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Q7Z699

- SPRE1_HUMAN

UniProt

Q7Z699 - SPRE1_HUMAN

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Protein

Sprouty-related, EVH1 domain-containing protein 1

Gene

SPRED1

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

Functioni

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

GO - Molecular functioni

  1. phosphatase binding Source: UniProtKB
  2. protein kinase binding Source: BHF-UCL
  3. protein serine/threonine kinase inhibitor activity Source: BHF-UCL
  4. stem cell factor receptor binding Source: UniProtKB

GO - Biological processi

  1. inactivation of MAPK activity Source: UniProtKB
  2. multicellular organismal development Source: InterPro
  3. negative regulation of peptidyl-threonine phosphorylation Source: BHF-UCL
  4. negative regulation of phosphatase activity Source: UniProtKB
  5. positive regulation of DNA damage response, signal transduction by p53 class mediator Source: BHF-UCL
  6. regulation of protein deacetylation Source: BHF-UCL
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Sprouty-related, EVH1 domain-containing protein 1
Short name:
Spred-1
Short name:
hSpred1
Gene namesi
Name:SPRED1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 15

Organism-specific databases

HGNCiHGNC:20249. SPRED1.

Subcellular locationi

Cell membrane 1 Publication; Peripheral membrane protein 1 Publication. Membranecaveola 1 Publication; Peripheral membrane protein 1 Publication. Nucleus 1 Publication
Note: Localized in cholesterol-rich membrane raft/caveola fractions.

GO - Cellular componenti

  1. cytoplasm Source: HPA
  2. nucleus Source: HPA
  3. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.4 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti31 – 311W → C in NFLS. 1 Publication
VAR_064827
Natural varianti44 – 441V → D in NFLS. 2 Publications
VAR_064828

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi611431. phenotype.
Orphaneti137605. Legius syndrome.
PharmGKBiPA134897382.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 444443Sprouty-related, EVH1 domain-containing protein 1PRO_0000076907Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine1 Publication
Modified residuei238 – 2381PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated on tyrosine.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ7Z699.
PaxDbiQ7Z699.
PRIDEiQ7Z699.

PTM databases

PhosphoSiteiQ7Z699.

Expressioni

Tissue specificityi

Weakly expressed in embryonic cell line HEK293.1 Publication

Gene expression databases

BgeeiQ7Z699.
CleanExiHS_SPRED1.
ExpressionAtlasiQ7Z699. baseline and differential.
GenevestigatoriQ7Z699.

Organism-specific databases

HPAiHPA042193.

Interactioni

Subunit structurei

Interacts with Ras. Interacts with TAOK2 and TESK1 (By similarity). Homodimer and heterodimer. Interacts with CAV1. Able to interact with SPRED2 to form heterodimers.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PPP1CAP621364EBI-5235340,EBI-357253
ZDHHC17Q8IUH53EBI-5235340,EBI-524753

Protein-protein interaction databases

BioGridi127800. 14 interactions.
IntActiQ7Z699. 12 interactions.
MINTiMINT-1198540.
STRINGi9606.ENSP00000299084.

Structurei

Secondary structure

1
444
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi13 – 2412Combined sources
Beta strandi26 – 294Combined sources
Beta strandi31 – 377Combined sources
Beta strandi40 – 5112Combined sources
Beta strandi54 – 6411Combined sources
Turni65 – 673Combined sources
Beta strandi70 – 756Combined sources
Beta strandi81 – 866Combined sources
Beta strandi89 – 946Combined sources
Beta strandi97 – 1059Combined sources
Helixi106 – 12116Combined sources
Helixi122 – 1243Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3SYXX-ray2.45A13-131[»]
ProteinModelPortaliQ7Z699.
SMRiQ7Z699. Positions 13-127.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini6 – 123118WH1PROSITE-ProRule annotationAdd
BLAST
Domaini233 – 28553KBDPROSITE-ProRule annotationAdd
BLAST
Domaini334 – 442109SPRPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi147 – 1504Poly-Ser

Sequence similaritiesi

Contains 1 KBD domain.PROSITE-ProRule annotation
Contains 1 SPR (sprouty) domain.PROSITE-ProRule annotation
Contains 1 WH1 domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG277322.
GeneTreeiENSGT00730000110272.
HOGENOMiHOG000220886.
HOVERGENiHBG057556.
InParanoidiQ7Z699.
KOiK04703.
OMAiCVTVFKV.
OrthoDBiEOG7T7GV7.
PhylomeDBiQ7Z699.
TreeFamiTF321411.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR023337. KBD.
IPR011993. PH_like_dom.
IPR007875. Sprouty.
IPR000697. WH1/EVH1.
[Graphical view]
PfamiPF05210. Sprouty. 1 hit.
PF00568. WH1. 1 hit.
[Graphical view]
PROSITEiPS51488. KBD. 1 hit.
PS51227. SPR. 1 hit.
PS50229. WH1. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q7Z699-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSEETATSDN DNSYARVRAV VMTRDDSSGG WLPLGGSGLS SVTVFKVPHQ
60 70 80 90 100
EENGCADFFI RGERLRDKMV VLECMLKKDL IYNKVTPTFH HWKIDDKKFG
110 120 130 140 150
LTFQSPADAR AFDRGIRRAI EDISQGCPES KNEAEGADDL QANEEDSSSS
160 170 180 190 200
LVKDHLFQQE TVVTSEPYRS SNIRPSPFED LNARRVYMQS QANQITFGQP
210 220 230 240 250
GLDIQSRSME YVQRQISKEC GSLKSQNRVP LKSIRHVSFQ DEDEIVRINP
260 270 280 290 300
RDILIRRYAD YRHPDMWKND LERDDADSSI QFSKPDSKKS DYLYSCGDET
310 320 330 340 350
KLSSPKDSVV FKTQPSSLKI KKSKRRKEDG ERSRCVYCQE RFNHEENVRG
360 370 380 390 400
KCQDAPDPIK RCIYQVSCML CAESMLYHCM SDSEGDFSDP CSCDTSDDKF
410 420 430 440
CLRWLALVAL SFIVPCMCCY VPLRMCHRCG EACGCCGGKH KAAG
Length:444
Mass (Da):50,477
Last modified:January 4, 2005 - v2
Checksum:i6FFDECCE590DB311
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti6 – 72AT → GL in AAP59414. (PubMed:15683364)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti31 – 311W → C in NFLS. 1 Publication
VAR_064827
Natural varianti44 – 441V → D in NFLS. 2 Publications
VAR_064828

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS32193.1.
RefSeqiNP_689807.1. NM_152594.2.
UniGeneiHs.525781.

Genome annotation databases

EnsembliENST00000299084; ENSP00000299084; ENSG00000166068.
GeneIDi161742.
KEGGihsa:161742.
UCSCiuc001zka.4. human.

Polymorphism databases

DMDMi57013078.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS32193.1.
RefSeqi NP_689807.1. NM_152594.2.
UniGenei Hs.525781.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3SYX X-ray 2.45 A 13-131 [» ]
ProteinModelPortali Q7Z699.
SMRi Q7Z699. Positions 13-127.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 127800. 14 interactions.
IntActi Q7Z699. 12 interactions.
MINTi MINT-1198540.
STRINGi 9606.ENSP00000299084.

PTM databases

PhosphoSitei Q7Z699.

Polymorphism databases

DMDMi 57013078.

Proteomic databases

MaxQBi Q7Z699.
PaxDbi Q7Z699.
PRIDEi Q7Z699.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000299084 ; ENSP00000299084 ; ENSG00000166068 .
GeneIDi 161742.
KEGGi hsa:161742.
UCSCi uc001zka.4. human.

Organism-specific databases

CTDi 161742.
GeneCardsi GC15P038545.
GeneReviewsi SPRED1.
HGNCi HGNC:20249. SPRED1.
HPAi HPA042193.
MIMi 609291. gene.
611431. phenotype.
neXtProti NX_Q7Z699.
Orphaneti 137605. Legius syndrome.
PharmGKBi PA134897382.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG277322.
GeneTreei ENSGT00730000110272.
HOGENOMi HOG000220886.
HOVERGENi HBG057556.
InParanoidi Q7Z699.
KOi K04703.
OMAi CVTVFKV.
OrthoDBi EOG7T7GV7.
PhylomeDBi Q7Z699.
TreeFami TF321411.

Miscellaneous databases

ChiTaRSi SPRED1. human.
GeneWikii SPRED1.
GenomeRNAii 161742.
NextBioi 88102.
PROi Q7Z699.
SOURCEi Search...

Gene expression databases

Bgeei Q7Z699.
CleanExi HS_SPRED1.
ExpressionAtlasi Q7Z699. baseline and differential.
Genevestigatori Q7Z699.

Family and domain databases

Gene3Di 2.30.29.30. 1 hit.
InterProi IPR023337. KBD.
IPR011993. PH_like_dom.
IPR007875. Sprouty.
IPR000697. WH1/EVH1.
[Graphical view ]
Pfami PF05210. Sprouty. 1 hit.
PF00568. WH1. 1 hit.
[Graphical view ]
PROSITEi PS51488. KBD. 1 hit.
PS51227. SPR. 1 hit.
PS50229. WH1. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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.
    , 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. 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. Cited for: INVOLVEMENT IN NFLS.
  8. 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. Cited for: VARIANT NFLS CYS-31.

Entry informationi

Entry nameiSPRE1_HUMAN
AccessioniPrimary (citable) accession number: Q7Z699
Secondary accession number(s): B2RPJ8, Q05D53, Q8N256
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 4, 2005
Last sequence update: January 4, 2005
Last modified: November 26, 2014
This is version 105 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 15
    Human chromosome 15: 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

External Data

Dasty 3