA. Translation: AAH18015.1. Sequence problems.
BC137480 mRNA. Translation: AAI37481.1.
BC137481 mRNA. Translation: AAI37482.1.
CCDSCCDS32193.1.
RefSeqNP_689807.1. NM_152594.2.
UniGeneHs.525781.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3SYXX-ray2.45A13-131[»]
ProteinModelPortalQ7Z699.
SMRQ7Z699. Positions 13-127.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid127800. 14 interactions.
IntActQ7Z699. 12 interactions.
MINTMINT-1198540.
STRING9606.ENSP00000299084.

PTM databases

PhosphoSiteQ7Z699.

Polymorphism databases

DMDM57013078.

Proteomic databases

MaxQBQ7Z699.
PaxDbQ7Z699.
PRIDEQ7Z699.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000299084; ENSP00000299084; ENSG00000166068.
GeneID161742.
KEGGhsa:161742.
UCSCuc001zka.4. human.

Organism-specific databases

CTD161742.
GeneCardsGC15P038545.
GeneReviewsSPRED1.
HGNCHGNC:20249. SPRED1.
HPAHPA042193.
MIM609291. gene.
611431. phenotype.
neXtProtNX_Q7Z699.
Orphanet137605. Legius syndrome.
PharmGKBPA134897382.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG277322.
HOGENOMHOG000220886.
HOVERGENHBG057556.
InParanoidQ7Z699.
KOK04703.
OMACVTVFKV.
OrthoDBEOG7T7GV7.
PhylomeDBQ7Z699.
TreeFamTF321411.

Gene expression databases

ArrayExpressQ7Z699.
BgeeQ7Z699.
CleanExHS_SPRED1.
GenevestigatorQ7Z699.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
InterProIPR023337. KBD.
IPR011993. PH_like_dom.
IPR007875. Sprouty.
IPR000697. WH1/EVH1.
[Graphical view]
PfamPF05210. Sprouty. 1 hit.
PF00568. WH1. 1 hit.
[Graphical view]
PROSITEPS51488. KBD. 1 hit.
PS51227. SPR. 1 hit.
PS50229. WH1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSPRED1. human.
GeneWikiSPRED1.
GenomeRNAi161742.
NextBio88102.
PROQ7Z699.
SOURCESearch...

Entry information

Entry nameSPRE1_HUMAN
AccessionPrimary (citable) accession number: Q7Z699
Secondary accession number(s): B2RPJ8, Q05D53, Q8N256
Entry history
Integrated into UniProtKB/Swiss-Prot: January 4, 2005
Last sequence update: January 4, 2005
Last modified: July 9, 2014
This is version 102 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM