CNT1_CAEEL
ID CNT1_CAEEL Reviewed; 826 AA.
AC Q9XXH8; Q9XXH9; Q9XZQ1; Q9XZQ2;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Arf-GAP with ANK repeat and PH domain-containing protein cnt-1 {ECO:0000305};
DE AltName: Full=CED-3 protease suppressor {ECO:0000303|PubMed:25383666};
DE AltName: Full=Centaurin 1 {ECO:0000312|WormBase:Y17G7B.15a};
DE Contains:
DE RecName: Full=Truncated ctn-1 {ECO:0000303|PubMed:25383666};
DE Short=tCNT-1 {ECO:0000303|PubMed:25383666};
DE Flags: Precursor;
GN Name=cnt-1 {ECO:0000312|WormBase:Y17G7B.15a};
GN Synonyms=cps-2 {ECO:0000303|PubMed:25383666};
GN ORFNames=Y17G7B.15 {ECO:0000312|WormBase:Y17G7B.15a};
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|EMBL:CAA10735.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:CAA10735.1};
RA Harrington L.S., Baylis H.A., Jackson T.R.;
RT "Investigating the functions of the centaurin proteins in phosphoinositide
RT signalling in C. elegans.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [2] {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 [3] {ECO:0000305}
RP FUNCTION, INTERACTION WITH RAB-10; RAB-8 AND RAB-35, AND SUBCELLULAR
RP LOCATION.
RX PubMed=22869721; DOI=10.1073/pnas.1205278109;
RA Shi A., Liu O., Koenig S., Banerjee R., Chen C.C., Eimer S., Grant B.D.;
RT "RAB-10-GTPase-mediated regulation of endosomal phosphatidylinositol-4,5-
RT bisphosphate.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:E2306-E2315(2012).
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DOMAIN, PROTEOLYTIC
RP CLEAVAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF LYS-284; ASP-382;
RP ASP-508 AND ASP-609.
RX PubMed=25383666; DOI=10.1038/nsmb.2915;
RA Nakagawa A., Sullivan K.D., Xue D.;
RT "Caspase-activated phosphoinositide binding by CNT-1 promotes apoptosis by
RT inhibiting the AKT pathway.";
RL Nat. Struct. Mol. Biol. 21:1082-1090(2014).
CC -!- FUNCTION: GTPase-activating protein for the ADP ribosylation factor
CC family (Probable). Regulates endosome recycling downstream of rab-10
CC and upstream of arf-6 (PubMed:22869721). {ECO:0000269|PubMed:22869721,
CC ECO:0000305|PubMed:22869721}.
CC -!- FUNCTION: Truncated cnt-1: Promotes apoptosis during embryonic
CC development. Produced by caspase ced-3-mediated cleavage, and
CC translocates to the plasma membrane where it prevents the activation of
CC the prosurvival Akt-1/2 and sgk-1 signaling pathway by competing with
CC Akt-1/2 for the binding to PtdIns(3,4,5)P3.
CC {ECO:0000269|PubMed:25383666}.
CC -!- SUBUNIT: Interacts (via C-terminal ankyrin repeat) with rab-10 (GTP-
CC bound form); the interaction is required for cnt-1 recruitment to
CC endosomes. Interacts (via C-terminal ankyrin repeat) with rab-8 (GTP-
CC bound form) and rab-35 (GTP-bound form). {ECO:0000269|PubMed:22869721}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25383666}.
CC Recycling endosome membrane {ECO:0000269|PubMed:22869721}; Peripheral
CC membrane protein {ECO:0000269|PubMed:22869721}. Basolateral cell
CC membrane {ECO:0000269|PubMed:22869721}; Peripheral membrane protein
CC {ECO:0000269|PubMed:22869721}. Apical cell membrane
CC {ECO:0000269|PubMed:22869721}; Peripheral membrane protein
CC {ECO:0000269|PubMed:22869721}. Note=Colocalizes with rab-10, rab-8,
CC rab-35 and clathrin chc-1 on recycling endosomes in the intestinal
CC epithelium. Partially colocalizes with early endosome marker rab-5 and
CC to a lesser extent with late endosome marker rme-1. Colocalizes with
CC arf-6 on endosomes of the basolateral recycling pathway.
CC {ECO:0000269|PubMed:22869721}.
CC -!- SUBCELLULAR LOCATION: [Truncated ctn-1]: Cell membrane
CC {ECO:0000269|PubMed:25383666}; Peripheral membrane protein
CC {ECO:0000269|PubMed:25383666}. Note=Binds PtdIns(3,4,5)P3 at the plasma
CC membrane. {ECO:0000269|PubMed:25383666}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:Y17G7B.15a};
CC IsoId=Q9XXH8-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:Y17G7B.15b};
CC IsoId=Q9XXH8-2; Sequence=VSP_058803;
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos.
CC {ECO:0000269|PubMed:25383666}.
CC -!- DOMAIN: The PH domain binds phosphatidylinositol phosphate (PIP),
CC phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol
CC 3,4,5-trisphosphate (PIP3), and to a lesser extent phosphatidic acid
CC and cardiolipin. {ECO:0000269|PubMed:25383666}.
CC -!- PTM: Cleaved by caspase ced-3 after Asp-382 and Asp-609. Cleavage at
CC Asp-382 is required for subsequent cleavage at Asp-609.
CC {ECO:0000269|PubMed:25383666}.
CC -!- DISRUPTION PHENOTYPE: Causes a delay in cell death during embryogenesis
CC characterized by a decrease in the number of cell corpses at the comma
CC and 1,5 fold stage and an increase in the number of cell corpses
CC between the 2-fold and the 3-fold stages.
CC {ECO:0000269|PubMed:25383666}.
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DR EMBL; AJ132698; CAA10734.1; -; mRNA.
DR EMBL; AJ132699; CAA10735.1; -; mRNA.
DR EMBL; BX284602; CAA19462.2; -; Genomic_DNA.
DR EMBL; BX284602; CAA19463.2; -; Genomic_DNA.
DR PIR; T26508; T26508.
DR PIR; T26509; T26509.
DR RefSeq; NP_001022412.1; NM_001027241.1.
DR RefSeq; NP_001022413.1; NM_001027242.2. [Q9XXH8-2]
DR AlphaFoldDB; Q9XXH8; -.
DR SMR; Q9XXH8; -.
DR DIP; DIP-26983N; -.
DR DIP; DIP-61532N; -.
DR IntAct; Q9XXH8; 4.
DR STRING; 6239.Y17G7B.15a; -.
DR EPD; Q9XXH8; -.
DR PaxDb; Q9XXH8; -.
DR PeptideAtlas; Q9XXH8; -.
DR EnsemblMetazoa; Y17G7B.15a.1; Y17G7B.15a.1; WBGene00000565. [Q9XXH8-1]
DR EnsemblMetazoa; Y17G7B.15b.1; Y17G7B.15b.1; WBGene00000565. [Q9XXH8-2]
DR GeneID; 174848; -.
DR UCSC; Y17G7B.15a; c. elegans.
DR CTD; 174848; -.
DR WormBase; Y17G7B.15a; CE28110; WBGene00000565; cnt-1. [Q9XXH8-1]
DR WormBase; Y17G7B.15b; CE25223; WBGene00000565; cnt-1. [Q9XXH8-2]
DR eggNOG; KOG0521; Eukaryota.
DR HOGENOM; CLU_012513_0_0_1; -.
DR InParanoid; Q9XXH8; -.
DR OMA; GSVMSCE; -.
DR OrthoDB; 751525at2759; -.
DR PhylomeDB; Q9XXH8; -.
DR PRO; PR:Q9XXH8; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00000565; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR ExpressionAtlas; Q9XXH8; baseline and differential.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0098592; C:cytoplasmic side of apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:WormBase.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:WormBase.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:WormBase.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:WormBase.
DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IMP:WormBase.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:1902647; P:negative regulation of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate biosynthetic process; IMP:UniProtKB.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IGI:WormBase.
DR GO; GO:1905751; P:positive regulation of endosome to plasma membrane protein transport; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR Gene3D; 1.10.220.150; -; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR Gene3D; 1.25.40.20; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR045258; ACAP1/2/3-like.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR037278; ARFGAP/RecO.
DR InterPro; IPR001164; ArfGAP_dom.
DR InterPro; IPR038508; ArfGAP_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR PANTHER; PTHR23180; PTHR23180; 1.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF01412; ArfGap; 1.
DR Pfam; PF00169; PH; 1.
DR PRINTS; PR00405; REVINTRACTNG.
DR SMART; SM00248; ANK; 3.
DR SMART; SM00105; ArfGap; 1.
DR SMART; SM00233; PH; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF57863; SSF57863; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 2.
DR PROSITE; PS50115; ARFGAP; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Apoptosis; Cell membrane; Cytoplasm;
KW Endocytosis; Endosome; Lipid-binding; Membrane; Metal-binding;
KW Protein transport; Reference proteome; Repeat; Transport; Zinc;
KW Zinc-finger.
FT CHAIN 1..826
FT /note="Arf-GAP with ANK repeat and PH domain-containing
FT protein cnt-1"
FT /evidence="ECO:0000305"
FT /id="PRO_0000439216"
FT CHAIN 1..382
FT /note="Truncated ctn-1"
FT /evidence="ECO:0000303|PubMed:25383666"
FT /id="PRO_0000439217"
FT DOMAIN 275..373
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 447..572
FT /note="Arf-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00288"
FT REPEAT 690..719
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 723..752
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 756..789
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT ZN_FING 462..485
FT /note="C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00288"
FT REGION 570..604
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 570..586
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 587..604
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 382..383
FT /note="Cleavage; by ced-3"
FT /evidence="ECO:0000269|PubMed:25383666"
FT SITE 609..610
FT /note="Cleavage; by ced-3"
FT /evidence="ECO:0000269|PubMed:25383666"
FT VAR_SEQ 1..262
FT /note="MTVSNNGMAMPSVPPKIDCSEAIQDSPKFRATVAQHAMYFNRLENRLNEMLR
FT HITAMIDFSKNYTNTFYKLTVSVNQLCDESFSGNPLASTTFQGLSEAYAHTVNLFRTYF
FT DHSNVVTFTKLSNFIKIELTKVAESRAHFENMSQSMDDALVKNASISRQKPADATEGRN
FT ALTAVGTCFAHTTLDYVANINIAHAHKDHMILDALWTLVRESSAFFSKGHATFDEWTAA
FT DNGAIADTIQTFAAKSKLIERKMQDVHSLVPKE -> MSTKSIATSSTASSSSSHHQEH
FT TVTELIMFFTSEEPPEPEPFSRSTEKSGIRTSKVITRTITISAETKLKMDLLEEQRREK
FT RVKLEIEKSRIRAENLQRMQEISSEPKTRGSKRSLMRRAAKRTKGRISSLLIRDSSVDS
FT GSITDKALKDKKRGLSLEWEVKDQGRFAESFSDSRLME (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_058803"
FT MUTAGEN 284
FT /note="K->A: Loss of phosphoinositide binding. Causes a
FT delay in apoptosis during embryonic development."
FT /evidence="ECO:0000269|PubMed:25383666"
FT MUTAGEN 382
FT /note="D->E: Loss of ced-3-mediated cleavage. Causes a
FT delay in apoptosis during embryonic development."
FT /evidence="ECO:0000269|PubMed:25383666"
FT MUTAGEN 508
FT /note="D->E: No effect on ced-3-mediated cleavage."
FT /evidence="ECO:0000269|PubMed:25383666"
FT MUTAGEN 609
FT /note="D->E: Partial loss of ced-3-mediated cleavage.
FT Cleavage at position D-382 is not affected."
FT /evidence="ECO:0000269|PubMed:25383666"
FT CONFLICT 228
FT /note="A -> G (in Ref. 1; CAA10734)"
FT /evidence="ECO:0000305"
FT CONFLICT 630
FT /note="P -> S (in Ref. 1; CAA10735)"
FT /evidence="ECO:0000305"
FT CONFLICT 695
FT /note="L -> F (in Ref. 1; CAA10735)"
FT /evidence="ECO:0000305"
FT CONFLICT 790
FT /note="N -> D (in Ref. 1; CAA10735)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 826 AA; 90583 MW; EF747E7B46A1F217 CRC64;
MTVSNNGMAM PSVPPKIDCS EAIQDSPKFR ATVAQHAMYF NRLENRLNEM LRHITAMIDF
SKNYTNTFYK LTVSVNQLCD ESFSGNPLAS TTFQGLSEAY AHTVNLFRTY FDHSNVVTFT
KLSNFIKIEL TKVAESRAHF ENMSQSMDDA LVKNASISRQ KPADATEGRN ALTAVGTCFA
HTTLDYVANI NIAHAHKDHM ILDALWTLVR ESSAFFSKGH ATFDEWTAAD NGAIADTIQT
FAAKSKLIER KMQDVHSLVP KEMFQHPSGM PIEPDVMMEG YLYKRSSNAF KTWNRRWFQI
KDKQLLYSHR STDLEPATIM EENLRICLVR PAPSNIDRIG CFELVTPTRI HLLQADSESL
CQDWMRALQR TILALHEGDS VDVASTSPRN KTTSMSSGVT LTSANAISPL SNAMDVTKGR
SVSDPASTYT SANTSSISTA AGFSSSTTAF EQVRRVPGNE VCADCGSPAP KWVSINLGVV
LCIECSGAHR SLGVQTSKVR SLCMDSIDNE LRDVLLALGN RQVNEIFLAH LPPADSIVPP
QINEKSARPA REAWIKAKYV ERRFAVAEDT RARSSATNRQ EHLKHKTSIG GNSSSNGVNR
SSSYADVQDA ESGGLLDADP WSADLSVPVP TASKRLSACG SDTNLDAIGS SSIDTKTVEW
DSVKEACECG DLLALMTAYA QGFDLNALHN GTTALHIATR NGQTAAVEFL LLNGAKINML
DEKLNTPLHL AAKEGHTLPV CQLLKRGADS NLANVDSKTP LDIAMECTHA DIVTLFRVTI
MRNDFNADFN NPMDETVEAV ISDIARRAAT EKEQKKTESL KSTSDI
