FBX43_HUMAN
ID FBX43_HUMAN Reviewed; 708 AA.
AC Q4G163;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 3.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=F-box only protein 43;
DE AltName: Full=Endogenous meiotic inhibitor 2;
GN Name=FBXO43; Synonyms=EMI2;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [2]
RP NOMENCLATURE.
RX PubMed=15520277; DOI=10.1101/gad.1255304;
RA Jin J., Cardozo T., Lovering R.C., Elledge S.J., Pagano M., Harper J.W.;
RT "Systematic analysis and nomenclature of mammalian F-box proteins.";
RL Genes Dev. 18:2573-2580(2004).
RN [3]
RP UBIQUITINATION, PHOSPHORYLATION AT SER-76 AND SER-334, AND MUTAGENESIS OF
RP 75-ASP-SER-76 AND 333-ASP-SER-334.
RX PubMed=15753281; DOI=10.1073/pnas.0501108102;
RA Tung J.J., Hansen D.V., Ban K.H., Loktev A.V., Summers M.K.,
RA Adler J.R. III, Jackson P.K.;
RT "A role for the anaphase-promoting complex inhibitor Emi2/XErp1, a homolog
RT of early mitotic inhibitor 1, in cytostatic factor arrest of Xenopus
RT eggs.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:4318-4323(2005).
RN [4]
RP PHOSPHORYLATION AT THR-234.
RX PubMed=16407128; DOI=10.1073/pnas.0509549102;
RA Hansen D.V., Tung J.J., Jackson P.K.;
RT "CaMKII and polo-like kinase 1 sequentially phosphorylate the cytostatic
RT factor Emi2/XErp1 to trigger its destruction and meiotic exit.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:608-613(2006).
CC -!- FUNCTION: Required to establish and maintain the arrest of oocytes at
CC the second meiotic metaphase until fertilization. Probably acts by
CC inhibiting the anaphase-promoting complex/cyclosome (APC/C) ubiquitin
CC ligase. Probably recognizes and binds to some phosphorylated proteins
CC and promotes their ubiquitination and degradation (Probable).
CC {ECO:0000305}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Part of a SCF (SKP1-cullin-F-box) protein ligase complex. May
CC interact with CDC20 (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q4G163; P30153: PPP2R1A; NbExp=3; IntAct=EBI-12053217, EBI-302388;
CC Q4G163; P63208: SKP1; NbExp=3; IntAct=EBI-12053217, EBI-307486;
CC -!- PTM: Phosphorylated on Ser-76, Thr-234 and Ser-334 in response to
CC calcium, which is a prerequisite for ubiquitination and proteasomal
CC degradation. {ECO:0000305|PubMed:15753281,
CC ECO:0000305|PubMed:16407128}.
CC -!- PTM: Ubiquitinated in response to calcium, which promotes proteasomal
CC degradation. {ECO:0000269|PubMed:15753281}.
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DR EMBL; AC021590; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS47904.1; -.
DR RefSeq; NP_001025031.2; NM_001029860.3.
DR AlphaFoldDB; Q4G163; -.
DR SMR; Q4G163; -.
DR BioGRID; 130316; 6.
DR ELM; Q4G163; -.
DR IntAct; Q4G163; 4.
DR MINT; Q4G163; -.
DR STRING; 9606.ENSP00000403293; -.
DR GlyGen; Q4G163; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q4G163; -.
DR PhosphoSitePlus; Q4G163; -.
DR BioMuta; FBXO43; -.
DR DMDM; 152031603; -.
DR MassIVE; Q4G163; -.
DR MaxQB; Q4G163; -.
DR PaxDb; Q4G163; -.
DR PeptideAtlas; Q4G163; -.
DR PRIDE; Q4G163; -.
DR ProteomicsDB; 62156; -.
DR Antibodypedia; 6910; 126 antibodies from 33 providers.
DR DNASU; 286151; -.
DR Ensembl; ENST00000428847.3; ENSP00000403293.2; ENSG00000156509.14.
DR GeneID; 286151; -.
DR KEGG; hsa:286151; -.
DR MANE-Select; ENST00000428847.3; ENSP00000403293.2; NM_001029860.4; NP_001025031.2.
DR UCSC; uc003yjd.4; human.
DR CTD; 286151; -.
DR DisGeNET; 286151; -.
DR GeneCards; FBXO43; -.
DR HGNC; HGNC:28521; FBXO43.
DR HPA; ENSG00000156509; Tissue enriched (testis).
DR MIM; 609110; gene.
DR neXtProt; NX_Q4G163; -.
DR OpenTargets; ENSG00000156509; -.
DR PharmGKB; PA134913061; -.
DR VEuPathDB; HostDB:ENSG00000156509; -.
DR eggNOG; ENOG502QRSQ; Eukaryota.
DR GeneTree; ENSGT00530000063692; -.
DR HOGENOM; CLU_029091_0_0_1; -.
DR InParanoid; Q4G163; -.
DR OMA; WKVSKNW; -.
DR OrthoDB; 521317at2759; -.
DR PhylomeDB; Q4G163; -.
DR TreeFam; TF101170; -.
DR PathwayCommons; Q4G163; -.
DR SignaLink; Q4G163; -.
DR SIGNOR; Q4G163; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 286151; 17 hits in 1119 CRISPR screens.
DR ChiTaRS; FBXO43; human.
DR GenomeRNAi; 286151; -.
DR Pharos; Q4G163; Tbio.
DR PRO; PR:Q4G163; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q4G163; protein.
DR Bgee; ENSG00000156509; Expressed in secondary oocyte and 115 other tissues.
DR ExpressionAtlas; Q4G163; baseline and differential.
DR Genevisible; Q4G163; HS.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0045835; P:negative regulation of meiotic nuclear division; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0007088; P:regulation of mitotic nuclear division; IBA:GO_Central.
DR InterPro; IPR002867; IBR_dom.
DR InterPro; IPR044064; ZF_ZBR.
DR SMART; SM00647; IBR; 1.
DR PROSITE; PS51872; ZF_ZBR; 1.
PE 1: Evidence at protein level;
KW Meiosis; Metal-binding; Phosphoprotein; Reference proteome;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..708
FT /note="F-box only protein 43"
FT /id="PRO_0000247233"
FT DOMAIN 490..547
FT /note="F-box"
FT ZN_FING 636..684
FT /note="ZBR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT REGION 35..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 320..426
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 682..708
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 320..344
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 392..407
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 640
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 643
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 658
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 663
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 668
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 671
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 676
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 681
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:15753281"
FT MOD_RES 234
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:16407128"
FT MOD_RES 334
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:15753281"
FT VARIANT 139
FT /note="P -> L (in dbSNP:rs2279102)"
FT /id="VAR_061168"
FT VARIANT 139
FT /note="P -> R (in dbSNP:rs2279102)"
FT /id="VAR_061169"
FT MUTAGEN 75..76
FT /note="DS->AA: Impairs ubiquitination and degradation in
FT response to calcium."
FT /evidence="ECO:0000269|PubMed:15753281"
FT MUTAGEN 333..334
FT /note="DS->AA: Impairs ubiquitination and degradation in
FT response to calcium."
FT /evidence="ECO:0000269|PubMed:15753281"
SQ SEQUENCE 708 AA; 78402 MW; E42A358AE7BD29D1 CRC64;
MSFKDKDERI SCLEAYVTLT SKSSRFTDET EILKMSQRHS GQAGTEAGNG ADSPPIVNSK
YSTFRDFCST SSFQDSGYNE LKSCSFDNID KEYLGKKEKG PTLLYEHPET SGLGLTHPLE
SPTQKKKCIL PRKEKDKTPE LCETPKISGK KCLPRRRLNV SFALLKGDFE SQNSSLESSI
SQVINLEKNI PSSASGFSRA NNFSPLVTST LKTEEVTSCS QKLRLNFSQQ KTSTIDDSKD
DCSLFEVECI SPIQGNNFKD SITHDFSDSS LCINDENACP ELLGSSVSGT TCGTDEDIFV
TPISNLVANI RFNASQILSP SPEVRGSIST PEDSGFNSLS LEKSEDSLSD QEGSFQELLQ
KHKGTPKVGD TIRKTRHLGR SRRLSTLREQ SSQSETEEEK QIVHPDSEKR AAAASAISEG
QLSSDESGDL TFSLKNLSKT PALQLVHELF MKSKRKRLQE NSGHEFLEQG DGEKIAVLQC
ILAGLIGKKM GIEKLDILTE LKYRNLKHIL AMVLESLTAE SLCSVWKVSR NWREIVVQDK
NANRRRKFYI TQLKTDSEGA VLNVEDAATR LQLLNRSALR SVQAQARIPG SQREQGSTLS
PWGEVLTPLA SSSVTHLSSK QEEYVKVAKT LFTDEALKPC PRCQSPAKYQ PYKKRGLCSR
TACGFDFCVL CLCAYHGSEE CSRGAAKPRN RKDALPGSAQ SKRNLKRL
