FXL15_HUMAN
ID FXL15_HUMAN Reviewed; 300 AA.
AC Q9H469; A1L4J8; B1AKX8; B1AKX9; B1AKY0; B1AKY1; C9JWA4; Q0D2Q3; Q49AL7;
AC Q5JWA5;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=F-box/LRR-repeat protein 15;
DE AltName: Full=F-box only protein 37;
GN Name=FBXL15; Synonyms=FBXO37;
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 GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hypothalamus, and Lung carcinoma;
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 [3]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN A SCF PROTEIN LIGASE
RP COMPLEX, AND INTERACTION WITH SMURF1; SMURF2 AND WWP2.
RX PubMed=21572392; DOI=10.1038/emboj.2011.155;
RA Cui Y., He S., Xing C., Lu K., Wang J., Xing G., Meng A., Jia S., He F.,
RA Zhang L.;
RT "SCF(FBXL15) regulates BMP signalling by directing the degradation of HECT-
RT type ubiquitin ligase Smurf1.";
RL EMBO J. 30:2675-2689(2011).
RN [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
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 SMURF1,
CC thereby acting as a positive regulator of the BMP signaling pathway.
CC Required for dorsal/ventral pattern formation and bone mass
CC maintenance. Also mediates ubiquitination of SMURF2 and WWP2.
CC {ECO:0000269|PubMed:21572392}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase
CC complex SCF(FBXL15) composed of CUL1, SKP1, RBX1 and FBXL15.
CC {ECO:0000269|PubMed:21572392}.
CC -!- INTERACTION:
CC Q9H469; Q9HCE7: SMURF1; NbExp=6; IntAct=EBI-6144096, EBI-976466;
CC Q9H469; Q9HAU4: SMURF2; NbExp=3; IntAct=EBI-6144096, EBI-396727;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21572392}.
CC -!- SIMILARITY: Belongs to the FBXL15 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH02912.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH36120.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL121928; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002912; AAH02912.1; ALT_INIT; mRNA.
DR EMBL; BC036120; AAH36120.1; ALT_INIT; mRNA.
DR EMBL; BC130566; AAI30567.1; -; mRNA.
DR CCDS; CCDS31273.1; -.
DR RefSeq; NP_077302.3; NM_024326.3.
DR RefSeq; XP_005270207.1; XM_005270150.4.
DR RefSeq; XP_005270208.1; XM_005270151.3.
DR RefSeq; XP_016872120.1; XM_017016631.1.
DR AlphaFoldDB; Q9H469; -.
DR SMR; Q9H469; -.
DR BioGRID; 122593; 30.
DR IntAct; Q9H469; 19.
DR MINT; Q9H469; -.
DR STRING; 9606.ENSP00000224862; -.
DR iPTMnet; Q9H469; -.
DR PhosphoSitePlus; Q9H469; -.
DR BioMuta; FBXL15; -.
DR DMDM; 239938631; -.
DR EPD; Q9H469; -.
DR jPOST; Q9H469; -.
DR MassIVE; Q9H469; -.
DR MaxQB; Q9H469; -.
DR PaxDb; Q9H469; -.
DR PeptideAtlas; Q9H469; -.
DR PRIDE; Q9H469; -.
DR ProteomicsDB; 80789; -.
DR Antibodypedia; 53264; 90 antibodies from 16 providers.
DR DNASU; 79176; -.
DR Ensembl; ENST00000369956.8; ENSP00000358972.3; ENSG00000107872.14.
DR GeneID; 79176; -.
DR KEGG; hsa:79176; -.
DR MANE-Select; ENST00000369956.8; ENSP00000358972.3; NM_024326.4; NP_077302.3.
DR UCSC; uc001kvk.2; human.
DR CTD; 79176; -.
DR DisGeNET; 79176; -.
DR GeneCards; FBXL15; -.
DR HGNC; HGNC:28155; FBXL15.
DR HPA; ENSG00000107872; Tissue enhanced (brain).
DR MIM; 610287; gene.
DR neXtProt; NX_Q9H469; -.
DR OpenTargets; ENSG00000107872; -.
DR PharmGKB; PA134928704; -.
DR VEuPathDB; HostDB:ENSG00000107872; -.
DR eggNOG; KOG1947; Eukaryota.
DR GeneTree; ENSGT00940000160250; -.
DR InParanoid; Q9H469; -.
DR OMA; HCHNVAE; -.
DR OrthoDB; 1154571at2759; -.
DR PhylomeDB; Q9H469; -.
DR TreeFam; TF326769; -.
DR PathwayCommons; Q9H469; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9H469; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 79176; 10 hits in 1118 CRISPR screens.
DR ChiTaRS; FBXL15; human.
DR GenomeRNAi; 79176; -.
DR Pharos; Q9H469; Tbio.
DR PRO; PR:Q9H469; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9H469; protein.
DR Bgee; ENSG00000107872; Expressed in adenohypophysis and 126 other tissues.
DR ExpressionAtlas; Q9H469; baseline and differential.
DR Genevisible; Q9H469; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0030282; P:bone mineralization; ISS:UniProtKB.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; ISS:UniProtKB.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR036047; F-box-like_dom_sf.
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; PF00646; F-box; 1.
DR Pfam; PF13516; LRR_6; 1.
DR SMART; SM00367; LRR_CC; 6.
DR SUPFAM; SSF81383; SSF81383; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Leucine-rich repeat; Reference proteome; Repeat;
KW Ubl conjugation pathway.
FT CHAIN 1..300
FT /note="F-box/LRR-repeat protein 15"
FT /id="PRO_0000119931"
FT DOMAIN 19..66
FT /note="F-box"
FT REPEAT 141..162
FT /note="LRR 1"
FT REPEAT 167..188
FT /note="LRR 2"
FT REPEAT 194..215
FT /note="LRR 3"
FT REPEAT 220..241
FT /note="LRR 4"
FT REPEAT 246..267
FT /note="LRR 5"
FT REGION 113..269
FT /note="Interaction with SMURF1"
FT /evidence="ECO:0000269|PubMed:21572392"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CONFLICT 164
FT /note="R -> H (in Ref. 2; AAH36120)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 300 AA; 32998 MW; 3AF8CAFDDF75D720 CRC64;
MEPPMEPSGG EQEPGAVRFL DLPWEDVLLP HVLNRVPLRQ LLRLQRVSRA FRSLVQLHLA
GLRRFDAAQV GPQIPRAALA RLLRDAEGLQ ELALAPCHEW LSDEDLVPVL ARNPQLRSVA
LGGCGQLSRR ALGALAEGCP RLQRLSLAHC DWVDGLALRG LADRCPALEE LDLTACRQLK
DEAIVYLAQR RGAGLRSLSL AVNANVGDAA VQELARNCPE LHHLDLTGCL RVGSDGVRTL
AEYCPVLRSL RVRHCHHVAE SSLSRLRKRG VDIDVEPPLH QALVLLQDMA GFAPFVNLQV
