ID FBXL2_HUMAN Reviewed; 423 AA. AC Q9UKC9; B4DQV0; E9PD06; Q6IAN3; Q9NVQ8; Q9UK27; Q9UKA5; Q9Y3Y9; DT 21-NOV-2003, integrated into UniProtKB/Swiss-Prot. DT 17-APR-2007, sequence version 3. DT 27-MAR-2024, entry version 186. DE RecName: Full=F-box/LRR-repeat protein 2 {ECO:0000305}; DE AltName: Full=F-box and leucine-rich repeat protein 2 {ECO:0000303|PubMed:22323446}; DE AltName: Full=F-box protein FBL2/FBL3 {ECO:0000303|PubMed:10945468}; GN Name=FBXL2 {ECO:0000303|PubMed:22323446, ECO:0000312|HGNC:HGNC:13598}; GN Synonyms=FBL2 {ECO:0000303|PubMed:10531035}, FBL3 GN {ECO:0000303|PubMed:10945468}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=10531035; DOI=10.1016/s0960-9822(00)80020-2; RA Cenciarelli C., Chiaur D.S., Guardavaccaro D., Parks W., Vidal M., RA Pagano M.; RT "Identification of a family of human F-box proteins."; RL Curr. Biol. 9:1177-1179(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH SKP1, AND TISSUE RP SPECIFICITY. RX PubMed=10531037; DOI=10.1016/s0960-9822(00)80021-4; RA Winston J.T., Koepp D.M., Zhu C., Elledge S.J., Harper J.W.; RT "A family of mammalian F-box proteins."; RL Curr. Biol. 9:1180-1182(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=10945468; DOI=10.1006/geno.2000.6211; RA Ilyin G.P., Rialland M., Pigeon C., Guguen-Guillouzo C.; RT "cDNA cloning and expression analysis of new members of the mammalian F-box RT protein family."; RL Genomics 67:40-47(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 174-423 (ISOFORM 1). RC TISSUE=Brain; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [9] RP INTERACTION WITH HEPATITIS C VIRUS NS5A AND NS5B (MICROBIAL INFECTION), RP ISOPRENYLATION AT CYS-420, MUTAGENESIS OF CYS-420, SUBCELLULAR LOCATION, RP AND DOMAIN. RX PubMed=15893726; DOI=10.1016/j.molcel.2005.04.004; RA Wang C., Gale M. Jr., Keller B.C., Huang H., Brown M.S., Goldstein J.L., RA Ye J.; RT "Identification of FBL2 as a geranylgeranylated cellular protein required RT for hepatitis C virus RNA replication."; RL Mol. Cell 18:425-434(2005). RN [10] RP FUNCTION. RX PubMed=22323446; DOI=10.1182/blood-2011-06-358911; RA Chen B.B., Glasser J.R., Coon T.A., Zou C., Miller H.L., Fenton M., RA McDyer J.F., Boyiadzis M., Mallampalli R.K.; RT "F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation RT to inhibit leukemic cell proliferation."; RL Blood 119:3132-3141(2012). RN [11] RP FUNCTION, AND INTERACTION WITH CALMODULIN. RX PubMed=22020328; DOI=10.1038/onc.2011.432; RA Chen B.B., Glasser J.R., Coon T.A., Mallampalli R.K.; RT "F-box protein FBXL2 exerts human lung tumor suppressor-like activity by RT ubiquitin-mediated degradation of cyclin D3 resulting in cell cycle RT arrest."; RL Oncogene 31:2566-2579(2012). RN [12] RP FUNCTION, IDENTIFICATION AS PART OF AN SCF COMPLEX, INTERACTION WITH PIK3R1 RP AND PTPN13, MUTAGENESIS OF CYS-420, AND DOMAIN. RX PubMed=23604317; DOI=10.1038/ncb2731; RA Kuchay S., Duan S., Schenkein E., Peschiaroli A., Saraf A., Florens L., RA Washburn M.P., Pagano M.; RT "FBXL2- and PTPL1-mediated degradation of p110-free p85beta regulatory RT subunit controls the PI(3)K signalling cascade."; RL Nat. Cell Biol. 15:472-480(2013). RN [13] RP FUNCTION, PATHWAY, AND UBIQUITINATION. RX PubMed=26037928; DOI=10.1074/jbc.m115.645549; RA Han S., Lear T.B., Jerome J.A., Rajbhandari S., Snavely C.A., Gulick D.L., RA Gibson K.F., Zou C., Chen B.B., Mallampalli R.K.; RT "Lipopolysaccharide primes the NALP3 inflammasome by inhibiting its RT ubiquitination and degradation mediated by the SCFFBXL2 E3 ligase."; RL J. Biol. Chem. 290:18124-18133(2015). RN [14] RP VARIANT [LARGE SCALE ANALYSIS] MET-226. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Calcium-activated substrate recognition component of the SCF CC (SKP1-cullin-F-box protein) E3 ubiquitin-protein ligase complex, CC SCF(FBXL2), which mediates the ubiquitination and subsequent CC proteasomal degradation of target proteins (PubMed:22020328, CC PubMed:22323446). Unlike many F-box proteins, FBXL2 does not seem to CC target phosphodegron within its substrates but rather calmodulin- CC binding motifs and is thereby antagonized by calmodulin CC (PubMed:22020328, PubMed:22323446). This is the case for the cyclins CC CCND2 and CCND3 which polyubiquitination and subsequent degradation are CC inhibited by calmodulin (PubMed:22020328, PubMed:22323446). Through CC CCND2 and CCND3 degradation induces cell-cycle arrest in G(0) CC (PubMed:22020328, PubMed:22323446). SCF(FBXL2) also mediates PIK3R2 CC ubiquitination and proteasomal degradation thereby regulating CC phosphatidylinositol 3-kinase signaling and autophagy CC (PubMed:23604317). PCYT1A monoubiquitination by SCF(FBXL2) and CC subsequent degradation regulates synthesis of phosphatidylcholine, CC which is utilized for formation of membranes and of pulmonary CC surfactant (By similarity). The SCF(FBXL2) complex acts as a regulator CC of inflammation by mediating ubiquitination and degradation of TRAF CC proteins (TRAF1, TRAF2, TRAF3, TRAF4, TRAF5 and TRAF6) (By similarity). CC The SCF(FBXL2) complex acts as a negative regulator of the NLRP3 CC inflammasome by mediating ubiquitination and degradation of NLRP3 CC (PubMed:26037928). {ECO:0000250|UniProtKB:Q8BH16, CC ECO:0000269|PubMed:22020328, ECO:0000269|PubMed:22323446, CC ECO:0000269|PubMed:23604317, ECO:0000269|PubMed:26037928}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:26037928}. CC -!- SUBUNIT: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase CC complex SCF(FBXL2) composed of CUL1, SKP1, RBX1 and FBXL2 CC (PubMed:10531037). Interacts with calmodulin; may antagonize substrate CC ubiquitination by SCF(FBXL2) (PubMed:22020328). May interact with CC PIK3R1 (PubMed:23604317). Interacts with PTPN13 (PubMed:23604317). CC {ECO:0000269|PubMed:10531037, ECO:0000269|PubMed:22020328, CC ECO:0000269|PubMed:23604317}. CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis C virus non- CC structural protein 5A (NS5A) and less efficiently, with hepatitis C CC virus non-structural protein 5B (NS5B); a reaction crucial for CC hepatitis C virus RNA replication. {ECO:0000269|PubMed:15893726}. CC -!- INTERACTION: CC Q9UKC9; P48643: CCT5; NbExp=3; IntAct=EBI-724253, EBI-355710; CC Q9UKC9; P08238: HSP90AB1; NbExp=2; IntAct=EBI-724253, EBI-352572; CC Q9UKC9; P63208: SKP1; NbExp=6; IntAct=EBI-724253, EBI-307486; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:15893726}; Lipid- CC anchor {ECO:0000269|PubMed:15893726}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9UKC9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UKC9-2; Sequence=VSP_044600; CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, kidney, liver, lung, CC pancreas and placenta. {ECO:0000269|PubMed:10531037}. CC -!- DOMAIN: The CAAX motif is a signal for the geranylgeranylation of FBXL2 CC and is required for its association with cell membranes and the CC recruitment of substrates to the active SCF(FBXL2) complex. CC {ECO:0000269|PubMed:15893726, ECO:0000303|PubMed:23604317}. CC -!- PTM: Phosphorylated by GSK-beta (GSK3B), promoting recognition by CC FBXO3, leading to its ubiquitination by the SCF(FBXO3) complex. CC {ECO:0000250|UniProtKB:Q8BH16}. CC -!- PTM: Ubiquitinated at Lys-201 by the SCF(FBXO3) complex in response to CC lipopolysaccharide (LPS), leading to its degradation by the proteasome. CC {ECO:0000305|PubMed:26037928}. CC -!- MISCELLANEOUS: Deletion of the F-box domain creates a dominant-negative CC protein that inhibits replication of hepatitis C virus RNA when CC overexpressed in a hepatoma cell line; this inhibition could be CC overcome by NS5A coexpression. {ECO:0000269|PubMed:15893726}. CC -!- SEQUENCE CAUTION: CC Sequence=AAF03128.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; 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; AF174589; AAF04510.1; -; mRNA. DR EMBL; AF176518; AAF03128.1; ALT_INIT; mRNA. DR EMBL; AF186273; AAD56248.1; -; mRNA. DR EMBL; AK001438; BAA91691.1; -; mRNA. DR EMBL; AK298967; BAG61062.1; -; mRNA. DR EMBL; CR457121; CAG33402.1; -; mRNA. DR EMBL; AC122176; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC123900; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC031556; AAH31556.1; -; mRNA. DR EMBL; AL049953; CAB43222.1; -; mRNA. DR CCDS; CCDS2658.1; -. [Q9UKC9-1] DR PIR; T08680; T08680. DR RefSeq; NP_001165184.1; NM_001171713.1. DR RefSeq; NP_036289.3; NM_012157.3. [Q9UKC9-1] DR PDB; 6O60; X-ray; 2.50 A; C=1-423. DR PDBsum; 6O60; -. DR AlphaFoldDB; Q9UKC9; -. DR SMR; Q9UKC9; -. DR BioGRID; 117355; 31. DR ComplexPortal; CPX-3292; SCF E3 ubiquitin ligase complex, FBXL2 variant. DR IntAct; Q9UKC9; 13. DR MINT; Q9UKC9; -. DR STRING; 9606.ENSP00000417601; -. DR GlyGen; Q9UKC9; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9UKC9; -. DR PhosphoSitePlus; Q9UKC9; -. DR BioMuta; FBXL2; -. DR DMDM; 145559475; -. DR EPD; Q9UKC9; -. DR jPOST; Q9UKC9; -. DR MassIVE; Q9UKC9; -. DR MaxQB; Q9UKC9; -. DR PaxDb; 9606-ENSP00000417601; -. DR PeptideAtlas; Q9UKC9; -. DR ProteomicsDB; 19556; -. DR ProteomicsDB; 84766; -. [Q9UKC9-1] DR Pumba; Q9UKC9; -. DR Antibodypedia; 27896; 190 antibodies from 28 providers. DR DNASU; 25827; -. DR Ensembl; ENST00000484457.6; ENSP00000417601.1; ENSG00000153558.17. [Q9UKC9-1] DR GeneID; 25827; -. DR KEGG; hsa:25827; -. DR MANE-Select; ENST00000484457.6; ENSP00000417601.1; NM_012157.5; NP_036289.3. DR UCSC; uc003cfp.4; human. [Q9UKC9-1] DR AGR; HGNC:13598; -. DR CTD; 25827; -. DR DisGeNET; 25827; -. DR GeneCards; FBXL2; -. DR HGNC; HGNC:13598; FBXL2. DR HPA; ENSG00000153558; Tissue enhanced (choroid). DR MIM; 605652; gene. DR neXtProt; NX_Q9UKC9; -. DR OpenTargets; ENSG00000153558; -. DR PharmGKB; PA28021; -. DR VEuPathDB; HostDB:ENSG00000153558; -. DR eggNOG; KOG4341; Eukaryota. DR GeneTree; ENSGT00940000153845; -. DR HOGENOM; CLU_016072_7_1_1; -. DR InParanoid; Q9UKC9; -. DR OMA; VTRDSCE; -. DR OrthoDB; 1078060at2759; -. DR PhylomeDB; Q9UKC9; -. DR TreeFam; TF313434; -. DR PathwayCommons; Q9UKC9; -. DR SignaLink; Q9UKC9; -. DR SIGNOR; Q9UKC9; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 25827; 7 hits in 1188 CRISPR screens. DR ChiTaRS; FBXL2; human. DR GeneWiki; FBXL2; -. DR GenomeRNAi; 25827; -. DR Pharos; Q9UKC9; Tbio. DR PRO; PR:Q9UKC9; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q9UKC9; Protein. DR Bgee; ENSG00000153558; Expressed in orbitofrontal cortex and 165 other cell types or tissues. DR ExpressionAtlas; Q9UKC9; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW. DR GO; GO:0036312; F:phosphatidylinositol 3-kinase regulatory subunit binding; IPI:UniProtKB. DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB. DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IDA:UniProtKB. DR GO; GO:0044830; P:modulation by host of viral RNA genome replication; IMP:UniProtKB. DR GO; GO:1900226; P:negative regulation of NLRP3 inflammasome complex assembly; IDA:UniProtKB. DR GO; GO:0036211; P:protein modification process; TAS:ProtInc. DR GO; GO:0006513; P:protein monoubiquitination; IEA:Ensembl. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; TAS:ProtInc. DR GO; GO:0010506; P:regulation of autophagy; IMP:UniProtKB. DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB. DR GO; GO:0051896; P:regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProtKB. DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR CDD; cd22115; F-box_FBXL2-like; 1. DR Gene3D; 1.20.1280.50; -; 1. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 2. DR InterPro; IPR001810; F-box_dom. DR InterPro; IPR001611; Leu-rich_rpt. DR InterPro; IPR006553; Leu-rich_rpt_Cys-con_subtyp. DR InterPro; IPR032675; LRR_dom_sf. DR PANTHER; PTHR13382; MITOCHONDRIAL ATP SYNTHASE COUPLING FACTOR B; 1. DR Pfam; PF12937; F-box-like; 1. DR Pfam; PF13516; LRR_6; 5. DR SMART; SM00256; FBOX; 1. DR SMART; SM00367; LRR_CC; 11. DR SUPFAM; SSF52047; RNI-like; 1. DR PROSITE; PS50181; FBOX; 1. DR Genevisible; Q9UKC9; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Calmodulin-binding; KW Host-virus interaction; Isopeptide bond; Leucine-rich repeat; Lipoprotein; KW Membrane; Phosphoprotein; Prenylation; Reference proteome; Repeat; KW Ubl conjugation; Ubl conjugation pathway. FT CHAIN 1..423 FT /note="F-box/LRR-repeat protein 2" FT /id="PRO_0000119840" FT DOMAIN 9..55 FT /note="F-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080" FT REPEAT 61..87 FT /note="LRR 1" FT REPEAT 88..113 FT /note="LRR 2" FT REPEAT 114..139 FT /note="LRR 3" FT REPEAT 140..165 FT /note="LRR 4" FT REPEAT 166..191 FT /note="LRR 5" FT REPEAT 192..217 FT /note="LRR 6" FT REPEAT 218..243 FT /note="LRR 7" FT REPEAT 244..269 FT /note="LRR 8" FT REPEAT 270..295 FT /note="LRR 9" FT REPEAT 296..321 FT /note="LRR 10" FT REPEAT 322..350 FT /note="LRR 11" FT REPEAT 351..375 FT /note="LRR 12" FT REPEAT 376..401 FT /note="LRR 13" FT REGION 80..90 FT /note="Interaction with Calmodulin" FT /evidence="ECO:0000250|UniProtKB:Q8BH16" FT MOTIF 420..423 FT /note="CAAX motif" FT MOD_RES 404 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q8BH16" FT LIPID 420 FT /note="S-geranylgeranyl cysteine" FT /evidence="ECO:0000305|PubMed:15893726" FT CROSSLNK 201 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q8BH16" FT VAR_SEQ 132..199 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044600" FT VARIANT 226 FT /note="V -> M (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036071" FT MUTAGEN 420 FT /note="C->S: Loss of geranylgeranylation and association to FT membranes. Loss of interaction with NS5A, PIK3R1 and FT PIK3R2. No effect on interaction with PTPN13." FT /evidence="ECO:0000269|PubMed:15893726, FT ECO:0000269|PubMed:23604317" FT CONFLICT 62 FT /note="T -> I (in Ref. 1; AAF04510, 2; AAF03128 and 5; FT CAG33402)" FT /evidence="ECO:0000305" FT CONFLICT 77 FT /note="G -> V (in Ref. 1; AAF04510)" FT /evidence="ECO:0000305" FT CONFLICT 81 FT /note="R -> K (in Ref. 4; BAA91691)" FT /evidence="ECO:0000305" FT CONFLICT 108 FT /note="H -> Q (in Ref. 4; BAG61062)" FT /evidence="ECO:0000305" FT CONFLICT 174 FT /note="I -> W (in Ref. 8; CAB43222)" FT /evidence="ECO:0000305" FT CONFLICT 320 FT /note="S -> P (in Ref. 8; CAB43222)" FT /evidence="ECO:0000305" FT CONFLICT 342 FT /note="R -> G (in Ref. 5; CAG33402)" FT /evidence="ECO:0000305" FT HELIX 10..14 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 17..24 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 29..35 FT /evidence="ECO:0007829|PDB:6O60" FT TURN 36..38 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 40..46 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 49..51 FT /evidence="ECO:0007829|PDB:6O60" FT STRAND 53..56 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 67..75 FT /evidence="ECO:0007829|PDB:6O60" FT STRAND 82..84 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 93..102 FT /evidence="ECO:0007829|PDB:6O60" FT STRAND 108..110 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 119..128 FT /evidence="ECO:0007829|PDB:6O60" FT STRAND 134..136 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 145..154 FT /evidence="ECO:0007829|PDB:6O60" FT STRAND 160..162 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 171..180 FT /evidence="ECO:0007829|PDB:6O60" FT STRAND 185..188 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 197..206 FT /evidence="ECO:0007829|PDB:6O60" FT STRAND 212..214 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 223..232 FT /evidence="ECO:0007829|PDB:6O60" FT STRAND 238..240 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 249..258 FT /evidence="ECO:0007829|PDB:6O60" FT STRAND 264..266 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 275..284 FT /evidence="ECO:0007829|PDB:6O60" FT STRAND 290..292 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 301..310 FT /evidence="ECO:0007829|PDB:6O60" FT STRAND 316..318 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 327..334 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 337..341 FT /evidence="ECO:0007829|PDB:6O60" FT STRAND 345..347 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 356..361 FT /evidence="ECO:0007829|PDB:6O60" FT STRAND 370..372 FT /evidence="ECO:0007829|PDB:6O60" FT HELIX 381..390 FT /evidence="ECO:0007829|PDB:6O60" FT STRAND 395..397 FT /evidence="ECO:0007829|PDB:6O60" SQ SEQUENCE 423 AA; 47062 MW; 61938E434618BA3D CRC64; MVFSNNDEGL INKKLPKELL LRIFSFLDIV TLCRCAQISK AWNILALDGS NWQRIDLFNF QTDVEGRVVE NISKRCGGFL RKLSLRGCIG VGDSSLKTFA QNCRNIEHLN LNGCTKITDS TCYSLSRFCS KLKHLDLTSC VSITNSSLKG ISEGCRNLEY LNLSWCDQIT KDGIEALVRG CRGLKALLLR GCTQLEDEAL KHIQNYCHEL VSLNLQSCSR ITDEGVVQIC RGCHRLQALC LSGCSNLTDA SLTALGLNCP RLQILEAARC SHLTDAGFTL LARNCHELEK MDLEECILIT DSTLIQLSIH CPKLQALSLS HCELITDDGI LHLSNSTCGH ERLRVLELDN CLLITDVALE HLENCRGLER LELYDCQQVT RAGIKRMRAQ LPHVKVHAYF APVTPPTAVA GSGQRLCRCC VIL //