FBXL5_MOUSE
ID FBXL5_MOUSE Reviewed; 690 AA.
AC Q8C2S5; Q14CG1; Q3TAK6; Q3TWC9; Q3UC66; Q80XI5; Q8BGF5; Q8BNL3; Q8C3Q8;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=F-box/LRR-repeat protein 5;
DE AltName: Full=F-box and leucine-rich repeat protein 5;
GN Name=Fbxl5;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3; 4 AND 5).
RC STRAIN=C57BL/6J, and NOD;
RC TISSUE=Bone marrow, Lung, Spleen, Testis, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Eye;
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).
CC -!- FUNCTION: Component of some SCF (SKP1-cullin-F-box) protein ligase
CC complex that plays a central role in iron homeostasis by promoting the
CC ubiquitination and subsequent degradation of IREB2/IRP2. Upon high iron
CC and oxygen level, it specifically recognizes and binds IREB2/IRP2,
CC promoting its ubiquitination and degradation by the proteasome.
CC Promotes ubiquitination and subsequent degradation of DCTN1/p150-glued
CC (By similarity). {ECO:0000250}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Part of a SCF (SKP1-cullin-F-box) protein ligase complex.
CC Interacts with ACO1, IREB2/IRP2; the interaction depends on the 4Fe-4S
CC cluster. Interacts with DCTN1/p150-glued (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q8C2S5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8C2S5-2; Sequence=VSP_008418;
CC Name=3;
CC IsoId=Q8C2S5-3; Sequence=VSP_008419, VSP_008420;
CC Name=4;
CC IsoId=Q8C2S5-4; Sequence=VSP_038530;
CC Name=5;
CC IsoId=Q8C2S5-5; Sequence=VSP_038529, VSP_008419, VSP_008420;
CC -!- DOMAIN: The hemerythrin-like region acts as an oxygen and iron sensor
CC by binding oxygen through a diiron metal-center. In absence of oxygen
CC and iron, the protein is ubiquitinated and degraded (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated upon iron and oxygen depletion, leading to its
CC degradation by the proteasome. Ubiquitination is regulated by the
CC hemerythrin-like region that acts as an oxygen and iron sensor (By
CC similarity). {ECO:0000250}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK029957; BAC26698.1; -; mRNA.
DR EMBL; AK041497; BAC30964.1; -; mRNA.
DR EMBL; AK082931; BAC38698.1; -; mRNA.
DR EMBL; AK085100; BAC39366.1; -; mRNA.
DR EMBL; AK088067; BAC40126.1; -; mRNA.
DR EMBL; AK150664; BAE29748.1; -; mRNA.
DR EMBL; AK159744; BAE35337.1; -; mRNA.
DR EMBL; AK171783; BAE42662.1; -; mRNA.
DR EMBL; BC047214; AAH47214.1; -; mRNA.
DR EMBL; BC113798; AAI13799.1; -; mRNA.
DR CCDS; CCDS19263.1; -. [Q8C2S5-3]
DR CCDS; CCDS51489.1; -. [Q8C2S5-1]
DR RefSeq; NP_001153435.1; NM_001159963.1. [Q8C2S5-1]
DR RefSeq; NP_848844.1; NM_178729.4. [Q8C2S5-3]
DR AlphaFoldDB; Q8C2S5; -.
DR SMR; Q8C2S5; -.
DR BioGRID; 232476; 3.
DR STRING; 10090.ENSMUSP00000045792; -.
DR PhosphoSitePlus; Q8C2S5; -.
DR PaxDb; Q8C2S5; -.
DR PRIDE; Q8C2S5; -.
DR Antibodypedia; 9778; 205 antibodies from 28 providers.
DR Ensembl; ENSMUST00000047857; ENSMUSP00000045792; ENSMUSG00000039753. [Q8C2S5-1]
DR Ensembl; ENSMUST00000087465; ENSMUSP00000084733; ENSMUSG00000039753. [Q8C2S5-3]
DR Ensembl; ENSMUST00000114047; ENSMUSP00000109681; ENSMUSG00000039753. [Q8C2S5-2]
DR Ensembl; ENSMUST00000121736; ENSMUSP00000112444; ENSMUSG00000039753. [Q8C2S5-5]
DR Ensembl; ENSMUST00000196483; ENSMUSP00000143703; ENSMUSG00000039753. [Q8C2S5-4]
DR GeneID; 242960; -.
DR KEGG; mmu:242960; -.
DR UCSC; uc008xhu.2; mouse. [Q8C2S5-1]
DR UCSC; uc008xhv.2; mouse. [Q8C2S5-4]
DR UCSC; uc008xhw.2; mouse. [Q8C2S5-3]
DR UCSC; uc008xhx.2; mouse. [Q8C2S5-5]
DR CTD; 26234; -.
DR MGI; MGI:2152883; Fbxl5.
DR VEuPathDB; HostDB:ENSMUSG00000039753; -.
DR eggNOG; ENOG502QS5I; Eukaryota.
DR GeneTree; ENSGT00390000006172; -.
DR HOGENOM; CLU_017503_0_0_1; -.
DR InParanoid; Q8C2S5; -.
DR OMA; GEMFCGH; -.
DR OrthoDB; 1282076at2759; -.
DR PhylomeDB; Q8C2S5; -.
DR TreeFam; TF331105; -.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-917937; Iron uptake and transport.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 242960; 8 hits in 72 CRISPR screens.
DR ChiTaRS; Fbxl5; mouse.
DR PRO; PR:Q8C2S5; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8C2S5; protein.
DR Bgee; ENSMUSG00000039753; Expressed in spermatocyte and 232 other tissues.
DR ExpressionAtlas; Q8C2S5; baseline and differential.
DR Genevisible; Q8C2S5; MM.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; ISS:UniProtKB.
DR GO; GO:0055072; P:iron ion homeostasis; IMP:MGI.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IMP:MGI.
DR GO; GO:0030163; P:protein catabolic process; IMP:MGI.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR CDD; cd12109; Hr_FBXL5; 1.
DR Gene3D; 3.80.10.10; -; 2.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR012312; Hemerythrin-like.
DR InterPro; IPR045808; Hr_FBXL5.
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; PF01814; Hemerythrin; 1.
DR Pfam; PF13516; LRR_6; 3.
DR SMART; SM00256; FBOX; 1.
DR SMART; SM00367; LRR_CC; 4.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS50181; FBOX; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cytoplasm; Iron; Leucine-rich repeat; Metal-binding;
KW Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..690
FT /note="F-box/LRR-repeat protein 5"
FT /id="PRO_0000119846"
FT DOMAIN 202..248
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT REPEAT 340..364
FT /note="LRR 1"
FT REPEAT 365..392
FT /note="LRR 2"
FT REPEAT 393..418
FT /note="LRR 3"
FT REPEAT 478..507
FT /note="LRR 4"
FT REPEAT 575..606
FT /note="LRR 5"
FT REPEAT 607..634
FT /note="LRR 6"
FT REPEAT 635..660
FT /note="LRR 7"
FT REGION 1..159
FT /note="Hemerythrin-like"
FT /evidence="ECO:0000250"
FT BINDING 15
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 57
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 58
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 61
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 61
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 80
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 126
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 130
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 130
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..28
FT /note="MAPFPDEVDVFTAPHWRMKQLVGRYCDK -> MRNNQELKYEIKWKHLDCSV
FT VE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008418"
FT VAR_SEQ 29..71
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_038529"
FT VAR_SEQ 298
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_038530"
FT VAR_SEQ 617..623
FT /note="ALTLGGG -> WVISPSC (in isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_008419"
FT VAR_SEQ 624..690
FT /note="Missing (in isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_008420"
FT CONFLICT 105
FT /note="Q -> R (in Ref. 1; BAC38698)"
FT /evidence="ECO:0000305"
FT CONFLICT 127
FT /note="M -> K (in Ref. 1; BAC40126)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 690 AA; 77894 MW; 9558476AFB3ECCA0 CRC64;
MAPFPDEVDV FTAPHWRMKQ LVGRYCDKLS KTNFSNNNDF RALLQSLYAT FKEFKMHEQI
ENEYIIGLLQ QRSQTIYNVH SDNKLSEMLS LFEKGLKNVK NEYEQLNYAK QLKERLEAFT
RDFLPHMKEE EEVFQPMLME YFTYEELKDI KKKVIAQHCS QKDTAELLRG LSLWNQAEER
QKVLKYSVDE KADTEAEVSE HSTGITHLPP EVMLSIFSYL NPQELCRCSQ VSTKWSQLAK
TGSLWKHLYP VHWARGDWYS GPATELDTEP DEEWVRNRKD ESRAFQEWDE DADIDESEES
AEESVAISIA QMEKRVLHGL IHNVLPYVGT SVKTLVLAYS SAVSSKMVRQ ILELCPNLEH
LDLTQTDISD SAFDSWSWLG CCQSLRHLDL SGCEKITDMA LEKISRALGV LTSHQSGFLK
SAGKAASTPW TSKDITMPST TQYACLHNLT DKGIGEEIDN EHSWTEPVSS ESLTSPYVWM
LDAEDLADIE DAVEWRHRNV ESLCVMETAS NFGCSSSGCY SKDIVGLRTS VCWQQHCASP
AFAYCGHSFC CTGTALRTMT TLPATSAMCR KALRTTLPRG KDLIYFGSEK SDQETGRVLL
FLSLSGCYQI TDHGLRALTL GGGLPYLEHL NLSGCLTVTG AGLQDLVSAC PSLNDEYFYY
CDNINGPHAD TASGCQNLQC GFRACCRSGE
