FBX5A_XENLA
ID FBX5A_XENLA Reviewed; 392 AA.
AC Q90Z80;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 82.
DE RecName: Full=F-box only protein 5-A {ECO:0000305};
DE AltName: Full=Early mitotic inhibitor 1-A;
GN Name=fbxo5-a; Synonyms=emi1-a;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAK62272.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH CDC20 AND SKP1;
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, MUTAGENESIS OF SER-10; SER-29;
RP SER-105; THR-123; 198-GLU-LEU-199; SER-328; CYS-341; CYS-346; CYS-351;
RP CYS-354; CYS-356 AND CYS-364, AND DOMAIN.
RX PubMed=11389834; DOI=10.1016/s0092-8674(01)00361-0;
RA Reimann J.D.R., Freed E., Hsu J.Y., Kramer E.R., Peters J.-M.,
RA Jackson P.K.;
RT "EMI1 is a mitotic regulator that interacts with Cdc20 and inhibits the
RT anaphase-promoting complex.";
RL Cell 105:645-655(2001).
RN [2] {ECO:0000312|EMBL:AAH88910.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Egg {ECO:0000312|EMBL:AAH88910.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP FUNCTION.
RX PubMed=11751633; DOI=10.1101/gad.945701;
RA Reimann J.D.R., Gardner B.E., Margottin-Goguet F., Jackson P.K.;
RT "Emi1 regulates the anaphase-promoting complex by a different mechanism
RT than Mad2 proteins.";
RL Genes Dev. 15:3278-3285(2001).
RN [4]
RP INTERACTION WITH CDC20, AND FUNCTION.
RX PubMed=11976684; DOI=10.1038/416850a;
RA Reimann J.D., Jackson P.K.;
RT "Emi1 is required for cytostatic factor arrest in vertebrate eggs.";
RL Nature 416:850-854(2002).
RN [5]
RP INDUCTION, DEVELOPMENTAL STAGE, FUNCTION, AND MUTAGENESIS OF SER-95 AND
RP SER-99.
RX PubMed=15314241; DOI=10.1073/pnas.0405300101;
RA Ohsumi K., Koyanagi A., Yamamoto T.M., Gotoh T., Kishimoto T.;
RT "Emi1-mediated M-phase arrest in Xenopus eggs is distinct from cytostatic
RT factor arrest.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:12531-12536(2004).
RN [6]
RP MUTAGENESIS OF SER-10; SER-29; SER-105; THR-123 AND SER-328, PROTEOLYSIS,
RP INTERACTION WITH PIN1; BTRC AND PLK1, SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=17159919; DOI=10.1038/sj.embor.7400853;
RA Bernis C., Vigneron S., Burgess A., Labbe J.C., Fesquet D., Castro A.,
RA Lorca T.;
RT "Pin1 stabilizes Emi1 during G2 phase by preventing its association with
RT SCF(betatrcp).";
RL EMBO Rep. 8:91-98(2007).
CC -!- FUNCTION: Regulates progression through early mitosis by inhibiting the
CC anaphase promoting complex/cyclosome (APC) (PubMed:15314241). Binds to
CC the APC activator cdc20 to prevent APC activation (PubMed:11389834).
CC Can also bind directly to the APC to inhibit substrate-binding
CC (PubMed:11751633). Required to arrest unfertilized eggs at metaphase of
CC meiosis II, by preventing their release from metaphase of meiosis II,
CC through inhibition of APC-dependent cyclin B destruction leading to
CC stabilization of cyclin B-cdk1 complex activity (PubMed:11976684).
CC {ECO:0000269|PubMed:11389834, ECO:0000269|PubMed:11751633,
CC ECO:0000269|PubMed:11976684, ECO:0000269|PubMed:15314241}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Part of a SCF (SKP1-cullin-F-box) protein ligase complex (By
CC similarity). Interacts with btrc (PubMed:17159919). Interacts with skp1
CC (PubMed:11389834). Interacts with cdc20 (PubMed:11976684,
CC PubMed:11389834). Interacts with pin1; stabilizes fbxo5 by preventing
CC its association with btrc in an isomerization-dependent pathway; this
CC interaction is present during G2 phase and prevents fbxo5 degradation
CC (PubMed:17159919). Interacts with plk1 (PubMed:17159919).
CC {ECO:0000250|UniProtKB:Q9UKT4, ECO:0000269|PubMed:11389834,
CC ECO:0000269|PubMed:11976684, ECO:0000269|PubMed:17159919}.
CC -!- INTERACTION:
CC Q90Z80; Q9I9K6: pin1.L; NbExp=3; IntAct=EBI-7161111, EBI-959114;
CC Q90Z80; P70032: plk1; NbExp=2; IntAct=EBI-7161111, EBI-3511304;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11389834,
CC ECO:0000269|PubMed:17159919}. Cytoplasm {ECO:0000269|PubMed:11389834,
CC ECO:0000269|PubMed:17159919}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:11389834}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:17159919}. Note=In
CC interphase, localizes in a punctate manner in the nucleus and cytoplasm
CC with some perinuclear concentration (PubMed:11389834, PubMed:17159919).
CC In mitotic cells, localizes throughout the cell, particularly at the
CC spindle (PubMed:11389834). At metaphase, localized at mitotic
CC centrosomes. Decreases centrosome localization as cells progressed
CC through telophase (PubMed:17159919). {ECO:0000269|PubMed:11389834,
CC ECO:0000269|PubMed:17159919}.
CC -!- DEVELOPMENTAL STAGE: Accumulates before mitosis with levels increasing
CC in S phase and decreasing in M phase (PubMed:11389834). Weakly detected
CC in cycling egg at the stage just before entry into M phase, but not
CC detected in immature (stage VI), metaphase-I and metaphase-II oocytes,
CC and cycling egg that has entered in M phase. Destroyed at every M phase
CC during both meiotic cycles and during cleavage cycles
CC (PubMed:15314241). Decreases at metaphase and completely disappears as
CC cells exited mitosis. First observed at 4 h (S phase) reaching a peak
CC at 7 h (G2 phase), and then a subsequent decrease from 9 to 10 h
CC corresponding to early and late M phases, respectively
CC (PubMed:17159919). {ECO:0000269|PubMed:11389834,
CC ECO:0000269|PubMed:15314241, ECO:0000269|PubMed:17159919}.
CC -!- INDUCTION: Expression is first activated after the gastrula stage of
CC development. {ECO:0000269|PubMed:15314241}.
CC -!- DOMAIN: The C-terminal region is required for APC inhibition.
CC {ECO:0000269|PubMed:11389834}.
CC -!- PTM: Proteolysed; proteolysis is induced by both cyclin B-cdk1 and
CC cyclin A-cdk1/2 complex through probable phosphorylation. Proteolysis
CC is inhibited by pin1 during G2. {ECO:0000269|PubMed:17159919}.
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DR EMBL; AF319594; AAK62272.1; -; mRNA.
DR EMBL; BC088910; AAH88910.1; -; mRNA.
DR RefSeq; NP_001082122.1; NM_001088653.1.
DR AlphaFoldDB; Q90Z80; -.
DR ELM; Q90Z80; -.
DR IntAct; Q90Z80; 3.
DR MINT; Q90Z80; -.
DR DNASU; 398237; -.
DR GeneID; 398237; -.
DR KEGG; xla:398237; -.
DR CTD; 398237; -.
DR Xenbase; XB-GENE-953951; fbxo5.S.
DR OMA; FDFCTRC; -.
DR OrthoDB; 521317at2759; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000186698; Chromosome 5S.
DR Bgee; 398237; Expressed in egg cell and 12 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005819; C:spindle; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1990948; F:ubiquitin ligase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0106061; P:negative regulation of exit from meiosis; IMP:UniProtKB.
DR GO; GO:0045841; P:negative regulation of mitotic metaphase/anaphase transition; IDA:UniProtKB.
DR GO; GO:1904667; P:negative regulation of ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:UniProtKB.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR044064; ZF_ZBR.
DR Pfam; PF00646; F-box; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS51872; ZF_ZBR; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Cytoplasm; Cytoskeleton; Metal-binding; Mitosis;
KW Nucleus; Reference proteome; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..392
FT /note="F-box only protein 5-A"
FT /id="PRO_0000258010"
FT DOMAIN 197..244
FT /note="F-box"
FT /evidence="ECO:0000255"
FT ZN_FING 319..367
FT /note="ZBR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 323
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 326
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 341
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 346
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 351
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 354
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 359
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 364
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT MUTAGEN 10
FT /note="S->A: Not mitotically degraded; when associated with
FT A-29; A-105; A-123 and A-328. Does not affect fbxo5
FT proteolysis. Impairs pin1 interaction. Impairs pin1
FT interaction; when associated with A-29. Impairs pin1
FT interaction; when associated with A-29 and A-105. Impairs
FT pin1 interaction; when associated with A-29; A-105 and A-
FT 123. Impairs pin1 interaction; when associated with A-29;
FT A-105; A-123 and A-328. Proteolysated in the presence of
FT Pin1. Degraded at G2 phase."
FT /evidence="ECO:0000269|PubMed:11389834,
FT ECO:0000269|PubMed:17159919"
FT MUTAGEN 29
FT /note="S->A: Not mitotically degraded; when associated with
FT A-10; A-105; A-123 and A-328. Delays fbxo5 proteolysis.
FT Does not affect pin1 interaction. Impairs pin1 interaction;
FT when associated with A-10. Impairs pin1 interaction; when
FT associated with A-10 and A-105. Impairs pin1 interaction;
FT when associated with A-10; A-105 and A-123. Impairs pin1
FT interaction; when associated with A-10; A-105; A-123 and A-
FT 328."
FT /evidence="ECO:0000269|PubMed:11389834,
FT ECO:0000269|PubMed:17159919"
FT MUTAGEN 95
FT /note="S->A: Does not affect protein expression in meiosis
FT II; when associated with A-99. Does not affect protein
FT expression in entered M phase; when associated with A-99.
FT Mostly inhibits the degradation of cyclin B at the meiosis
FT I exit, maintains cdk1 activity at a high level, and
FT arrests meiosis I at metaphase; when associated with A-99."
FT /evidence="ECO:0000269|PubMed:15314241"
FT MUTAGEN 99
FT /note="S->A: Does not affect protein expression in meiosis
FT II; when associated with A-95. Does not affect protein
FT expression in entered M phase; when associated with A-95.
FT Mostly inhibits the degradation of cyclin B at the meiosis
FT I exit, maintains cdk1 activity at a high level, and
FT arrests meiosis I at metaphase; when associated with A-95."
FT /evidence="ECO:0000269|PubMed:15314241"
FT MUTAGEN 105
FT /note="S->A: Not mitotically degraded; when associated with
FT A-10; A-29; A-123 and A-328. Does not affect fbxo5
FT proteolysis. Does not affect pin1 interaction. Impairs pin1
FT interaction; when associated with A-10 and A-29. Impairs
FT pin1 interaction; when associated with A-10; A-29 and A-
FT 123. Impairs pin1 interaction; when associated with A-10;
FT A-29; A-123 and A-328."
FT /evidence="ECO:0000269|PubMed:11389834,
FT ECO:0000269|PubMed:17159919"
FT MUTAGEN 123
FT /note="T->A: Not mitotically degraded; when associated with
FT A-10; A-29; A-105 and A-328. Delays fbxo5 proteolysis. Does
FT not affect pin1 interaction. Impairs pin1 interaction; when
FT associated with A-10; A-29 and A-105. Impairs pin1
FT interaction; when associated with A-10; A-29; A-105 and A-
FT 328."
FT /evidence="ECO:0000269|PubMed:11389834,
FT ECO:0000269|PubMed:17159919"
FT MUTAGEN 198..199
FT /note="EL->AA: Abolishes binding to skp1."
FT /evidence="ECO:0000269|PubMed:11389834"
FT MUTAGEN 328
FT /note="S->A: Not mitotically degraded; when associated with
FT A-10; A-29; A-105 and A-123. Does not affect fbxo5
FT proteolysis. Does not affect pin1 interaction. Impairs pin1
FT interaction; when associated with A-10; A-29; A-105 and A-
FT 123."
FT /evidence="ECO:0000269|PubMed:11389834,
FT ECO:0000269|PubMed:17159919"
FT MUTAGEN 341
FT /note="C->S: Does not inhibit APC."
FT /evidence="ECO:0000269|PubMed:11389834"
FT MUTAGEN 346
FT /note="C->S: Does not inhibit APC."
FT /evidence="ECO:0000269|PubMed:11389834"
FT MUTAGEN 351
FT /note="C->S: Does not inhibit APC."
FT /evidence="ECO:0000269|PubMed:11389834"
FT MUTAGEN 354
FT /note="C->S: Does not inhibit APC; when associated with S-
FT 356."
FT /evidence="ECO:0000269|PubMed:11389834"
FT MUTAGEN 356
FT /note="C->S: Does not inhibit APC; when associated with S-
FT 354."
FT /evidence="ECO:0000269|PubMed:11389834"
FT MUTAGEN 364
FT /note="C->S: Does not inhibit APC."
FT /evidence="ECO:0000269|PubMed:11389834"
SQ SEQUENCE 392 AA; 44142 MW; 06E6627033263612 CRC64;
MMCGFASNQS PKKLSSKKSS ATNVHLEISP VKHHPPCKVY ENVQGSCLDS AICTTVAKCA
DLTDDLPVHN KENLLHRLND LETNSYEEYS ALQDSGYSSI LQNDSPCQDE TDRKVSDIQV
RETPKNFMSY QRPFHTLSKI NLPILRFEEA VCSTLKKMRK TNKKIDWNAV DVVCGGNYGL
EHLIGKSMGL ERFDILAELF HRDFKHLLTK ILRHLSAMDL INVISVSTTW RKLLQKDNWA
YNAYKLGCKE LCEKRAKVSS HTATRDESLC RVPLASVQKV AASSLCTSKK QSKNKNGGLS
CNRLAEFIEV AQTLKNDQSL KVCVDCGSPA KHDPCLHRAI CTRESCKLDF CTRCSCKYHF
SKSCLMSKPG SYRIPSEPLP GSKKSKQNLR RL
