TBC8_CAEEL
ID TBC8_CAEEL Reviewed; 913 AA.
AC I2HAA0; I2HA99;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2012, sequence version 1.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=Rab GTPase-activating protein tbc-8 {ECO:0000305};
DE AltName: Full=TBC domain family member 8 {ECO:0000312|WormBase:C38H2.1a};
GN Name=tbc-8 {ECO:0000312|WormBase:C38H2.1a};
GN ORFNames=C38H2.1 {ECO:0000312|WormBase:C38H2.1a};
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, INTERACTION WITH RAB-19 AND RIC-19, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ARG-707.
RX PubMed=22654674; DOI=10.1371/journal.pgen.1002722;
RA Hannemann M., Sasidharan N., Hegermann J., Kutscher L.M., Koenig S.,
RA Eimer S.;
RT "TBC-8, a putative RAB-2 GAP, regulates dense core vesicle maturation in
RT Caenorhabditis elegans.";
RL PLoS Genet. 8:e1002722-e1002722(2012).
RN [3] {ECO:0000305}
RP INTERACTION WITH RUND-1.
RX PubMed=24698274; DOI=10.1016/j.neuron.2014.02.017;
RA Ailion M., Hannemann M., Dalton S., Pappas A., Watanabe S., Hegermann J.,
RA Liu Q., Han H.F., Gu M., Goulding M.Q., Sasidharan N., Schuske K.,
RA Hullett P., Eimer S., Jorgensen E.M.;
RT "Two Rab2 interactors regulate dense-core vesicle maturation.";
RL Neuron 82:167-180(2014).
CC -!- FUNCTION: Interacts with numerous Rab family members, functioning as
CC Rab effector for some, and as GTPase activator for others
CC (PubMed:22654674). GTPase activator for rab-2 (PubMed:22654674). In
CC association with ric-19 activates rab-2 during dense core vesicle
CC maturation in cholinergic motoneurons (PubMed:22654674).
CC {ECO:0000269|PubMed:22654674}.
CC -!- SUBUNIT: Interacts with rab-19 (PubMed:22654674). Interacts with ric-
CC 19; the interaction is direct and may be required for the activation of
CC rab-2 and dense vesicle maturation in cholinergic motoneurons
CC (PubMed:22654674). Interacts (via RUN domain) with rund-1
CC (PubMed:24698274). Does not interact with unc-108 (GTP-bound form)
CC (PubMed:22654674). {ECO:0000269|PubMed:22654674,
CC ECO:0000269|PubMed:24698274}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network
CC {ECO:0000269|PubMed:22654674}. Early endosome
CC {ECO:0000269|PubMed:22654674}. Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:22654674}; Peripheral membrane protein
CC {ECO:0000269|PubMed:22654674}. Note=Co-localizes with ric-19 at
CC cytoplasmic vesicle membranes in neurons.
CC {ECO:0000269|PubMed:22654674}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:C38H2.1a};
CC IsoId=I2HAA0-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:C38H2.1b};
CC IsoId=I2HAA0-2; Sequence=VSP_061542;
CC -!- TISSUE SPECIFICITY: Expressed in neurons in the head, tail and ventral
CC nerve cord (at protein level). {ECO:0000269|PubMed:22654674}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in neuronal dense
CC core vesicle trafficking defects whereby fewer dense core vesicles are
CC transported to axons of the dorsal nerve cord.
CC {ECO:0000269|PubMed:22654674}.
CC -!- SIMILARITY: Belongs to the RUTBC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BX284603; CCH63806.1; -; Genomic_DNA.
DR EMBL; BX284603; CCH63807.1; -; Genomic_DNA.
DR RefSeq; NP_001255072.1; NM_001268143.1.
DR RefSeq; NP_001255073.1; NM_001268144.1.
DR SMR; I2HAA0; -.
DR STRING; 6239.C38H2.1a; -.
DR EPD; I2HAA0; -.
DR PaxDb; I2HAA0; -.
DR PeptideAtlas; I2HA99; -.
DR EnsemblMetazoa; C38H2.1a.1; C38H2.1a.1; WBGene00008018.
DR GeneID; 176454; -.
DR KEGG; cel:CELE_C38H2.1; -.
DR CTD; 176454; -.
DR WormBase; C38H2.1a; CE47567; WBGene00008018; tbc-8. [I2HAA0-1]
DR WormBase; C38H2.1b; CE47487; WBGene00008018; tbc-8. [I2HAA0-2]
DR eggNOG; KOG1648; Eukaryota.
DR GeneTree; ENSGT00940000168017; -.
DR HOGENOM; CLU_006235_0_0_1; -.
DR InParanoid; I2HAA0; -.
DR OMA; LWPKSMR; -.
DR OrthoDB; 171826at2759; -.
DR PhylomeDB; I2HAA0; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00008018; Expressed in larva and 3 other tissues.
DR ExpressionAtlas; I2HAA0; baseline and differential.
DR GO; GO:0005829; C:cytosol; IDA:WormBase.
DR GO; GO:0005769; C:early endosome; IDA:WormBase.
DR GO; GO:0005797; C:Golgi medial cisterna; IDA:WormBase.
DR GO; GO:0000138; C:Golgi trans cisterna; IDA:WormBase.
DR GO; GO:0005096; F:GTPase activator activity; IBA:GO_Central.
DR GO; GO:0031267; F:small GTPase binding; IPI:WormBase.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:1990502; P:dense core granule maturation; IMP:WormBase.
DR CDD; cd15784; PH_RUTBC; 1.
DR Gene3D; 1.20.58.900; -; 1.
DR InterPro; IPR000195; Rab-GTPase-TBC_dom.
DR InterPro; IPR035969; Rab-GTPase_TBC_sf.
DR InterPro; IPR004012; Run_dom.
DR InterPro; IPR037213; Run_dom_sf.
DR InterPro; IPR037745; SGSM1/2.
DR InterPro; IPR021935; SGSM1/2_RBD.
DR Pfam; PF12068; PH_RBD; 1.
DR Pfam; PF00566; RabGAP-TBC; 1.
DR Pfam; PF02759; RUN; 1.
DR SMART; SM00593; RUN; 1.
DR SMART; SM00164; TBC; 1.
DR SUPFAM; SSF140741; SSF140741; 1.
DR SUPFAM; SSF47923; SSF47923; 2.
DR PROSITE; PS50826; RUN; 1.
DR PROSITE; PS50086; TBC_RABGAP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasmic vesicle; Endosome; Golgi apparatus;
KW GTPase activation; Membrane; Reference proteome.
FT CHAIN 1..913
FT /note="Rab GTPase-activating protein tbc-8"
FT /id="PRO_0000456037"
FT DOMAIN 106..240
FT /note="RUN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00178"
FT DOMAIN 597..844
FT /note="Rab-GAP TBC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00163"
FT VAR_SEQ 1..228
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_061542"
FT MUTAGEN 707
FT /note="R->A: Interacts with unc-108 (GTP-bound form).
FT Disrupts dense vesicle maturation in cholinergic
FT motoneurons."
FT /evidence="ECO:0000269|PubMed:22654674"
SQ SEQUENCE 913 AA; 105248 MW; A331C68B3DC200B4 CRC64;
MQMFRHSSAD MWRAKKPTLE RRSTDGRRSS IVDWINGLSD NNNYKSDHWV EKHDEGCERM
TRNGSVCAVE ESEPDVPTQH REVLLTKLKI EIKNIMAEHG AKKYLNLNSP YVTSLCIAVD
ACIMDGLRRR LLTLFNSPSS MSLLQIIAKS NGPAQQVLDQ TREIEELRTS AIPVHLIWIR
EALYLKSLST IINHFIDSKS VRRYYDNSAL LLDPVKGRLV ATLMMAPCMV TYRRMSNRIE
QEATAEELVE GATRGSTSTV PSRPPLSITR QVSSIAASVE RNGSVSRDYV FSLHHSCKST
LLYGKNNVCV AMNGSDFAKG YMSLQKFYDG NLSLKWVPNQ LMHASSQPSS GHSNNGEFTN
IWKNTINIEM QDIIYIHLHQ KDEISPTCLT FVNCEGVQSA PFQLPAGQHS IAFLSSLETG
LAPLLRLDPP LWVGTTKEKI LPRLRKRSTA VANPAMLDYV FRLVRTSGVE PAPEDIEDPL
APTSHSPPIH DNCVSLPNSP YIVDNVDSIV NFQIGTACQS MRNQIMARAF YGWLTYVRHL
RTIRTHLLHL VDTKTLICDD DCDPVDEKFW KQARAEPTEE NEKEFLKRVY WRGIEGINTK
EVRRMAWPYL LGLFEWNESP ESRLEQFTSQ YWQDIEEWRV LEAEVRRRDE EAFRAARARK
AASPVREESC DVFEDPNEPT CSQHYDRENL ITLFRANLHR IDKDVERCDR NLMFFSNKDN
LESLRRVMYT YVRRNLEEGY TQGMCDLLAP LLVTFEDEAL TLECFSLLML RQRGKFPQRP
GMSKCLLNLR SLIQVVDPQI YALISDIDYA QALSFAFRWF LLDFKRELSY ECTYKVWEVI
WAAQRLRITD DFAIFFGLAT ITNYHDVLIT NNFDYTDMIK FFNEMAERHD CSRLLSSART
HVKCLQNLVQ HLK
