ID   FBX16_HUMAN             Reviewed;         292 AA.
AC   Q8IX29; Q3T1B2; Q3T1B3; Q3T1B4;
DT   09-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   10-JUN-2026, entry version 161.
DE   RecName: Full=F-box only protein 16;
GN   Name=FBXO16; Synonyms=FBX16;
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), AND TISSUE SPECIFICITY.
RX   PubMed=12243353;
RA   Cheng H., Ma Y., Ni X., Jiang M., Guo L., Jin W., Xu W., Cao G., Ji C.,
RA   Yin K., Gu S., Ma Y., Xie Y., Mao Y.;
RT   "cDNA cloning and expression analysis of a novel human F-box only
RT   protein.";
RL   Mol. Cells 14:56-59(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16421571; DOI=10.1038/nature04406;
RA   Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA   Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA   Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA   Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA   Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA   Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA   Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA   Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA   Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA   O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA   Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA   Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA   Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA   Platzer M., Shimizu N., Lander E.S.;
RT   "DNA sequence and analysis of human chromosome 8.";
RL   Nature 439:331-335(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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   FUNCTION, INTERACTION WITH CTNNB1, AND SUBCELLULAR LOCATION.
RX   PubMed=30714168; DOI=10.1002/path.5252;
RA   Paul D., Islam S., Manne R.K., Dinesh U.S., Malonia S.K., Maity B.,
RA   Boppana R., Rapole S., Shetty P.K., Santra M.K.;
RT   "F-box protein FBXO16 functions as a tumor suppressor by attenuating
RT   nuclear beta-catenin function.";
RL   J. Pathol. 248:266-279(2019).
RN   [5]
RP   FUNCTION, AND INTERACTION WITH HNRNPL.
RX   PubMed=34333526; DOI=10.1038/s41419-021-04040-9;
RA   Ji M., Zhao Z., Li Y., Xu P., Shi J., Li Z., Wang K., Huang X., Ji J.,
RA   Liu W., Liu B.;
RT   "FBXO16-mediated hnRNPL ubiquitination and degradation plays a tumor
RT   suppressor role in ovarian cancer.";
RL   Cell Death Dis. 12:758-758(2021).
RN   [6]
RP   FUNCTION, AND INTERACTION WITH ULK1.
RX   PubMed=39384743; DOI=10.1038/s41419-024-07120-8;
RA   Zhang Z., Liu X., Chu C., Zhang Y., Li W., Yu X., Han Q., Sun H., Zhang Y.,
RA   Zhu X., Chen L., Wei R., Fan N., Zhou M., Li X.;
RT   "MIR937 amplification potentiates ovarian cancer progression by attenuating
RT   FBXO16 inhibition on ULK1-mediated autophagy.";
RL   Cell Death Dis. 15:735-735(2024).
RN   [7]
RP   FUNCTION, AND INTERACTION WITH RELA.
RX   PubMed=40529355; DOI=10.3389/fimmu.2025.1524110;
RA   Sugimoto-Ishige A., Jodo A., Tanaka T.;
RT   "Fbxo16 mediates degradation of NF-kappaB p65 subunit and inhibits
RT   inflammatory response in dendritic cells.";
RL   Front. Immunol. 16:1524110-1524110(2025).
CC   -!- FUNCTION: Substrate recognition component of an SCF (SKP1-CUL1-F-box
CC       protein) E3 ubiquitin-protein ligase complex that mediates the
CC       ubiquitination and subsequent proteasomal degradation of target
CC       proteins. Functions as a putative tumor suppressor by targeting nuclear
CC       beta-catenin/CTNNB1 for degradation independently of upstream
CC       activating signals, thereby inhibiting epithelial-to-mesenchymal
CC       transition (PubMed:30714168). Controls the ubiquitination and
CC       degradation of hnRNPL (PubMed:34333526). Negatively regulates NF-kappa-
CC       B signaling by mediating the polyubiquitination and degradation of RELA
CC       (PubMed:40529355). Inhibits autophagy by promoting 'Lys-48'-linked
CC       polyubiquitination of the serine/threonine-protein kinase ULK1
CC       (PubMed:39384743). {ECO:0000269|PubMed:30714168,
CC       ECO:0000269|PubMed:34333526, ECO:0000269|PubMed:39384743,
CC       ECO:0000269|PubMed:40529355}.
CC   -!- SUBUNIT: Part of a SCF (SKP1-cullin-F-box) protein ligase complex.
CC       Interacts with CTNNB1 (PubMed:30714168). Interacts with HNRNPL
CC       (PubMed:34333526). Interacts with RELA (PubMed:40529355). Interacts
CC       with ULK1 (PubMed:39384743). {ECO:0000269|PubMed:30714168,
CC       ECO:0000269|PubMed:34333526, ECO:0000269|PubMed:39384743,
CC       ECO:0000269|PubMed:40529355}.
CC   -!- INTERACTION:
CC       Q8IX29; P25800: LMO1; NbExp=3; IntAct=EBI-12063229, EBI-8639312;
CC       Q8IX29; Q9UBU8-2: MORF4L1; NbExp=3; IntAct=EBI-12063229, EBI-10288852;
CC       Q8IX29; Q15014: MORF4L2; NbExp=3; IntAct=EBI-12063229, EBI-399257;
CC       Q8IX29; Q9UKK6: NXT1; NbExp=5; IntAct=EBI-12063229, EBI-301889;
CC       Q8IX29; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-12063229, EBI-2130429;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q8IX29-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8IX29-2; Sequence=VSP_045600;
CC   -!- TISSUE SPECIFICITY: Expressed in heart, spleen and colon.
CC       {ECO:0000269|PubMed:12243353}.
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DR   EMBL; AF453435; AAN76812.1; -; mRNA.
DR   EMBL; AC025871; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC074986; AAH74986.1; -; mRNA.
DR   EMBL; BC102026; AAI02027.1; -; mRNA.
DR   EMBL; BC102027; AAI02028.1; -; mRNA.
DR   EMBL; BC102028; AAI02029.1; -; mRNA.
DR   CCDS; CCDS59099.1; -. [Q8IX29-2]
DR   CCDS; CCDS6068.1; -. [Q8IX29-1]
DR   RefSeq; NP_001245140.1; NM_001258211.2. [Q8IX29-2]
DR   RefSeq; NP_758954.1; NM_172366.4. [Q8IX29-1]
DR   AlphaFoldDB; Q8IX29; -.
DR   SMR; Q8IX29; -.
DR   BioGRID; 127606; 18.
DR   ComplexPortal; CPX-7926; SCF E3 ubiquitin ligase complex, FBXO16 variant.
DR   FunCoup; Q8IX29; 99.
DR   IntAct; Q8IX29; 15.
DR   STRING; 9606.ENSP00000369604; -.
DR   iPTMnet; Q8IX29; -.
DR   PhosphoSitePlus; Q8IX29; -.
DR   BioMuta; FBXO16; -.
DR   DMDM; 30580423; -.
DR   MassIVE; Q8IX29; -.
DR   PaxDb; 9606-ENSP00000369604; -.
DR   PeptideAtlas; Q8IX29; -.
DR   ProteomicsDB; 61869; -.
DR   ProteomicsDB; 70969; -. [Q8IX29-1]
DR   Antibodypedia; 23118; 106 antibodies from 15 providers.
DR   DNASU; 157574; -.
DR   Ensembl; ENST00000380254.7; ENSP00000369604.2; ENSG00000214050.9. [Q8IX29-1]
DR   Ensembl; ENST00000518734.5; ENSP00000429687.1; ENSG00000214050.9. [Q8IX29-2]
DR   Ensembl; ENST00000902912.1; ENSP00000572971.1; ENSG00000214050.9. [Q8IX29-1]
DR   GeneID; 157574; -.
DR   KEGG; hsa:157574; -.
DR   MANE-Select; ENST00000380254.7; ENSP00000369604.2; NM_172366.4; NP_758954.1.
DR   UCSC; uc003xgu.5; human. [Q8IX29-1]
DR   AGR; HGNC:13618; -.
DR   ClinPGx; PA134901223; -.
DR   CTD; 157574; -.
DR   DisGeNET; 157574; -.
DR   GeneCards; FBXO16; -.
DR   HGNC; HGNC:13618; FBXO16.
DR   HPA; ENSG00000214050; Tissue enhanced (epididymis, pituitary gland).
DR   MIM; 608519; gene.
DR   OpenTargets; ENSG00000214050; -.
DR   VEuPathDB; HostDB:ENSG00000214050; -.
DR   eggNOG; KOG0274; Eukaryota.
DR   GeneTree; ENSGT00940000159021; -.
DR   HOGENOM; CLU_065593_0_0_1; -.
DR   InParanoid; Q8IX29; -.
DR   OMA; DRWSDGQ; -.
DR   OrthoDB; 10257471at2759; -.
DR   PAN-GO; Q8IX29; 0 GO annotations based on evolutionary models.
DR   PhylomeDB; Q8IX29; -.
DR   PathwayCommons; Q8IX29; -.
DR   SignaLink; Q8IX29; -.
DR   Agora; ENSG00000214050; -.
DR   BioGRID-ORCS; 157574; 7 hits in 1185 CRISPR screens.
DR   ChiTaRS; FBXO16; human.
DR   GenomeRNAi; 157574; -.
DR   Pharos; Q8IX29; Tdark.
DR   PRO; PR:Q8IX29; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   RNAct; Q8IX29; protein.
DR   Bgee; ENSG00000214050; Expressed in adenohypophysis and 118 other cell types or tissues.
DR   ExpressionAtlas; Q8IX29; baseline and differential.
DR   GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; NAS:ComplexPortal.
DR   CDD; cd22172; F-box_FBXO16; 1.
DR   Gene3D; 1.20.1280.50; -; 1.
DR   InterPro; IPR036047; F-box-like_dom_sf.
DR   InterPro; IPR001810; F-box_dom.
DR   InterPro; IPR052805; GEF_Ubiquitin-Prot_Reg.
DR   PANTHER; PTHR46857; EPITHELIAL CELL-TRANSFORMING SEQUENCE 2 ONCOGENE-LIKE; 1.
DR   PANTHER; PTHR46857:SF2; F-BOX ONLY PROTEIN 16; 1.
DR   Pfam; PF12937; F-box-like; 1.
DR   SMART; SM00256; FBOX; 1.
DR   SUPFAM; SSF81383; F-box domain; 1.
DR   PROSITE; PS50181; FBOX; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Proteomics identification; Reference proteome;
KW   Ubl conjugation pathway.
FT   CHAIN           1..292
FT                   /note="F-box only protein 16"
FT                   /id="PRO_0000119896"
FT   DOMAIN          86..132
FT                   /note="F-box"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT   REGION          188..224
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          238..292
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        194..204
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        260..273
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         34..45
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_045600"
FT   VARIANT         75
FT                   /note="R -> Q (in dbSNP:rs3735726)"
FT                   /id="VAR_020409"
FT   VARIANT         254
FT                   /note="M -> I (in dbSNP:rs1390963)"
FT                   /id="VAR_024442"
FT   VARIANT         255
FT                   /note="T -> N (in dbSNP:rs7016831)"
FT                   /id="VAR_049041"
FT   CONFLICT        254..255
FT                   /note="MT -> IN (in Ref. 3; AAI02028)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   292 AA;  34588 MW;  0A7030EFE682EDFD CRC64;
     MMAFAPPKNT DGPKMQTKMS TWTPLNHQLL NDRVFEERRA LLGKWFDKWT DSQRRRILTG
     LLERCSLSQQ KFCCRKLQEK IPAEALDFTT KLPRVLSLYI FSFLDPRSLC RCAQVCWHWK
     NLAELDQLWM LKCLRFNWYI NFSPTPFEQG IWKKHYIQMV KELHITKPKT PPKDGFVIAD
     VQLVTSNSPE EKQSPLSAFR SSSSLRKKNN SGEKALPPWR SSDKHPTDII RFNYLDNRDP
     METVQQGRRK RNQMTPDFSR QSHDKKNKLQ DRTRLRKAQS MMSRRNPFPL CP
//