PAC1_CAEEL
ID PAC1_CAEEL Reviewed; 1605 AA.
AC P34288; B3VIA5; B5MBW1; P34414; P34588; P34589; Q8ST20; Q9TY64;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 4.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=GTPase-activating protein pac-1;
DE AltName: Full=GTPase-activating protein GAP;
DE Short=CeGAP;
DE AltName: Full=Protein par-6-at-contacts;
GN Name=pac-1; Synonyms=gap; ORFNames=C04D8.1;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), FUNCTION, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF ARG-985.
RX PubMed=18583611; DOI=10.1126/science.1156063;
RA Anderson D.C., Gill J.S., Cinalli R.M., Nance J.;
RT "Polarization of the C. elegans embryo by RhoGAP-mediated exclusion of PAR-
RT 6 from cell contacts.";
RL Science 320:1771-1774(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=7906398; DOI=10.1038/368032a0;
RA Wilson R., Ainscough R., Anderson K., Baynes C., Berks M., Bonfield J.,
RA Burton J., Connell M., Copsey T., Cooper J., Coulson A., Craxton M.,
RA Dear S., Du Z., Durbin R., Favello A., Fraser A., Fulton L., Gardner A.,
RA Green P., Hawkins T., Hillier L., Jier M., Johnston L., Jones M.,
RA Kershaw J., Kirsten J., Laisster N., Latreille P., Lightning J., Lloyd C.,
RA Mortimore B., O'Callaghan M., Parsons J., Percy C., Rifken L., Roopra A.,
RA Saunders D., Shownkeen R., Sims M., Smaldon N., Smith A., Smith M.,
RA Sonnhammer E., Staden R., Sulston J., Thierry-Mieg J., Thomas K.,
RA Vaudin M., Vaughan K., Waterston R., Watson A., Weinstock L.,
RA Wilkinson-Sproat J., Wohldman P.;
RT "2.2 Mb of contiguous nucleotide sequence from chromosome III of C.
RT elegans.";
RL Nature 368:32-38(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 167-1605 (ISOFORM A), AND FUNCTION.
RC STRAIN=Bristol N2;
RX PubMed=8288633; DOI=10.1016/s0021-9258(17)42184-3;
RA Chen W., Blanc J., Lim L.;
RT "Characterization of a promiscuous GTPase-activating protein that has a
RT bcr-related domain from Caenorhabditis elegans.";
RL J. Biol. Chem. 269:820-823(1994).
RN [5]
RP FUNCTION, ASSOCIATION WITH THE CATENIN-CADHERIN COMPLEX, INTERACTION WITH
RP PICC-1, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=25938815; DOI=10.1038/ncb3168;
RA Klompstra D., Anderson D.C., Yeh J.Y., Zilberman Y., Nance J.;
RT "An instructive role for C. elegans E-cadherin in translating cell contact
RT cues into cortical polarity.";
RL Nat. Cell Biol. 17:726-735(2015).
CC -!- FUNCTION: GTPase-activating protein for members of the Rho subfamily
CC including Rac1, RhoA and cdc42 and other Ras-related subfamilies
CC including let-60 (PubMed:18583611, PubMed:8288633). Mediates radial
CC (inner-outer) polarity and gastrulation by excluding par-6 from
CC contacted cell surfaces; acts by inactivating cdc42 at inner cell
CC surfaces which limits active cdc42 to outer cell surfaces devoid of
CC cell-cell contacts, where cdc42 can bind and recruit par-6
CC (PubMed:18583611, PubMed:8288633, PubMed:25938815). Required for
CC blastomere polarization (PubMed:25938815).
CC {ECO:0000269|PubMed:18583611, ECO:0000269|PubMed:25938815,
CC ECO:0000269|PubMed:8288633}.
CC -!- SUBUNIT: Associated with the catenin-cadherin complex consisting of
CC hmr-1, hmp-1 and hmp-2; this is mediated by interaction with picc-1.
CC {ECO:0000269|PubMed:25938815}.
CC -!- INTERACTION:
CC P34288; H2KYP0: picc-1; NbExp=4; IntAct=EBI-2918318, EBI-315998;
CC P34288-2; Q9XVU8: atn-1; NbExp=3; IntAct=EBI-11465290, EBI-2924098;
CC P34288-2; P90900: ifa-4; NbExp=3; IntAct=EBI-11465290, EBI-322249;
CC P34288-2; Q9NAN2: par-6; NbExp=3; IntAct=EBI-11465290, EBI-318782;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell junction
CC {ECO:0000269|PubMed:18583611, ECO:0000269|PubMed:25938815}. Cell
CC junction, adherens junction {ECO:0000269|PubMed:25938815}. Note=Locates
CC to inner but not outer surfaces of early embryonic somatic (EES) cells
CC (PubMed:18583611). Specifically localizes to cell contacts in hmr-1-
CC dependent and -independent manner in embryos (PubMed:25938815).
CC {ECO:0000269|PubMed:18583611, ECO:0000269|PubMed:25938815}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:C04D8.1a}; Synonyms=Long
CC {ECO:0000303|PubMed:25938815};
CC IsoId=P34288-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:C04D8.1b}; Synonyms=Short
CC {ECO:0000303|PubMed:25938815};
CC IsoId=P34288-2; Sequence=VSP_036484;
CC -!- DEVELOPMENTAL STAGE: Expressed in four-cell stage embryos.
CC {ECO:0000269|PubMed:25938815}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown of isoform a results in
CC mis-localization of par-6 in embryos. {ECO:0000269|PubMed:25938815}.
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DR EMBL; EU752496; ACE78177.1; -; mRNA.
DR EMBL; FO080326; CCD62880.1; -; Genomic_DNA.
DR EMBL; FO080326; CCD62881.1; -; Genomic_DNA.
DR EMBL; U02289; AAA18934.1; -; mRNA.
DR PIR; S44647; S44647.
DR PIR; S44746; S44746.
DR PIR; S44876; S44876.
DR PIR; S44877; S44877.
DR RefSeq; NP_001129833.1; NM_001136361.2. [P34288-2]
DR RefSeq; NP_498877.4; NM_066476.6. [P34288-1]
DR AlphaFoldDB; P34288; -.
DR SMR; P34288; -.
DR BioGRID; 41405; 18.
DR DIP; DIP-61635N; -.
DR IntAct; P34288; 18.
DR STRING; 6239.C04D8.1c; -.
DR EPD; P34288; -.
DR PaxDb; P34288; -.
DR EnsemblMetazoa; C04D8.1a.1; C04D8.1a.1; WBGene00015418. [P34288-1]
DR EnsemblMetazoa; C04D8.1b.1; C04D8.1b.1; WBGene00015418. [P34288-2]
DR GeneID; 176201; -.
DR KEGG; cel:CELE_C04D8.1; -.
DR CTD; 176201; -.
DR WormBase; C04D8.1a; CE43148; WBGene00015418; pac-1. [P34288-1]
DR WormBase; C04D8.1b; CE42977; WBGene00015418; pac-1. [P34288-2]
DR eggNOG; KOG4407; Eukaryota.
DR InParanoid; P34288; -.
DR OrthoDB; 162100at2759; -.
DR Reactome; R-CEL-6798695; Neutrophil degranulation.
DR Reactome; R-CEL-8980692; RHOA GTPase cycle.
DR Reactome; R-CEL-9013148; CDC42 GTPase cycle.
DR Reactome; R-CEL-9013149; RAC1 GTPase cycle.
DR Reactome; R-CEL-9013405; RHOD GTPase cycle.
DR Reactome; R-CEL-9013424; RHOV GTPase cycle.
DR Reactome; R-CEL-9035034; RHOF GTPase cycle.
DR PRO; PR:P34288; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00015418; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR ExpressionAtlas; P34288; baseline and differential.
DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
DR GO; GO:0030054; C:cell junction; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
DR GO; GO:0008104; P:protein localization; IMP:WormBase.
DR GO; GO:0007265; P:Ras protein signal transduction; IDA:UniProtKB.
DR GO; GO:0010470; P:regulation of gastrulation; IMP:WormBase.
DR GO; GO:0043087; P:regulation of GTPase activity; IBA:GO_Central.
DR GO; GO:0007266; P:Rho protein signal transduction; IDA:UniProtKB.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR000198; RhoGAP_dom.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00324; RhoGAP; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50238; RHOGAP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Cytoplasm; GTPase activation;
KW Reference proteome.
FT CHAIN 1..1605
FT /note="GTPase-activating protein pac-1"
FT /id="PRO_0000056659"
FT DOMAIN 599..726
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 948..1146
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT REGION 1..574
FT /note="Required for localization to adherens junctions"
FT /evidence="ECO:0000269|PubMed:25938815"
FT REGION 293..430
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 529..556
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 574..593
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 728..752
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 846..942
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1152..1176
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1207..1258
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1277..1339
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1438..1533
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1554..1605
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 296..318
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 349..366
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 384..430
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 846..908
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 920..940
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1240..1258
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1277..1321
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1323..1339
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1438..1519
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1554..1576
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 300
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000303|PubMed:18583611"
FT /id="VSP_036484"
FT MUTAGEN 985
FT /note="R->A: Probably disrupts GTPase-activating activity.
FT Unable to rescue par-6 localization in pac-1 mutant
FT embryos."
FT /evidence="ECO:0000269|PubMed:18583611"
FT CONFLICT 564
FT /note="L -> I (in Ref. 4; AAA18934)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1605 AA; 173395 MW; C2B0BAA89DC00458 CRC64;
MEEHHRRLHV KAERASVIGG DIVDGAFGSW ALRAARSEHQ LKQQSNEDLA QNARISALLG
EMRPRMSAMP PNGHQQQYQP QLRRKANTTN IVDVSSQVPS ARNAIYGSWQ DRHRPTRLYG
SQLVSSSSTL PKYDQLYCNT ASPLTGNGST NTIATTGIRR EPPEYGNVGR SVSTWQVTNS
EHRPSLQAGW LKSSRPLARG ALSPAAYFRD LENRHGSGAS SPIVGGLSVV AVPITQRHAP
TAGLAPISDD ISTSKVSLDT ENQQLNNEDS DKISGSALSR NTPRQASFMA AMQRHPLKES
STSIESNGGG TNTEEDQTVS ATSKEDPSED TGHDDPEETQ EISETPIRRS RNRNASLRNR
QSSRSLGGLD FEKLRMGTAR VGDSNEATAE NGTSSSSSRK NSRDDGLTSS PTTVAGPVFT
TSSTSSISTS GEASSTAVAA AAAGSVAATT SRQTSSNSSV DSNHNEAMKM IRRARPKSYV
LATSASMNED VLSSSIIANE QSSSISHDTT TSGRELPSSL MGSTISMEMR SGGASSATTT
TTSNSGQQTS RSLNAPHPPA THRLQRFIAL FNSSKTSDGS GEHKKSRMKR SRTSLPASRF
ALPGTILQRD GVARQTWVKH QEIALGKSGK RNNWEDRWAV LCRRSLYLCV ESPAYTTEKT
IELGSHTRVD VCNAIVDIAY DWLSSSFSKQ RHVVRIVTQN RSEHLIELNT ESEMLSWISV
LQSSSEDGIA TGSSVDENEL STTGRHNNNA VSNSSALLHN SQSIASLASS SCSTATTSEF
LNSQHTLQQQ QQQQTNQKHQ QTVNELSAGI VSHLPTSKSF GGLSTTASST TENAKNRLIM
HRYIAKNSQL QSPTANKKME TDPSTVPSSS QTMATTSSSF HHHSSQAGPS RDIENGEAPT
ATATTPKSGR KWKKSKAAKQ GSGGGSSGSS SGSQQQGAAG APQPVLGVRI ADCPTGSCED
HVPMIVQACV CVIETYGMDT VGIYRIPGNT AAVNALKESL SNRGFDSVDL SKVESLDPRW
RDVNVVSSLL KMFLRKLPEP LLTDKLYPFF IDANRISTHH NRLHKLRNLL RKLPRPHYDT
LRFLIVHLSE ITKHSDVNKM ECRNLALMFG PSIVRPSDDN MATMVTHMSD QCKIIETLIH
YNLWMFDESS TTEDAVPEQH PADGQNPLEP GGYGVGVPTG VSAASFNDMH NLIRKANEDQ
AAAMMNEGKG QKIKNMLRRN SRRDKSKSKL KIESTAPAAV NPRGWTQPTP SNTSAASVES
AFCGNYQERD IDAEIESRQT VSPQMTSGSA DGASSTRLDQ SPSLESSLGS LPDTSRTEPI
LGSSGYDDDE AKEAARRKRQ EEMYSARRIF IAGAAGAAAA ATTTADAEKA AIDALANHSQ
HLHLASSPAF EVLSEETREK IRRMQKKQSW HDTKELRSGE LLKTYSPTKD LTDALSCTSD
YSTTSSAPLS TNPPLAVACA DQPNSSSDYA SSDPSPCARN PSTSPASRPS NLAISPAQLH
ATSSSGQSHQ PMSRSQKIRL RTKLGSRDPA RRHTLSDVDT LKEGRLDKLA RWFGIRKSSP
DVSRDEVSDD EKNHQEAPPL PAAAPPVIVR TSPNELTPVS GDELL
