ID   FBXL5_BOVIN             Reviewed;         691 AA.
AC   A2VE78;
DT   15-DEC-2009, integrated into UniProtKB/Swiss-Prot.
DT   20-MAR-2007, sequence version 1.
DT   03-AUG-2022, entry version 83.
DE   RecName: Full=F-box/LRR-repeat protein 5;
DE   AltName: Full=F-box and leucine-rich repeat protein 5;
GN   Name=FBXL5;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Fetal lung;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
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   -!- 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}.
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DR   EMBL; BC133613; AAI33614.1; -; mRNA.
DR   RefSeq; NP_001075909.1; NM_001082440.1.
DR   AlphaFoldDB; A2VE78; -.
DR   SMR; A2VE78; -.
DR   STRING; 9913.ENSBTAP00000028266; -.
DR   PaxDb; A2VE78; -.
DR   PRIDE; A2VE78; -.
DR   Ensembl; ENSBTAT00000028266; ENSBTAP00000028266; ENSBTAG00000021214.
DR   GeneID; 519695; -.
DR   KEGG; bta:519695; -.
DR   CTD; 26234; -.
DR   VEuPathDB; HostDB:ENSBTAG00000021214; -.
DR   VGNC; VGNC:28891; FBXL5.
DR   eggNOG; ENOG502QS5I; Eukaryota.
DR   GeneTree; ENSGT00390000006172; -.
DR   InParanoid; A2VE78; -.
DR   OMA; GEMFCGH; -.
DR   OrthoDB; 1282076at2759; -.
DR   UniPathway; UPA00143; -.
DR   Proteomes; UP000009136; Chromosome 6.
DR   Bgee; ENSBTAG00000021214; Expressed in neutrophil and 103 other tissues.
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; ISS:UniProtKB.
DR   GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl.
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   Cytoplasm; Iron; Leucine-rich repeat; Metal-binding; Reference proteome;
KW   Repeat; Ubl conjugation; Ubl conjugation pathway.
FT   CHAIN           1..691
FT                   /note="F-box/LRR-repeat protein 5"
FT                   /id="PRO_0000390464"
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          479..508
FT                   /note="LRR 4"
FT   REPEAT          576..607
FT                   /note="LRR 5"
FT   REPEAT          608..635
FT                   /note="LRR 6"
FT   REPEAT          636..661
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"
SQ   SEQUENCE   691 AA;  78412 MW;  15A5BA66BDE12331 CRC64;
     MAPFPEEVDV FTAPHWRMKQ LVGLYCDKLS KTNFSNNNDF RALLQSLYAT FKEFKMHEQI
     ENEYIIGLLQ QRSQTIYNVH SDNKLSEMLS LFEKGLKNVK NEYEQLNYAK QLKERLEAFT
     KDFLPHMKEE EEVFQPMLME YFTYEELKDI KKKVIAQHCS QKDTAELLRG LSLWNQAEER
     QKFFKYSVDE KSDKEAEVSE QSTGITHLPP EVMVSIFSYL NPQELCRCSQ VSTKWSQLAK
     TGSLWKHLYP VHWARGDWYS GPAAELDTEP DEEWVKSRRD ESRAFQEWDE DADIDESEES
     GEESIAISIA QMEKRLLHGL IHNVLPYVGT SVKTLVLAYS SAVSSKMVRQ ILELCPNLEH
     LDLTQTDISD SAFDSWSWLG CCQSLRHLDL SGCEKITDVA LEKISRALGI LTTHESGLLK
     TSTSKVTSTT WKNKDITMQS FKQSACLHDV TNKDIGEEVD NEHPWTKPIS SDDFTSPYVW
     MLDAEDLADI EDAVEWRHRN VESLCVMETA SNFSCPSSAC YSKDIVGLRT SVCWQQHCAS
     PAFAYCGHSY CCTGTALRTM SALPESSALC RKAPRTRLLR EKDLIYSGSE KSDQETGRVL
     LFLSLSGCYQ ITDHGLRVLT LGGGLPYLEH LNLSGCLTVT GAGLQDLVSA CPSLNDEYFY
     YCDNINGPHA DTASGCQNLQ CGFRACCRSG E