TBC3A_HUMAN
ID TBC3A_HUMAN Reviewed; 549 AA.
AC Q8IZP1; A6NGX2; A8K007; Q6DCB4; Q9H0B9; Q9UDD4;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 07-JAN-2015, sequence version 6.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=TBC1 domain family member 3;
DE AltName: Full=Prostate cancer gene 17 protein;
DE AltName: Full=Protein TRE17-alpha;
DE AltName: Full=Rab GTPase-activating protein PRC17;
GN Name=TBC1D3; Synonyms=PRC17, TBC1D3A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP VARIANT PRO-526.
RX PubMed=12359748;
RA Pei L., Peng Y., Yang Y., Ling X.B., Van Eyndhoven W.G., Nguyen K.C.,
RA Rubin M., Hoey T., Powers S., Li J.;
RT "PRC17, a novel oncogene encoding a Rab GTPase-activating protein, is
RT amplified in prostate cancer.";
RL Cancer Res. 62:5420-5424(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-526.
RC TISSUE=Adipose tissue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-52.
RX PubMed=8471161; DOI=10.1089/dna.1993.12.107;
RA Onno M., Nakamura T., Mariage-Samson R., Hillova J., Hill M.;
RT "Human TRE17 oncogene is generated from a family of homologous polymorphic
RT sequences by single-base changes.";
RL DNA Cell Biol. 12:107-118(1993).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-52.
RC TISSUE=Placenta;
RX PubMed=8406013; DOI=10.1016/0378-1119(93)90295-e;
RA Onno M., Nakamura T., Hillova J., Hill M.;
RT "Identification of novel sequences in the repertoire of hypervariable TRE17
RT genes from immortalized nonmalignant and malignant human keratinocytes.";
RL Gene 131:209-215(1993).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=12604796; DOI=10.1073/pnas.0437015100;
RA Paulding C.A., Ruvolo M., Haber D.A.;
RT "The Tre2 (USP6) oncogene is a hominoid-specific gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:2507-2511(2003).
RN [9]
RP MISCELLANEOUS, AND COPY NUMBER VARIATION.
RX PubMed=21030649; DOI=10.1126/science.1197005;
RA Sudmant P.H., Kitzman J.O., Antonacci F., Alkan C., Malig M., Tsalenko A.,
RA Sampas N., Bruhn L., Shendure J., Eichler E.E.;
RT "Diversity of human copy number variation and multicopy genes.";
RL Science 330:641-646(2010).
RN [10]
RP PALMITOYLATION AT CYS-318 AND CYS-325, UBIQUITINATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=23578663; DOI=10.1016/j.bbrc.2013.04.001;
RA Kong C., Lange J.J., Samovski D., Su X., Liu J., Sundaresan S., Stahl P.D.;
RT "Ubiquitination and degradation of the hominoid-specific oncoprotein TBC1D3
RT is regulated by protein palmitoylation.";
RL Biochem. Biophys. Res. Commun. 434:388-393(2013).
CC -!- FUNCTION: Acts as a GTPase activating protein for RAB5. Does not act on
CC RAB4 or RAB11. {ECO:0000269|PubMed:12359748}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23578663};
CC Lipid-anchor {ECO:0000269|PubMed:23578663}. Note=Associated with lipid
CC rafts.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IZP1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IZP1-2; Sequence=VSP_056829, VSP_056830;
CC -!- TISSUE SPECIFICITY: Expressed in liver, skeletal muscle, kidney,
CC pancreas, spleen, testis, ovary, small intestine and peripheral blood
CC leukocytes. Overexpressed in prostate cancers.
CC {ECO:0000269|PubMed:12359748, ECO:0000269|PubMed:12604796}.
CC -!- PTM: Ubiquitinated by a CUL7-based E3 ligase, which leads to
CC proteasomal degradation. {ECO:0000269|PubMed:23578663}.
CC -!- PTM: Palmitoylation is required for membrane localization and protects
CC TBC1D3 from ubiquitination. {ECO:0000269|PubMed:23578663}.
CC -!- MISCELLANEOUS: TBC1D3 is encoded by a collection of very similar
CC paralogs with multiple copies of each paralog, some human genomes
CC encoding well over 50 copies depending on ethnic origin of the donor.
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DR EMBL; AF540953; AAN33117.1; -; mRNA.
DR EMBL; AL136860; CAB66794.1; -; mRNA.
DR EMBL; AK289372; BAF82061.1; -; mRNA.
DR EMBL; AC244154; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC078140; AAH78140.1; -; mRNA.
DR EMBL; X71377; CAB94197.1; -; Genomic_DNA.
DR CCDS; CCDS45658.1; -. [Q8IZP1-1]
DR RefSeq; NP_001001418.5; NM_001001418.6. [Q8IZP1-1]
DR RefSeq; NP_001116863.3; NM_001123391.3. [Q8IZP1-1]
DR AlphaFoldDB; Q8IZP1; -.
DR SMR; Q8IZP1; -.
DR IntAct; Q8IZP1; 3.
DR STRING; 9606.ENSP00000478683; -.
DR iPTMnet; Q8IZP1; -.
DR PhosphoSitePlus; Q8IZP1; -.
DR SwissPalm; Q8IZP1; -.
DR BioMuta; TBC1D3; -.
DR DMDM; 294862542; -.
DR MassIVE; Q8IZP1; -.
DR PaxDb; Q8IZP1; -.
DR PeptideAtlas; Q8IZP1; -.
DR PRIDE; Q8IZP1; -.
DR Antibodypedia; 75940; 29 antibodies from 12 providers.
DR DNASU; 414059; -.
DR Ensembl; ENST00000620215.3; ENSP00000478683.1; ENSG00000274611.4. [Q8IZP1-1]
DR GeneID; 414060; -.
DR GeneID; 729873; -.
DR KEGG; hsa:414060; -.
DR KEGG; hsa:729873; -.
DR MANE-Select; ENST00000620215.3; ENSP00000478683.1; NM_001123391.4; NP_001116863.3.
DR MANE-Select; ENST00000622206.2; ENSP00000482345.1; NM_001001418.6; NP_001001418.5.
DR UCSC; uc032ffp.2; human. [Q8IZP1-1]
DR CTD; 414060; -.
DR CTD; 729873; -.
DR DisGeNET; 414060; -.
DR DisGeNET; 729873; -.
DR GeneCards; TBC1D3; -.
DR HGNC; HGNC:19031; TBC1D3.
DR HPA; ENSG00000274611; Low tissue specificity.
DR MIM; 607741; gene.
DR neXtProt; NX_Q8IZP1; -.
DR OpenTargets; ENSG00000274611; -.
DR PharmGKB; PA134941179; -.
DR VEuPathDB; HostDB:ENSG00000274611; -.
DR eggNOG; KOG1102; Eukaryota.
DR GeneTree; ENSGT00940000163624; -.
DR HOGENOM; CLU_005350_10_5_1; -.
DR InParanoid; Q8IZP1; -.
DR OMA; EDYEMQA; -.
DR OrthoDB; 976276at2759; -.
DR TreeFam; TF318099; -.
DR PathwayCommons; Q8IZP1; -.
DR Reactome; R-HSA-8854214; TBC/RABGAPs.
DR SignaLink; Q8IZP1; -.
DR BioGRID-ORCS; 414060; 379 hits in 537 CRISPR screens.
DR BioGRID-ORCS; 729873; 38 hits in 564 CRISPR screens.
DR Pharos; Q8IZP1; Tdark.
DR PRO; PR:Q8IZP1; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8IZP1; protein.
DR Bgee; ENSG00000274611; Expressed in mucosa of stomach and 84 other tissues.
DR Genevisible; Q8IZP1; HS.
DR GO; GO:0031901; C:early endosome membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005096; F:GTPase activator activity; IBA:GO_Central.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR InterPro; IPR000195; Rab-GTPase-TBC_dom.
DR InterPro; IPR035969; Rab-GTPase_TBC_sf.
DR Pfam; PF00566; RabGAP-TBC; 1.
DR SMART; SM00164; TBC; 1.
DR SUPFAM; SSF47923; SSF47923; 1.
DR PROSITE; PS50086; TBC_RABGAP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; GTPase activation; Lipoprotein;
KW Membrane; Palmitate; Proto-oncogene; Reference proteome; Ubl conjugation.
FT CHAIN 1..549
FT /note="TBC1 domain family member 3"
FT /id="PRO_0000208025"
FT DOMAIN 101..293
FT /note="Rab-GAP TBC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00163"
FT REGION 350..419
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 391..413
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 318
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:23578663"
FT LIPID 325
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:23578663"
FT VAR_SEQ 255..291
FT /note="DKKDLCGQCSPLGCLIRILIDGISLGLTLRLWDVYLV -> SASRRRPGVAR
FT GHVFATGSLIPGPGMRTLCSSILGPL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056829"
FT VAR_SEQ 292..549
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056830"
FT VARIANT 526
FT /note="Q -> P (in dbSNP:rs1567681955)"
FT /evidence="ECO:0000269|PubMed:12359748,
FT ECO:0000269|PubMed:14702039"
FT /id="VAR_063088"
FT CONFLICT 117
FT /note="T -> I (in Ref. 1; AAN33117)"
FT /evidence="ECO:0000305"
FT CONFLICT 122
FT /note="L -> M (in Ref. 5; AAH78140)"
FT /evidence="ECO:0000305"
FT CONFLICT 137
FT /note="R -> K (in Ref. 2; CAB66794 and 3; BAF82061)"
FT /evidence="ECO:0000305"
FT CONFLICT 354..358
FT /note="KGDLP -> QGDLQ (in Ref. 3; BAF82061)"
FT /evidence="ECO:0000305"
FT CONFLICT 354
FT /note="K -> Q (in Ref. 1; AAN33117)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 549 AA; 62187 MW; 12F56291F685F06E CRC64;
MDVVEVAGSW WAQEREDIIM KYEKGHRAGL PEDKGPKPFR SYNNNVDHLG IVHETELPPL
TAREAKQIRR EISRKSKWVD MLGDWEKYKS SRKLIDRAYK GMPMNIRGPM WSVLLNTEEM
KLKNPGRYQI MKEKGKRSSE HIQRIDRDVS GTLRKHIFFR DRYGTKQREL LHILLAYEEY
NPEVGYCRDL SHIAALFLLY LPEEDAFWAL VQLLASERHS LQGFHSPNGG TVQGLQDQQE
HVVATSQPKT MGHQDKKDLC GQCSPLGCLI RILIDGISLG LTLRLWDVYL VEGEQALMPI
TRIAFKVQQK RLTKTSRCGP WARFCNRFVD TWARDEDTVL KHLRASMKKL TRKKGDLPPP
AKPEQGSSAS RPVPASRGGK TLCKGDRQAP PGPPARFPRP IWSASPPRAP RSSTPCPGGA
VREDTYPVGT QGVPSPALAQ GGPQGSWRFL QWNSMPRLPT DLDVEGPWFR HYDFRQSCWV
RAISQEDQLA PCWQAEHPAE RVRSAFAAPS TDSDQGTPFR ARDEQQCAPT SGPCLCGLHL
ESSQFPPGF
