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Q9Z0Z3

- SKP2_MOUSE

UniProt

Q9Z0Z3 - SKP2_MOUSE

Protein

S-phase kinase-associated protein 2

Gene

Skp2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 121 (01 Oct 2014)
      Sequence version 1 (01 May 1999)
      Previous versions | rss
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    Functioni

    Substrate recognition component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription. The SCF complex provides substrate specificity and interacts with both, the E2 ubiquitin-conjugating enzyme and the substrate. Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. Degradation of CDKN1B/p27kip also requires CKS1. Promotes ubiquitination and destruction of CDH1 in a CK1-Dependent Manner, thereby regulating cell migration By similarity.By similarity

    Pathwayi

    GO - Molecular functioni

    1. protein binding Source: MGI

    GO - Biological processi

    1. cellular response to cell-matrix adhesion Source: Ensembl
    2. G1/S transition of mitotic cell cycle Source: MGI
    3. G2/M transition of mitotic cell cycle Source: MGI
    4. positive regulation of intracellular estrogen receptor signaling pathway Source: MGI
    5. positive regulation of smooth muscle cell proliferation Source: Ensembl
    6. protein polyubiquitination Source: MGI
    7. regulation of cell cycle Source: MGI
    8. ubiquitin-dependent protein catabolic process Source: MGI

    Keywords - Biological processi

    Ubl conjugation pathway

    Enzyme and pathway databases

    ReactomeiREACT_199115. Antigen processing: Ubiquitination & Proteasome degradation.
    REACT_220647. SCF(Skp2)-mediated degradation of p27/p21.
    REACT_226135. APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    S-phase kinase-associated protein 2
    Alternative name(s):
    Cyclin-A/CDK2-associated protein p45
    F-box protein Skp2
    F-box/WD-40 protein 1
    Short name:
    FWD1
    Gene namesi
    Name:Skp2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 15

    Organism-specific databases

    MGIiMGI:1351663. Skp2.

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell
    3. SCF ubiquitin ligase complex Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 424424S-phase kinase-associated protein 2PRO_0000119955Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei64 – 641PhosphoserineBy similarity
    Modified residuei68 – 681N6-acetyllysine; by p300/EP300By similarity
    Modified residuei71 – 711N6-acetyllysine; by p300/EP300By similarity
    Modified residuei179 – 1791PhosphoserineBy similarity

    Post-translational modificationi

    Ubiquitinated by the APC/C complex, leading to its degradation by the proteasome. Deubiquitinated by USP13 By similarity.By similarity
    Acetylation at Lys-68 and Lys-71 increases stability through impairment of APC/C-mediated proteolysis and promotes cytoplasmic retention. Deacetylated by SIRT3 By similarity.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiQ9Z0Z3.

    PTM databases

    PhosphoSiteiQ9Z0Z3.

    Expressioni

    Gene expression databases

    ArrayExpressiQ9Z0Z3.
    BgeeiQ9Z0Z3.
    CleanExiMM_SKP2.
    GenevestigatoriQ9Z0Z3.

    Interactioni

    Subunit structurei

    Part of a SCF(SKP2) complex consisting of CUL1, RBX1, SKP1 and SKP2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Interacts directly with CUL1 and SKP1. Interacts with CKS1. Interacts with the cyclin-A-CDK2 complex. Interacts with ORC1, phosphorylated CDT1, phosphorylated RBL2, ELF4, phosphorylated RAG2, FOXO1, UBP43, MYC, TOB1, TAL1 and KMT2A/MLL1. Interacts with TRIM21 By similarity.By similarity

    Protein-protein interaction databases

    BioGridi205208. 12 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9Z0Z3.
    SMRiQ9Z0Z3. Positions 95-419.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini94 – 14047F-boxPROSITE-ProRule annotationAdd
    BLAST
    Repeati151 – 17626LRR 1Add
    BLAST
    Repeati177 – 20428LRR 2Add
    BLAST
    Repeati210 – 23425LRR 3Add
    BLAST
    Repeati235 – 25723LRR 4Add
    BLAST
    Repeati258 – 28427LRR 5Add
    BLAST
    Repeati286 – 30823LRR 6Add
    BLAST
    Repeati309 – 33022LRR 7Add
    BLAST
    Repeati334 – 35623LRR 8Add
    BLAST
    Repeati359 – 37820LRR 9Add
    BLAST
    Repeati380 – 40122LRR 10Add
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi67 – 737Nuclear localization signalBy similarity

    Sequence similaritiesi

    Contains 1 F-box domain.PROSITE-ProRule annotation
    Contains 10 LRR (leucine-rich) repeats.Curated

    Keywords - Domaini

    Leucine-rich repeat, Repeat

    Phylogenomic databases

    eggNOGiNOG263321.
    GeneTreeiENSGT00390000007918.
    HOGENOMiHOG000247037.
    HOVERGENiHBG047488.
    InParanoidiQ9Z0Z3.
    KOiK03875.
    OMAiEIWGIRC.
    OrthoDBiEOG7PGDRM.
    PhylomeDBiQ9Z0Z3.
    TreeFamiTF352582.

    Family and domain databases

    InterProiIPR001810. F-box_dom.
    [Graphical view]
    PfamiPF00646. F-box. 1 hit.
    [Graphical view]
    SMARTiSM00256. FBOX. 1 hit.
    [Graphical view]
    SUPFAMiSSF81383. SSF81383. 1 hit.
    PROSITEiPS50181. FBOX. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9Z0Z3-1) [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

    MHRKHLQEIP DQSGNVTTSF TWGWDSSKTS ELLSGMGVSA LEKEEVDSEN    50
    IPHGLLSNLG HPQSPPRKRV KGKGSDKDFV IIRRPKLSRE NFPGVSWDSL 100
    PDELLLGIFS CLCLPELLRV SGVCKRWYRL SLDESLWQSL DLAGKNLHPD 150
    VTVRLLSRGV VAFRCPRSFM EQPLGESFSS FRVQHMDLSN SVINVSNLHK 200
    ILSECSKLQN LSLEGLQLSD PIVKTLAQNE NLVRLNLCGC SGFSESAVAT 250
    LLSSCSRLDE LNLSWCFDFT EKHVQAAVAH LPNTITQLNL SGYRKNLQKT 300
    DLCTIIKRCP NLIRLDLSDS IMLKNDCFPE FFQLNYLQHL SLSRCYDIIP 350
    DTLLELGEIP TLKTLQVFGI VPEGTLQLLR EALPRLQINC AYFTTIARPT 400
    MDSKKNLEIW GIKCRLTLQK PSCL 424
    Length:424
    Mass (Da):47,766
    Last modified:May 1, 1999 - v1
    Checksum:i5B7945C979D26AF9
    GO
    Isoform 2 (identifier: Q9Z0Z3-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         355-424: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:354
    Mass (Da):39,871
    Checksum:iE6D8A1AC6B680856
    GO
    Isoform 3 (identifier: Q9Z0Z3-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         132-424: Missing.

    Show »
    Length:131
    Mass (Da):14,743
    Checksum:i24E1A1BF3BC115FF
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti340 – 3401L → H in BAC28108. (PubMed:16141072)Curated
    Sequence conflicti353 – 3531L → V in BAC31819. (PubMed:16141072)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei132 – 424293Missing in isoform 3. 2 PublicationsVSP_008433Add
    BLAST
    Alternative sequencei355 – 42470Missing in isoform 2. 1 PublicationVSP_008434Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF083215 mRNA. Translation: AAD16037.1.
    AK032979 mRNA. Translation: BAC28108.1.
    AK044212 mRNA. Translation: BAC31819.1.
    AK037002 mRNA. No translation available.
    BC003468 mRNA. Translation: AAH03468.1.
    CCDSiCCDS37037.1. [Q9Z0Z3-1]
    RefSeqiNP_038815.1. NM_013787.3. [Q9Z0Z3-1]
    UniGeneiMm.35584.

    Genome annotation databases

    EnsembliENSMUST00000096482; ENSMUSP00000094225; ENSMUSG00000054115. [Q9Z0Z3-1]
    ENSMUST00000110585; ENSMUSP00000106215; ENSMUSG00000054115. [Q9Z0Z3-2]
    GeneIDi27401.
    KEGGimmu:27401.
    UCSCiuc007vff.1. mouse. [Q9Z0Z3-1]
    uc007vfi.2. mouse. [Q9Z0Z3-3]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF083215 mRNA. Translation: AAD16037.1 .
    AK032979 mRNA. Translation: BAC28108.1 .
    AK044212 mRNA. Translation: BAC31819.1 .
    AK037002 mRNA. No translation available.
    BC003468 mRNA. Translation: AAH03468.1 .
    CCDSi CCDS37037.1. [Q9Z0Z3-1 ]
    RefSeqi NP_038815.1. NM_013787.3. [Q9Z0Z3-1 ]
    UniGenei Mm.35584.

    3D structure databases

    ProteinModelPortali Q9Z0Z3.
    SMRi Q9Z0Z3. Positions 95-419.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 205208. 12 interactions.

    PTM databases

    PhosphoSitei Q9Z0Z3.

    Proteomic databases

    PRIDEi Q9Z0Z3.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000096482 ; ENSMUSP00000094225 ; ENSMUSG00000054115 . [Q9Z0Z3-1 ]
    ENSMUST00000110585 ; ENSMUSP00000106215 ; ENSMUSG00000054115 . [Q9Z0Z3-2 ]
    GeneIDi 27401.
    KEGGi mmu:27401.
    UCSCi uc007vff.1. mouse. [Q9Z0Z3-1 ]
    uc007vfi.2. mouse. [Q9Z0Z3-3 ]

    Organism-specific databases

    CTDi 6502.
    MGIi MGI:1351663. Skp2.

    Phylogenomic databases

    eggNOGi NOG263321.
    GeneTreei ENSGT00390000007918.
    HOGENOMi HOG000247037.
    HOVERGENi HBG047488.
    InParanoidi Q9Z0Z3.
    KOi K03875.
    OMAi EIWGIRC.
    OrthoDBi EOG7PGDRM.
    PhylomeDBi Q9Z0Z3.
    TreeFami TF352582.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .
    Reactomei REACT_199115. Antigen processing: Ubiquitination & Proteasome degradation.
    REACT_220647. SCF(Skp2)-mediated degradation of p27/p21.
    REACT_226135. APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.

    Miscellaneous databases

    NextBioi 305392.
    PROi Q9Z0Z3.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9Z0Z3.
    Bgeei Q9Z0Z3.
    CleanExi MM_SKP2.
    Genevestigatori Q9Z0Z3.

    Family and domain databases

    InterProi IPR001810. F-box_dom.
    [Graphical view ]
    Pfami PF00646. F-box. 1 hit.
    [Graphical view ]
    SMARTi SM00256. FBOX. 1 hit.
    [Graphical view ]
    SUPFAMi SSF81383. SSF81383. 1 hit.
    PROSITEi PS50181. FBOX. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Targeted disruption of Skp2 results in accumulation of cyclin E and p27(Kip1), polyploidy and centrosome overduplication."
      Nakayama K., Nagahama H., Minamishima Y.A., Matsumoto M., Nakamichi I., Kitagawa K., Shirane M., Tsunematsu R., Tsukiyama T., Ishida N., Kitagawa M., Nakayama K., Hatakeyama S.
      EMBO J. 19:2069-2081(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH CYCE.
      Strain: C57BL/6 X CBA.
      Tissue: Thymus.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
      Strain: C57BL/6J.
      Tissue: Mesonephros, Retina and Vagina.
    3. "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 3).
      Tissue: Mammary gland.

    Entry informationi

    Entry nameiSKP2_MOUSE
    AccessioniPrimary (citable) accession number: Q9Z0Z3
    Secondary accession number(s): Q8BSG7
    , Q8C8Y9, Q8CB22, Q99J53
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 3, 2003
    Last sequence update: May 1, 1999
    Last modified: October 1, 2014
    This is version 121 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3