Reviewed, UniProtKB/Swiss-Prot Q13309 (SKP2_HUMAN)

Names and origin

Protein names

Recommended name:
    S-phase kinase-associated protein 2
Alternative name(s):
    F-box protein Skp2
    Cyclin A/CDK2-associated protein p45
    p45skp2
    F-box/LRR-repeat protein 1

Gene names

Name:	SKP2
Synonyms:	FBXL1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	424 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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 ORC1L, CDT1, RBL2, MLL, CDK9, RAG2, FOXO1A, UBP43, and probably MYC, TOB1 and TAL1. Degradation of TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Part of the SCF(SKP2) complex consisting of CUL1, RBX1, SKP1 and SKP2. Interacts directly with CUL1 and SKP1. Interacts with CKS1. Interacts with the cyclin A-CDK2 complex. Interacts with ORC1L, phosphorylated CDT1, phosphorylated RBL2, ELF4, phosphorylated RAG2, FOXO1A, UBP43, MYC, TOB1, TAL1 and MLL.
Sequence similarities	Contains 1 F-box domain. Contains 8 LRR (leucine-rich) repeats.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Leucine-rich repeat Repeat
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	G1/S transition of mitotic cell cycle Ref.1 Traceable author statement. Source: ProtInc cell proliferation Ref.1 Traceable author statement. Source: ProtInc ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein binding Ref.6 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CKS1B	P61024	2	EBI-456291,EBI-456371
CUL1	Q13616	2	EBI-456291,EBI-359390
DUSP1	P28562	1	EBI-456291,EBI-975493
MYC	P01106	2	EBI-456291,EBI-447544
ORC1L	Q13415	2	EBI-456291,EBI-374847

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q13309-1)

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.

Isoform 2 (identifier: Q13309-2)

Also known as: SKP2-beta;

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

Isoform 3 (identifier: Q13309-3)

Also known as: SKP2-gamma;

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 424

424

S-phase kinase-associated protein 2

PRO_0000119954

Regions

Domain

94 – 140

47

F-box

Repeat

180 – 204

25

LRR 1

Repeat

210 – 234

25

LRR 2

Repeat

258 – 284

27

LRR 3

Repeat

286 – 308

23

LRR 4

Repeat

309 – 330

22

LRR 5

Repeat

334 – 356

23

LRR 6

Repeat

359 – 378

20

LRR 7

Repeat

380 – 403

24

LRR 8

Amino acid modifications

Modified residue

64

1

Phosphoserine

Modified residue

179

1

Phosphoserine

Natural variations

Alternative sequence

355 – 424

70

ELGEI…KPSCL → LVTRAGVRIRLDSDIGCPQT YRTSKLKSSHKLFCQHVRVI CIFVCDFYFYRLVLKQ in isoform 2.

VSP_008432

Alternative sequence

355 – 424

70

ELGEI…KPSCL → AGIYQNQNSHSNYNVSQVSH EGFKVGAGLLSSLVTRAGVR IRLDSDIGCPQTYRTSKLKS SHKLFCQHVRVICIFVCDFY FYRLVLKQ in isoform 3.

VSP_008431

Natural variant

85

1

P → L: dbSNP rs3913486.

VAR_016984

Natural variant

87

1

L → I: dbSNP rs3913487.

VAR_016985

Experimental info

Sequence conflict

185

1

H → D in AAC50242. Ref.1

Sequence conflict

215

1

Missing in AAC50242. Ref.1

Sequence conflict

238

1

S → P in AAC50242. Ref.1

Sequence conflict

241

1

S → P in AAC50242. Ref.1

Sequence conflict

244 – 247

4

SEFA → PKFP in AAC50242. Ref.1

Sequence conflict

251

1

L → F in AAC50242. Ref.1

Sequence conflict

256

1

S → P in AAC50242. Ref.1

Sequence conflict

268

1

D → N in AAC50242. Ref.1

Sequence conflict

285

1

I → M in AAC50242. Ref.1

Sequence conflict

319

1

D → N in AAC50242. Ref.1

Sequence conflict

332

1

F → S in AAC50242. Ref.1

Secondary structure

1

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424

Helix Strand Turn

Details...

Helix

102 – 109

8

Helix

114 – 116

3

Helix

117 – 121

5

Helix

125 – 131

7

Helix

134 – 136

3

Beta strand

138 – 141

4

Helix

149 – 157

9

Beta strand

161 – 164

4

Beta strand

185 – 187

3

Helix

195 – 202

8

Beta strand

209 – 212

4

Helix

220 – 226

7

Beta strand

233 – 236

4

Helix

245 – 254

10

Beta strand

260 – 262

3

Helix

271 – 280

10

Beta strand

287 – 289

3

Helix

294 – 296

3

Helix

299 – 308

10

Beta strand

313 – 316

4

Helix

325 – 333

9

Beta strand

339 – 341

3

Helix

350 – 358

9

Beta strand

364 – 366

3

Helix

376 – 382

7

Beta strand

386 – 389

4

Beta strand

415 – 417

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (SKP2-alpha) [UniParc]. Last modified October 3, 2003. Version 2. Checksum: F29B7C338A7A37E9	FASTA	424	47,761
	10 20 30 40 50 60 MHRKHLQEIP DLSSNVATSF TWGWDSSKTS ELLSGMGVSA LEKEEPDSEN IPQELLSNLG 70 80 90 100 110 120 HPESPPRKRL KSKGSDKDFV IVRRPKLNRE NFPGVSWDSL PDELLLGIFS CLCLPELLKV 130 140 150 160 170 180 SGVCKRWYRL ASDESLWQTL DLTGKNLHPD VTGRLLSQGV IAFRCPRSFM DQPLAEHFSP 190 200 210 220 230 240 FRVQHMDLSN SVIEVSTLHG ILSQCSKLQN LSLEGLRLSD PIVNTLAKNS NLVRLNLSGC 250 260 270 280 290 300 SGFSEFALQT LLSSCSRLDE LNLSWCFDFT EKHVQVAVAH VSETITQLNL SGYRKNLQKS 310 320 330 340 350 360 DLSTLVRRCP NLVHLDLSDS VMLKNDCFQE FFQLNYLQHL SLSRCYDIIP ETLLELGEIP 370 380 390 400 410 420 TLKTLQVFGI VPDGTLQLLK EALPHLQINC SHFTTIARPT IGNKKNQEIW GIKCRLTLQK PSCL
	Isoform 2 (SKP2-beta) [UniParc]. Checksum: 8CB41CC9968695E3		410	46,576
	10 20 30 40 50 60 MHRKHLQEIP DLSSNVATSF TWGWDSSKTS ELLSGMGVSA LEKEEPDSEN IPQELLSNLG 70 80 90 100 110 120 HPESPPRKRL KSKGSDKDFV IVRRPKLNRE NFPGVSWDSL PDELLLGIFS CLCLPELLKV 130 140 150 160 170 180 SGVCKRWYRL ASDESLWQTL DLTGKNLHPD VTGRLLSQGV IAFRCPRSFM DQPLAEHFSP 190 200 210 220 230 240 FRVQHMDLSN SVIEVSTLHG ILSQCSKLQN LSLEGLRLSD PIVNTLAKNS NLVRLNLSGC 250 260 270 280 290 300 SGFSEFALQT LLSSCSRLDE LNLSWCFDFT EKHVQVAVAH VSETITQLNL SGYRKNLQKS 310 320 330 340 350 360 DLSTLVRRCP NLVHLDLSDS VMLKNDCFQE FFQLNYLQHL SLSRCYDIIP ETLLLVTRAG 370 380 390 400 410 VRIRLDSDIG CPQTYRTSKL KSSHKLFCQH VRVICIFVCD FYFYRLVLKQ
	Isoform 3 (SKP2-gamma) [UniParc]. Checksum: 9A002FC610C2DB53		442	49,951
	10 20 30 40 50 60 MHRKHLQEIP DLSSNVATSF TWGWDSSKTS ELLSGMGVSA LEKEEPDSEN IPQELLSNLG 70 80 90 100 110 120 HPESPPRKRL KSKGSDKDFV IVRRPKLNRE NFPGVSWDSL PDELLLGIFS CLCLPELLKV 130 140 150 160 170 180 SGVCKRWYRL ASDESLWQTL DLTGKNLHPD VTGRLLSQGV IAFRCPRSFM DQPLAEHFSP 190 200 210 220 230 240 FRVQHMDLSN SVIEVSTLHG ILSQCSKLQN LSLEGLRLSD PIVNTLAKNS NLVRLNLSGC 250 260 270 280 290 300 SGFSEFALQT LLSSCSRLDE LNLSWCFDFT EKHVQVAVAH VSETITQLNL SGYRKNLQKS 310 320 330 340 350 360 DLSTLVRRCP NLVHLDLSDS VMLKNDCFQE FFQLNYLQHL SLSRCYDIIP ETLLAGIYQN 370 380 390 400 410 420 QNSHSNYNVS QVSHEGFKVG AGLLSSLVTR AGVRIRLDSD IGCPQTYRTS KLKSSHKLFC 430 440 QHVRVICIFV CDFYFYRLVL KQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase." Zhang H., Kobayashi R., Galaktionov K., Beach D. Cell 82:915-925(1995) [PubMed: 7553852] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 6-19; 31-58; 80-86 AND 365-372, INTERACTION WITH CYCLIN A-CDK2 COMPLEX.
[2]	"Human SKP2-like protein." Yamaguchi T. Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3). Tissue: Liver.
[3]	"Androgenic regulation of Skp2 in androgen-dependent and -independent LNCaP human prostate tumor cells." Kokontis J.M., Fukuchi J., Liao S. Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Prostatic carcinoma.
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Placenta.
[5]	"The pRb-related protein p130 is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCF(Skp2)." Tedesco D., Lukas J., Reed S.I. Genes Dev. 16:2946-2957(2002) [PubMed: 12435635] [Abstract] Cited for: INTERACTION WITH RBL2, FUNCTION IN UBIQUITINATION OF RBL2.
[6]	"Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication." Mendez J., Zou-Yang X.H., Kim S.Y., Hidaka M., Tansey W.P., Stillman B. Mol. Cell 9:481-491(2002) [PubMed: 11931757] [Abstract] Cited for: INTERACTION WITH ORC1L, FUNCTION IN UBIQUITINATION OF ORC1L.
[7]	"The SCF(Skp2) ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation." Li X., Zhao Q., Liao R., Sun P., Wu X. J. Biol. Chem. 278:30854-30858(2003) [PubMed: 12840033] [Abstract] Cited for: INTERACTION WITH CDT1, FUNCTION IN UBIQUITINATION OF CDT1.
[8]	"The F-box protein Skp2 participates in c-Myc proteosomal degradation and acts as a cofactor for c-Myc-regulated transcription." von der Lehr N., Johansson S., Wu S., Bahram F., Castell A., Cetinkaya C., Hydbring P., Weidung I., Nakayama K., Nakayama K.I., Soderberg O., Kerppola T.K., Larsson L.G. Mol. Cell 11:1189-1200(2003) [PubMed: 12769844] [Abstract] Cited for: INTERACTION WITH MYC, FUNCTION IN UBIQUITINATION OF MYC.
[9]	"The ISG15 isopeptidase UBP43 is regulated by proteolysis via the SCFSkp2 ubiquitin ligase." Tokarz S., Berset C., La Rue J., Friedman K., Nakayama K., Nakayama K., Zhang D.E., Lanker S. J. Biol. Chem. 279:46424-46430(2004) [PubMed: 15342634] [Abstract] Cited for: INTERACTION WITH UBP43, FUNCTION IN UBIQUITINATION OF UBP43.
[10]	"Ubiquitination of p21Cip1/WAF1 by SCFSkp2: substrate requirement and ubiquitination site selection." Wang W., Nacusi L., Sheaff R.J., Liu X. Biochemistry 44:14553-14564(2005) [PubMed: 16262255] [Abstract] Cited for: FUNCTION IN UBIQUITINATION OF CDKN1A.
[11]	"Ubiquitylation of RAG-2 by Skp2-SCF links destruction of the V(D)J recombinase to the cell cycle." Jiang H., Chang F.C., Ross A.E., Lee J., Nakayama K., Nakayama K., Desiderio S. Mol. Cell 18:699-709(2005) [PubMed: 15949444] [Abstract] Cited for: INTERACTION WITH RAG2, FUNCTION IN UBIQUITINATION OF RAG2.
[12]	"Ubiquitylation of Cdk9 by Skp2 facilitates optimal Tat transactivation." Barboric M., Zhang F., Besenicar M., Plemenitas A., Peterlin B.M. J. Virol. 79:11135-11141(2005) [PubMed: 16103164] [Abstract] Cited for: FUNCTION IN UBIQUITINATION OF CDK9.
[13]	"Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation." Huang H., Regan K.M., Wang F., Wang D., Smith D.I., van Deursen J.M., Tindall D.J. Proc. Natl. Acad. Sci. U.S.A. 102:1649-1654(2005) [PubMed: 15668399] [Abstract] Cited for: INTERACTION WITH FOXO1A, FUNCTION IN UBIQUITINATION OF FOXO1A.
[14]	"Degradation of Tob1 mediated by SCFSkp2-dependent ubiquitination." Hiramatsu Y., Kitagawa K., Suzuki T., Uchida C., Hattori T., Kikuchi H., Oda T., Hatakeyama S., Nakayama K.I., Yamamoto T., Konno H., Kitagawa M. Cancer Res. 66:8477-8483(2006) [PubMed: 16951159] [Abstract] Cited for: INTERACTION WITH TOB1, FUNCTION IN UBIQUITINATION OF TOB1.
[15]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64, MASS SPECTROMETRY. Tissue: Epithelium.
[16]	"The ETS protein MEF is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCFSkp2." Liu Y., Hedvat C.V., Mao S., Zhu X.H., Yao J., Nguyen H., Koff A., Nimer S.D. Mol. Cell. Biol. 26:3114-3123(2006) [PubMed: 16581786] [Abstract] Cited for: INTERACTION WITH ELF4, FUNCTION IN UBIQUITINATION OF ELF4.
[17]	"Bimodal degradation of MLL by SCFSkp2 and APCCdc20 assures cell cycle execution: a critical regulatory circuit lost in leukemogenic MLL fusions." Liu H., Cheng E.H., Hsieh J.J. Genes Dev. 21:2385-2398(2007) [