ID   FXL12_HUMAN             Reviewed;         326 AA.
AC   Q9NXK8; B3KSJ8; Q9H5K4;
DT   07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   27-MAR-2024, entry version 175.
DE   RecName: Full=F-box/LRR-repeat protein 12;
DE   AltName: Full=F-box and leucine-rich repeat protein 12;
DE   AltName: Full=F-box protein FBL12;
GN   Name=FBXL12; Synonyms=FBL12;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Colon mucosa, and Thymus;
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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Lymph;
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   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., Buerckstuemmer T.,
RA   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   [5]
RP   FUNCTION.
RX   PubMed=23707388; DOI=10.1016/j.cellsig.2013.05.012;
RA   Mallampalli R.K., Kaercher L., Snavely C., Pulijala R., Chen B.B., Coon T.,
RA   Zhao J., Agassandian M.;
RT   "Fbxl12 triggers G1 arrest by mediating degradation of calmodulin kinase
RT   I.";
RL   Cell. Signal. 25:2047-2059(2013).
RN   [6]
RP   VARIANT HIS-63.
RX   PubMed=21248752; DOI=10.1038/nature09639;
RA   Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA   Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA   Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA   Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA   Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA   Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA   Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA   Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT   "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT   PBRM1 in renal carcinoma.";
RL   Nature 469:539-542(2011).
CC   -!- FUNCTION: Substrate-recognition component of the SCF (SKP1-CUL1-F-box
CC       protein)-type E3 ubiquitin ligase complex. Mediates the
CC       polyubiquitination and proteasomal degradation of CAMK1 leading to
CC       disruption of cyclin D1/CDK4 complex assembly which results in G1 cell
CC       cycle arrest in lung epithelia. {ECO:0000269|PubMed:23707388}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Interacts with SKP1 and CUL1. {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q9NXK8; P49918: CDKN1C; NbExp=6; IntAct=EBI-719790, EBI-519256;
CC       Q9NXK8; Q8NF50-2: DOCK8; NbExp=3; IntAct=EBI-719790, EBI-10174653;
CC       Q9NXK8; P57678: GEMIN4; NbExp=3; IntAct=EBI-719790, EBI-356700;
CC       Q9NXK8; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-719790, EBI-739832;
CC       Q9NXK8; Q9H0A6: RNF32; NbExp=2; IntAct=EBI-719790, EBI-724829;
CC       Q9NXK8; P63208: SKP1; NbExp=7; IntAct=EBI-719790, EBI-307486;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9NXK8-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9NXK8-2; Sequence=VSP_008859;
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DR   EMBL; AK000195; BAA91002.1; -; mRNA.
DR   EMBL; AK027004; BAB15622.1; -; mRNA.
DR   EMBL; AK093760; BAG52760.1; -; mRNA.
DR   EMBL; CH471106; EAW84051.1; -; Genomic_DNA.
DR   EMBL; BC001586; AAH01586.1; -; mRNA.
DR   CCDS; CCDS12218.1; -. [Q9NXK8-1]
DR   CCDS; CCDS82287.1; -. [Q9NXK8-2]
DR   RefSeq; NP_001303865.1; NM_001316936.1.
DR   RefSeq; NP_001303866.1; NM_001316937.1. [Q9NXK8-2]
DR   RefSeq; NP_001303867.1; NM_001316938.1. [Q9NXK8-2]
DR   RefSeq; NP_001303868.1; NM_001316939.1. [Q9NXK8-2]
DR   RefSeq; NP_001303869.1; NM_001316940.1. [Q9NXK8-2]
DR   RefSeq; NP_001303870.1; NM_001316941.1. [Q9NXK8-2]
DR   RefSeq; NP_001303871.1; NM_001316942.1. [Q9NXK8-2]
DR   RefSeq; NP_060173.1; NM_017703.2. [Q9NXK8-1]
DR   AlphaFoldDB; Q9NXK8; -.
DR   SMR; Q9NXK8; -.
DR   BioGRID; 120200; 100.
DR   ComplexPortal; CPX-2658; SCF E3 ubiquitin ligase complex, FBXL12 variant.
DR   IntAct; Q9NXK8; 20.
DR   MINT; Q9NXK8; -.
DR   STRING; 9606.ENSP00000247977; -.
DR   iPTMnet; Q9NXK8; -.
DR   PhosphoSitePlus; Q9NXK8; -.
DR   BioMuta; FBXL12; -.
DR   DMDM; 38257780; -.
DR   EPD; Q9NXK8; -.
DR   jPOST; Q9NXK8; -.
DR   MassIVE; Q9NXK8; -.
DR   MaxQB; Q9NXK8; -.
DR   PaxDb; 9606-ENSP00000247977; -.
DR   PeptideAtlas; Q9NXK8; -.
DR   ProteomicsDB; 83107; -. [Q9NXK8-1]
DR   ProteomicsDB; 83108; -. [Q9NXK8-2]
DR   Pumba; Q9NXK8; -.
DR   Antibodypedia; 25087; 169 antibodies from 27 providers.
DR   DNASU; 54850; -.
DR   Ensembl; ENST00000247977.9; ENSP00000247977.3; ENSG00000127452.9. [Q9NXK8-1]
DR   Ensembl; ENST00000585379.5; ENSP00000467359.1; ENSG00000127452.9. [Q9NXK8-2]
DR   Ensembl; ENST00000591009.1; ENSP00000468369.1; ENSG00000127452.9. [Q9NXK8-2]
DR   GeneID; 54850; -.
DR   KEGG; hsa:54850; -.
DR   MANE-Select; ENST00000247977.9; ENSP00000247977.3; NM_017703.3; NP_060173.1.
DR   UCSC; uc002mme.3; human. [Q9NXK8-1]
DR   AGR; HGNC:13611; -.
DR   CTD; 54850; -.
DR   GeneCards; FBXL12; -.
DR   HGNC; HGNC:13611; FBXL12.
DR   HPA; ENSG00000127452; Low tissue specificity.
DR   MIM; 609079; gene.
DR   neXtProt; NX_Q9NXK8; -.
DR   OpenTargets; ENSG00000127452; -.
DR   PharmGKB; PA134934043; -.
DR   VEuPathDB; HostDB:ENSG00000127452; -.
DR   eggNOG; KOG1947; Eukaryota.
DR   GeneTree; ENSGT00390000003354; -.
DR   HOGENOM; CLU_024577_1_0_1; -.
DR   InParanoid; Q9NXK8; -.
DR   OMA; GRHMKQL; -.
DR   OrthoDB; 840819at2759; -.
DR   PhylomeDB; Q9NXK8; -.
DR   TreeFam; TF313434; -.
DR   PathwayCommons; Q9NXK8; -.
DR   Reactome; R-HSA-8951664; Neddylation.
DR   Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   SignaLink; Q9NXK8; -.
DR   SIGNOR; Q9NXK8; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 54850; 49 hits in 1200 CRISPR screens.
DR   ChiTaRS; FBXL12; human.
DR   GenomeRNAi; 54850; -.
DR   Pharos; Q9NXK8; Tdark.
DR   PRO; PR:Q9NXK8; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q9NXK8; Protein.
DR   Bgee; ENSG00000127452; Expressed in thymus and 197 other cell types or tissues.
DR   ExpressionAtlas; Q9NXK8; baseline and differential.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0019005; C:SCF ubiquitin ligase complex; IBA:GO_Central.
DR   GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR   GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR   CDD; cd22123; F-box_FBXL12; 1.
DR   Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1.
DR   InterPro; IPR036047; F-box-like_dom_sf.
DR   InterPro; IPR001810; F-box_dom.
DR   InterPro; IPR032675; LRR_dom_sf.
DR   PANTHER; PTHR16134; F-BOX/TPR REPEAT PROTEIN POF3; 1.
DR   PANTHER; PTHR16134:SF3; F-BOX_LRR-REPEAT PROTEIN 12; 1.
DR   Pfam; PF12937; F-box-like; 1.
DR   SMART; SM00256; FBOX; 1.
DR   SUPFAM; SSF81383; F-box domain; 1.
DR   SUPFAM; SSF52047; RNI-like; 1.
DR   PROSITE; PS50181; FBOX; 1.
DR   Genevisible; Q9NXK8; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Leucine-rich repeat; Reference proteome; Repeat;
KW   Ubl conjugation pathway.
FT   CHAIN           1..326
FT                   /note="F-box/LRR-repeat protein 12"
FT                   /id="PRO_0000119857"
FT   DOMAIN          1..47
FT                   /note="F-box"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT   REPEAT          51..78
FT                   /note="LRR 1"
FT   REPEAT          86..111
FT                   /note="LRR 2"
FT   REPEAT          113..133
FT                   /note="LRR 3"
FT   REPEAT          161..185
FT                   /note="LRR 4"
FT   REPEAT          186..211
FT                   /note="LRR 5"
FT   REPEAT          212..236
FT                   /note="LRR 6"
FT   REPEAT          237..261
FT                   /note="LRR 7"
FT   REPEAT          266..291
FT                   /note="LRR 8"
FT   VAR_SEQ         1..53
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_008859"
FT   VARIANT         63
FT                   /note="L -> H (found in a renal cell carcinoma case;
FT                   somatic mutation)"
FT                   /evidence="ECO:0000269|PubMed:21248752"
FT                   /id="VAR_064712"
SQ   SEQUENCE   326 AA;  37026 MW;  1BC5C2A40CB91D68 CRC64;
     MATLVELPDS VLLEIFSYLP VRDRIRISRV CHRWKRLVDD RWLWRHVDLT LYTMRPKVMW
     HLLRRYMASR LHSLRMGGYL FSGSQAPQLS PALLRALGQK CPNLKRLCLH VADLSMVPIT
     SLPSTLRTLE LHSCEISMAW LHKQQDPTVL PLLECIVLDR VPAFRDEHLQ GLTRFRALRS
     LVLGGTYRVT ETGLDAGLQE LSYLQRLEVL GCTLSADSTL LAISRHLRDV RKIRLTVRGL
     SAPGLAVLEG MPALESLCLQ GPLVTPEMPS PTEILSSCLT MPKLRVLELQ GLGWEGQEAE
     KILCKGLPHC MVIVRACPKE SMDWWM
//