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Protein

S-phase kinase-associated protein 1

Gene

SKP1

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

Functioni

Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5, CEP68 and probably NFKB2 (PubMed:25704143). SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of cyclin E, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO11) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF) directs ubiquitination of CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1 and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2. SCF(FBXO10) directs ubiquitination of BCL2.5 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

  • beta-catenin binding Source: ParkinsonsUK-UCL
  • cullin family protein binding Source: ParkinsonsUK-UCL
  • protein domain specific binding Source: CAFA
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-1169091. Activation of NF-kappaB in B cells.
R-HSA-1170546. Prolactin receptor signaling.
R-HSA-174113. SCF-beta-TrCP mediated degradation of Emi1.
R-HSA-180534. Vpu mediated degradation of CD4.
R-HSA-187577. SCF(Skp2)-mediated degradation of p27/p21.
R-HSA-195253. Degradation of beta-catenin by the destruction complex.
R-HSA-202424. Downstream TCR signaling.
R-HSA-2122947. NOTCH1 Intracellular Domain Regulates Transcription.
R-HSA-2565942. Regulation of PLK1 Activity at G2/M Transition.
R-HSA-2644606. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
R-HSA-2644607. Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling.
R-HSA-2871837. FCERI mediated NF-kB activation.
R-HSA-2894862. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
R-HSA-400253. Circadian Clock.
R-HSA-446652. Interleukin-1 family signaling.
R-HSA-5607761. Dectin-1 mediated noncanonical NF-kB signaling.
R-HSA-5607764. CLEC7A (Dectin-1) signaling.
R-HSA-5610780. Degradation of GLI1 by the proteasome.
R-HSA-5610783. Degradation of GLI2 by the proteasome.
R-HSA-5610785. GLI3 is processed to GLI3R by the proteasome.
R-HSA-5676590. NIK-->noncanonical NF-kB signaling.
R-HSA-5684264. MAP3K8 (TPL2)-dependent MAPK1/3 activation.
R-HSA-69231. Cyclin D associated events in G1.
R-HSA-8854050. FBXL7 down-regulates AURKA during mitotic entry and in early mitosis.
R-HSA-8939902. Regulation of RUNX2 expression and activity.
R-HSA-8951664. Neddylation.
R-HSA-917937. Iron uptake and transport.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SIGNORiP63208.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
S-phase kinase-associated protein 1
Alternative name(s):
Cyclin-A/CDK2-associated protein p19
Short name:
p19A
Organ of Corti protein 2
Short name:
OCP-2
Organ of Corti protein II
Short name:
OCP-II
RNA polymerase II elongation factor-like protein
SIII
Transcription elongation factor B polypeptide 1-like
p19skp1
Gene namesi
Name:SKP1
Synonyms:EMC19, OCP2, SKP1A, TCEB1L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000113558.18.
HGNCiHGNC:10899. SKP1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Organism-specific databases

DisGeNETi6500.
OpenTargetsiENSG00000113558.
PharmGKBiPA162403424.

Chemistry databases

DrugBankiDB06980. (2S)-2-(1H-indol-3-yl)hexanoic acid.
DB06981. (2S)-2-(1H-indol-3-yl)pentanoic acid.
DB06982. (2S)-8-[(tert-butoxycarbonyl)amino]-2-(1H-indol-3-yl)octanoic acid.
DB07950. 1H-INDOL-3-YLACETIC ACID.
DB01750. Naphthalen-1-Yl-Acetic Acid.

Polymorphism and mutation databases

BioMutaiSKP1.
DMDMi52783797.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00001872512 – 163S-phase kinase-associated protein 1Add BLAST162

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei131PhosphothreonineCombined sources1
Cross-linki142Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP63208.
MaxQBiP63208.
PaxDbiP63208.
PeptideAtlasiP63208.
PRIDEiP63208.
TopDownProteomicsiP63208-1. [P63208-1]

2D gel databases

SWISS-2DPAGEiP63208.

PTM databases

iPTMnetiP63208.
PhosphoSitePlusiP63208.
SwissPalmiP63208.

Expressioni

Gene expression databases

BgeeiENSG00000113558.
CleanExiHS_SKP1.
ExpressionAtlasiP63208. baseline and differential.
GenevisibleiP63208. HS.

Organism-specific databases

HPAiCAB012982.
HPA053745.
HPA058134.

Interactioni

Subunit structurei

Component of multiple SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complexes formed of CUL1, SKP1, RBX1 and a variable F-box domain-containing protein as substrate-specific subunit. Component of the SCF(FBXW11) complex containing FBXW11. Component of the SCF(SKP2) complex containing SKP2, in which it interacts directly with SKP1, SKP2 and RBX1. Component of the SCF(FBXW2) complex containing FBXw2. Component of the SCF(FBXO32) complex containing FBXO32. Component of the probable SCF(FBXO7) complex containing FBXO7. Component of the SCF(FBXO10) complex containing FBXO10. Component of the SCF(FBXO11) complex containing FBXO11. Component of the SCF(FBXO25) complex containing FBXO25. Component of the SCF(FBXO33) complex containing FBXO33. Component of the probable SCF(FBXO4) complex containing FBXO4. Component of the SCF(FBXO44) complex, composed of SKP1, CUL1 and FBXO44. Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC. This complex binds phosphorylated NFKBIA. Part of a SCF complex consisting of CUL1, RBX1, SKP1 and FBXO2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Component of the SCF(FBXO17) complex, composed of SKP1, CUL1 and FBXO17. Component of the SCF(FBXO27) complex, composed of SKP1, CUL1 and FBXO27. Component of the SCF(CCNF) complex consisting of CUL1, RBX1, SKP1 and CCNF. Component of the SCF(FBXL3) complex composed of CUL1, SKP1, RBX1 and FBXL3. Component of the SCF(FBXL21) complex composed of CUL1, SKP1, RBX1 and FBXL21. Component of the SCF(FBXO9) composed of CUL1, SKP1, RBX1 and FBXO9. Component of the SCF(FBXW7) composed of CUL1, SKP1, RBX1 and FBXW7. Interacts with CEP68 (PubMed:25503564).13 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Q6TVJ22EBI-307497,EBI-15718764From Orf virus (strain Goat/Texas/SA00/2000).
Q6TVJ42EBI-307497,EBI-15718558From Orf virus (strain Goat/Texas/SA00/2000).
Q6TVJ72EBI-307497,EBI-15718586From Orf virus (strain Goat/Texas/SA00/2000).
Q6TVW25EBI-307497,EBI-15718527From Orf virus (strain Goat/Texas/SA00/2000).
ANKRD36BP1Q96IX93EBI-307486,EBI-744859
APIPQ96GX93EBI-307486,EBI-359248
BTRCQ9Y2976EBI-307486,EBI-307461
CCNFP410026EBI-307486,EBI-1207574
CDKN1AP389363EBI-307486,EBI-375077
CTNNB1P352223EBI-307486,EBI-491549
CUL1Q1361610EBI-307486,EBI-359390
FBXL12Q9NXK88EBI-307486,EBI-719790
FBXL2Q9UKC95EBI-307486,EBI-724253
FBXL20Q96IG23EBI-307486,EBI-8835647
Fbxl21Q8BFZ43EBI-307486,EBI-6898235From Mus musculus.
Fbxl3Q8C4V43EBI-307486,EBI-1266589From Mus musculus.
FBXL5Q9UKA112EBI-307486,EBI-2692340
FBXL8Q96CD014EBI-307486,EBI-2321097
FBXO11Q86XK26EBI-307486,EBI-1047804
FBXO17Q96EF614EBI-307486,EBI-2510157
FBXO2Q9UK2210EBI-307486,EBI-4287196
Fbxo2Q80UW24EBI-307497,EBI-2314714From Mus musculus.
FBXO22Q8NEZ56EBI-307486,EBI-2510137
FBXO25Q8TCJ0-33EBI-307486,EBI-6262578
FBXO27Q8NI296EBI-307486,EBI-6425694
FBXO28Q9NVF77EBI-307486,EBI-740282
FBXO3Q9UK999EBI-307486,EBI-2509901
FBXO33Q7Z6M22EBI-307486,EBI-8555452
FBXO4Q9UKT59EBI-307486,EBI-960409
FBXO44Q9H4M35EBI-307486,EBI-2322644
FBXO44Q9H4M3-24EBI-307486,EBI-12104696
FBXO46Q6PJ614EBI-307486,EBI-2322982
FBXO48Q5FWF76EBI-307486,EBI-11961122
FBXO6Q9NRD13EBI-307486,EBI-3938499
FBXO7Q9Y3I17EBI-307486,EBI-1161222
FBXO9Q9UK972EBI-307486,EBI-2869927
FBXW11Q9UKB17EBI-307486,EBI-355189
FBXW2Q9UKT84EBI-307486,EBI-914727
FBXW4P577752EBI-307486,EBI-2372268
FBXW5Q969U64EBI-307486,EBI-741068
FBXW5Q969U6-13EBI-307497,EBI-16031873
FBXW7Q969H05EBI-307486,EBI-359574
FBXW8Q8N3Y12EBI-307486,EBI-914770
FBXW9Q5XUX14EBI-307486,EBI-2322729
KCTD9Q7L2733EBI-307486,EBI-4397613
KDM2AQ9Y2K72EBI-307486,EBI-765758
KDM2BQ8NHM52EBI-307486,EBI-3955564
LMO2P257913EBI-307486,EBI-739696
MED21Q135035EBI-307497,EBI-394678
MYCQ149012EBI-307486,EBI-7982457
PPP1CAP621363EBI-307486,EBI-357253
SKP2Q1330913EBI-307486,EBI-456291
SKP2Q13309-17EBI-307497,EBI-15490084
SUGT1Q9Y2Z0-22EBI-307486,EBI-10768076
TTC21AA0A0B4J1Y23EBI-307486,EBI-10220701
TTC9CQ8N5M48EBI-307486,EBI-2851213

GO - Molecular functioni

  • beta-catenin binding Source: ParkinsonsUK-UCL
  • cullin family protein binding Source: ParkinsonsUK-UCL
  • protein domain specific binding Source: CAFA

Protein-protein interaction databases

BioGridi112391. 252 interactors.
CORUMiP63208.
DIPiDIP-31606N.
IntActiP63208. 174 interactors.
MINTiMINT-5001195.
STRINGi9606.ENSP00000231487.

Structurei

Secondary structure

1163
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi3 – 7Combined sources5
Beta strandi9 – 12Combined sources4
Beta strandi13 – 17Combined sources5
Helixi18 – 22Combined sources5
Helixi25 – 33Combined sources9
Beta strandi44 – 46Combined sources3
Beta strandi47 – 50Combined sources4
Helixi52 – 65Combined sources14
Helixi87 – 92Combined sources6
Helixi97 – 110Combined sources14
Helixi113 – 127Combined sources15
Beta strandi128 – 130Combined sources3
Helixi132 – 138Combined sources7
Helixi149 – 156Combined sources8
Turni157 – 159Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FQVX-ray2.80B/D/F/H/J/L/N/P1-69[»]
B/D/F/H/J/L/N/P83-163[»]
1FS1X-ray1.80B/D1-147[»]
1FS2X-ray2.90B/D1-147[»]
1LDKX-ray3.10D2-140[»]
1P22X-ray2.95B1-163[»]
2ASSX-ray3.00A2-160[»]
2ASTX-ray2.30A2-160[»]
2E31X-ray2.40B1-163[»]
2E32X-ray3.52B/D1-163[»]
2OVPX-ray2.90A1-69[»]
A82-149[»]
2OVQX-ray2.60A1-69[»]
A82-149[»]
2OVRX-ray2.50A1-69[»]
A82-149[»]
3L2OX-ray2.80A1-69[»]
A82-163[»]
3WSOX-ray2.60B1-163[»]
4I6JX-ray2.70C1-163[»]
5IBKX-ray2.50A/D1-69[»]
A/D82-163[»]
5JH5X-ray2.55B2-163[»]
5K35X-ray2.85B1-163[»]
5V4BX-ray2.60A1-163[»]
ProteinModelPortaliP63208.
SMRiP63208.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP63208.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni104 – 163Interaction with the F-box domain of F-box proteinsBy similarityAdd BLAST60

Sequence similaritiesi

Belongs to the SKP1 family.Curated

Phylogenomic databases

eggNOGiKOG1724. Eukaryota.
COG5201. LUCA.
GeneTreeiENSGT00390000012652.
HOGENOMiHOG000172184.
HOVERGENiHBG057008.
InParanoidiP63208.
KOiK03094.
OMAiENKWCEE.
OrthoDBiEOG091G0OU2.
PhylomeDBiP63208.
TreeFamiTF354233.

Family and domain databases

InterProiView protein in InterPro
IPR016897. SKP1.
IPR001232. SKP1-like.
IPR036296. SKP1-like_dim_sf.
IPR011333. SKP1/BTB/POZ_sf.
IPR016072. Skp1_comp_dimer.
IPR016073. Skp1_comp_POZ.
PfamiView protein in Pfam
PF01466. Skp1. 1 hit.
PF03931. Skp1_POZ. 1 hit.
PIRSFiPIRSF028729. E3_ubiquit_lig_SCF_Skp. 1 hit.
SMARTiView protein in SMART
SM00512. Skp1. 1 hit.
SUPFAMiSSF54695. SSF54695. 1 hit.
SSF81382. SSF81382. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P63208-1) [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
MPSIKLQSSD GEIFEVDVEI AKQSVTIKTM LEDLGMDDEG DDDPVPLPNV
60 70 80 90 100
NAAILKKVIQ WCTHHKDDPP PPEDDENKEK RTDDIPVWDQ EFLKVDQGTL
110 120 130 140 150
FELILAANYL DIKGLLDVTC KTVANMIKGK TPEEIRKTFN IKNDFTEEEE
160
AQVRKENQWC EEK
Length:163
Mass (Da):18,658
Last modified:January 23, 2007 - v2
Checksum:iC794D62AFB75528A
GO
Isoform 2 (identifier: P63208-2) [UniParc] [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     154-163: RKENQWCEEK → GSTQFCL

Note: No experimental confirmation available.
Show »
Length:160
Mass (Da):18,063
Checksum:iA376AA50007A3D2D
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_007555154 – 163RKENQWCEEK → GSTQFCL in isoform 2. 1 Publication10

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U33760 mRNA. Translation: AAC50241.1.
Z47087 mRNA. Translation: CAA87392.1.
CH471062 Genomic DNA. Translation: EAW62270.1.
CH471062 Genomic DNA. Translation: EAW62271.1.
CH471062 Genomic DNA. Translation: EAW62272.1.
CH471062 Genomic DNA. Translation: EAW62276.1.
BC009839 mRNA. Translation: AAH09839.1.
BC020798 mRNA. Translation: AAH20798.1.
BC025673 mRNA. Translation: AAH25673.1.
BC065730 mRNA. Translation: AAH65730.1.
U37558 mRNA. Translation: AAA79202.1.
CCDSiCCDS4171.1.
CCDS4172.1. [P63208-2]
PIRiI39170.
RefSeqiNP_008861.2. NM_006930.3. [P63208-2]
NP_733779.1. NM_170679.2. [P63208-1]
UniGeneiHs.171626.

Genome annotation databases

EnsembliENST00000353411; ENSP00000231487; ENSG00000113558. [P63208-1]
ENST00000517625; ENSP00000429961; ENSG00000113558. [P63208-1]
ENST00000522552; ENSP00000429472; ENSG00000113558. [P63208-2]
ENST00000522855; ENSP00000429686; ENSG00000113558. [P63208-1]
GeneIDi6500.
KEGGihsa:6500.
UCSCiuc003kzc.5. human.

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSKP1_HUMAN
AccessioniPrimary (citable) accession number: P63208
Secondary accession number(s): D3DQ97
, D3DQ98, P34991, Q8TAY2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 27, 2004
Last sequence update: January 23, 2007
Last modified: November 22, 2017
This is version 155 of the entry and version 2 of the sequence. See 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families