P63208 (SKP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
S-phase kinase-associated protein 1

Alternative name(s):
Cyclin-A/CDK2-associated protein p19
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
p19A
p19skp1

Gene names

Name:	SKP1
Synonyms:	EMC19, OCP2, SKP1A, TCEB1L

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	163 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. 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(Cyclin F) directs ubiquitination of CP110. Ref.16 Ref.19
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Component of an E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC. Part of a SCF(BTRC)-like complex lacking CUL1, which is associated with phosphorylated NFKBIA and RELA; RELA interacts directly with NFKBIA. Component of the SCF(FBXO44) complex, composed of SKP1, CUL1 and FBXO44. Identified in a complex with SKP2, CKS1B and CDKN1B. Interacts with the cyclin A/CDK2 complex. Part of a SCF-like complex consisting of CUL7, RBX1, SKP1 and FBXW8. Part of several SCF complexes containing SKP1 and one of the F-box proteins. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Interacts with FBXO2, FBXO4, FBXW7 and TRIM21. Interacts with FBXO45 By similarity. 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(Cyclin F) complex consisting of CUL1, RBX1, SKP1 and CCNF. Ref.7 Ref.8 Ref.9 Ref.10 Ref.16
Sequence similarities	Belongs to the SKP1 family.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Alternative splicing Polymorphism
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	G1/S transition of mitotic cell cycle Traceable author statement. Source: Reactome S phase of mitotic cell cycle Traceable author statement. Source: Reactome SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Inferred from direct assay. Source: UniProtKB anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Traceable author statement. Source: Reactome histone H2A monoubiquitination Inferred from direct assay. Source: UniProtKB positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Traceable author statement. Source: Reactome viral reproduction Traceable author statement. Source: Reactome
Cellular component	SCF ubiquitin ligase complex Inferred from direct assay Ref.9Ref.11. Source: UniProtKB cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular function	protein binding Inferred from physical interaction Ref.9Ref.10Ref.19. Source: UniProtKB ubiquitin-protein ligase activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BTRC	Q9Y297	3	EBI-307486,EBI-307461
CUL1	Q13616	6	EBI-307486,EBI-359390
FBXL8	Q96CD0	3	EBI-307486,EBI-2321097
FBXO46	Q6PJ61	2	EBI-307486,EBI-2322982
FBXW11	Q9UKB1	4	EBI-307486,EBI-355189
FBXW5	Q969U6	2	EBI-307486,EBI-741068
FBXW9	Q5XUX1	3	EBI-307486,EBI-2322729
PPP1CA	P62136	3	EBI-307486,EBI-357253
SKP2	Q13309	5	EBI-307486,EBI-456291

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P63208-1)

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: P63208-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.5

Chain

2 – 163

162

S-phase kinase-associated protein 1

PRO_0000187251

Regions

Region

104 – 163

60

Interaction with the F-box domain of F-box proteins By similarity

Natural variations

Alternative sequence

154 – 163

10

RKENQWCEEK → GSTQFCL in isoform 2.

VSP_007555

Natural variant

14

1

F → L.
Corresponds to variant rs11538034 [ dbSNP | Ensembl ].

VAR_051999

Secondary structure

1

.

.

.

.

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.

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.

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.

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.

.

.

.

.

163

Helix Strand Turn

Details...

Beta strand

3 – 7

5

Beta strand

13 – 17

5

Helix

18 – 22

5

Helix

25 – 33

9

Beta strand

43 – 46

4

Helix

52 – 65

14

Helix

87 – 92

6

Helix

97 – 110

14

Helix

113 – 127

15

Helix

132 – 138

7

Helix

149 – 156

8

Turn

157 – 159

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: C794D62AFB75528A	FASTA	163	18,658
	10 20 30 40 50 60 MPSIKLQSSD GEIFEVDVEI AKQSVTIKTM LEDLGMDDEG DDDPVPLPNV NAAILKKVIQ 70 80 90 100 110 120 WCTHHKDDPP PPEDDENKEK RTDDIPVWDQ EFLKVDQGTL FELILAANYL DIKGLLDVTC 130 140 150 160 KTVANMIKGK TPEEIRKTFN IKNDFTEEEE AQVRKENQWC EEK
	Isoform 2 [UniParc] [UniParc]. Checksum: A376AA50007A3D2D	FASTA	160	18,063
	10 20 30 40 50 60 MPSIKLQSSD GEIFEVDVEI AKQSVTIKTM LEDLGMDDEG DDDPVPLPNV NAAILKKVIQ 70 80 90 100 110 120 WCTHHKDDPP PPEDDENKEK RTDDIPVWDQ EFLKVDQGTL FELILAANYL DIKGLLDVTC 130 140 150 160 KTVANMIKGK TPEEIRKTFN IKNDFTEEEE AQVGSTQFCL

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).
[2]	"A novel cDNA with homology to an RNA polymerase II elongation factors maps to human chromosome 5q31 (TCEB1L) and to mouse chromosome 11 (Tceb1l)." Sowden J., Morrison K., Schofield J., Putt W., Edwards Y. Genomics 29:145-151(1995) [PubMed: 8530064] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] (ISOFORMS 1 AND 2). Tissue: Lung, Skin and Uterus.
[5]	Golaz O., Hughes G.J., Frutiger S., Paquet N., Bairoch A., Pasquali C., Sanchez J.-C., Tissot J.-D., Appel R.D., Walzer C., Balant L., Hochstrasser D.F. Submitted (FEB-1994) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-11. Tissue: Erythrocyte.
[6]	"Human inner ear OCP2 cDNA maps to 5q22-5q35.2 with related sequences on chromosomes 4p16.2-4p14, 5p13-5q22, 7pter-q22, 10 and 12p13-12qter." Liang Y., Chen H., Asher J.H. Jr., Chang C.-C., Friedman T.B. Gene 184:163-167(1997) [PubMed: 9031623] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 14-163 (ISOFORM 1). Tissue: Inner ear.
[7]	"CUL7: a DOC domain-containing cullin selectively binds Skp1.Fbx29 to form an SCF-like complex." Dias D.C., Dolios G., Wang R., Pan Z.Q. Proc. Natl. Acad. Sci. U.S.A. 99:16601-16606(2002) [PubMed: 12481031] [Abstract] Cited for: INTERACTION WITH FBXW8, IDENTIFICATION IN SCF-LIKE COMPLEX.
[8]	"Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses." Matsuzawa S., Reed J.C. Mol. Cell 7:915-926(2001) [PubMed: 11389839] [Abstract] Cited for: SUBUNIT OF A COMPLEX WITH SIAH1; CACYBP; UBE2D1; APC AND TBL1X.
[9]	"Regulation of p27 degradation and S-phase progression by Ro52 RING finger protein." Sabile A., Meyer A.M., Wirbelauer C., Hess D., Kogel U., Scheffner M., Krek W. Mol. Cell. Biol. 26:5994-6004(2006) [PubMed: 16880511] [Abstract] Cited for: INTERACTION WITH THE SCF(SKP2)-LIKE COMPLEX, INTERACTION WITH TRIM21.
[10]	"Diversity in tissue expression, substrate binding, and SCF complex formation for a lectin family of ubiquitin ligases." Glenn K.A., Nelson R.F., Wen H.M., Mallinger A.J., Paulson H.L. J. Biol. Chem. 283:12717-12729(2008) [PubMed: 18203720] [Abstract] Cited for: INTERACTION WITH FBXO44; FBXO17 AND FBXO27, IDENTIFICATION IN SCF-COMPLEX.
[11]	"SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity through CP110 degradation." D'Angiolella V., Donato V., Vijayakumar S., Saraf A., Florens L., Washburn M.P., Dynlacht B., Pagano M. Nature 466:138-142(2010) [PubMed: 20596027] [Abstract] Cited for: IDENTIFICATION IN THE SCF(CYCLIN F) COMPLEX.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"Insights into SCF ubiquitin ligases from the structure of the Skp1-Skp2 complex." Schulman B.A., Carrano A.C., Jeffrey P.D., Bowen Z., Kinnucan E.R.E., Finnin M.S., Elledge S.J., Harper J.W., Pagano M., Pavletich N.P. Nature 408:381-386(2000) [PubMed: 11099048] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF THE SKP1-SKP2 COMPLEX.
[14]	"Structure of the Cul1-Rbx1-Skp1-F box Skp2 SCF ubiquitin ligase complex." Zheng N., Schulman B.A., Song L., Miller J.J., Jeffrey P.D., Wang P., Chu C., Koepp D.M., Elledge S.J., Pagano M., Conaway R.C., Conaway J.W., Harper J.W., Pavletich N.P. Nature 416:703-709(2002) [PubMed: 11961546] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN SCF COMPLEX WITH CUL1; RBX1 AND SKP2.
[15]	"Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin ligase." Wu G., Xu G., Schulman B.A., Jeffrey P.D., Harper J.W., Pavletich N.P. Mol. Cell 11:1445-1456(2003) [PubMed: 12820959] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) IN COMPLEX WITH 176-606 OF BTRC AND CTNNB1.
[16]	"Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase." Hao B., Zheng N., Schulman B.A., Wu G., Miller J.J., Pagano M., Pavletich N.P. Mol. Cell 20:9-19(2005) [PubMed: 16209941] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 3-159 IN COMPLEX WITH SKP2; CKS1B AND CDKN1B PHOSPHOPEPTIDE, SUBUNIT, FUNCTION.
[17]	"Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases." Hao B., Oehlmann S., Sowa M.E., Harper J.W., Pavletich N.P. Mol. Cell 26:131-143(2007) [PubMed: 17434132] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH FBXW7 AND CCNE PEPTIDE.
[18]	"Structural basis for the selection of glycosylated substrates by SCF(Fbs1) ubiquitin ligase." Mizushima T., Yoshida Y., Kumanomidou T., Hasegawa Y., Suzuki A., Yamane T., Tanaka K. Proc. Natl. Acad. Sci. U.S.A. 104:5777-5781(2007) [PubMed: 17389369] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH FBXO2.
[19]	"Structural basis of dimerization-dependent ubiquitination by the SCF(Fbx4) ubiquitin ligase." Li Y., Hao B. J. Biol. Chem. 285:13896-13906(2010) [PubMed: 20181953] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH FBXO4, FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00172421.
IPI00301364.

PIR

I39170.

RefSeq

NP_008861.2. NM_006930.3.
NP_733779.1. NM_170679.2.

UniGene

Hs.171626.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FQV	X-ray	2.80	B/D/F/H/J/L/N/P	1-163	[»]
1FS1	X-ray	1.80	B/D	1-147	[»]
1FS2	X-ray	2.90	B/D	1-147	[»]
1LDK	X-ray	3.10	D	2-140	[»]
1P22	X-ray	2.95	B	1-163	[»]
2ASS	X-ray	3.00	A	3-159	[»]
2AST	X-ray	2.30	A	3-159	[»]
2E31	X-ray	2.40	B	1-163	[»]
2E32	X-ray	3.52	B/D	1-163	[»]
2OVP	X-ray	2.90	A	1-163	[»]
2OVQ	X-ray	2.60	A	1-163	[»]
2OVR	X-ray	2.50	A	1-163	[»]
3L2O	X-ray	2.80	A	3-163	[»]

ProteinModelPortal

P63208.

SMR

P63208. Positions 3-160.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-17012N.
DIP-31606N.

IntAct

P63208. 41 interactions.

MINT

MINT-5001195.

STRING

P63208.

PTM databases

PhosphoSite

P63208.

Polymorphism databases

DMDM

52783797.

2D gel databases

SWISS-2DPAGE

P63208.

Proteomic databases

PeptideAtlas

P63208.

PRIDE

P63208.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000353411; ENSP00000231487; ENSG00000113558.

GeneID

6500.

KEGG

hsa:6500.

UCSC

uc003kzc.2. human.
uc003kzd.2. human.

Organism-specific databases

CTD

6500.

GeneCards

GC05M133521.

H-InvDB

HIX0200736.

HGNC

HGNC:10899. SKP1.

HPA

CAB012982.

MIM

601434. gene.

neXtProt

NX_P63208.

PharmGKB

PA162403424.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG20930.

HOGENOM

HBG622018.

HOVERGEN

HBG057008.

InParanoid

P63208.

OMA

SWDVEFL.

OrthoDB

EOG498V26.

PhylomeDB

P63208.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_152. Cell Cycle, Mitotic.
REACT_24941. Circadian Clock.
REACT_6185. HIV Infection.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P63208.

Bgee

P63208.

CleanEx

HS_SKP1.

Genevestigator

P63208.

GermOnline

ENSG00000113558. Homo sapiens.

Family and domain databases

InterPro

IPR011333. BTB/POZ_fold.
IPR016897. E3_ubiquit_lig_SCF_Skp.
IPR001232. Skp1_comp.
IPR016072. Skp1_comp_dimer.
IPR016073. Skp1_comp_POZ.
[Graphical view]

Gene3D

G3DSA:3.30.710.10. BTB/POZ_fold. 1 hit.

KO

K03094.

PANTHER

PTHR11165. Skp1. 1 hit.

Pfam

PF01466. Skp1. 1 hit.
PF03931. Skp1_POZ. 1 hit.
[Graphical view]

PIRSF

PIRSF028729. E3_ubiquit_lig_SCF_Skp. 1 hit.

SMART

SM00512. Skp1. 1 hit.
[Graphical view]

SUPFAM

SSF54695. BTB/POZ_fold. 1 hit.
SSF81382. Skp1_comp_dimer. 1 hit.

ProtoNet

Search...

Other

NextBio

25267.

SOURCE

Search...

Entry information

Entry name

SKP1_HUMAN

Accession

Primary (citable) accession number: P63208
Secondary accession number(s): D3DQ97 , D3DQ98, P34991, Q8TAY2

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 27, 2004
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 92 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.