ID SKP2_HUMAN STANDARD; PRT; 424 AA. AC Q13309; Q8TDZ0; Q8TDZ1; Q9BV69; DT 10-OCT-2003 (Rel. 42, Created) DT 10-OCT-2003 (Rel. 42, Last sequence update) DT 15-JUN-2004 (Rel. 44, Last annotation update) DE S-phase kinase-associated protein 2 (F-box protein Skp2) (Cyclin DE A/CDK2-associated protein p45) (p45skp2). GN SKP2. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. (ISOFORM 1), SEQUENCE OF 6-19; 31-58; 80-86 AND RP 365-372, AND INTERACTION WITH CYCLIN A/CDK2 COMPLEX. RX MEDLINE=96016087; PubMed=7553852; 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 SEQUENCE FROM N.A. (ISOFORMS 1; 2 AND 3). RC TISSUE=Liver; RA Yamaguchi T.; RT "human SKP2-like protein."; RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases. RN [3] RP SEQUENCE FROM N.A. (ISOFORM 1). RC TISSUE=Prostatic carcinoma; RA Kokontis J.M., Fukuchi J., Liao S.; RT "Androgenic regulation of Skp2 in androgen-dependent and -independent RT LNCaP human prostate tumor cells."; RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases. RN [4] RP SEQUENCE FROM N.A. (ISOFORM 2). RC TISSUE=Placenta; RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [5] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 101-153 IN COMPLEX WITH 1-147 RP OF SKP1. RX MEDLINE=20548724; PubMed=11099048; DOI=10.1038/35042620; RA Schulman B.A., Carrano A.C., Jeffrey P.D., Bowen Z., Kinnucan E.R., 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 RT Skp1-Skp2 complex."; RL Nature 408:381-386(2000). RN [6] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN COMPLEX WITH CUL1; SKP1 AND RP RBX1, AND INTERACTION WITH CKS1. RX MEDLINE=21959435; 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 boxSkp2 SCF ubiquitin ligase RT complex."; RL Nature 416:703-709(2002). CC -!- FUNCTION: Substrate recognition component of the SCF (SKP1-CUL1-F- CC box protein) E3 ubiquitin ligase complex which mediates the CC ubiquitination and subsequent proteasomal degradation of target CC proteins involved in cell cycle progression, signal transduction CC and transcription. Specifically recognizes phosphorylated CC CDKN1B/p27kip and is involved in regulation of G1/S transition. CC Degradation of CDKN1B/p27kip also requires CKS1. CC -!- PATHWAY: Ubiquitin conjugation; third step. CC -!- SUBUNIT: Part of a SCF complex consisting of CUL1, RBX1, SKP1 and CC SKP2. Interacts directly with CUL1 and SKP1. Interacts with CKS1. CC Interacts with the cyclin A/CDK2 complex. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=SKP2-alpha; CC IsoId=Q13309-1; Sequence=Displayed; CC Name=2; Synonyms=SKP2-beta; CC IsoId=Q13309-2; Sequence=VSP_008432; CC Name=3; Synonyms=SKP2-gamma; CC IsoId=Q13309-3; Sequence=VSP_008431; CC -!- SIMILARITY: Contains 1 F-box domain. CC -!- SIMILARITY: Contains 8 leucine-rich (LRR) repeats. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U33761; AAC50242.1; ALT_INIT. DR EMBL; AB050979; BAB87200.1; -. DR EMBL; AB050980; BAB87201.1; -. DR EMBL; AB050981; BAB87202.1; -. DR EMBL; AY029177; AAK31593.1; -. DR EMBL; BC001441; AAH01441.1; -. DR EMBL; BC007441; AAH07441.1; -. DR PDB; 1FQV; 29-NOV-00. DR PDB; 1FS1; 29-NOV-00. DR PDB; 1LDK; 08-MAY-02. DR MIM; 601436; -. DR GO; GO:0008283; P:cell proliferation; TAS. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS. DR GO; GO:0000074; P:regulation of cell cycle; TAS. DR InterPro; IPR001810; F-box. DR InterPro; IPR001611; LRR. DR InterPro; IPR007089; LRR_cys. DR InterPro; IPR008945; Skp1_Skp2. DR Pfam; PF00646; F-box; 1. DR Pfam; PF00560; LRR; 5. DR SMART; SM00256; FBOX; 1. DR PROSITE; PS50181; FBOX; 1. KW Ubl conjugation pathway; Repeat; Leucine-rich repeat; KW Alternative splicing; Polymorphism; 3D-structure; KW Direct protein sequencing. FT DOMAIN 94 140 F-box. FT REPEAT 180 204 LRR 1. FT REPEAT 210 234 LRR 2. FT REPEAT 258 284 LRR 3. FT REPEAT 286 308 LRR 4. FT REPEAT 309 330 LRR 5. FT REPEAT 334 356 LRR 6. FT REPEAT 359 378 LRR 7. FT REPEAT 380 403 LRR 8. FT VARSPLIC 355 424 ELGEIPTLKTLQVFGIVPDGTLQLLKEALPHLQINCSHFTT FT IARPTIGNKKNQEIWGIKCRLTLQKPSCL -> AGIYQNQN FT SHSNYNVSQVSHEGFKVGAGLLSSLVTRAGVRIRLDSDIGC FT PQTYRTSKLKSSHKLFCQHVRVICIFVCDFYFYRLVLKQ FT (in isoform 3). FT /FTId=VSP_008431. FT VARSPLIC 355 424 ELGEIPTLKTLQVFGIVPDGTLQLLKEALPHLQINCSHFTT FT IARPTIGNKKNQEIWGIKCRLTLQKPSCL -> LVTRAGVR FT IRLDSDIGCPQTYRTSKLKSSHKLFCQHVRVICIFVCDFYF FT YRLVLKQ (in isoform 2). FT /FTId=VSP_008432. FT VARIANT 85 85 P -> L (in dbSNP:3913486). FT /FTId=VAR_016984. FT VARIANT 87 87 L -> I (in dbSNP:3913487). FT /FTId=VAR_016985. FT CONFLICT 185 185 H -> D (in Ref. 1). FT CONFLICT 215 215 Missing (in Ref. 1). FT CONFLICT 238 238 S -> P (in Ref. 1). FT CONFLICT 241 241 S -> P (in Ref. 1). FT CONFLICT 244 247 SEFA -> PKFP (in Ref. 1). FT CONFLICT 251 251 L -> F (in Ref. 1). FT CONFLICT 256 256 S -> P (in Ref. 1). FT CONFLICT 268 268 D -> N (in Ref. 1). FT CONFLICT 285 285 I -> M (in Ref. 1). FT CONFLICT 319 319 D -> N (in Ref. 1). FT CONFLICT 332 332 F -> S (in Ref. 1). SQ SEQUENCE 424 AA; 47760 MW; F29B7C338A7A37E9 CRC64; MHRKHLQEIP DLSSNVATSF TWGWDSSKTS ELLSGMGVSA LEKEEPDSEN IPQELLSNLG HPESPPRKRL KSKGSDKDFV IVRRPKLNRE NFPGVSWDSL PDELLLGIFS CLCLPELLKV SGVCKRWYRL ASDESLWQTL DLTGKNLHPD VTGRLLSQGV IAFRCPRSFM DQPLAEHFSP FRVQHMDLSN SVIEVSTLHG ILSQCSKLQN LSLEGLRLSD PIVNTLAKNS NLVRLNLSGC SGFSEFALQT LLSSCSRLDE LNLSWCFDFT EKHVQVAVAH VSETITQLNL SGYRKNLQKS DLSTLVRRCP NLVHLDLSDS VMLKNDCFQE FFQLNYLQHL SLSRCYDIIP ETLLELGEIP TLKTLQVFGI VPDGTLQLLK EALPHLQINC SHFTTIARPT IGNKKNQEIW GIKCRLTLQK PSCL //