Full text data of SKP1
SKP1
(EMC19, OCP2, SKP1A, TCEB1L)
[Confidence: high (present in two of the MS resources)]
S-phase kinase-associated protein 1 (Cyclin-A/CDK2-associated protein p19; Organ of Corti protein 2; OCP-2; Organ of Corti protein II; OCP-II; RNA polymerase II elongation factor-like protein; SIII; Transcription elongation factor B; p19A; p19skp1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
S-phase kinase-associated protein 1 (Cyclin-A/CDK2-associated protein p19; Organ of Corti protein 2; OCP-2; Organ of Corti protein II; OCP-II; RNA polymerase II elongation factor-like protein; SIII; Transcription elongation factor B; p19A; p19skp1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00172421
IPI00172421 S-phase kinase-associated protein 1A isoform a 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 soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00172421 S-phase kinase-associated protein 1A isoform a 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 soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P63208
ID SKP1_HUMAN Reviewed; 163 AA.
AC P63208; D3DQ97; D3DQ98; P34991; Q8TAY2;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 113.
DE RecName: Full=S-phase kinase-associated protein 1;
DE AltName: Full=Cyclin-A/CDK2-associated protein p19;
DE AltName: Full=Organ of Corti protein 2;
DE Short=OCP-2;
DE AltName: Full=Organ of Corti protein II;
DE Short=OCP-II;
DE AltName: Full=RNA polymerase II elongation factor-like protein;
DE AltName: Full=SIII;
DE AltName: Full=Transcription elongation factor B;
DE AltName: Full=p19A;
DE AltName: Full=p19skp1;
GN Name=SKP1; Synonyms=EMC19, OCP2, SKP1A, TCEB1L;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=7553852; DOI=10.1016/0092-8674(95)90271-6;
RA Zhang H., Kobayashi R., Galaktionov K., Beach D.;
RT "p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S
RT phase kinase.";
RL Cell 82:915-925(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8530064; DOI=10.1006/geno.1995.1225;
RA Sowden J., Morrison K., Schofield J., Putt W., Edwards Y.;
RT "A novel cDNA with homology to an RNA polymerase II elongation factors
RT maps to human chromosome 5q31 (TCEB1L) and to mouse chromosome 11
RT (Tceb1l).";
RL Genomics 29:145-151(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lung, Skin, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 2-11.
RC TISSUE=Erythrocyte;
RA Golaz O., Hughes G.J., Frutiger S., Paquet N., Bairoch A.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Appel R.D., Walzer C.,
RA Balant L., Hochstrasser D.F.;
RL Submitted (FEB-1994) to UniProtKB.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-163 (ISOFORM 1).
RC TISSUE=Inner ear;
RX PubMed=9031623; DOI=10.1016/S0378-1119(96)00590-2;
RA Liang Y., Chen H., Asher J.H. Jr., Chang C.-C., Friedman T.B.;
RT "Human inner ear OCP2 cDNA maps to 5q22-5q35.2 with related sequences
RT on chromosomes 4p16.2-4p14, 5p13-5q22, 7pter-q22, 10 and 12p13-
RT 12qter.";
RL Gene 184:163-167(1997).
RN [7]
RP INTERACTION WITH FBXW8, AND IDENTIFICATION IN SCF-LIKE COMPLEX.
RX PubMed=12481031; DOI=10.1073/pnas.252646399;
RA Dias D.C., Dolios G., Wang R., Pan Z.Q.;
RT "CUL7: a DOC domain-containing cullin selectively binds Skp1.Fbx29 to
RT form an SCF-like complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16601-16606(2002).
RN [8]
RP SUBUNIT OF A COMPLEX WITH SIAH1; CACYBP; UBE2D1; APC AND TBL1X.
RX PubMed=11389839; DOI=10.1016/S1097-2765(01)00242-8;
RA Matsuzawa S., Reed J.C.;
RT "Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin
RT degradation linked to p53 responses.";
RL Mol. Cell 7:915-926(2001).
RN [9]
RP INTERACTION WITH THE SCF(SKP2)-LIKE COMPLEX, AND INTERACTION WITH
RP TRIM21.
RX PubMed=16880511; DOI=10.1128/MCB.01630-05;
RA Sabile A., Meyer A.M., Wirbelauer C., Hess D., Kogel U., Scheffner M.,
RA Krek W.;
RT "Regulation of p27 degradation and S-phase progression by Ro52 RING
RT finger protein.";
RL Mol. Cell. Biol. 26:5994-6004(2006).
RN [10]
RP INTERACTION WITH FBXO44; FBXO17 AND FBXO27, AND IDENTIFICATION IN
RP SCF-COMPLEX.
RX PubMed=18203720; DOI=10.1074/jbc.M709508200;
RA Glenn K.A., Nelson R.F., Wen H.M., Mallinger A.J., Paulson H.L.;
RT "Diversity in tissue expression, substrate binding, and SCF complex
RT formation for a lectin family of ubiquitin ligases.";
RL J. Biol. Chem. 283:12717-12729(2008).
RN [11]
RP IDENTIFICATION IN THE SCF(CCNF) COMPLEX.
RX PubMed=20596027; DOI=10.1038/nature09140;
RA D'Angiolella V., Donato V., Vijayakumar S., Saraf A., Florens L.,
RA Washburn M.P., Dynlacht B., Pagano M.;
RT "SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity
RT through CP110 degradation.";
RL Nature 466:138-142(2010).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-131, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-131, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP FUNCTION IN UBIQUITINATION OF BCL6, AND IDENTIFICATION IN THE
RP SCF(FBXO11) COMPLEX.
RX PubMed=22113614; DOI=10.1038/nature10688;
RA Duan S., Cermak L., Pagan J.K., Rossi M., Martinengo C.,
RA di Celle P.F., Chapuy B., Shipp M., Chiarle R., Pagano M.;
RT "FBXO11 targets BCL6 for degradation and is inactivated in diffuse
RT large B-cell lymphomas.";
RL Nature 481:90-93(2012).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF THE SKP1-SKP2 COMPLEX.
RX PubMed=11099048; DOI=10.1038/35042620;
RA Schulman B.A., Carrano A.C., Jeffrey P.D., Bowen Z., Kinnucan E.R.E.,
RA Finnin M.S., Elledge S.J., Harper J.W., Pagano M., Pavletich N.P.;
RT "Insights into SCF ubiquitin ligases from the structure of the Skp1-
RT Skp2 complex.";
RL Nature 408:381-386(2000).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN SCF COMPLEX WITH CUL1; RBX1
RP AND SKP2.
RX PubMed=11961546; DOI=10.1038/416703a;
RA Zheng N., Schulman B.A., Song L., Miller J.J., Jeffrey P.D., Wang P.,
RA Chu C., Koepp D.M., Elledge S.J., Pagano M., Conaway R.C.,
RA Conaway J.W., Harper J.W., Pavletich N.P.;
RT "Structure of the Cul1-Rbx1-Skp1-F box Skp2 SCF ubiquitin ligase
RT complex.";
RL Nature 416:703-709(2002).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) IN COMPLEX WITH 176-606 OF BTRC
RP AND CTNNB1.
RX PubMed=12820959; DOI=10.1016/S1097-2765(03)00234-X;
RA Wu G., Xu G., Schulman B.A., Jeffrey P.D., Harper J.W.,
RA Pavletich N.P.;
RT "Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction
RT motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin
RT ligase.";
RL Mol. Cell 11:1445-1456(2003).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 3-159 IN COMPLEX WITH SKP2;
RP CKS1B AND CDKN1B PHOSPHOPEPTIDE, SUBUNIT, AND FUNCTION.
RX PubMed=16209941; DOI=10.1016/j.molcel.2005.09.003;
RA Hao B., Zheng N., Schulman B.A., Wu G., Miller J.J., Pagano M.,
RA Pavletich N.P.;
RT "Structural basis of the Cks1-dependent recognition of p27(Kip1) by
RT the SCF(Skp2) ubiquitin ligase.";
RL Mol. Cell 20:9-19(2005).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH FBXW7 AND CCNE1
RP PEPTIDE.
RX PubMed=17434132; DOI=10.1016/j.molcel.2007.02.022;
RA Hao B., Oehlmann S., Sowa M.E., Harper J.W., Pavletich N.P.;
RT "Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated
RT substrate recognition by SCF ubiquitin ligases.";
RL Mol. Cell 26:131-143(2007).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH FBXO2.
RX PubMed=17389369; DOI=10.1073/pnas.0610312104;
RA Mizushima T., Yoshida Y., Kumanomidou T., Hasegawa Y., Suzuki A.,
RA Yamane T., Tanaka K.;
RT "Structural basis for the selection of glycosylated substrates by
RT SCF(Fbs1) ubiquitin ligase.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:5777-5781(2007).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH FBXO4, AND
RP FUNCTION.
RX PubMed=20181953; DOI=10.1074/jbc.M110.111518;
RA Li Y., Hao B.;
RT "Structural basis of dimerization-dependent ubiquitination by the
RT SCF(Fbx4) ubiquitin ligase.";
RL J. Biol. Chem. 285:13896-13906(2010).
CC -!- FUNCTION: Essential component of the SCF (SKP1-CUL1-F-box protein)
CC ubiquitin ligase complex, which mediates the ubiquitination of
CC proteins involved in cell cycle progression, signal transduction
CC and transcription. In the SCF complex, serves as an adapter that
CC links the F-box protein to CUL1. The functional specificity of the
CC SCF complex depends on the F-box protein as substrate recognition
CC component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of
CC CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs
CC ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs
CC ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A,
CC FBXO5 and probably NFKB2. SCF(SKP2) directs ubiquitination of
CC phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S
CC transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2,
CC ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7)
CC directs ubiquitination of cyclin E, NOTCH1 released notch
CC intracellular domain (NICD), and probably PSEN1. SCF(FBXW2)
CC directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination
CC of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5.
CC SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO11) directs
CC ubiquitination of BCL6 and DTL but does not seem to direct
CC ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of
CC NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the
CC associated NFKB1-RELA dimer to translocate into the nucleus and to
CC activate transcription. SCF(CCNF) directs ubiquitination of
CC CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1
CC and CRY2. SCF(FBXO9) direct ubiquitination of TTI1 and TELO2.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of multiple SCF (SKP1-CUL1-F-box) E3 ubiquitin-
CC protein ligase complexes formed of CUL1, SKP1, RBX1 and a variable
CC F-box domain-containing protein as substrate-specific subunit.
CC Component of the SCF(FBXW11) complex containing FBXW11. Component
CC of the SCF(SKP2) complex containing SKP2, in which it interacts
CC directly with SKP1, SKP2 and RBX1. Component of the SCF(FBXW2)
CC complex containing FBXw2. Component of the SCF(FBXO32) complex
CC containing FBXO32. Component of the probable SCF(FBXO7) complex
CC containing FBXO7. Component of the SCF(FBXO11) complex containing
CC FBXO11. Component of the SCF(FBXO25) complex containing FBXO25.
CC Component of the SCF(FBXO33) complex containing FBXO33. Component
CC of the probable SCF(FBXO4) complex containing FBXO4. Component of
CC the SCF(FBXO44) complex, composed of SKP1, CUL1 and FBXO44.
CC Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and
CC BTRC. This complex binds phosphorylated NFKBIA. Part of a SCF
CC complex consisting of CUL1, RBX1, SKP1 and FBXO2. Component of a
CC SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2.
CC Component of the SCF(FBXO17) complex, composed of SKP1, CUL1 and
CC FBXO17. Component of the SCF(FBXO27) complex, composed of SKP1,
CC CUL1 and FBXO27. Component of the SCF(CCNF) complex consisting of
CC CUL1, RBX1, SKP1 and CCNF. Component of the SCF(FBXL3) complex
CC composed of CUL1, SKP1, RBX1 and FBXL3. Component of the
CC SCF(FBXL21) complex composed of CUL1, SKP1, RBX1 and FBXL21.
CC Component of the SCF(FBXO9) composed of CUL1, SKP1, RBX1 and
CC FBXO9. Component of the SCF(FBXW7) composed of CUL1, SKP1, RBX1
CC and FBXW7.
CC -!- INTERACTION:
CC Q9Y297:BTRC; NbExp=5; IntAct=EBI-307486, EBI-307461;
CC P41002:CCNF; NbExp=6; IntAct=EBI-307486, EBI-1207574;
CC P38936:CDKN1A; NbExp=2; IntAct=EBI-307486, EBI-375077;
CC Q13616:CUL1; NbExp=9; IntAct=EBI-307486, EBI-359390;
CC O95905:ECD; NbExp=3; IntAct=EBI-307486, EBI-2557598;
CC Q96CD0:FBXL8; NbExp=3; IntAct=EBI-307486, EBI-2321097;
CC Q86XK2:FBXO11; NbExp=2; IntAct=EBI-307486, EBI-1047804;
CC Q9UK99:FBXO3; NbExp=2; IntAct=EBI-307486, EBI-2509901;
CC Q6PJ61:FBXO46; NbExp=3; IntAct=EBI-307486, EBI-2322982;
CC Q9Y3I1:FBXO7; NbExp=2; IntAct=EBI-307486, EBI-1161222;
CC Q9UKB1:FBXW11; NbExp=4; IntAct=EBI-307486, EBI-355189;
CC Q9UKT8:FBXW2; NbExp=3; IntAct=EBI-307486, EBI-914727;
CC Q969U6:FBXW5; NbExp=3; IntAct=EBI-307486, EBI-741068;
CC Q969H0:FBXW7; NbExp=2; IntAct=EBI-307486, EBI-359574;
CC Q5XUX1:FBXW9; NbExp=3; IntAct=EBI-307486, EBI-2322729;
CC Q14901:MYC; NbExp=2; IntAct=EBI-307486, EBI-7982457;
CC P62136:PPP1CA; NbExp=3; IntAct=EBI-307486, EBI-357253;
CC Q13309:SKP2; NbExp=15; IntAct=EBI-307486, EBI-456291;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P63208-1, P34991-1;
CC Sequence=Displayed;
CC Name=2;
CC IsoId=P63208-2, P34991-2;
CC Sequence=VSP_007555;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Belongs to the SKP1 family.
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DR EMBL; U33760; AAC50241.1; -; mRNA.
DR EMBL; Z47087; CAA87392.1; -; mRNA.
DR EMBL; CH471062; EAW62270.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62271.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62272.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62276.1; -; Genomic_DNA.
DR EMBL; BC009839; AAH09839.1; -; mRNA.
DR EMBL; BC020798; AAH20798.1; -; mRNA.
DR EMBL; BC025673; AAH25673.1; -; mRNA.
DR EMBL; BC065730; AAH65730.1; -; mRNA.
DR EMBL; U37558; AAA79202.1; -; mRNA.
DR PIR; I39170; I39170.
DR RefSeq; NP_008861.2; NM_006930.3.
DR RefSeq; NP_733779.1; NM_170679.2.
DR UniGene; Hs.171626; -.
DR PDB; 1FQV; X-ray; 2.80 A; B/D/F/H/J/L/N/P=1-163.
DR PDB; 1FS1; X-ray; 1.80 A; B/D=1-147.
DR PDB; 1FS2; X-ray; 2.90 A; B/D=1-147.
DR PDB; 1LDK; X-ray; 3.10 A; D=2-140.
DR PDB; 1P22; X-ray; 2.95 A; B=1-163.
DR PDB; 2ASS; X-ray; 3.00 A; A=3-159.
DR PDB; 2AST; X-ray; 2.30 A; A=3-159.
DR PDB; 2E31; X-ray; 2.40 A; B=1-163.
DR PDB; 2E32; X-ray; 3.52 A; B/D=1-163.
DR PDB; 2OVP; X-ray; 2.90 A; A=1-163.
DR PDB; 2OVQ; X-ray; 2.60 A; A=1-163.
DR PDB; 2OVR; X-ray; 2.50 A; A=1-163.
DR PDB; 3L2O; X-ray; 2.80 A; A=3-163.
DR PDB; 4I6J; X-ray; 2.70 A; C=1-163.
DR PDBsum; 1FQV; -.
DR PDBsum; 1FS1; -.
DR PDBsum; 1FS2; -.
DR PDBsum; 1LDK; -.
DR PDBsum; 1P22; -.
DR PDBsum; 2ASS; -.
DR PDBsum; 2AST; -.
DR PDBsum; 2E31; -.
DR PDBsum; 2E32; -.
DR PDBsum; 2OVP; -.
DR PDBsum; 2OVQ; -.
DR PDBsum; 2OVR; -.
DR PDBsum; 3L2O; -.
DR PDBsum; 4I6J; -.
DR ProteinModelPortal; P63208; -.
DR SMR; P63208; 3-160.
DR DIP; DIP-31606N; -.
DR IntAct; P63208; 72.
DR MINT; MINT-5001195; -.
DR STRING; 9606.ENSP00000231487; -.
DR PhosphoSite; P63208; -.
DR DMDM; 52783797; -.
DR SWISS-2DPAGE; P63208; -.
DR PaxDb; P63208; -.
DR PeptideAtlas; P63208; -.
DR PRIDE; P63208; -.
DR DNASU; 6500; -.
DR Ensembl; ENST00000353411; ENSP00000231487; ENSG00000113558.
DR Ensembl; ENST00000517625; ENSP00000429961; ENSG00000113558.
DR Ensembl; ENST00000522552; ENSP00000429472; ENSG00000113558.
DR Ensembl; ENST00000522855; ENSP00000429686; ENSG00000113558.
DR GeneID; 6500; -.
DR KEGG; hsa:6500; -.
DR UCSC; uc003kzc.4; human.
DR CTD; 6500; -.
DR GeneCards; GC05M133521; -.
DR H-InvDB; HIX0129723; -.
DR HGNC; HGNC:10899; SKP1.
DR HPA; CAB012982; -.
DR MIM; 601434; gene.
DR neXtProt; NX_P63208; -.
DR PharmGKB; PA162403424; -.
DR eggNOG; COG5201; -.
DR HOGENOM; HOG000172184; -.
DR HOVERGEN; HBG057008; -.
DR InParanoid; P63208; -.
DR KO; K03094; -.
DR OMA; VIQWCTY; -.
DR OrthoDB; EOG7QVM4C; -.
DR PhylomeDB; P63208; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_24941; Circadian Clock.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00143; -.
DR ChiTaRS; SKP1; human.
DR EvolutionaryTrace; P63208; -.
DR GeneWiki; SKP1A; -.
DR GenomeRNAi; 6500; -.
DR NextBio; 25267; -.
DR PRO; PR:P63208; -.
DR ArrayExpress; P63208; -.
DR Bgee; P63208; -.
DR CleanEx; HS_SKP1; -.
DR Genevestigator; P63208; -.
DR GO; GO:0031467; C:Cul7-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
DR GO; GO:0031145; P:anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; TAS:Reactome.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0035518; P:histone H2A monoubiquitination; IDA:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; TAS:Reactome.
DR GO; GO:0051437; P:positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle; TAS:Reactome.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR011333; BTB/POZ_fold.
DR InterPro; IPR016897; E3_ubiquit_lig_SCF_Skp.
DR InterPro; IPR001232; Skp1_comp.
DR InterPro; IPR016072; Skp1_comp_dimer.
DR InterPro; IPR016073; Skp1_comp_POZ.
DR PANTHER; PTHR11165; PTHR11165; 1.
DR Pfam; PF01466; Skp1; 1.
DR Pfam; PF03931; Skp1_POZ; 1.
DR PIRSF; PIRSF028729; E3_ubiquit_lig_SCF_Skp; 1.
DR SMART; SM00512; Skp1; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
DR SUPFAM; SSF81382; SSF81382; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Phosphoprotein; Polymorphism;
KW Reference proteome; Ubl conjugation pathway.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 163 S-phase kinase-associated protein 1.
FT /FTId=PRO_0000187251.
FT REGION 104 163 Interaction with the F-box domain of F-
FT box proteins (By similarity).
FT MOD_RES 131 131 Phosphothreonine.
FT VAR_SEQ 154 163 RKENQWCEEK -> GSTQFCL (in isoform 2).
FT /FTId=VSP_007555.
FT VARIANT 14 14 F -> L (in dbSNP:rs11538034).
FT /FTId=VAR_051999.
FT STRAND 3 7
FT STRAND 9 12
FT STRAND 13 17
FT HELIX 18 22
FT HELIX 25 33
FT STRAND 44 46
FT STRAND 47 50
FT HELIX 52 65
FT HELIX 87 92
FT HELIX 97 110
FT HELIX 113 127
FT STRAND 128 130
FT HELIX 132 138
FT HELIX 149 156
FT TURN 157 159
SQ SEQUENCE 163 AA; 18658 MW; C794D62AFB75528A CRC64;
MPSIKLQSSD GEIFEVDVEI AKQSVTIKTM LEDLGMDDEG DDDPVPLPNV NAAILKKVIQ
WCTHHKDDPP PPEDDENKEK RTDDIPVWDQ EFLKVDQGTL FELILAANYL DIKGLLDVTC
KTVANMIKGK TPEEIRKTFN IKNDFTEEEE AQVRKENQWC EEK
//
ID SKP1_HUMAN Reviewed; 163 AA.
AC P63208; D3DQ97; D3DQ98; P34991; Q8TAY2;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 113.
DE RecName: Full=S-phase kinase-associated protein 1;
DE AltName: Full=Cyclin-A/CDK2-associated protein p19;
DE AltName: Full=Organ of Corti protein 2;
DE Short=OCP-2;
DE AltName: Full=Organ of Corti protein II;
DE Short=OCP-II;
DE AltName: Full=RNA polymerase II elongation factor-like protein;
DE AltName: Full=SIII;
DE AltName: Full=Transcription elongation factor B;
DE AltName: Full=p19A;
DE AltName: Full=p19skp1;
GN Name=SKP1; Synonyms=EMC19, OCP2, SKP1A, TCEB1L;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=7553852; DOI=10.1016/0092-8674(95)90271-6;
RA Zhang H., Kobayashi R., Galaktionov K., Beach D.;
RT "p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S
RT phase kinase.";
RL Cell 82:915-925(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8530064; DOI=10.1006/geno.1995.1225;
RA Sowden J., Morrison K., Schofield J., Putt W., Edwards Y.;
RT "A novel cDNA with homology to an RNA polymerase II elongation factors
RT maps to human chromosome 5q31 (TCEB1L) and to mouse chromosome 11
RT (Tceb1l).";
RL Genomics 29:145-151(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lung, Skin, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 2-11.
RC TISSUE=Erythrocyte;
RA Golaz O., Hughes G.J., Frutiger S., Paquet N., Bairoch A.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Appel R.D., Walzer C.,
RA Balant L., Hochstrasser D.F.;
RL Submitted (FEB-1994) to UniProtKB.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-163 (ISOFORM 1).
RC TISSUE=Inner ear;
RX PubMed=9031623; DOI=10.1016/S0378-1119(96)00590-2;
RA Liang Y., Chen H., Asher J.H. Jr., Chang C.-C., Friedman T.B.;
RT "Human inner ear OCP2 cDNA maps to 5q22-5q35.2 with related sequences
RT on chromosomes 4p16.2-4p14, 5p13-5q22, 7pter-q22, 10 and 12p13-
RT 12qter.";
RL Gene 184:163-167(1997).
RN [7]
RP INTERACTION WITH FBXW8, AND IDENTIFICATION IN SCF-LIKE COMPLEX.
RX PubMed=12481031; DOI=10.1073/pnas.252646399;
RA Dias D.C., Dolios G., Wang R., Pan Z.Q.;
RT "CUL7: a DOC domain-containing cullin selectively binds Skp1.Fbx29 to
RT form an SCF-like complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16601-16606(2002).
RN [8]
RP SUBUNIT OF A COMPLEX WITH SIAH1; CACYBP; UBE2D1; APC AND TBL1X.
RX PubMed=11389839; DOI=10.1016/S1097-2765(01)00242-8;
RA Matsuzawa S., Reed J.C.;
RT "Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin
RT degradation linked to p53 responses.";
RL Mol. Cell 7:915-926(2001).
RN [9]
RP INTERACTION WITH THE SCF(SKP2)-LIKE COMPLEX, AND INTERACTION WITH
RP TRIM21.
RX PubMed=16880511; DOI=10.1128/MCB.01630-05;
RA Sabile A., Meyer A.M., Wirbelauer C., Hess D., Kogel U., Scheffner M.,
RA Krek W.;
RT "Regulation of p27 degradation and S-phase progression by Ro52 RING
RT finger protein.";
RL Mol. Cell. Biol. 26:5994-6004(2006).
RN [10]
RP INTERACTION WITH FBXO44; FBXO17 AND FBXO27, AND IDENTIFICATION IN
RP SCF-COMPLEX.
RX PubMed=18203720; DOI=10.1074/jbc.M709508200;
RA Glenn K.A., Nelson R.F., Wen H.M., Mallinger A.J., Paulson H.L.;
RT "Diversity in tissue expression, substrate binding, and SCF complex
RT formation for a lectin family of ubiquitin ligases.";
RL J. Biol. Chem. 283:12717-12729(2008).
RN [11]
RP IDENTIFICATION IN THE SCF(CCNF) COMPLEX.
RX PubMed=20596027; DOI=10.1038/nature09140;
RA D'Angiolella V., Donato V., Vijayakumar S., Saraf A., Florens L.,
RA Washburn M.P., Dynlacht B., Pagano M.;
RT "SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity
RT through CP110 degradation.";
RL Nature 466:138-142(2010).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-131, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-131, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP FUNCTION IN UBIQUITINATION OF BCL6, AND IDENTIFICATION IN THE
RP SCF(FBXO11) COMPLEX.
RX PubMed=22113614; DOI=10.1038/nature10688;
RA Duan S., Cermak L., Pagan J.K., Rossi M., Martinengo C.,
RA di Celle P.F., Chapuy B., Shipp M., Chiarle R., Pagano M.;
RT "FBXO11 targets BCL6 for degradation and is inactivated in diffuse
RT large B-cell lymphomas.";
RL Nature 481:90-93(2012).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF THE SKP1-SKP2 COMPLEX.
RX PubMed=11099048; DOI=10.1038/35042620;
RA Schulman B.A., Carrano A.C., Jeffrey P.D., Bowen Z., Kinnucan E.R.E.,
RA Finnin M.S., Elledge S.J., Harper J.W., Pagano M., Pavletich N.P.;
RT "Insights into SCF ubiquitin ligases from the structure of the Skp1-
RT Skp2 complex.";
RL Nature 408:381-386(2000).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN SCF COMPLEX WITH CUL1; RBX1
RP AND SKP2.
RX PubMed=11961546; DOI=10.1038/416703a;
RA Zheng N., Schulman B.A., Song L., Miller J.J., Jeffrey P.D., Wang P.,
RA Chu C., Koepp D.M., Elledge S.J., Pagano M., Conaway R.C.,
RA Conaway J.W., Harper J.W., Pavletich N.P.;
RT "Structure of the Cul1-Rbx1-Skp1-F box Skp2 SCF ubiquitin ligase
RT complex.";
RL Nature 416:703-709(2002).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) IN COMPLEX WITH 176-606 OF BTRC
RP AND CTNNB1.
RX PubMed=12820959; DOI=10.1016/S1097-2765(03)00234-X;
RA Wu G., Xu G., Schulman B.A., Jeffrey P.D., Harper J.W.,
RA Pavletich N.P.;
RT "Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction
RT motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin
RT ligase.";
RL Mol. Cell 11:1445-1456(2003).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 3-159 IN COMPLEX WITH SKP2;
RP CKS1B AND CDKN1B PHOSPHOPEPTIDE, SUBUNIT, AND FUNCTION.
RX PubMed=16209941; DOI=10.1016/j.molcel.2005.09.003;
RA Hao B., Zheng N., Schulman B.A., Wu G., Miller J.J., Pagano M.,
RA Pavletich N.P.;
RT "Structural basis of the Cks1-dependent recognition of p27(Kip1) by
RT the SCF(Skp2) ubiquitin ligase.";
RL Mol. Cell 20:9-19(2005).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH FBXW7 AND CCNE1
RP PEPTIDE.
RX PubMed=17434132; DOI=10.1016/j.molcel.2007.02.022;
RA Hao B., Oehlmann S., Sowa M.E., Harper J.W., Pavletich N.P.;
RT "Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated
RT substrate recognition by SCF ubiquitin ligases.";
RL Mol. Cell 26:131-143(2007).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH FBXO2.
RX PubMed=17389369; DOI=10.1073/pnas.0610312104;
RA Mizushima T., Yoshida Y., Kumanomidou T., Hasegawa Y., Suzuki A.,
RA Yamane T., Tanaka K.;
RT "Structural basis for the selection of glycosylated substrates by
RT SCF(Fbs1) ubiquitin ligase.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:5777-5781(2007).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH FBXO4, AND
RP FUNCTION.
RX PubMed=20181953; DOI=10.1074/jbc.M110.111518;
RA Li Y., Hao B.;
RT "Structural basis of dimerization-dependent ubiquitination by the
RT SCF(Fbx4) ubiquitin ligase.";
RL J. Biol. Chem. 285:13896-13906(2010).
CC -!- FUNCTION: Essential component of the SCF (SKP1-CUL1-F-box protein)
CC ubiquitin ligase complex, which mediates the ubiquitination of
CC proteins involved in cell cycle progression, signal transduction
CC and transcription. In the SCF complex, serves as an adapter that
CC links the F-box protein to CUL1. The functional specificity of the
CC SCF complex depends on the F-box protein as substrate recognition
CC component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of
CC CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs
CC ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs
CC ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A,
CC FBXO5 and probably NFKB2. SCF(SKP2) directs ubiquitination of
CC phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S
CC transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2,
CC ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7)
CC directs ubiquitination of cyclin E, NOTCH1 released notch
CC intracellular domain (NICD), and probably PSEN1. SCF(FBXW2)
CC directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination
CC of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5.
CC SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO11) directs
CC ubiquitination of BCL6 and DTL but does not seem to direct
CC ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of
CC NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the
CC associated NFKB1-RELA dimer to translocate into the nucleus and to
CC activate transcription. SCF(CCNF) directs ubiquitination of
CC CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1
CC and CRY2. SCF(FBXO9) direct ubiquitination of TTI1 and TELO2.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of multiple SCF (SKP1-CUL1-F-box) E3 ubiquitin-
CC protein ligase complexes formed of CUL1, SKP1, RBX1 and a variable
CC F-box domain-containing protein as substrate-specific subunit.
CC Component of the SCF(FBXW11) complex containing FBXW11. Component
CC of the SCF(SKP2) complex containing SKP2, in which it interacts
CC directly with SKP1, SKP2 and RBX1. Component of the SCF(FBXW2)
CC complex containing FBXw2. Component of the SCF(FBXO32) complex
CC containing FBXO32. Component of the probable SCF(FBXO7) complex
CC containing FBXO7. Component of the SCF(FBXO11) complex containing
CC FBXO11. Component of the SCF(FBXO25) complex containing FBXO25.
CC Component of the SCF(FBXO33) complex containing FBXO33. Component
CC of the probable SCF(FBXO4) complex containing FBXO4. Component of
CC the SCF(FBXO44) complex, composed of SKP1, CUL1 and FBXO44.
CC Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and
CC BTRC. This complex binds phosphorylated NFKBIA. Part of a SCF
CC complex consisting of CUL1, RBX1, SKP1 and FBXO2. Component of a
CC SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2.
CC Component of the SCF(FBXO17) complex, composed of SKP1, CUL1 and
CC FBXO17. Component of the SCF(FBXO27) complex, composed of SKP1,
CC CUL1 and FBXO27. Component of the SCF(CCNF) complex consisting of
CC CUL1, RBX1, SKP1 and CCNF. Component of the SCF(FBXL3) complex
CC composed of CUL1, SKP1, RBX1 and FBXL3. Component of the
CC SCF(FBXL21) complex composed of CUL1, SKP1, RBX1 and FBXL21.
CC Component of the SCF(FBXO9) composed of CUL1, SKP1, RBX1 and
CC FBXO9. Component of the SCF(FBXW7) composed of CUL1, SKP1, RBX1
CC and FBXW7.
CC -!- INTERACTION:
CC Q9Y297:BTRC; NbExp=5; IntAct=EBI-307486, EBI-307461;
CC P41002:CCNF; NbExp=6; IntAct=EBI-307486, EBI-1207574;
CC P38936:CDKN1A; NbExp=2; IntAct=EBI-307486, EBI-375077;
CC Q13616:CUL1; NbExp=9; IntAct=EBI-307486, EBI-359390;
CC O95905:ECD; NbExp=3; IntAct=EBI-307486, EBI-2557598;
CC Q96CD0:FBXL8; NbExp=3; IntAct=EBI-307486, EBI-2321097;
CC Q86XK2:FBXO11; NbExp=2; IntAct=EBI-307486, EBI-1047804;
CC Q9UK99:FBXO3; NbExp=2; IntAct=EBI-307486, EBI-2509901;
CC Q6PJ61:FBXO46; NbExp=3; IntAct=EBI-307486, EBI-2322982;
CC Q9Y3I1:FBXO7; NbExp=2; IntAct=EBI-307486, EBI-1161222;
CC Q9UKB1:FBXW11; NbExp=4; IntAct=EBI-307486, EBI-355189;
CC Q9UKT8:FBXW2; NbExp=3; IntAct=EBI-307486, EBI-914727;
CC Q969U6:FBXW5; NbExp=3; IntAct=EBI-307486, EBI-741068;
CC Q969H0:FBXW7; NbExp=2; IntAct=EBI-307486, EBI-359574;
CC Q5XUX1:FBXW9; NbExp=3; IntAct=EBI-307486, EBI-2322729;
CC Q14901:MYC; NbExp=2; IntAct=EBI-307486, EBI-7982457;
CC P62136:PPP1CA; NbExp=3; IntAct=EBI-307486, EBI-357253;
CC Q13309:SKP2; NbExp=15; IntAct=EBI-307486, EBI-456291;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P63208-1, P34991-1;
CC Sequence=Displayed;
CC Name=2;
CC IsoId=P63208-2, P34991-2;
CC Sequence=VSP_007555;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Belongs to the SKP1 family.
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DR EMBL; U33760; AAC50241.1; -; mRNA.
DR EMBL; Z47087; CAA87392.1; -; mRNA.
DR EMBL; CH471062; EAW62270.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62271.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62272.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62276.1; -; Genomic_DNA.
DR EMBL; BC009839; AAH09839.1; -; mRNA.
DR EMBL; BC020798; AAH20798.1; -; mRNA.
DR EMBL; BC025673; AAH25673.1; -; mRNA.
DR EMBL; BC065730; AAH65730.1; -; mRNA.
DR EMBL; U37558; AAA79202.1; -; mRNA.
DR PIR; I39170; I39170.
DR RefSeq; NP_008861.2; NM_006930.3.
DR RefSeq; NP_733779.1; NM_170679.2.
DR UniGene; Hs.171626; -.
DR PDB; 1FQV; X-ray; 2.80 A; B/D/F/H/J/L/N/P=1-163.
DR PDB; 1FS1; X-ray; 1.80 A; B/D=1-147.
DR PDB; 1FS2; X-ray; 2.90 A; B/D=1-147.
DR PDB; 1LDK; X-ray; 3.10 A; D=2-140.
DR PDB; 1P22; X-ray; 2.95 A; B=1-163.
DR PDB; 2ASS; X-ray; 3.00 A; A=3-159.
DR PDB; 2AST; X-ray; 2.30 A; A=3-159.
DR PDB; 2E31; X-ray; 2.40 A; B=1-163.
DR PDB; 2E32; X-ray; 3.52 A; B/D=1-163.
DR PDB; 2OVP; X-ray; 2.90 A; A=1-163.
DR PDB; 2OVQ; X-ray; 2.60 A; A=1-163.
DR PDB; 2OVR; X-ray; 2.50 A; A=1-163.
DR PDB; 3L2O; X-ray; 2.80 A; A=3-163.
DR PDB; 4I6J; X-ray; 2.70 A; C=1-163.
DR PDBsum; 1FQV; -.
DR PDBsum; 1FS1; -.
DR PDBsum; 1FS2; -.
DR PDBsum; 1LDK; -.
DR PDBsum; 1P22; -.
DR PDBsum; 2ASS; -.
DR PDBsum; 2AST; -.
DR PDBsum; 2E31; -.
DR PDBsum; 2E32; -.
DR PDBsum; 2OVP; -.
DR PDBsum; 2OVQ; -.
DR PDBsum; 2OVR; -.
DR PDBsum; 3L2O; -.
DR PDBsum; 4I6J; -.
DR ProteinModelPortal; P63208; -.
DR SMR; P63208; 3-160.
DR DIP; DIP-31606N; -.
DR IntAct; P63208; 72.
DR MINT; MINT-5001195; -.
DR STRING; 9606.ENSP00000231487; -.
DR PhosphoSite; P63208; -.
DR DMDM; 52783797; -.
DR SWISS-2DPAGE; P63208; -.
DR PaxDb; P63208; -.
DR PeptideAtlas; P63208; -.
DR PRIDE; P63208; -.
DR DNASU; 6500; -.
DR Ensembl; ENST00000353411; ENSP00000231487; ENSG00000113558.
DR Ensembl; ENST00000517625; ENSP00000429961; ENSG00000113558.
DR Ensembl; ENST00000522552; ENSP00000429472; ENSG00000113558.
DR Ensembl; ENST00000522855; ENSP00000429686; ENSG00000113558.
DR GeneID; 6500; -.
DR KEGG; hsa:6500; -.
DR UCSC; uc003kzc.4; human.
DR CTD; 6500; -.
DR GeneCards; GC05M133521; -.
DR H-InvDB; HIX0129723; -.
DR HGNC; HGNC:10899; SKP1.
DR HPA; CAB012982; -.
DR MIM; 601434; gene.
DR neXtProt; NX_P63208; -.
DR PharmGKB; PA162403424; -.
DR eggNOG; COG5201; -.
DR HOGENOM; HOG000172184; -.
DR HOVERGEN; HBG057008; -.
DR InParanoid; P63208; -.
DR KO; K03094; -.
DR OMA; VIQWCTY; -.
DR OrthoDB; EOG7QVM4C; -.
DR PhylomeDB; P63208; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_24941; Circadian Clock.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00143; -.
DR ChiTaRS; SKP1; human.
DR EvolutionaryTrace; P63208; -.
DR GeneWiki; SKP1A; -.
DR GenomeRNAi; 6500; -.
DR NextBio; 25267; -.
DR PRO; PR:P63208; -.
DR ArrayExpress; P63208; -.
DR Bgee; P63208; -.
DR CleanEx; HS_SKP1; -.
DR Genevestigator; P63208; -.
DR GO; GO:0031467; C:Cul7-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
DR GO; GO:0031145; P:anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; TAS:Reactome.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0035518; P:histone H2A monoubiquitination; IDA:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; TAS:Reactome.
DR GO; GO:0051437; P:positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle; TAS:Reactome.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR011333; BTB/POZ_fold.
DR InterPro; IPR016897; E3_ubiquit_lig_SCF_Skp.
DR InterPro; IPR001232; Skp1_comp.
DR InterPro; IPR016072; Skp1_comp_dimer.
DR InterPro; IPR016073; Skp1_comp_POZ.
DR PANTHER; PTHR11165; PTHR11165; 1.
DR Pfam; PF01466; Skp1; 1.
DR Pfam; PF03931; Skp1_POZ; 1.
DR PIRSF; PIRSF028729; E3_ubiquit_lig_SCF_Skp; 1.
DR SMART; SM00512; Skp1; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
DR SUPFAM; SSF81382; SSF81382; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Phosphoprotein; Polymorphism;
KW Reference proteome; Ubl conjugation pathway.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 163 S-phase kinase-associated protein 1.
FT /FTId=PRO_0000187251.
FT REGION 104 163 Interaction with the F-box domain of F-
FT box proteins (By similarity).
FT MOD_RES 131 131 Phosphothreonine.
FT VAR_SEQ 154 163 RKENQWCEEK -> GSTQFCL (in isoform 2).
FT /FTId=VSP_007555.
FT VARIANT 14 14 F -> L (in dbSNP:rs11538034).
FT /FTId=VAR_051999.
FT STRAND 3 7
FT STRAND 9 12
FT STRAND 13 17
FT HELIX 18 22
FT HELIX 25 33
FT STRAND 44 46
FT STRAND 47 50
FT HELIX 52 65
FT HELIX 87 92
FT HELIX 97 110
FT HELIX 113 127
FT STRAND 128 130
FT HELIX 132 138
FT HELIX 149 156
FT TURN 157 159
SQ SEQUENCE 163 AA; 18658 MW; C794D62AFB75528A CRC64;
MPSIKLQSSD GEIFEVDVEI AKQSVTIKTM LEDLGMDDEG DDDPVPLPNV NAAILKKVIQ
WCTHHKDDPP PPEDDENKEK RTDDIPVWDQ EFLKVDQGTL FELILAANYL DIKGLLDVTC
KTVANMIKGK TPEEIRKTFN IKNDFTEEEE AQVRKENQWC EEK
//
MIM
601434
*RECORD*
*FIELD* NO
601434
*FIELD* TI
*601434 S-PHASE KINASE-ASSOCIATED PROTEIN 1A; SKP1A
;;SKP1;;
CDK2/CYCLIN A-ASSOCIATED PROTEIN p19A;;
read moreORGAN OF CORTI PROTEIN 2; OCP2;;
TRANSCRIPTION ELONGATION FACTOR B, 1-LIKE; TCEB1L
*FIELD* TX
CLONING
Chen et al. (1995) cloned the gene encoding OCP2 from a guinea pig organ
of Corti cDNA library. They reported significant sequence similarity
with TCEB1 (600788), a subunit of transcription factor SIII (or elongin)
that regulates the activity of the RNA polymerase II elongation complex.
Immunohistochemical staining by Chen et al. (1995) confirmed that OCP2
is localized abundantly in nonsensory cells in the organ of Corti; in
addition, it was detected at a lower concentration in vestibular sensory
organs, as well as auditory and vestibular brainstem nuclei. The results
suggested that OCP2 may be involved in transcription regulation for the
development or maintenance of specialized functions of the inner ear.
Sowden et al. (1995) characterized cDNAs isolated from both mouse and
human embryo cDNA libraries and designated them Tceb1l and TCEB1L,
respectively. Predicted amino acid sequence showed significant homology
with TCEB1 (600788), the eukaryotic elongation factor, also called
elongin C, which is a component of the SIII elongation complex. The
TCEB1L gene is highly conserved throughout vertebrates. The TCEB1L gene
showed a restricted pattern of expression in the early mouse embryo,
where it is absent from the neurectoderm; later, Tceb1l was expressed in
the caudal region of the neural tube, followed by widespread expression
in many tissues, including the brain and spinal cord.
Zhang et al. (1995) cloned and sequenced the p19/SKP1 gene. Liang et al.
(1997) reported that the coding region of OCP2 (TCEB1L) is identical to
that of p19.
GENE FUNCTION
Zhang et al. (1995) found that p45/SKP2 (601436) appears to serve as a
bridge between p19 and the CDK2 (116953)/cyclin A (123835) complex.
Bai et al. (1996) cloned SKP1 and determined that it binds to cyclin F
(CCNF; 600227), SKP2, and potentially to other regulatory proteins that
may be involved in ubiquitin proteolysis. Binding occurs through a novel
motif, termed the F box. The F box contains about 40 residues and, in
approximately half of the F-box proteins identified by Bai et al.
(1996), it was associated with leucine-rich regions (LRRs), as in SKP2,
or with WD40 repeats, as in BTRC (603482).
Maniatis (1999) reviewed the work of Winston et al. (1999) and others
concerning the SCF (SKP1, CUL1 (603134), F-box protein) ubiquitin ligase
complex. CUL1 acts as a scaffold for SKP1 and the F-box-containing BTRC
protein in the SCF complex, which regulates the function of nuclear
factor kappa-B (see 164011) and beta-catenin (see 116806).
Matsuzawa and Reed (2001) elucidated a network of protein interactions
in which SIAH1 (602212), SIP (606186), SKP1, and EBI (300196)
collaborate in a pathway controlling beta-catenin levels, affecting
activity of beta-catenin-dependent TCF (e.g., TCF1; 142410) and LEF
(e.g., LEF1; 153245) transcription factors.
Dias et al. (2002) found that CUL7 (609577) assembled an SCF-ROC1 (RBX1;
603814)-like E3 ligase complex containing SKP1, CUL7, FBX29 (FBXW8;
609073), and ROC1 in human embryonic kidney cells. CUL7 specifically
interacted with SKP1-FBX29, but not with SKP1 alone. CUL7 did not
interact with SKP1-beta-TRCP2 (FBXW11; 605651) or SKP1-SKP2.
Immunoprecipitated CUL7-ROC1 complexes converted monomeric ubiquitin
into high molecular mass ubiquitin conjugates when incubated with E1
(see UBE1C; 603172) and UBC5C (UBE2D3; 602963).
Arai et al. (2003) found that mouse Cul7 formed a specific SCF-like
complex with Skp1, Fbx29, Rbx1, and Fap68 (GLMN; 601749). Cul7
associated with Skp1 in an Fbx29-dependent manner, and Fbx29 protein
stability decreased in the absence of Cul7.
BIOCHEMICAL FEATURES
- Crystal Structure
F-box proteins are the substrate recognition components of SCF
ubiquitin-protein ligases. Schulman et al. (2000) described the crystal
structure of the SKP1-SKP2 complex. They determined that the complex
resembles a sickle, with SKP1 and the F box of SKP2 representing the
handle and the LRRs of SKP2 representing the blade. The N-terminal 125
amino acids of SKP1 form an alpha/beta structure similar to that of the
BTB/POZ domain fold, but with a 2-helix C-terminal extension. The 10
LRRs of SKP2, each consisting of a beta strand and an alpha helix, pack
into a curved structure. The crystal structure suggested that there is a
conserved core interface that recruits F-box proteins to SCF ligases and
a second variable interface that provides a basis for specificity. The F
box may also help position the substrate for the ubiquitination
reaction.
Zheng et al. (2002) reported the crystal structure to 3.2-angstrom
resolution of the quaternary complex containing CUL1, RBX1 (603814),
SKP1, and the F box of SKP2, and the 3.0-angstrom structure of the
CUL1-RBX1 complex. CUL1 is an elongated protein that consists of a long
stalk and a globular domain. The globular domain binds the RING finger
protein RBX1 through an intermolecular beta-sheet, forming a 2-subunit
catalytic core that recruits the ubiquitin-conjugating enzyme. The long
stalk, which consists of 3 repeats of a novel 5-helix motif, binds the
SKP1-F box(SKP2) protein substrate recognition complex at its tip. CUL1
serves as a rigid scaffold that organizes the SKP1-F box(SKP2) and RBX1
subunits, holding them over 100 angstroms apart. The structure suggests
that CUL1 may contribute to catalysis through the positioning of the
substrate and the ubiquitin-conjugating enzyme, and that this model is
supported by CUL1 mutations designed to eliminate the rigidity of the
scaffold.
MAPPING
By fluorescence in situ hybridization, Sowden et al. (1995) assigned the
TCEB1L gene to chromosome 5q31, and by analysis of interspecific
backcross matings they mapped the mouse homolog to a region of syntenic
homology on chromosome 11.
Demetrick et al. (1996) mapped the SKP1A gene to 7q11.2 by fluorescence
in situ hybridization, but this was later determined to be a pseudogene
of TCEB1 (TCEB1P; see 600788). See also SKP1B (601435).
Liang et al. (1997) mapped the OCP2 gene to chromosome 5q22-q35.2 by
Southern and PCR analysis of human/rodent somatic cell hybrids and
reported OCP2-like sequences on chromosomes 4, 5, 7, 10, and 12.
By interspecific backcross analyses, Chen et al. (1995) mapped the mouse
Ocp2 gene to mouse chromosome 11 and a related sequence to chromosome 4.
*FIELD* RF
1. Arai, T.; Kasper, J. S.; Skaar, J. R.; Ali, S. H.; Takahashi, C.;
DeCaprio, J. A.: Targeted disruption of p185/Cul7 gene results in
abnormal vascular morphogenesis. Proc. Nat. Acad. Sci. 100: 9855-9860,
2003.
2. Bai, C.; Sen, P.; Hofmann, K.; Ma, L.; Goebl, M.; Harper, J. W.;
Elledge, S. J.: SKP1 connects cell cycle regulators to the ubiquitin
proteolysis machinery through a novel motif, the F-box. Cell 86:
263-274, 1996.
3. Chen, H.; Thalmann, I.; Adams, J. C.; Avraham, K. B.; Copeland,
N. G.; Jenkins, N. A.; Beier, D. R.; Corey, D. P.; Thalmann, R.; Duyk,
G. M.: cDNA cloning, tissue distribution and chromosomal localization
of Ocp2, a gene encoding a putative transcription-associated factor
predominantly expressed in the auditory organs. Genomics 27: 389-398,
1995.
4. Demetrick, D. J.; Zhang, H.; Beach, D. H.: Chromosomal mapping
of the genes for the human CDK2/cyclin A-associated proteins p19 (SKP1A
and SKP1B) and p45 (SKP2). Cytogenet. Cell Genet. 73: 104-107, 1996.
5. Dias, D. C.; Dolios, G.; Wang, R.; Pan, Z.-Q.: CUL7: A DOC domain-containing
cullin selectively binds Skp1-Fbx29 to form an SCF-like complex. Proc.
Nat. Acad. Sci. 99: 16601-16606, 2002.
6. Liang, Y.; Chen, H.; Asher, J. H., Jr.; Chang, C.-C.; Friedman,
T. B.: 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. Gene 184: 163-167, 1997.
7. Maniatis, T.: A ubiquitin ligase complex essential for the NF-kappa-B,
Wnt/Wingless, and Hedgehog signaling pathways. Genes Dev. 13: 505-510,
1999.
8. Matsuzawa, S.; Reed, J. C.: Siah-1, SIP, and Ebi collaborate in
a novel pathway for beta-catenin degradation linked to p53 responses. Molec.
Cell 7: 915-926, 2001.
9. 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.: Insights into the SCF ubiquitin ligases from the
structure of the Skp1-Skp2 complex. Nature 408: 381-386, 2000.
10. Sowden, J.; Morrison, K.; Schofield, J.; Putt, W.; Edwards, Y.
: A novel cDNA with homology to an RNA polymerase II elongation factors
maps to human chromosome 5q31 (TCEB1L) and to mouse chromosome 11
(Tceb1l). Genomics 29: 145-151, 1995.
11. Winston, J. T.; Strack, P.; Beer-Romero, P.; Chu, C. Y.; Elledge,
S. J.; Harper, J. W.: The SCF(beta-TRCP)-ubiquitin ligase complex
associates specifically with phosphorylated destruction motifs in
I-kappa-B-alpha and beta-catenin and stimulates I-kappa-B-alpha ubiquitination
in vitro. Genes Dev. 13: 270-283, 1999. Note: Erratum: Genes Dev.
13: 1050 only, 1999.
12. Zhang, H.; Kobayashi, R.; Galaktionov, K.; Beach, D.: p19Skp1
and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase. Cell 82:
915-925, 1995.
13. 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.:
Structure of the Cul1-Rbx1-Skp1-F box(Skp2) SCF ubiquitin ligase complex. Nature 416:
703-709, 2002.
*FIELD* CN
Patricia A. Hartz - updated: 9/13/2005
Ada Hamosh - updated: 4/30/2002
Stylianos E. Antonarakis - updated: 8/9/2001
Paul J. Converse - updated: 11/15/2000
Paul J. Converse - updated: 9/1/2000
Victor A. McKusick - updated: 6/18/1997
*FIELD* CD
Victor A. McKusick: 9/20/1996
*FIELD* ED
terry: 03/14/2013
alopez: 1/12/2010
terry: 1/6/2010
mgross: 9/13/2005
terry: 3/4/2005
carol: 2/11/2003
alopez: 4/30/2002
terry: 4/30/2002
mgross: 8/24/2001
mgross: 8/9/2001
mgross: 11/15/2000
mgross: 9/1/2000
mark: 6/18/1997
mark: 5/13/1997
mark: 9/20/1996
*RECORD*
*FIELD* NO
601434
*FIELD* TI
*601434 S-PHASE KINASE-ASSOCIATED PROTEIN 1A; SKP1A
;;SKP1;;
CDK2/CYCLIN A-ASSOCIATED PROTEIN p19A;;
read moreORGAN OF CORTI PROTEIN 2; OCP2;;
TRANSCRIPTION ELONGATION FACTOR B, 1-LIKE; TCEB1L
*FIELD* TX
CLONING
Chen et al. (1995) cloned the gene encoding OCP2 from a guinea pig organ
of Corti cDNA library. They reported significant sequence similarity
with TCEB1 (600788), a subunit of transcription factor SIII (or elongin)
that regulates the activity of the RNA polymerase II elongation complex.
Immunohistochemical staining by Chen et al. (1995) confirmed that OCP2
is localized abundantly in nonsensory cells in the organ of Corti; in
addition, it was detected at a lower concentration in vestibular sensory
organs, as well as auditory and vestibular brainstem nuclei. The results
suggested that OCP2 may be involved in transcription regulation for the
development or maintenance of specialized functions of the inner ear.
Sowden et al. (1995) characterized cDNAs isolated from both mouse and
human embryo cDNA libraries and designated them Tceb1l and TCEB1L,
respectively. Predicted amino acid sequence showed significant homology
with TCEB1 (600788), the eukaryotic elongation factor, also called
elongin C, which is a component of the SIII elongation complex. The
TCEB1L gene is highly conserved throughout vertebrates. The TCEB1L gene
showed a restricted pattern of expression in the early mouse embryo,
where it is absent from the neurectoderm; later, Tceb1l was expressed in
the caudal region of the neural tube, followed by widespread expression
in many tissues, including the brain and spinal cord.
Zhang et al. (1995) cloned and sequenced the p19/SKP1 gene. Liang et al.
(1997) reported that the coding region of OCP2 (TCEB1L) is identical to
that of p19.
GENE FUNCTION
Zhang et al. (1995) found that p45/SKP2 (601436) appears to serve as a
bridge between p19 and the CDK2 (116953)/cyclin A (123835) complex.
Bai et al. (1996) cloned SKP1 and determined that it binds to cyclin F
(CCNF; 600227), SKP2, and potentially to other regulatory proteins that
may be involved in ubiquitin proteolysis. Binding occurs through a novel
motif, termed the F box. The F box contains about 40 residues and, in
approximately half of the F-box proteins identified by Bai et al.
(1996), it was associated with leucine-rich regions (LRRs), as in SKP2,
or with WD40 repeats, as in BTRC (603482).
Maniatis (1999) reviewed the work of Winston et al. (1999) and others
concerning the SCF (SKP1, CUL1 (603134), F-box protein) ubiquitin ligase
complex. CUL1 acts as a scaffold for SKP1 and the F-box-containing BTRC
protein in the SCF complex, which regulates the function of nuclear
factor kappa-B (see 164011) and beta-catenin (see 116806).
Matsuzawa and Reed (2001) elucidated a network of protein interactions
in which SIAH1 (602212), SIP (606186), SKP1, and EBI (300196)
collaborate in a pathway controlling beta-catenin levels, affecting
activity of beta-catenin-dependent TCF (e.g., TCF1; 142410) and LEF
(e.g., LEF1; 153245) transcription factors.
Dias et al. (2002) found that CUL7 (609577) assembled an SCF-ROC1 (RBX1;
603814)-like E3 ligase complex containing SKP1, CUL7, FBX29 (FBXW8;
609073), and ROC1 in human embryonic kidney cells. CUL7 specifically
interacted with SKP1-FBX29, but not with SKP1 alone. CUL7 did not
interact with SKP1-beta-TRCP2 (FBXW11; 605651) or SKP1-SKP2.
Immunoprecipitated CUL7-ROC1 complexes converted monomeric ubiquitin
into high molecular mass ubiquitin conjugates when incubated with E1
(see UBE1C; 603172) and UBC5C (UBE2D3; 602963).
Arai et al. (2003) found that mouse Cul7 formed a specific SCF-like
complex with Skp1, Fbx29, Rbx1, and Fap68 (GLMN; 601749). Cul7
associated with Skp1 in an Fbx29-dependent manner, and Fbx29 protein
stability decreased in the absence of Cul7.
BIOCHEMICAL FEATURES
- Crystal Structure
F-box proteins are the substrate recognition components of SCF
ubiquitin-protein ligases. Schulman et al. (2000) described the crystal
structure of the SKP1-SKP2 complex. They determined that the complex
resembles a sickle, with SKP1 and the F box of SKP2 representing the
handle and the LRRs of SKP2 representing the blade. The N-terminal 125
amino acids of SKP1 form an alpha/beta structure similar to that of the
BTB/POZ domain fold, but with a 2-helix C-terminal extension. The 10
LRRs of SKP2, each consisting of a beta strand and an alpha helix, pack
into a curved structure. The crystal structure suggested that there is a
conserved core interface that recruits F-box proteins to SCF ligases and
a second variable interface that provides a basis for specificity. The F
box may also help position the substrate for the ubiquitination
reaction.
Zheng et al. (2002) reported the crystal structure to 3.2-angstrom
resolution of the quaternary complex containing CUL1, RBX1 (603814),
SKP1, and the F box of SKP2, and the 3.0-angstrom structure of the
CUL1-RBX1 complex. CUL1 is an elongated protein that consists of a long
stalk and a globular domain. The globular domain binds the RING finger
protein RBX1 through an intermolecular beta-sheet, forming a 2-subunit
catalytic core that recruits the ubiquitin-conjugating enzyme. The long
stalk, which consists of 3 repeats of a novel 5-helix motif, binds the
SKP1-F box(SKP2) protein substrate recognition complex at its tip. CUL1
serves as a rigid scaffold that organizes the SKP1-F box(SKP2) and RBX1
subunits, holding them over 100 angstroms apart. The structure suggests
that CUL1 may contribute to catalysis through the positioning of the
substrate and the ubiquitin-conjugating enzyme, and that this model is
supported by CUL1 mutations designed to eliminate the rigidity of the
scaffold.
MAPPING
By fluorescence in situ hybridization, Sowden et al. (1995) assigned the
TCEB1L gene to chromosome 5q31, and by analysis of interspecific
backcross matings they mapped the mouse homolog to a region of syntenic
homology on chromosome 11.
Demetrick et al. (1996) mapped the SKP1A gene to 7q11.2 by fluorescence
in situ hybridization, but this was later determined to be a pseudogene
of TCEB1 (TCEB1P; see 600788). See also SKP1B (601435).
Liang et al. (1997) mapped the OCP2 gene to chromosome 5q22-q35.2 by
Southern and PCR analysis of human/rodent somatic cell hybrids and
reported OCP2-like sequences on chromosomes 4, 5, 7, 10, and 12.
By interspecific backcross analyses, Chen et al. (1995) mapped the mouse
Ocp2 gene to mouse chromosome 11 and a related sequence to chromosome 4.
*FIELD* RF
1. Arai, T.; Kasper, J. S.; Skaar, J. R.; Ali, S. H.; Takahashi, C.;
DeCaprio, J. A.: Targeted disruption of p185/Cul7 gene results in
abnormal vascular morphogenesis. Proc. Nat. Acad. Sci. 100: 9855-9860,
2003.
2. Bai, C.; Sen, P.; Hofmann, K.; Ma, L.; Goebl, M.; Harper, J. W.;
Elledge, S. J.: SKP1 connects cell cycle regulators to the ubiquitin
proteolysis machinery through a novel motif, the F-box. Cell 86:
263-274, 1996.
3. Chen, H.; Thalmann, I.; Adams, J. C.; Avraham, K. B.; Copeland,
N. G.; Jenkins, N. A.; Beier, D. R.; Corey, D. P.; Thalmann, R.; Duyk,
G. M.: cDNA cloning, tissue distribution and chromosomal localization
of Ocp2, a gene encoding a putative transcription-associated factor
predominantly expressed in the auditory organs. Genomics 27: 389-398,
1995.
4. Demetrick, D. J.; Zhang, H.; Beach, D. H.: Chromosomal mapping
of the genes for the human CDK2/cyclin A-associated proteins p19 (SKP1A
and SKP1B) and p45 (SKP2). Cytogenet. Cell Genet. 73: 104-107, 1996.
5. Dias, D. C.; Dolios, G.; Wang, R.; Pan, Z.-Q.: CUL7: A DOC domain-containing
cullin selectively binds Skp1-Fbx29 to form an SCF-like complex. Proc.
Nat. Acad. Sci. 99: 16601-16606, 2002.
6. Liang, Y.; Chen, H.; Asher, J. H., Jr.; Chang, C.-C.; Friedman,
T. B.: 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. Gene 184: 163-167, 1997.
7. Maniatis, T.: A ubiquitin ligase complex essential for the NF-kappa-B,
Wnt/Wingless, and Hedgehog signaling pathways. Genes Dev. 13: 505-510,
1999.
8. Matsuzawa, S.; Reed, J. C.: Siah-1, SIP, and Ebi collaborate in
a novel pathway for beta-catenin degradation linked to p53 responses. Molec.
Cell 7: 915-926, 2001.
9. 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.: Insights into the SCF ubiquitin ligases from the
structure of the Skp1-Skp2 complex. Nature 408: 381-386, 2000.
10. Sowden, J.; Morrison, K.; Schofield, J.; Putt, W.; Edwards, Y.
: A novel cDNA with homology to an RNA polymerase II elongation factors
maps to human chromosome 5q31 (TCEB1L) and to mouse chromosome 11
(Tceb1l). Genomics 29: 145-151, 1995.
11. Winston, J. T.; Strack, P.; Beer-Romero, P.; Chu, C. Y.; Elledge,
S. J.; Harper, J. W.: The SCF(beta-TRCP)-ubiquitin ligase complex
associates specifically with phosphorylated destruction motifs in
I-kappa-B-alpha and beta-catenin and stimulates I-kappa-B-alpha ubiquitination
in vitro. Genes Dev. 13: 270-283, 1999. Note: Erratum: Genes Dev.
13: 1050 only, 1999.
12. Zhang, H.; Kobayashi, R.; Galaktionov, K.; Beach, D.: p19Skp1
and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase. Cell 82:
915-925, 1995.
13. 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.:
Structure of the Cul1-Rbx1-Skp1-F box(Skp2) SCF ubiquitin ligase complex. Nature 416:
703-709, 2002.
*FIELD* CN
Patricia A. Hartz - updated: 9/13/2005
Ada Hamosh - updated: 4/30/2002
Stylianos E. Antonarakis - updated: 8/9/2001
Paul J. Converse - updated: 11/15/2000
Paul J. Converse - updated: 9/1/2000
Victor A. McKusick - updated: 6/18/1997
*FIELD* CD
Victor A. McKusick: 9/20/1996
*FIELD* ED
terry: 03/14/2013
alopez: 1/12/2010
terry: 1/6/2010
mgross: 9/13/2005
terry: 3/4/2005
carol: 2/11/2003
alopez: 4/30/2002
terry: 4/30/2002
mgross: 8/24/2001
mgross: 8/9/2001
mgross: 11/15/2000
mgross: 9/1/2000
mark: 6/18/1997
mark: 5/13/1997
mark: 9/20/1996