FBXL7_HUMAN
ID FBXL7_HUMAN Reviewed; 491 AA.
AC Q9UJT9; B9EGF1; D6RDY7; O94926;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=F-box/LRR-repeat protein 7;
DE AltName: Full=F-box and leucine-rich repeat protein 7;
DE AltName: Full=F-box protein FBL6/FBL7;
GN Name=FBXL7; Synonyms=FBL6, FBL7, KIAA0840;
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=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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
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).
RN [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Testis;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 41-483 (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 [8]
RP FUNCTION.
RX PubMed=25778398; DOI=10.1074/jbc.m114.629931;
RA Liu Y., Lear T., Iannone O., Shiva S., Corey C., Rajbhandari S., Jerome J.,
RA Chen B.B., Mallampalli R.K.;
RT "The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial Function by
RT Mediating the Ubiquitylation and Proteasomal Degradation of Survivin.";
RL J. Biol. Chem. 290:11843-11852(2015).
RN [9]
RP FUNCTION, AND INTERACTION WITH BIRC5.
RX PubMed=28218735; DOI=10.1038/oncsis.2016.80;
RA Kamran M., Long Z.J., Xu D., Lv S.S., Liu B., Wang C.L., Xu J., Lam E.W.,
RA Liu Q.;
RT "Aurora kinase A regulates Survivin stability through targeting FBXL7 in
RT gastric cancer drug resistance and prognosis.";
RL Oncogenesis 6:E298-E298(2017).
CC -!- FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F-box
CC protein) E3 ubiquitin-protein ligase complex (PubMed:25778398). During
CC mitosis, it mediates the ubiquitination and subsequent proteasomal
CC degradation of AURKA, causing mitotic arrest (By similarity). It also
CC regulates mitochondrial function by mediating the ubiquitination and
CC proteasomal degradation of the apoptosis inhibitor BIRC5
CC (PubMed:25778398, PubMed:28218735). {ECO:0000250|UniProtKB:Q5BJ29,
CC ECO:0000269|PubMed:25778398, ECO:0000269|PubMed:28218735}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:25778398, ECO:0000269|PubMed:28218735}.
CC -!- SUBUNIT: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase
CC complex SCF(FBXL7) composed of CUL1, SKP1, RBX1 and FBXL7 (By
CC similarity). Interacts with AURKA; interaction takes place during
CC mitosis but not in interphase (By similarity). Interacts with BIRC5;
CC this interaction allows BIRC5 to be polyubiquitinated by the SCF(FBXL7)
CC E3 ubiquitin-protein ligase complex (PubMed:28218735).
CC {ECO:0000250|UniProtKB:Q5BJ29, ECO:0000269|PubMed:28218735}.
CC -!- INTERACTION:
CC Q9UJT9; A0A0C3SFZ9: FCHO1; NbExp=3; IntAct=EBI-914660, EBI-11977403;
CC Q9UJT9; Q92609: TBC1D5; NbExp=3; IntAct=EBI-914660, EBI-742381;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000250|UniProtKB:Q5BJ29}. Note=Localizes to
CC the centrosome during spindle formation.
CC {ECO:0000250|UniProtKB:Q5BJ29}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UJT9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UJT9-2; Sequence=VSP_054751;
CC -!- SIMILARITY: Belongs to the FBXL7 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA74863.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF199356; AAF09248.1; -; mRNA.
DR EMBL; AB020647; BAA74863.2; ALT_INIT; mRNA.
DR EMBL; AC091970; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC091872; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC027332; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010638; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010477; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471102; EAX08029.1; -; Genomic_DNA.
DR EMBL; BC075061; AAH75061.1; -; mRNA.
DR EMBL; BC136424; AAI36425.1; -; mRNA.
DR EMBL; AF174593; AAF04514.1; -; mRNA.
DR CCDS; CCDS54833.1; -. [Q9UJT9-1]
DR CCDS; CCDS64129.1; -. [Q9UJT9-2]
DR RefSeq; NP_001265246.1; NM_001278317.1. [Q9UJT9-2]
DR RefSeq; NP_036436.1; NM_012304.4. [Q9UJT9-1]
DR RefSeq; XP_011512300.1; XM_011513998.1. [Q9UJT9-2]
DR AlphaFoldDB; Q9UJT9; -.
DR SMR; Q9UJT9; -.
DR BioGRID; 116803; 13.
DR IntAct; Q9UJT9; 7.
DR STRING; 9606.ENSP00000423630; -.
DR iPTMnet; Q9UJT9; -.
DR PhosphoSitePlus; Q9UJT9; -.
DR BioMuta; FBXL7; -.
DR DMDM; 37537858; -.
DR MassIVE; Q9UJT9; -.
DR MaxQB; Q9UJT9; -.
DR PaxDb; Q9UJT9; -.
DR PeptideAtlas; Q9UJT9; -.
DR PRIDE; Q9UJT9; -.
DR ProteomicsDB; 14203; -.
DR ProteomicsDB; 84649; -. [Q9UJT9-1]
DR Antibodypedia; 5190; 67 antibodies from 19 providers.
DR DNASU; 23194; -.
DR Ensembl; ENST00000504595.2; ENSP00000423630.1; ENSG00000183580.10. [Q9UJT9-1]
DR Ensembl; ENST00000510662.1; ENSP00000425184.1; ENSG00000183580.10. [Q9UJT9-2]
DR GeneID; 23194; -.
DR KEGG; hsa:23194; -.
DR MANE-Select; ENST00000504595.2; ENSP00000423630.1; NM_012304.5; NP_036436.1.
DR UCSC; uc003jfn.3; human. [Q9UJT9-1]
DR CTD; 23194; -.
DR DisGeNET; 23194; -.
DR GeneCards; FBXL7; -.
DR HGNC; HGNC:13604; FBXL7.
DR HPA; ENSG00000183580; Low tissue specificity.
DR MIM; 605656; gene.
DR neXtProt; NX_Q9UJT9; -.
DR OpenTargets; ENSG00000183580; -.
DR PharmGKB; PA28027; -.
DR VEuPathDB; HostDB:ENSG00000183580; -.
DR eggNOG; KOG1947; Eukaryota.
DR GeneTree; ENSGT00940000158009; -.
DR HOGENOM; CLU_016072_5_0_1; -.
DR InParanoid; Q9UJT9; -.
DR OMA; MIYCASI; -.
DR OrthoDB; 1027299at2759; -.
DR PhylomeDB; Q9UJT9; -.
DR TreeFam; TF313434; -.
DR PathwayCommons; Q9UJT9; -.
DR Reactome; R-HSA-8854050; FBXL7 down-regulates AURKA during mitotic entry and in early mitosis.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9UJT9; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 23194; 11 hits in 1116 CRISPR screens.
DR ChiTaRS; FBXL7; human.
DR GeneWiki; FBXL7; -.
DR GenomeRNAi; 23194; -.
DR Pharos; Q9UJT9; Tbio.
DR PRO; PR:Q9UJT9; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9UJT9; protein.
DR Bgee; ENSG00000183580; Expressed in secondary oocyte and 196 other tissues.
DR ExpressionAtlas; Q9UJT9; baseline and differential.
DR Genevisible; Q9UJT9; HS.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; NAS:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; NAS:UniProtKB.
DR Gene3D; 3.80.10.10; -; 2.
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; PF12937; F-box-like; 1.
DR Pfam; PF13516; LRR_6; 5.
DR SMART; SM00256; FBOX; 1.
DR SMART; SM00367; LRR_CC; 11.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS50181; FBOX; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Cell division; Cytoplasm; Cytoskeleton;
KW Leucine-rich repeat; Mitosis; Reference proteome; Repeat;
KW Ubl conjugation pathway.
FT CHAIN 1..491
FT /note="F-box/LRR-repeat protein 7"
FT /id="PRO_0000119849"
FT DOMAIN 111..157
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT REPEAT 170..195
FT /note="LRR 1"
FT REPEAT 196..221
FT /note="LRR 2"
FT REPEAT 222..247
FT /note="LRR 3"
FT REPEAT 253..281
FT /note="LRR 4"
FT REPEAT 282..307
FT /note="LRR 5"
FT REPEAT 308..333
FT /note="LRR 6"
FT REPEAT 334..359
FT /note="LRR 7"
FT REPEAT 360..385
FT /note="LRR 8"
FT REPEAT 386..411
FT /note="LRR 9"
FT REPEAT 412..437
FT /note="LRR 10"
FT REPEAT 438..463
FT /note="LRR 11"
FT REGION 1..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..57
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..47
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_054751"
SQ SEQUENCE 491 AA; 54575 MW; A70C092A4E748C69 CRC64;
MGANNGKQYG SEGKGSSSIS SDVSSSTDHT PTKAQKNVAT SEDSDLSMRT LSTPSPALIC
PPNLPGFQNG RGSSTSSSSI TGETVAMVHS PPPTRLTHPL IRLASRPQKE QASIDRLPDH
SMVQIFSFLP TNQLCRCARV CRRWYNLAWD PRLWRTIRLT GETINVDRAL KVLTRRLCQD
TPNVCLMLET VTVSGCRRLT DRGLYTIAQC CPELRRLEVS GCYNISNEAV FDVVSLCPNL
EHLDVSGCSK VTCISLTREA SIKLSPLHGK QISIRYLDMT DCFVLEDEGL HTIAAHCTQL
THLYLRRCVR LTDEGLRYLV IYCASIKELS VSDCRFVSDF GLREIAKLES RLRYLSIAHC
GRVTDVGIRY VAKYCSKLRY LNARGCEGIT DHGVEYLAKN CTKLKSLDIG KCPLVSDTGL
ECLALNCFNL KRLSLKSCES ITGQGLQIVA ANCFDLQTLN VQDCEVSVEA LRFVKRHCKR
CVIEHTNPAF F