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Q9Z0Z3

- SKP2_MOUSE

UniProt

Q9Z0Z3 - SKP2_MOUSE

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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

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 - 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
Complete GO annotation...

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. aggresome Source: Ensembl
  2. cytoplasm Source: UniProtKB-KW
  3. nucleolus Source: Ensembl
  4. SCF ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

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

MaxQBiQ9Z0Z3.
PRIDEiQ9Z0Z3.

PTM databases

PhosphoSiteiQ9Z0Z3.

Expressioni

Gene expression databases

BgeeiQ9Z0Z3.
CleanExiMM_SKP2.
ExpressionAtlasiQ9Z0Z3. baseline and differential.
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

        10         20         30         40         50
MHRKHLQEIP DQSGNVTTSF TWGWDSSKTS ELLSGMGVSA LEKEEVDSEN
60 70 80 90 100
IPHGLLSNLG HPQSPPRKRV KGKGSDKDFV IIRRPKLSRE NFPGVSWDSL
110 120 130 140 150
PDELLLGIFS CLCLPELLRV SGVCKRWYRL SLDESLWQSL DLAGKNLHPD
160 170 180 190 200
VTVRLLSRGV VAFRCPRSFM EQPLGESFSS FRVQHMDLSN SVINVSNLHK
210 220 230 240 250
ILSECSKLQN LSLEGLQLSD PIVKTLAQNE NLVRLNLCGC SGFSESAVAT
260 270 280 290 300
LLSSCSRLDE LNLSWCFDFT EKHVQAAVAH LPNTITQLNL SGYRKNLQKT
310 320 330 340 350
DLCTIIKRCP NLIRLDLSDS IMLKNDCFPE FFQLNYLQHL SLSRCYDIIP
360 370 380 390 400
DTLLELGEIP TLKTLQVFGI VPEGTLQLLR EALPRLQINC AYFTTIARPT
410 420
MDSKKNLEIW GIKCRLTLQK PSCL
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

MaxQBi Q9Z0Z3.
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

Bgeei Q9Z0Z3.
CleanExi MM_SKP2.
ExpressionAtlasi Q9Z0Z3. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 122 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