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Q7Z698

- SPRE2_HUMAN

UniProt

Q7Z698 - SPRE2_HUMAN

Protein

Sprouty-related, EVH1 domain-containing protein 2

Gene

SPRED2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 102 (01 Oct 2014)
      Sequence version 2 (25 Jul 2006)
      Previous versions | rss
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    Functioni

    Tyrosine kinase substrate that inhibits growth-factor-mediated activation of MAP kinase.

    GO - Molecular functioni

    1. protein 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. positive regulation of DNA damage response, signal transduction by p53 class mediator Source: BHF-UCL
    5. regulation of protein deacetylation Source: BHF-UCL

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sprouty-related, EVH1 domain-containing protein 2
    Short name:
    Spred-2
    Gene namesi
    Name:SPRED2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:17722. SPRED2.

    Subcellular locationi

    Membrane By similarity; Peripheral membrane protein By similarity; Cytoplasmic side By similarity. Cytoplasmic vesiclesecretory vesicle membrane Curated; Peripheral membrane protein Curated; Cytoplasmic side Curated. Cytoplasm
    Note: Especially found in the cytoplasm of the stratum spinosum cells called membrane-coated granules.

    GO - Cellular componenti

    1. cytoplasm Source: HPA
    2. nucleus Source: HPA
    3. plasma membrane Source: Ensembl
    4. transport vesicle membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Cytoplasmic vesicle, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134956365.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 418418Sprouty-related, EVH1 domain-containing protein 2PRO_0000076910Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei228 – 2281Phosphotyrosine1 Publication
    Modified residuei231 – 2311Phosphotyrosine1 Publication

    Post-translational modificationi

    Phosphorylated on tyrosine. Phosphorylation of Tyr-228 and Tyr-231 are required for ubiquitination.1 Publication
    Ubiquitinated; leading to degradation by the proteasome.1 Publication

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ7Z698.
    PaxDbiQ7Z698.
    PRIDEiQ7Z698.

    PTM databases

    PhosphoSiteiQ7Z698.

    Expressioni

    Tissue specificityi

    Expressed in liver, skin, small intestine, salivary gland and prostate.1 Publication

    Gene expression databases

    ArrayExpressiQ7Z698.
    BgeeiQ7Z698.
    CleanExiHS_SPRED2.
    GenevestigatoriQ7Z698.

    Organism-specific databases

    HPAiCAB037223.
    HPA038256.

    Interactioni

    Subunit structurei

    Interacts with Ras By similarity. Homodimer and heterodimer. Able to interact with SPRED1 to form heterodimers.By similarity1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ZDHHC17Q8IUH53EBI-7082156,EBI-524753

    Protein-protein interaction databases

    BioGridi128344. 5 interactions.
    IntActiQ7Z698. 2 interactions.
    MINTiMINT-8020116.
    STRINGi9606.ENSP00000348753.

    Structurei

    Secondary structure

    1
    418
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi5 – 84
    Beta strandi11 – 2313
    Beta strandi27 – 326
    Beta strandi39 – 446
    Beta strandi57 – 6711
    Beta strandi69 – 779
    Beta strandi81 – 855
    Beta strandi88 – 925
    Beta strandi94 – 10411
    Helixi105 – 12319

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2JP2NMR-A1-124[»]
    ProteinModelPortaliQ7Z698.
    SMRiQ7Z698. Positions 1-124.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ7Z698.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini5 – 122118WH1PROSITE-ProRule annotationAdd
    BLAST
    Domaini201 – 25757KBDPROSITE-ProRule annotationAdd
    BLAST
    Domaini308 – 416109SPRPROSITE-ProRule annotationAdd
    BLAST

    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.
    HOGENOMiHOG000220886.
    HOVERGENiHBG057556.
    InParanoidiQ7Z698.
    KOiK04703.
    OrthoDBiEOG7T7GV7.
    PhylomeDBiQ7Z698.
    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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q7Z698-1) [UniParc]FASTAAdd to Basket

    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

    MTEETHPDDD SYIVRVKAVV MTRDDSSGGW FPQEGGGISR VGVCKVMHPE    50
    GNGRSGFLIH GERQKDKLVV LECYVRKDLV YTKANPTFHH WKVDNRKFGL 100
    TFQSPADARA FDRGVRKAIE DLIEGSTTSS STIHNEAELG DDDVFTTATD 150
    SSSNSSQKRE QPTRTISSPT SCEHRRIYTL GHLHDSYPTD HYHLDQPMPR 200
    PYRQVSFPDD DEEIVRINPR EKIWMTGYED YRHAPVRGKY PDPSEDADSS 250
    YVRFAKGEVP KHDYNYPYVD SSDFGLGEDP KGRGGSVIKT QPSRGKSRRR 300
    KEDGERSRCV YCRDMFNHEE NRRGHCQDAP DSVRTCIRRV SCMWCADSML 350
    YHCMSDPEGD YTDPCSCDTS DEKFCLRWMA LIALSFLAPC MCCYLPLRAC 400
    YHCGVMCRCC GGKHKAAA 418
    Length:418
    Mass (Da):47,558
    Last modified:July 25, 2006 - v2
    Checksum:iCA4FE80C45008851
    GO
    Isoform 2 (identifier: Q7Z698-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-9: MTEETHPDD → MASPGS

    Note: No experimental confirmation available.

    Show »
    Length:415
    Mass (Da):47,033
    Checksum:i2E6F7236B9F0FB3C
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti33 – 331Q → R in BAH12943. (PubMed:14702039)Curated
    Sequence conflicti202 – 2021Y → C in AAP59415. (PubMed:15683364)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 99MTEETHPDD → MASPGS in isoform 2. 1 PublicationVSP_043755

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY299090 mRNA. Translation: AAP59415.1.
    AK299079 mRNA. Translation: BAH12943.1.
    AC012370 Genomic DNA. No translation available.
    AC097503 Genomic DNA. No translation available.
    CH471053 Genomic DNA. Translation: EAW99905.1.
    CH471053 Genomic DNA. Translation: EAW99906.1.
    BC111495 mRNA. Translation: AAI11496.1.
    BC130292 mRNA. Translation: AAI30293.1.
    BC136334 mRNA. Translation: AAI36335.1.
    CCDSiCCDS33211.1. [Q7Z698-1]
    CCDS46308.1. [Q7Z698-2]
    RefSeqiNP_001121682.1. NM_001128210.1. [Q7Z698-2]
    NP_861449.2. NM_181784.2. [Q7Z698-1]
    XP_006712029.1. XM_006711966.1. [Q7Z698-1]
    UniGeneiHs.59332.

    Genome annotation databases

    EnsembliENST00000356388; ENSP00000348753; ENSG00000198369. [Q7Z698-1]
    ENST00000443619; ENSP00000393697; ENSG00000198369. [Q7Z698-2]
    GeneIDi200734.
    KEGGihsa:200734.
    UCSCiuc002sdr.4. human. [Q7Z698-1]
    uc010fcw.3. human. [Q7Z698-2]

    Polymorphism databases

    DMDMi110825745.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY299090 mRNA. Translation: AAP59415.1 .
    AK299079 mRNA. Translation: BAH12943.1 .
    AC012370 Genomic DNA. No translation available.
    AC097503 Genomic DNA. No translation available.
    CH471053 Genomic DNA. Translation: EAW99905.1 .
    CH471053 Genomic DNA. Translation: EAW99906.1 .
    BC111495 mRNA. Translation: AAI11496.1 .
    BC130292 mRNA. Translation: AAI30293.1 .
    BC136334 mRNA. Translation: AAI36335.1 .
    CCDSi CCDS33211.1. [Q7Z698-1 ]
    CCDS46308.1. [Q7Z698-2 ]
    RefSeqi NP_001121682.1. NM_001128210.1. [Q7Z698-2 ]
    NP_861449.2. NM_181784.2. [Q7Z698-1 ]
    XP_006712029.1. XM_006711966.1. [Q7Z698-1 ]
    UniGenei Hs.59332.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2JP2 NMR - A 1-124 [» ]
    ProteinModelPortali Q7Z698.
    SMRi Q7Z698. Positions 1-124.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 128344. 5 interactions.
    IntActi Q7Z698. 2 interactions.
    MINTi MINT-8020116.
    STRINGi 9606.ENSP00000348753.

    PTM databases

    PhosphoSitei Q7Z698.

    Polymorphism databases

    DMDMi 110825745.

    Proteomic databases

    MaxQBi Q7Z698.
    PaxDbi Q7Z698.
    PRIDEi Q7Z698.

    Protocols and materials databases

    DNASUi 200734.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000356388 ; ENSP00000348753 ; ENSG00000198369 . [Q7Z698-1 ]
    ENST00000443619 ; ENSP00000393697 ; ENSG00000198369 . [Q7Z698-2 ]
    GeneIDi 200734.
    KEGGi hsa:200734.
    UCSCi uc002sdr.4. human. [Q7Z698-1 ]
    uc010fcw.3. human. [Q7Z698-2 ]

    Organism-specific databases

    CTDi 200734.
    GeneCardsi GC02M065537.
    HGNCi HGNC:17722. SPRED2.
    HPAi CAB037223.
    HPA038256.
    MIMi 609292. gene.
    neXtProti NX_Q7Z698.
    PharmGKBi PA134956365.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG277322.
    HOGENOMi HOG000220886.
    HOVERGENi HBG057556.
    InParanoidi Q7Z698.
    KOi K04703.
    OrthoDBi EOG7T7GV7.
    PhylomeDBi Q7Z698.
    TreeFami TF321411.

    Miscellaneous databases

    ChiTaRSi SPRED2. human.
    EvolutionaryTracei Q7Z698.
    GeneWikii SPRED2.
    GenomeRNAii 200734.
    NextBioi 89969.
    PROi Q7Z698.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q7Z698.
    Bgeei Q7Z698.
    CleanExi HS_SPRED2.
    Genevestigatori Q7Z698.

    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

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH SPRED1.
      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] (ISOFORM 2).
    3. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "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] (ISOFORM 1).
      Tissue: Brain and Ovary.
    6. "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.
    7. "Spred-2 steady-state levels are regulated by phosphorylation and Cbl-mediated ubiquitination."
      Lock P., I S.T.T., Straffon A.F., Schieb H., Hovens C.M., Stylli S.S.
      Biochem. Biophys. Res. Commun. 351:1018-1023(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION, PHOSPHORYLATION AT TYR-228 AND TYR-231.
    8. "1H, 13C and 15N resonance assignment of the human Spred2 EVH1 domain."
      Zimmermann J., Jarchau T., Walter U., Oschkinat H., Ball L.J.
      J. Biomol. NMR 29:435-436(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 1-124.

    Entry informationi

    Entry nameiSPRE2_HUMAN
    AccessioniPrimary (citable) accession number: Q7Z698
    Secondary accession number(s): A1L3V4
    , B7Z5K7, D6W5F7, E9PEP0, Q2NKX6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 4, 2005
    Last sequence update: July 25, 2006
    Last modified: October 1, 2014
    This is version 102 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 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3