ID FBXL5_PONAB Reviewed; 691 AA.
AC Q5R6E1;
DT 15-DEC-2009, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 27-MAR-2024, entry version 100.
DE RecName: Full=F-box/LRR-repeat protein 5;
DE AltName: Full=F-box and leucine-rich repeat protein 5;
GN Name=FBXL5;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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. The C-terminal
CC domain of FBXL5 contains a redox-sensitive [2Fe-2S] cluster that, upon
CC oxidation, promotes binding to IRP2 to effect its oxygen-dependent
CC degradation. Under iron deficiency conditions, the N-terminal
CC hemerythrin-like (Hr) region, which contains a diiron metal center,
CC cannot bind iron and undergoes conformational changes that destabilize
CC the FBXL5 protein and cause its ubiquitination and degradation. When
CC intracellular iron levels start rising, the Hr region is stabilized.
CC Additional increases in iron levels facilitate the assembly and
CC incorporation of a redox active [2Fe-2S] cluster in the C-terminal
CC domain. Only when oxygen level is high enough to maintain the cluster
CC in its oxidized state can FBXL5 recruit IRP2 as a substrate for
CC polyubiquination and degradation. Promotes ubiquitination and
CC subsequent degradation of the dynactin complex component DCTN1. Within
CC the nucleus, promotes the ubiquitination of SNAI1; preventing its
CC interaction with DNA and promoting its degradation. Negatively
CC regulates DNA damage response by mediating the ubiquitin-proteasome
CC degradation of the DNA repair protein NABP2.
CC {ECO:0000250|UniProtKB:Q9UKA1}.
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0000250|UniProtKB:Q9UKA1};
CC -!- ACTIVITY REGULATION: An iron-sulfur cluster promotes IRP2
CC polyubiquitination and degradation in response to both iron and oxygen
CC concentrations. {ECO:0000250|UniProtKB:Q9UKA1}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Part of a SCF (SKP1-cullin-F-box) protein ligase complex.
CC Interacts with ACO1/IRP1, IREB2/IRP2; the interaction depends on the
CC [2Fe-2S] cluster. Interacts with DCTN1/p150-glued.
CC {ECO:0000250|UniProtKB:Q9UKA1}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q9UKA1}. Nucleus {ECO:0000250|UniProtKB:Q9UKA1}.
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: Polybiquitinated 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.
CC Undergoes constitutive ubiquitin-dependent degradation at the steady
CC state by HERC2. {ECO:0000250|UniProtKB:Q9UKA1}.
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; CR860550; CAH92675.1; -; mRNA.
DR RefSeq; NP_001126565.1; NM_001133093.1.
DR AlphaFoldDB; Q5R6E1; -.
DR SMR; Q5R6E1; -.
DR STRING; 9601.ENSPPYP00000016331; -.
DR GeneID; 100173556; -.
DR KEGG; pon:100173556; -.
DR CTD; 26234; -.
DR eggNOG; ENOG502QS5I; Eukaryota.
DR InParanoid; Q5R6E1; -.
DR OrthoDB; 2913997at2759; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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:0051536; F:iron-sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0006879; P:intracellular iron ion homeostasis; ISS:UniProtKB.
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; cd22118; F-box_FBXL5; 1.
DR CDD; cd12109; Hr_FBXL5; 1.
DR Gene3D; 1.20.1280.50; -; 1.
DR Gene3D; 1.20.120.520; nmb1532 protein domain like; 1.
DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 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 PANTHER; PTHR13318:SF19; F-BOX_LRR-REPEAT PROTEIN 5; 1.
DR PANTHER; PTHR13318; UNCHARACTERIZED; 1.
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; F-box domain; 1.
DR SUPFAM; SSF52047; RNI-like; 1.
DR PROSITE; PS50181; FBOX; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Iron; Iron-sulfur; Leucine-rich repeat; Metal-binding; Nucleus;
KW Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..691
FT /note="F-box/LRR-repeat protein 5"
FT /id="PRO_0000390465"
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|UniProtKB:Q9UKA1"
FT BINDING 15
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UKA1"
FT BINDING 57
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UKA1"
FT BINDING 58
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UKA1"
FT BINDING 61
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UKA1"
FT BINDING 61
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UKA1"
FT BINDING 80
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UKA1"
FT BINDING 126
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UKA1"
FT BINDING 130
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UKA1"
FT BINDING 130
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UKA1"
FT BINDING 662
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250|UniProtKB:Q9UKA1"
FT BINDING 676
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250|UniProtKB:Q9UKA1"
FT BINDING 686
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250|UniProtKB:Q9UKA1"
FT BINDING 687
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000250|UniProtKB:Q9UKA1"
SQ SEQUENCE 691 AA; 78553 MW; 3F225397BAB6A674 CRC64;
MAPFPEEVDV FTAPHWRTKQ LVGLYCDKLS KTNFSNNNDF RALLQSLYAT FKEFKMHEQI
ENEYIIGLLQ QRSQTIYNVH SDNKLSEMLS LFEKGLKNVK NEYEQLNYAK QLKERLEAFT
RDFLPHMKEE EEVFQPMLME YFTYEELKDI KKKVIAQHCS QKDTAELLRG LSLWNHAEER
QKFFKYSVDE KSDKEAEVSE HSTGITHLPP EVMLSIFSYL NPQELCRCSQ VSMKWSQLTK
TGSLWKHLYP VHWARGDWYS GPATGLDTEP DEEWVKNRKD ESRAFHEWDE DADIDESEES
VEESIAISIA QMEKRLLHGL IHNVLPYVGT SVKTLVLAYS SAVSSKMVRQ ILELCPNLEH
LDLTQTDISD SAFDSWSWLG CCQSLRHLDL SGCEKITDVA LEKISRALGI LTSHQSGFLK
TSTSKITSTT WKNKDVTMQS TKQYAYLHDL TNKGIGEEID NEHPWTKPVS SENFTSPYLW
MLDAEDLADI EDTVEWRHRN VESLCVVETA SNFSCSTSGC FSKDIVGLRT SVCWQQHCAS
PAFAYCGHSF CCTGTALRTM SALPESSAMC RKASRTRLPR GKDLIYFGSE KSDQETGRVL
LFLSLSGCYQ ITDHGLRVLT LGGGLPYLEH LNLSGCLTIT GAGLQDLVSA CPSLNDEYFY
YCDNINGPHA DTASGCQNLQ CGFRACCRSG E
//
