FXL21_HUMAN
ID FXL21_HUMAN Reviewed; 434 AA.
AC Q9UKT6;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 25-MAY-2022, entry version 143.
DE RecName: Full=Putative F-box/LRR-repeat protein 21;
DE AltName: Full=F-box and leucine-rich repeat protein 21;
DE AltName: Full=F-box and leucine-rich repeat protein 3B;
DE AltName: Full=F-box/LRR-repeat protein 3B;
GN Name=FBXL21P {ECO:0000312|HGNC:HGNC:13600};
GN Synonyms=FBL21, FBL3, FBXL21, FBXL3B, FBXL3P;
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], AND INTERACTION WITH SKP1 AND CUL1.
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
CC -!- FUNCTION: Substrate-recognition component of the SCF(FBXL21) E3
CC ubiquitin ligase complex involved in circadian rhythm function. Plays a
CC key role in the maintenance of both the speed and the robustness of the
CC circadian clock oscillation. The SCF(FBXL21) complex mainly acts in the
CC cytosol and mediates ubiquitination of CRY proteins (CRY1 and CRY2),
CC leading to CRY proteins stabilization. The SCF(FBXL21) complex
CC counteracts the activity of the SCF(FBXL3) complex and protects CRY
CC proteins from degradation. Involved in the hypothalamic suprachiasmatic
CC nucleus (SCN) clock regulating temporal organization of the daily
CC activities (By similarity). {ECO:0000250}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with CRY1 and CRY2 (By similarity). Part of the SCF
CC (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL21)
CC composed of CUL1, SKP1, RBX1 and FBXL21. {ECO:0000250,
CC ECO:0000269|PubMed:10531035}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Nucleus
CC {ECO:0000250}. Note=Mainly localizes in the cytosol. Present at low
CC level in the nucleus (By similarity). {ECO:0000250}.
CC -!- CAUTION: Could be the product of a pseudogene. The reference genome
CC assembly (GRCh38/hg38) corresponds to a non-functional allele with a
CC stop codon at position 56 suggesting that this gene may be a
CC pseudogene, at least in some part of the population. The existence of a
CC functional transcript at this locus is supported by only one sequence
CC submission. {ECO:0000305, ECO:0000305|PubMed:10531035}.
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DR EMBL; AF129533; AAF04467.1; -; mRNA.
DR EMBL; AC002428; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_036291.2; NM_012159.4.
DR AlphaFoldDB; Q9UKT6; -.
DR SMR; Q9UKT6; -.
DR BioGRID; 117614; 8.
DR IntAct; Q9UKT6; 1.
DR iPTMnet; Q9UKT6; -.
DR PhosphoSitePlus; Q9UKT6; -.
DR BioMuta; HGNC:13600; -.
DR DMDM; 37537865; -.
DR EPD; Q9UKT6; -.
DR MassIVE; Q9UKT6; -.
DR PeptideAtlas; Q9UKT6; -.
DR PRIDE; Q9UKT6; -.
DR GeneCards; FBXL21P; -.
DR HGNC; HGNC:13600; FBXL21P.
DR MIM; 609087; gene.
DR neXtProt; NX_Q9UKT6; -.
DR PharmGKB; PA28023; -.
DR InParanoid; Q9UKT6; -.
DR PhylomeDB; Q9UKT6; -.
DR PathwayCommons; Q9UKT6; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SIGNOR; Q9UKT6; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 26223; 2 hits in 226 CRISPR screens.
DR GenomeRNAi; 26223; -.
DR Pharos; Q9UKT6; Tdark.
DR PRO; PR:Q9UKT6; -.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; Q9UKT6; protein.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; NAS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; NAS:UniProtKB.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; IBA:GO_Central.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR032675; LRR_dom_sf.
DR Pfam; PF12937; F-box-like; 1.
DR SMART; SM00256; FBOX; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS50181; FBOX; 1.
PE 5: Uncertain;
KW Biological rhythms; Cytoplasm; Leucine-rich repeat; Nucleus;
KW Reference proteome; Repeat; Ubl conjugation pathway.
FT CHAIN 1..434
FT /note="Putative F-box/LRR-repeat protein 21"
FT /id="PRO_0000119873"
FT DOMAIN 39..85
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT REPEAT 158..187
FT /note="LRR 1"
FT REPEAT 190..213
FT /note="LRR 2"
FT REPEAT 214..239
FT /note="LRR 3"
FT REPEAT 242..265
FT /note="LRR 4"
FT REPEAT 322..347
FT /note="LRR 5"
FT REPEAT 349..374
FT /note="LRR 6"
FT REPEAT 375..400
FT /note="LRR 7"
FT VARIANT 76
FT /note="F -> L (in dbSNP:rs7705168)"
FT /id="VAR_049034"
FT VARIANT 209
FT /note="P -> L (in dbSNP:rs40986)"
FT /id="VAR_049035"
SQ SEQUENCE 434 AA; 49152 MW; 1D35DB334899224E CRC64;
MKRNSLSVEN KIVQLSGAAK QPKVGFYSSL NQTHTHTVLL DWGSLPHHVV LQIFQYLPLL
DRACASSVCR RWNEVFHISD LWRKFEFELN QSATSSFKST HPDLIQQIIK KHFAHLQYVS
FKVDSSAESA EAACDILSQL VNCSIQTLGL ISTAKPSFMN VSESHFVSAL TVVFINSKSL
SSIKIEDTPV DDPSLKILVA NNSDTLRLPK MSSCPHVSSD GILCVADRCQ GLRELALNYY
ILTDELFLAL SSETHVNLEH LRIDVVSENP GQIKFHAVKK HSWDALIKHS PRVNVVMHFF
LYEEEFETFF KEETPVTHLY FGRSVSKVVL GRVGLNCPRL IELVVCANDL QPLDNELICI
AEHCTNLTAL GLSKCEVSCS AFIRFVRLCE RRLTQLSVME EVLIPDEDYS LDEIHTEVSK
YLGRVWFPDV MPLW
