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Protein

S-phase kinase-associated protein 2

Gene

Skp2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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 similarity1 Publication

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

GO - Biological processi

  • cellular response to cell-matrix adhesion Source: Ensembl
  • G1/S transition of mitotic cell cycle Source: MGI
  • G2/M transition of mitotic cell cycle Source: MGI
  • positive regulation of intracellular estrogen receptor signaling pathway Source: MGI
  • positive regulation of protein polyubiquitination Source: MGI
  • positive regulation of smooth muscle cell proliferation Source: Ensembl
  • protein polyubiquitination Source: MGI
  • regulation of apoptotic process Source: MGI
  • regulation of cell cycle Source: MGI
  • ubiquitin-dependent protein catabolic process Source: MGI
Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-174178. APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
R-MMU-187577. SCF(Skp2)-mediated degradation of p27/p21.
R-MMU-5689880. Ub-specific processing proteases.
R-MMU-69231. Cyclin D associated events in G1.
R-MMU-983168. Antigen processing: Ubiquitination & Proteasome degradation.
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
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:1351663. Skp2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001199551 – 424S-phase kinase-associated protein 2Add BLAST424

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei64PhosphoserineBy similarity1
Modified residuei68N6-acetyllysine; by p300/EP300By similarity1
Modified residuei71N6-acetyllysine; by p300/EP300By similarity1
Modified residuei75PhosphoserineBy similarity1
Modified residuei179PhosphoserineBy similarity1

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

PaxDbiQ9Z0Z3.
PRIDEiQ9Z0Z3.

PTM databases

iPTMnetiQ9Z0Z3.
PhosphoSitePlusiQ9Z0Z3.

Expressioni

Gene expression databases

BgeeiENSMUSG00000054115.
CleanExiMM_SKP2.
ExpressionAtlasiQ9Z0Z3. baseline and differential.
GenevisibleiQ9Z0Z3. MM.

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. 13 interactors.
STRINGi10090.ENSMUSP00000094225.

Structurei

3D structure databases

ProteinModelPortaliQ9Z0Z3.
SMRiQ9Z0Z3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini94 – 140F-boxPROSITE-ProRule annotationAdd BLAST47
Repeati151 – 176LRR 1Add BLAST26
Repeati177 – 204LRR 2Add BLAST28
Repeati210 – 234LRR 3Add BLAST25
Repeati235 – 257LRR 4Add BLAST23
Repeati258 – 284LRR 5Add BLAST27
Repeati286 – 308LRR 6Add BLAST23
Repeati309 – 330LRR 7Add BLAST22
Repeati334 – 356LRR 8Add BLAST23
Repeati359 – 378LRR 9Add BLAST20
Repeati380 – 401LRR 10Add BLAST22

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi67 – 73Nuclear localization signalBy similarity7

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

eggNOGiKOG2120. Eukaryota.
ENOG410Z2W2. LUCA.
GeneTreeiENSGT00390000007918.
HOGENOMiHOG000247037.
HOVERGENiHBG047488.
InParanoidiQ9Z0Z3.
KOiK03875.
OMAiEIWGIRC.
OrthoDBiEOG091G0EYN.
PhylomeDBiQ9Z0Z3.
TreeFamiTF352582.

Family and domain databases

Gene3Di3.80.10.10. 1 hit.
InterProiIPR001810. F-box_dom.
IPR032675. L_dom-like.
IPR006553. Leu-rich_rpt_Cys-con_subtyp.
[Graphical view]
PfamiPF12937. F-box-like. 1 hit.
[Graphical view]
SMARTiSM00256. FBOX. 1 hit.
SM00367. LRR_CC. 4 hits.
[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. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Sequence conflicti340L → H in BAC28108 (PubMed:16141072).Curated1
Sequence conflicti353L → V in BAC31819 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_008433132 – 424Missing in isoform 3. 2 PublicationsAdd BLAST293
Alternative sequenceiVSP_008434355 – 424Missing in isoform 2. 1 PublicationAdd BLAST70

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.2. mouse. [Q9Z0Z3-1]
uc007vfi.3. mouse. [Q9Z0Z3-3]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliQ9Z0Z3.
SMRiQ9Z0Z3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi205208. 13 interactors.
STRINGi10090.ENSMUSP00000094225.

PTM databases

iPTMnetiQ9Z0Z3.
PhosphoSitePlusiQ9Z0Z3.

Proteomic databases

PaxDbiQ9Z0Z3.
PRIDEiQ9Z0Z3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi6502.
MGIiMGI:1351663. Skp2.

Phylogenomic databases

eggNOGiKOG2120. Eukaryota.
ENOG410Z2W2. LUCA.
GeneTreeiENSGT00390000007918.
HOGENOMiHOG000247037.
HOVERGENiHBG047488.
InParanoidiQ9Z0Z3.
KOiK03875.
OMAiEIWGIRC.
OrthoDBiEOG091G0EYN.
PhylomeDBiQ9Z0Z3.
TreeFamiTF352582.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-MMU-174178. APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
R-MMU-187577. SCF(Skp2)-mediated degradation of p27/p21.
R-MMU-5689880. Ub-specific processing proteases.
R-MMU-69231. Cyclin D associated events in G1.
R-MMU-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

PROiQ9Z0Z3.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000054115.
CleanExiMM_SKP2.
ExpressionAtlasiQ9Z0Z3. baseline and differential.
GenevisibleiQ9Z0Z3. MM.

Family and domain databases

Gene3Di3.80.10.10. 1 hit.
InterProiIPR001810. F-box_dom.
IPR032675. L_dom-like.
IPR006553. Leu-rich_rpt_Cys-con_subtyp.
[Graphical view]
PfamiPF12937. F-box-like. 1 hit.
[Graphical view]
SMARTiSM00256. FBOX. 1 hit.
SM00367. LRR_CC. 4 hits.
[Graphical view]
SUPFAMiSSF81383. SSF81383. 1 hit.
PROSITEiPS50181. FBOX. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 142 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.