SKP2_MOUSE
ID SKP2_MOUSE Reviewed; 424 AA.
AC Q9Z0Z3; Q8BSG7; Q8C8Y9; Q8CB22; Q99J53;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=S-phase kinase-associated protein 2;
DE AltName: Full=Cyclin-A/CDK2-associated protein p45;
DE AltName: Full=F-box protein Skp2;
DE AltName: Full=F-box/WD-40 protein 1;
DE Short=FWD1;
GN Name=Skp2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND INTERACTION WITH
RP CYCLIN-E.
RC STRAIN=C57BL/6 X CBA; TISSUE=Thymus;
RX PubMed=10790373; DOI=10.1093/emboj/19.9.2069;
RA Nakayama K., Nagahama H., Minamishima Y.A., Matsumoto M., Nakamichi I.,
RA Kitagawa K., Shirane M., Tsunematsu R., Tsukiyama T., Ishida N.,
RA Kitagawa M., Nakayama K., Hatakeyama S.;
RT "Targeted disruption of Skp2 results in accumulation of cyclin E and
RT p27(Kip1), polyploidy and centrosome overduplication.";
RL EMBO J. 19:2069-2081(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Mesonephros, Retina, and Vagina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Mammary gland;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH CARM1.
RX PubMed=30366907; DOI=10.1101/gad.315564.118;
RA Liu Y., Wang T., Ji Y.J., Johnson K., Liu H., Johnson K., Bailey S.,
RA Suk Y., Lu Y.N., Liu M., Wang J.;
RT "A C9orf72-CARM1 axis regulates lipid metabolism under glucose starvation-
RT induced nutrient stress.";
RL Genes Dev. 32:1380-1397(2018).
CC -!- FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F-box
CC protein) E3 ubiquitin-protein ligase complex which mediates the
CC ubiquitination and subsequent proteasomal degradation of target
CC proteins involved in cell cycle progression, signal transduction and
CC transcription (By similarity). Specifically recognizes phosphorylated
CC CDKN1B/p27kip and is involved in regulation of G1/S transition
CC (PubMed:10790373). Degradation of CDKN1B/p27kip also requires CKS1.
CC Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2,
CC FOXO1, UBP43, YTHDF2, and probably MYC, TOB1 and TAL1. Degradation of
CC TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1
CC or CCNE2 and CDK2. Promotes ubiquitination and destruction of CDH1 in a
CC CK1-dependent manner, thereby regulating cell migration (By
CC similarity). {ECO:0000250|UniProtKB:Q13309,
CC ECO:0000269|PubMed:10790373}.
CC -!- FUNCTION: Through the ubiquitin-mediated proteasomal degradation of
CC viral proteins may have an antiviral activity.
CC {ECO:0000250|UniProtKB:Q13309}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Part of a SCF(SKP2) complex consisting of CUL1, RBX1, SKP1 and
CC SKP2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1,
CC TRIM21 and SKP2. Interacts directly with CUL1 and SKP1. Interacts with
CC ASB2 which is the substrate-recognition component of a probable ECS E3
CC ubiquitin-protein ligase complex; ASB2 is likely to bridge the
CC formation of dimeric E3-ubiquitin-protein ligase complexes composed of
CC an ECS complex and an SCF(SKP2) complex. Interacts with CKS1. Interacts
CC with the cyclin-A-CDK2 complex. Interacts with ORC1, phosphorylated
CC CDT1, phosphorylated RBL2, ELF4, phosphorylated RAG2, FOXO1, UBP43,
CC MYC, TOB1, TAL1 and KMT2A/MLL1. Interacts with TRIM21 (By similarity).
CC Interacts with cyclin-E (PubMed:10790373). Interacts with CARM1
CC (PubMed:30366907). {ECO:0000250|UniProtKB:Q13309,
CC ECO:0000269|PubMed:10790373, ECO:0000269|PubMed:30366907}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9Z0Z3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Z0Z3-2; Sequence=VSP_008434;
CC Name=3;
CC IsoId=Q9Z0Z3-3; Sequence=VSP_008433;
CC -!- PTM: Ubiquitinated by the APC/C complex, leading to its degradation by
CC the proteasome. Deubiquitinated by USP13 (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Acetylation at Lys-68 and Lys-71 increases stability through
CC impairment of APC/C-mediated proteolysis and promotes cytoplasmic
CC retention. Deacetylated by SIRT3 (By similarity). {ECO:0000250}.
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DR EMBL; AF083215; AAD16037.1; -; mRNA.
DR EMBL; AK032979; BAC28108.1; -; mRNA.
DR EMBL; AK044212; BAC31819.1; -; mRNA.
DR EMBL; AK037002; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC003468; AAH03468.1; -; mRNA.
DR CCDS; CCDS37037.1; -. [Q9Z0Z3-1]
DR RefSeq; NP_038815.1; NM_013787.3. [Q9Z0Z3-1]
DR AlphaFoldDB; Q9Z0Z3; -.
DR SMR; Q9Z0Z3; -.
DR BioGRID; 205208; 13.
DR STRING; 10090.ENSMUSP00000094225; -.
DR iPTMnet; Q9Z0Z3; -.
DR PhosphoSitePlus; Q9Z0Z3; -.
DR jPOST; Q9Z0Z3; -.
DR MaxQB; Q9Z0Z3; -.
DR PaxDb; Q9Z0Z3; -.
DR PRIDE; Q9Z0Z3; -.
DR ProteomicsDB; 257026; -. [Q9Z0Z3-1]
DR ProteomicsDB; 257027; -. [Q9Z0Z3-2]
DR ProteomicsDB; 257028; -. [Q9Z0Z3-3]
DR Antibodypedia; 22921; 463 antibodies from 41 providers.
DR DNASU; 27401; -.
DR Ensembl; ENSMUST00000096482; ENSMUSP00000094225; ENSMUSG00000054115. [Q9Z0Z3-1]
DR Ensembl; ENSMUST00000110585; ENSMUSP00000106215; ENSMUSG00000054115. [Q9Z0Z3-2]
DR GeneID; 27401; -.
DR KEGG; mmu:27401; -.
DR UCSC; uc007vff.2; mouse. [Q9Z0Z3-1]
DR UCSC; uc007vfi.3; mouse. [Q9Z0Z3-3]
DR CTD; 6502; -.
DR MGI; MGI:1351663; Skp2.
DR VEuPathDB; HostDB:ENSMUSG00000054115; -.
DR eggNOG; KOG2120; Eukaryota.
DR GeneTree; ENSGT00390000007918; -.
DR HOGENOM; CLU_032515_2_0_1; -.
DR InParanoid; Q9Z0Z3; -.
DR OMA; FVEELHF; -.
DR OrthoDB; 1333044at2759; -.
DR PhylomeDB; Q9Z0Z3; -.
DR TreeFam; TF352582; -.
DR Reactome; R-MMU-174178; APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
DR Reactome; R-MMU-187577; SCF(Skp2)-mediated degradation of p27/p21.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-68949; Orc1 removal from chromatin.
DR Reactome; R-MMU-69231; Cyclin D associated events in G1.
DR Reactome; R-MMU-8939902; Regulation of RUNX2 expression and activity.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-9708530; Regulation of BACH1 activity.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 27401; 17 hits in 74 CRISPR screens.
DR ChiTaRS; Skp2; mouse.
DR PRO; PR:Q9Z0Z3; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q9Z0Z3; protein.
DR Bgee; ENSMUSG00000054115; Expressed in maxillary prominence and 234 other tissues.
DR ExpressionAtlas; Q9Z0Z3; baseline and differential.
DR Genevisible; Q9Z0Z3; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0051607; P:defense response to virus; ISO:MGI.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IDA:MGI.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IMP:MGI.
DR GO; GO:0045087; P:innate immune response; ISO:MGI.
DR GO; GO:0033148; P:positive regulation of intracellular estrogen receptor signaling pathway; IGI:MGI.
DR GO; GO:1902916; P:positive regulation of protein polyubiquitination; IDA:MGI.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; IPI:MGI.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:MGI.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR006553; Leu-rich_rpt_Cys-con_subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR Pfam; PF12937; F-box-like; 1.
DR SMART; SM00256; FBOX; 1.
DR SMART; SM00367; LRR_CC; 4.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS50181; FBOX; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; Leucine-rich repeat; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..424
FT /note="S-phase kinase-associated protein 2"
FT /id="PRO_0000119955"
FT DOMAIN 94..140
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT REPEAT 151..176
FT /note="LRR 1"
FT REPEAT 177..204
FT /note="LRR 2"
FT REPEAT 210..234
FT /note="LRR 3"
FT REPEAT 235..257
FT /note="LRR 4"
FT REPEAT 258..284
FT /note="LRR 5"
FT REPEAT 286..308
FT /note="LRR 6"
FT REPEAT 309..330
FT /note="LRR 7"
FT REPEAT 334..356
FT /note="LRR 8"
FT REPEAT 359..378
FT /note="LRR 9"
FT REPEAT 380..401
FT /note="LRR 10"
FT REGION 52..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 67..73
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOD_RES 64
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13309"
FT MOD_RES 68
FT /note="N6-acetyllysine; by p300/EP300"
FT /evidence="ECO:0000250|UniProtKB:Q13309"
FT MOD_RES 71
FT /note="N6-acetyllysine; by p300/EP300"
FT /evidence="ECO:0000250|UniProtKB:Q13309"
FT MOD_RES 75
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13309"
FT MOD_RES 179
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13309"
FT VAR_SEQ 132..424
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_008433"
FT VAR_SEQ 355..424
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008434"
FT CONFLICT 340
FT /note="L -> H (in Ref. 2; BAC28108)"
FT /evidence="ECO:0000305"
FT CONFLICT 353
FT /note="L -> V (in Ref. 2; BAC31819)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 424 AA; 47766 MW; 5B7945C979D26AF9 CRC64;
MHRKHLQEIP DQSGNVTTSF TWGWDSSKTS ELLSGMGVSA LEKEEVDSEN IPHGLLSNLG
HPQSPPRKRV KGKGSDKDFV IIRRPKLSRE NFPGVSWDSL PDELLLGIFS CLCLPELLRV
SGVCKRWYRL SLDESLWQSL DLAGKNLHPD VTVRLLSRGV VAFRCPRSFM EQPLGESFSS
FRVQHMDLSN SVINVSNLHK ILSECSKLQN LSLEGLQLSD PIVKTLAQNE NLVRLNLCGC
SGFSESAVAT LLSSCSRLDE LNLSWCFDFT EKHVQAAVAH LPNTITQLNL SGYRKNLQKT
DLCTIIKRCP NLIRLDLSDS IMLKNDCFPE FFQLNYLQHL SLSRCYDIIP DTLLELGEIP
TLKTLQVFGI VPEGTLQLLR EALPRLQINC AYFTTIARPT MDSKKNLEIW GIKCRLTLQK
PSCL
