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Protein

S-phase kinase-associated protein 2

Gene

SKP2

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

Functioni

Substrate recognition component of a 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. Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, FOXO1, UBP43, and probably MYC, TOB1 and TAL1. Degradation of TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2. Promotes ubiquitination and destruction of CDH1 in a CK1-Dependent Manner, thereby regulating cell migration.14 Publications

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

Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-174178. APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
R-HSA-187577. SCF(Skp2)-mediated degradation of p27/p21.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-69231. Cyclin D associated events in G1.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SIGNORiQ13309.
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/LRR-repeat protein 1
p45skp2
Gene namesi
Name:SKP2
Synonyms:FBXL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:10901. SKP2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • nucleolus Source: HPA
  • nucleoplasm Source: Reactome
  • nucleus Source: HPA
  • SCF ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi6502.
OpenTargetsiENSG00000145604.
PharmGKBiPA35801.

Polymorphism and mutation databases

BioMutaiSKP2.
DMDMi37537922.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001199541 – 424S-phase kinase-associated protein 2Add BLAST424

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei64PhosphoserineCombined sources1
Modified residuei68N6-acetyllysine; by p300/EP3001 Publication1
Modified residuei71N6-acetyllysine; by p300/EP3001 Publication1
Modified residuei72PhosphoserineCombined sources1
Modified residuei75PhosphoserineCombined sources1
Modified residuei179PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated by the APC/C complex, leading to its degradation by the proteasome. Deubiquitinated by USP13.1 Publication
Acetylation at Lys-68 and Lys-71 increases stability through impairment of APC/C-mediated proteolysis and promotes cytoplasmic retention. Deacetylated by SIRT3.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ13309.
MaxQBiQ13309.
PaxDbiQ13309.
PeptideAtlasiQ13309.
PRIDEiQ13309.
TopDownProteomicsiQ13309-1. [Q13309-1]

PTM databases

iPTMnetiQ13309.
PhosphoSitePlusiQ13309.

Expressioni

Gene expression databases

BgeeiENSG00000145604.
CleanExiHS_SKP2.
ExpressionAtlasiQ13309. baseline and differential.
GenevisibleiQ13309. HS.

Organism-specific databases

HPAiCAB013491.
CAB013533.
HPA051196.
HPA054633.

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 TRIM21.15 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-456291,EBI-456291
CDH1A5D8W42EBI-456291,EBI-7793316
Cdh1P098032EBI-456291,EBI-984420From a different organism.
CDKN1AP389362EBI-456291,EBI-375077
CDKN1BP465274EBI-456291,EBI-519280
CKS1BP610246EBI-456291,EBI-456371
CUL1Q136169EBI-456291,EBI-359390
DUSP1P285623EBI-456291,EBI-975493
EP300Q094723EBI-456291,EBI-447295
FZR1Q9UM112EBI-456291,EBI-724997
MYCP011062EBI-456291,EBI-447544
ORC1Q134152EBI-456291,EBI-374847
PHBP352322EBI-7791408,EBI-354213
RBX1P628773EBI-456291,EBI-398523
SIRT3Q9NTG75EBI-456291,EBI-724621
SKP1P6320816EBI-456291,EBI-307486
XQ4AE163EBI-456291,EBI-7418293From a different organism.

Protein-protein interaction databases

BioGridi112393. 164 interactors.
DIPiDIP-17011N.
IntActiQ13309. 51 interactors.
MINTiMINT-152160.
STRINGi9606.ENSP00000274255.

Structurei

Secondary structure

1424
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi97 – 100Combined sources4
Helixi102 – 109Combined sources8
Helixi114 – 116Combined sources3
Helixi117 – 121Combined sources5
Helixi125 – 131Combined sources7
Helixi134 – 136Combined sources3
Beta strandi137 – 141Combined sources5
Helixi149 – 157Combined sources9
Beta strandi161 – 164Combined sources4
Beta strandi180 – 182Combined sources3
Beta strandi185 – 187Combined sources3
Helixi195 – 202Combined sources8
Beta strandi209 – 212Combined sources4
Helixi220 – 226Combined sources7
Beta strandi233 – 236Combined sources4
Helixi245 – 254Combined sources10
Beta strandi260 – 262Combined sources3
Helixi271 – 280Combined sources10
Beta strandi287 – 289Combined sources3
Helixi294 – 296Combined sources3
Helixi299 – 308Combined sources10
Beta strandi313 – 316Combined sources4
Helixi325 – 333Combined sources9
Beta strandi339 – 341Combined sources3
Helixi350 – 358Combined sources9
Beta strandi364 – 366Combined sources3
Helixi376 – 382Combined sources7
Beta strandi386 – 389Combined sources4
Beta strandi402 – 404Combined sources3
Beta strandi415 – 417Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FQVX-ray2.80A/C/E/G/I/K/M/O89-424[»]
1FS1X-ray1.80A/C89-141[»]
1FS2X-ray2.90A/C89-398[»]
1LDKX-ray3.10E97-137[»]
2ASSX-ray3.00B89-424[»]
2ASTX-ray2.30B89-424[»]
ProteinModelPortaliQ13309.
SMRiQ13309.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13309.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini94 – 140F-boxPROSITE-ProRule annotationAdd BLAST47
Repeati151 – 176LRR 11 PublicationAdd BLAST26
Repeati177 – 204LRR 21 PublicationAdd BLAST28
Repeati210 – 234LRR 31 PublicationAdd BLAST25
Repeati235 – 257LRR 41 PublicationAdd BLAST23
Repeati258 – 284LRR 51 PublicationAdd BLAST27
Repeati286 – 308LRR 61 PublicationAdd BLAST23
Repeati309 – 330LRR 71 PublicationAdd BLAST22
Repeati334 – 356LRR 81 PublicationAdd BLAST23
Repeati359 – 378LRR 91 PublicationAdd BLAST20
Repeati380 – 401LRR 101 PublicationAdd BLAST22

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi67 – 73Nuclear localization signal1 Publication7

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.
InParanoidiQ13309.
KOiK03875.
OMAiEIWGIRC.
PhylomeDBiQ13309.
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. 5 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: Q13309-1) [UniParc]FASTAAdd to basket
Also known as: SKP2-alpha

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 DLSSNVATSF TWGWDSSKTS ELLSGMGVSA LEKEEPDSEN
60 70 80 90 100
IPQELLSNLG HPESPPRKRL KSKGSDKDFV IVRRPKLNRE NFPGVSWDSL
110 120 130 140 150
PDELLLGIFS CLCLPELLKV SGVCKRWYRL ASDESLWQTL DLTGKNLHPD
160 170 180 190 200
VTGRLLSQGV IAFRCPRSFM DQPLAEHFSP FRVQHMDLSN SVIEVSTLHG
210 220 230 240 250
ILSQCSKLQN LSLEGLRLSD PIVNTLAKNS NLVRLNLSGC SGFSEFALQT
260 270 280 290 300
LLSSCSRLDE LNLSWCFDFT EKHVQVAVAH VSETITQLNL SGYRKNLQKS
310 320 330 340 350
DLSTLVRRCP NLVHLDLSDS VMLKNDCFQE FFQLNYLQHL SLSRCYDIIP
360 370 380 390 400
ETLLELGEIP TLKTLQVFGI VPDGTLQLLK EALPHLQINC SHFTTIARPT
410 420
IGNKKNQEIW GIKCRLTLQK PSCL
Length:424
Mass (Da):47,761
Last modified:October 3, 2003 - v2
Checksum:iF29B7C338A7A37E9
GO
Isoform 2 (identifier: Q13309-2) [UniParc]FASTAAdd to basket
Also known as: SKP2-beta

The sequence of this isoform differs from the canonical sequence as follows:
     355-424: ELGEIPTLKT...RLTLQKPSCL → LVTRAGVRIR...FYFYRLVLKQ

Show »
Length:410
Mass (Da):46,576
Checksum:i8CB41CC9968695E3
GO
Isoform 3 (identifier: Q13309-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-169: Missing.
     180-224: Missing.

Note: No experimental confirmation available.
Show »
Length:210
Mass (Da):23,763
Checksum:i06BF227E9F6974C9
GO

Sequence cautioni

The sequence AAC50242 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAB87202 differs from that shown. Probable cloning artifact.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti185H → D in AAC50242 (PubMed:7553852).Curated1
Sequence conflicti215Missing in AAC50242 (PubMed:7553852).Curated1
Sequence conflicti238S → P in AAC50242 (PubMed:7553852).Curated1
Sequence conflicti241S → P in AAC50242 (PubMed:7553852).Curated1
Sequence conflicti244 – 247SEFA → PKFP in AAC50242 (PubMed:7553852).Curated4
Sequence conflicti251L → F in AAC50242 (PubMed:7553852).Curated1
Sequence conflicti256S → P in AAC50242 (PubMed:7553852).Curated1
Sequence conflicti268D → N in AAC50242 (PubMed:7553852).Curated1
Sequence conflicti285I → M in AAC50242 (PubMed:7553852).Curated1
Sequence conflicti319D → N in AAC50242 (PubMed:7553852).Curated1
Sequence conflicti332F → S in AAC50242 (PubMed:7553852).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01698485P → L.Corresponds to variant rs3913486dbSNPEnsembl.1
Natural variantiVAR_01698587L → I.Corresponds to variant rs3913487dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0449311 – 169Missing in isoform 3. 1 PublicationAdd BLAST169
Alternative sequenceiVSP_044932180 – 224Missing in isoform 3. 1 PublicationAdd BLAST45
Alternative sequenceiVSP_008432355 – 424ELGEI…KPSCL → LVTRAGVRIRLDSDIGCPQT YRTSKLKSSHKLFCQHVRVI CIFVCDFYFYRLVLKQ in isoform 2. 2 PublicationsAdd BLAST70

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U33761 mRNA. Translation: AAC50242.1. Different initiation.
AB050979 mRNA. Translation: BAB87200.1.
AB050980 mRNA. Translation: BAB87201.1.
AB050981 mRNA. Translation: BAB87202.1. Sequence problems.
AY029177 mRNA. Translation: AAK31593.1.
AK291255 mRNA. Translation: BAF83944.1.
AK296223 mRNA. Translation: BAG58946.1.
AC008942 Genomic DNA. No translation available.
CH471119 Genomic DNA. Translation: EAW55936.1.
BC001441 mRNA. Translation: AAH01441.1.
BC007441 mRNA. Translation: AAH07441.1.
CCDSiCCDS3915.1. [Q13309-2]
CCDS3916.1. [Q13309-1]
CCDS58944.1. [Q13309-4]
PIRiI39171.
RefSeqiNP_001230049.1. NM_001243120.1. [Q13309-4]
NP_005974.2. NM_005983.3. [Q13309-1]
NP_116026.1. NM_032637.3. [Q13309-2]
UniGeneiHs.23348.

Genome annotation databases

EnsembliENST00000274254; ENSP00000274254; ENSG00000145604. [Q13309-2]
ENST00000274255; ENSP00000274255; ENSG00000145604. [Q13309-1]
ENST00000620197; ENSP00000478031; ENSG00000145604. [Q13309-4]
GeneIDi6502.
KEGGihsa:6502.
UCSCiuc003jkc.3. human. [Q13309-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U33761 mRNA. Translation: AAC50242.1. Different initiation.
AB050979 mRNA. Translation: BAB87200.1.
AB050980 mRNA. Translation: BAB87201.1.
AB050981 mRNA. Translation: BAB87202.1. Sequence problems.
AY029177 mRNA. Translation: AAK31593.1.
AK291255 mRNA. Translation: BAF83944.1.
AK296223 mRNA. Translation: BAG58946.1.
AC008942 Genomic DNA. No translation available.
CH471119 Genomic DNA. Translation: EAW55936.1.
BC001441 mRNA. Translation: AAH01441.1.
BC007441 mRNA. Translation: AAH07441.1.
CCDSiCCDS3915.1. [Q13309-2]
CCDS3916.1. [Q13309-1]
CCDS58944.1. [Q13309-4]
PIRiI39171.
RefSeqiNP_001230049.1. NM_001243120.1. [Q13309-4]
NP_005974.2. NM_005983.3. [Q13309-1]
NP_116026.1. NM_032637.3. [Q13309-2]
UniGeneiHs.23348.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FQVX-ray2.80A/C/E/G/I/K/M/O89-424[»]
1FS1X-ray1.80A/C89-141[»]
1FS2X-ray2.90A/C89-398[»]
1LDKX-ray3.10E97-137[»]
2ASSX-ray3.00B89-424[»]
2ASTX-ray2.30B89-424[»]
ProteinModelPortaliQ13309.
SMRiQ13309.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112393. 164 interactors.
DIPiDIP-17011N.
IntActiQ13309. 51 interactors.
MINTiMINT-152160.
STRINGi9606.ENSP00000274255.

PTM databases

iPTMnetiQ13309.
PhosphoSitePlusiQ13309.

Polymorphism and mutation databases

BioMutaiSKP2.
DMDMi37537922.

Proteomic databases

EPDiQ13309.
MaxQBiQ13309.
PaxDbiQ13309.
PeptideAtlasiQ13309.
PRIDEiQ13309.
TopDownProteomicsiQ13309-1. [Q13309-1]

Protocols and materials databases

DNASUi6502.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000274254; ENSP00000274254; ENSG00000145604. [Q13309-2]
ENST00000274255; ENSP00000274255; ENSG00000145604. [Q13309-1]
ENST00000620197; ENSP00000478031; ENSG00000145604. [Q13309-4]
GeneIDi6502.
KEGGihsa:6502.
UCSCiuc003jkc.3. human. [Q13309-1]

Organism-specific databases

CTDi6502.
DisGeNETi6502.
GeneCardsiSKP2.
HGNCiHGNC:10901. SKP2.
HPAiCAB013491.
CAB013533.
HPA051196.
HPA054633.
MIMi601436. gene.
neXtProtiNX_Q13309.
OpenTargetsiENSG00000145604.
PharmGKBiPA35801.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2120. Eukaryota.
ENOG410Z2W2. LUCA.
GeneTreeiENSGT00390000007918.
HOGENOMiHOG000247037.
HOVERGENiHBG047488.
InParanoidiQ13309.
KOiK03875.
OMAiEIWGIRC.
PhylomeDBiQ13309.
TreeFamiTF352582.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-HSA-174178. APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
R-HSA-187577. SCF(Skp2)-mediated degradation of p27/p21.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-69231. Cyclin D associated events in G1.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SIGNORiQ13309.

Miscellaneous databases

ChiTaRSiSKP2. human.
EvolutionaryTraceiQ13309.
GeneWikiiSKP2.
GenomeRNAii6502.
PROiQ13309.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145604.
CleanExiHS_SKP2.
ExpressionAtlasiQ13309. baseline and differential.
GenevisibleiQ13309. HS.

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. 5 hits.
[Graphical view]
SUPFAMiSSF81383. SSF81383. 1 hit.
PROSITEiPS50181. FBOX. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSKP2_HUMAN
AccessioniPrimary (citable) accession number: Q13309
Secondary accession number(s): A8K5E0
, B4DJT4, Q8TDZ0, Q8TDZ1, Q9BV69
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: October 3, 2003
Last modified: November 30, 2016
This is version 172 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.