FBXL2_HUMAN
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 03-AUG-2022, entry version 177.
DE RecName: Full=F-box/LRR-repeat protein 2 {ECO:0000305};
DE AltName: Full=F-box and leucine-rich repeat protein 2 {ECO:0000312|HGNC:HGNC:13598};
DE AltName: Full=F-box protein FBL2/FBL3 {ECO:0000303|PubMed:10945468, ECO:0000312|EMBL:AAF04510.1};
GN Name=FBXL2 {ECO:0000312|HGNC:HGNC:13598};
GN Synonyms=FBL2 {ECO:0000312|EMBL:AAF04510.1},
GN FBL3 {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, AND INTERACTION WITH CCND2.
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 CCND3.
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
RP PIK3R1; PIK3R2 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 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. Unlike many F-box proteins,
CC FBXL2 does not seem to target phosphodegron within its substrates but
CC rather calmodulin-binding motifs and is thereby antagonized by
CC calmodulin. This is the case for the cyclins CCND2 and CCND3 which
CC polyubiquitination and subsequent degradation are inhibited by
CC calmodulin. Through CCND2 and CCND3 degradation induces cell-cycle
CC arrest in G(0) (PubMed:22020328, PubMed:22323446). SCF(FBXL2) also
CC mediates PIK3R2 ubiquitination and proteasomal degradation thereby
CC regulating 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). {ECO:0000250|UniProtKB:Q8BH16,
CC ECO:0000269|PubMed:22020328, ECO:0000269|PubMed:22323446,
CC ECO:0000269|PubMed:23604317}.
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 PCYT1A. Interacts with calmodulin;
CC may antagonize substrate ubiquitination by SCF(FBXL2) (By similarity).
CC Interacts with CCND2 and CCND3 (PubMed:22323446, PubMed:22020328).
CC Interacts with PIK3R2; PIK3R2 is a substrate ubiquitinated by the
CC SCF(FBXL2) complex (PubMed:23604317). May interact with PIK3R1
CC (PubMed:23604317). Interacts with PTPN13.
CC {ECO:0000250|UniProtKB:Q8BH16, ECO:0000269|PubMed:10531037,
CC ECO:0000269|PubMed:15893726, ECO:0000269|PubMed:22020328,
CC ECO:0000269|PubMed:22323446, ECO:0000269|PubMed:23604317,
CC ECO:0000303|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 -!- 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; 28.
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; Q9UKC9; -.
DR PeptideAtlas; Q9UKC9; -.
DR PRIDE; Q9UKC9; -.
DR ProteomicsDB; 19556; -.
DR ProteomicsDB; 84766; -. [Q9UKC9-1]
DR Antibodypedia; 27896; 179 antibodies from 27 providers.
DR DNASU; 25827; -.
DR Ensembl; ENST00000484457.6; ENSP00000417601.1; ENSG00000153558.16. [Q9UKC9-1]
DR Ensembl; ENST00000538892.5; ENSP00000441228.1; ENSG00000153558.16. [Q9UKC9-2]
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 CTD; 25827; -.
DR DisGeNET; 25827; -.
DR GeneCards; FBXL2; -.
DR HGNC; HGNC:13598; FBXL2.
DR HPA; ENSG00000153558; Low tissue specificity.
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; NCKGISD; -.
DR OrthoDB; 1046098at2759; -.
DR PhylomeDB; Q9UKC9; -.
DR TreeFam; TF313434; -.
DR PathwayCommons; Q9UKC9; -.
DR SignaLink; Q9UKC9; -.
DR BioGRID-ORCS; 25827; 7 hits in 1110 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 163 other tissues.
DR ExpressionAtlas; Q9UKC9; baseline and differential.
DR Genevisible; Q9UKC9; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
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:0044830; P:modulation by host of viral RNA genome replication; IMP: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:0014066; P:regulation of phosphatidylinositol 3-kinase signaling; IDA:UniProtKB.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR Gene3D; 3.80.10.10; -; 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 Pfam; PF12937; F-box-like; 1.
DR Pfam; PF13516; LRR_6; 5.
DR SMART; SM00256; FBOX; 1.
DR SMART; SM00367; LRR_CC; 11.
DR PROSITE; PS50181; FBOX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Calmodulin-binding;
KW Host-virus interaction; Leucine-rich repeat; Lipoprotein; Membrane;
KW Prenylation; Reference proteome; Repeat; 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 LIPID 420
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000305|PubMed:15893726"
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
