AFG2H_CAEEL
ID AFG2H_CAEEL Reviewed; 724 AA.
AC Q21222;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=ATPase family protein 2 homolog {ECO:0000305};
DE EC=3.6.4.10 {ECO:0000269|PubMed:18854144};
DE AltName: Full=Cell division cycle-related protein 48.3 {ECO:0000312|WormBase:K04G2.3};
GN Name=cdc-48.3 {ECO:0000312|WormBase:K04G2.3};
GN ORFNames=K04G2.3 {ECO:0000312|WormBase:K04G2.3};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15716356; DOI=10.1091/mbc.e04-08-0726;
RA Poteryaev D., Squirrell J.M., Campbell J.M., White J.G., Spang A.;
RT "Involvement of the actin cytoskeleton and homotypic membrane fusion in ER
RT dynamics in Caenorhabditis elegans.";
RL Mol. Biol. Cell 16:2139-2153(2005).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH AIR-2, SUBCELLULAR LOCATION,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF LYS-285; ARG-365 AND ARG-367.
RX PubMed=18854144; DOI=10.1016/j.devcel.2008.08.005;
RA Heallen T.R., Adams H.P., Furuta T., Verbrugghe K.J., Schumacher J.M.;
RT "An Afg2/Spaf-related Cdc48-like AAA ATPase regulates the stability and
RT activity of the C. elegans Aurora B kinase AIR-2.";
RL Dev. Cell 15:603-616(2008).
CC -!- FUNCTION: ATP-dependent chaperone which uses the energy provided by ATP
CC hydrolysis to generate mechanical force to disassemble protein
CC complexes (By similarity). Required for various steps of embryonic
CC mitosis including centrosome duplication, spindle assembly, ER dynamics
CC and cell cycle progression (PubMed:15716356, PubMed:18854144).
CC Regulates the stability and activity of kinase air-2, a component of
CC the chromosomal passenger complex (CPC) (PubMed:18854144). Inhibits
CC air-2 kinase activity from metaphase to late telophase and negatively
CC regulates air-2 stability during mitotic exit (PubMed:18854144).
CC Controls ER transition into sheet-like structures at the onset of
CC mitosis, possibly by regulating homotypic membrane fusion
CC (PubMed:15716356). {ECO:0000250|UniProtKB:P32794,
CC ECO:0000269|PubMed:15716356, ECO:0000269|PubMed:18854144}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.10;
CC Evidence={ECO:0000269|PubMed:18854144};
CC -!- SUBUNIT: Homohexamer; ATP binding induces oligomerization (By
CC similarity). Forms a ring-shaped particle of about 12 nm diameter, that
CC displays 6-fold radial symmetry (By similarity). Interacts (via N-
CC terminus) with kinase air-2; the interaction is direct and inhibits
CC air-2 kinase activity in an ATPase-dependent manner.
CC {ECO:0000250|UniProtKB:P32794, ECO:0000269|PubMed:18854144}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18854144}.
CC -!- DOMAIN: The first ATP-binding region binds ATP with low affinity
CC whereas the second ATP-binding region binds ATP with high affinity.
CC {ECO:0000250|UniProtKB:P32794}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes embryonic
CC lethality (PubMed:15716356, PubMed:18854144). The first embryonic cell
CC divisions have mitotic spindle and chromosome segregation defects, and
CC mitotic progression is significantly delayed (PubMed:18854144). At late
CC telophase/G1, air-2 accumulates at the spindle midbody abnormally
CC persisting following cleavage furrow ingression and into the next
CC mitotic cycle (PubMed:18854144). Loss of inhibition of air-2 kinase
CC activity (PubMed:18854144). Also, causes defects in ER dynamics
CC characterized by a failure of the ER to form a sheet structure at the
CC onset of mitosis and remains in large aggregates throughout mitosis
CC (PubMed:15716356). In an air-2 (os207) mutant background, which lacks
CC air-2 catalytic activity, restores normal mitosis and thus embryonic
CC viability (PubMed:18854144). {ECO:0000269|PubMed:15716356,
CC ECO:0000269|PubMed:18854144}.
CC -!- SIMILARITY: Belongs to the AAA ATPase family. AFG2 subfamily.
CC {ECO:0000305}.
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DR EMBL; BX284601; CAB00040.1; -; Genomic_DNA.
DR PIR; T23322; T23322.
DR RefSeq; NP_492211.1; NM_059810.4.
DR AlphaFoldDB; Q21222; -.
DR SMR; Q21222; -.
DR STRING; 6239.K04G2.3; -.
DR EPD; Q21222; -.
DR PaxDb; Q21222; -.
DR PeptideAtlas; Q21222; -.
DR EnsemblMetazoa; K04G2.3.1; K04G2.3.1; WBGene00010562.
DR GeneID; 172586; -.
DR KEGG; cel:CELE_K04G2.3; -.
DR UCSC; K04G2.3; c. elegans.
DR CTD; 172586; -.
DR WormBase; K04G2.3; CE06097; WBGene00010562; cdc-48.3.
DR eggNOG; KOG0730; Eukaryota.
DR GeneTree; ENSGT00940000157323; -.
DR HOGENOM; CLU_000688_18_0_1; -.
DR InParanoid; Q21222; -.
DR OMA; KRIRPTG; -.
DR OrthoDB; 194195at2759; -.
DR PhylomeDB; Q21222; -.
DR PRO; PR:Q21222; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00010562; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:WormBase.
DR GO; GO:0019901; F:protein kinase binding; IPI:WormBase.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IDA:WormBase.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IDA:WormBase.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR041569; AAA_lid_3.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR003960; ATPase_AAA_CS.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00004; AAA; 1.
DR Pfam; PF17862; AAA_lid_3; 1.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR PROSITE; PS00674; AAA; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell cycle; Cell division; Chaperone; Cytoplasm; Hydrolase;
KW Mitosis; Nucleotide-binding; Reference proteome.
FT CHAIN 1..724
FT /note="ATPase family protein 2 homolog"
FT /id="PRO_0000445231"
FT BINDING 281..287
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P32794"
FT BINDING 503..508
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P32794"
FT MUTAGEN 285
FT /note="K->T: Severe loss of catalytic activity. Prevents
FT inhibition of air-2 kinase activity without affecting the
FT interaction with air-2."
FT /evidence="ECO:0000269|PubMed:18854144"
FT MUTAGEN 365
FT /note="R->A: Does not prevent inhibition of air-2 kinase
FT activity or interaction with air-2."
FT /evidence="ECO:0000269|PubMed:18854144"
FT MUTAGEN 367
FT /note="R->A: No effect on catalytic activity. Prevents
FT inhibition of air-2 kinase activity or interaction with
FT air-2."
FT /evidence="ECO:0000269|PubMed:18854144"
SQ SEQUENCE 724 AA; 79549 MW; DE99E76385A261AF CRC64;
MSSAKKKPSL VTCPQCNAVV LTKDSLRHQD FCGKPVVESE IACAQNGTLR GFNVAVDKAE
GFLPPDAVGW EKEHSILINQ QTMESLGLLA RQPVRIIHSS DSFIGIVWPC KEVALLKVSI
ISSRIARERM ITLESCGRVE KLKSLSVTVK TSLTLNPALS GFLEAYLSHS YLQYNSSVDL
KYLGQNVTVT PEEPIESKMS AMGIDDDKKR NSKVVSTAVG YKIQILNASA EGSTSDVLQT
LPTDLSNIGG CFTAKQVLED YVISPVRQKE SPCSVLIWGL PGSGKTLLLK EVALVLSGST
TYIGSCEELM ELNGVTTGNI VIVDVNELEK ENTKANRALS FLLGDEKKCV ILCVRSSETL
DIGFRVRFPI EAEITVPTQD ERLDILSKIG NIYNFPLELH LDVARHTHGF TGGDLCSLLK
AAKFARGRTH LERVNDARKR IRPTGIRQFI LEVPNVSWND IGGNEELKLE IQQAVIWPQK
HPEAFERFGI DPPAGILLYG PPGCSKTLIA RALASEAKMN FLAVKGPELF SKWVGDSEKA
IRDLFSRARQ VAPTIVFFDE IDAVGSSRGS EKSSGVSDRV LAQLLTELDG LEKSSRVILL
AATNRPDQLD SALLRPGRLD RAIYVGLPCE VTRRAILEMR TKKMKFDDTV RTIDKLVEKT
SGYSGAELVA VCRTAAMFAM RESIDATIVQ WTHFEQALAA VVSRTEAYLL EIYDDFKAGR
ASNA
