TBCD8_HUMAN
ID TBCD8_HUMAN Reviewed; 1140 AA.
AC O95759; A6NDL4; A8K9W1; B9A6K4; Q53SQ4; Q9UQ32;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 3.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=TBC1 domain family member 8;
DE AltName: Full=AD 3;
DE AltName: Full=Vascular Rab-GAP/TBC-containing protein;
GN Name=TBC1D8; Synonyms=VRP;
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 2), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 248-980 (ISOFORMS 1/2), AND VARIANTS ALA-317 AND LEU-1073.
RC TISSUE=Capillary endothelium;
RX PubMed=10373574; DOI=10.1093/nar/27.13.2591;
RA Yonekura H., Migita H., Sakurai S., Wang H., Harada S., Abedin M.J.,
RA Yamagishi S., Yamamoto H.;
RT "Antisense display -- a method for functional gene screening: evaluation in
RT a cell-free system and isolation of angiogenesis-related genes.";
RL Nucleic Acids Res. 27:2591-2600(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-317.
RC TISSUE=Brain;
RX PubMed=19077034; DOI=10.1111/j.1365-2443.2008.01251.x;
RA Ishibashi K., Kanno E., Itoh T., Fukuda M.;
RT "Identification and characterization of a novel Tre-2/Bub2/Cdc16 (TBC)
RT protein that possesses Rab3A-GAP activity.";
RL Genes Cells 14:41-52(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 80-1140 (ISOFORM 1), AND VARIANTS
RP ALA-317 AND GLY-1079.
RC TISSUE=Trachea;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: May act as a GTPase-activating protein for Rab family
CC protein(s).
CC -!- INTERACTION:
CC O95759; Q13077: TRAF1; NbExp=3; IntAct=EBI-10979580, EBI-359224;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O95759-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95759-2; Sequence=VSP_038340;
CC -!- DOMAIN: The arginine and glutamine fingers are critical for the GTPase-
CC activating mechanism, they pull out Rab's 'switch 2' glutamine and
CC insert in Rab's active site. {ECO:0000250}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAY14824.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAF85515.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB024057; BAA75489.1; -; mRNA.
DR EMBL; AB017114; BAA76517.1; -; mRNA.
DR EMBL; AB449889; BAH16632.1; -; mRNA.
DR EMBL; AC016738; AAY14824.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC013722; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK292826; BAF85515.1; ALT_INIT; mRNA.
DR CCDS; CCDS46375.1; -. [O95759-1]
DR RefSeq; NP_001095896.1; NM_001102426.2. [O95759-1]
DR AlphaFoldDB; O95759; -.
DR SMR; O95759; -.
DR BioGRID; 116311; 52.
DR IntAct; O95759; 5.
DR STRING; 9606.ENSP00000366036; -.
DR iPTMnet; O95759; -.
DR PhosphoSitePlus; O95759; -.
DR BioMuta; TBC1D8; -.
DR EPD; O95759; -.
DR jPOST; O95759; -.
DR MassIVE; O95759; -.
DR MaxQB; O95759; -.
DR PaxDb; O95759; -.
DR PeptideAtlas; O95759; -.
DR PRIDE; O95759; -.
DR ProteomicsDB; 51034; -. [O95759-1]
DR ProteomicsDB; 51035; -. [O95759-2]
DR Antibodypedia; 32896; 80 antibodies from 17 providers.
DR DNASU; 11138; -.
DR Ensembl; ENST00000376840.8; ENSP00000366036.4; ENSG00000204634.13. [O95759-1]
DR GeneID; 11138; -.
DR KEGG; hsa:11138; -.
DR UCSC; uc010fiv.4; human. [O95759-1]
DR CTD; 11138; -.
DR DisGeNET; 11138; -.
DR GeneCards; TBC1D8; -.
DR HGNC; HGNC:17791; TBC1D8.
DR HPA; ENSG00000204634; Low tissue specificity.
DR neXtProt; NX_O95759; -.
DR OpenTargets; ENSG00000204634; -.
DR PharmGKB; PA134885935; -.
DR VEuPathDB; HostDB:ENSG00000204634; -.
DR eggNOG; KOG4347; Eukaryota.
DR GeneTree; ENSGT00940000158977; -.
DR HOGENOM; CLU_003535_0_1_1; -.
DR InParanoid; O95759; -.
DR OrthoDB; 450360at2759; -.
DR PhylomeDB; O95759; -.
DR TreeFam; TF313145; -.
DR PathwayCommons; O95759; -.
DR SignaLink; O95759; -.
DR BioGRID-ORCS; 11138; 14 hits in 1071 CRISPR screens.
DR ChiTaRS; TBC1D8; human.
DR GenomeRNAi; 11138; -.
DR Pharos; O95759; Tdark.
DR PRO; PR:O95759; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O95759; protein.
DR Bgee; ENSG00000204634; Expressed in mucosa of stomach and 199 other tissues.
DR ExpressionAtlas; O95759; baseline and differential.
DR Genevisible; O95759; HS.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005096; F:GTPase activator activity; IBA:GO_Central.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:0008015; P:blood circulation; TAS:ProtInc.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:ProtInc.
DR CDD; cd13349; PH-GRAM1_TBC1D8; 1.
DR CDD; cd13353; PH-GRAM2_TBC1D8; 1.
DR Gene3D; 2.30.29.30; -; 2.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR004182; GRAM.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR000195; Rab-GTPase-TBC_dom.
DR InterPro; IPR035969; Rab-GTPase_TBC_sf.
DR InterPro; IPR036009; TBC1D8_PH-GRAM1.
DR InterPro; IPR036016; TBC1D8_PH-GRAM2.
DR Pfam; PF02893; GRAM; 2.
DR Pfam; PF00566; RabGAP-TBC; 1.
DR SMART; SM00568; GRAM; 2.
DR SMART; SM00164; TBC; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF47923; SSF47923; 2.
DR PROSITE; PS50086; TBC_RABGAP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; GTPase activation; Reference proteome; Repeat.
FT CHAIN 1..1140
FT /note="TBC1 domain family member 8"
FT /id="PRO_0000208033"
FT DOMAIN 145..212
FT /note="GRAM 1"
FT DOMAIN 285..353
FT /note="GRAM 2"
FT DOMAIN 505..692
FT /note="Rab-GAP TBC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00163"
FT REGION 1031..1070
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 552
FT /note="Arginine finger"
FT /evidence="ECO:0000250"
FT SITE 591
FT /note="Glutamine finger"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..243
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10373574"
FT /id="VSP_038340"
FT VARIANT 317
FT /note="T -> A (in dbSNP:rs2289953)"
FT /evidence="ECO:0000269|PubMed:10373574,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:19077034"
FT /id="VAR_047500"
FT VARIANT 954
FT /note="G -> R (in dbSNP:rs1062062)"
FT /id="VAR_024654"
FT VARIANT 1073
FT /note="F -> L (in dbSNP:rs1057580)"
FT /evidence="ECO:0000269|PubMed:10373574"
FT /id="VAR_060542"
FT VARIANT 1079
FT /note="R -> G (in dbSNP:rs746924)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_022128"
FT VARIANT 1108
FT /note="M -> V (in dbSNP:rs3739011)"
FT /id="VAR_022129"
FT CONFLICT 977..979
FT /note="EKD -> KKK (in Ref. 1; BAA76517)"
FT /evidence="ECO:0000305"
FT CONFLICT 1117
FT /note="I -> T (in Ref. 4; BAF85515)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1140 AA; 130835 MW; 84A98A876F8DD108 CRC64;
MWLKPEEVLL KNALKLWVTQ KSSCYFILQR RRGHGEGGGR LTGRLVGALD AVLDSNARVA
PFRILLQVPG SQVYSPIACG ATLEEINQHW DWLEQNLLHT LSVFDNKDDI ASFVKGKVKA
LIAEETSSRL AEQEEEPEKF REALVKFEAR FNFPEAEKLV TYYSCCCWKG RVPRQGWLYL
SINHLCFYSF FLGKELKLVV PWVDIQKLER TSNVFLTDTI RITTQNKERD FSMFLNLDEV
FKVMEQLADV TLRRLLDNEV FDLDPDLQEP SQITKRDLEA RAQNEFFRAF FRLPRKEKLH
AVVDCSLWTP FSRCHTTGRM FASDSYICFA SREDGCCKII LPLREVVSIE KMEDTSLLPH
PIIVSIRSKV AFQFIELRDR DSLVEALLAR LKQVHANHPV HYDTSADDDM ASLVFHSTSM
CSDHRFGDLE MMSSQNSEES EKEKSPLMHP DALVTAFQQS GSQSPDSRMS REQIKISLWN
DHFVEYGRTV CMFRTEKIRK LVAMGIPESL RGRLWLLFSD AVTDLASHPG YYGNLVEESL
GKCCLVTEEI ERDLHRSLPE HPAFQNETGI AALRRVLTAY AHRNPKIGYC QSMNILTSVL
LLYTKEEEAF WLLVAVCERM LPDYFNHRVI GAQVDQSVFE ELIKGHLPEL AEHMNDLSAL
ASVSLSWFLT LFLSIMPLES AVNVVDCFFY DGIKAIFQLG LAVLEANAED LCSSKDDGQA
LMILSRFLDH IKNEDSPGPP VGSHHAFFSD DQEPYPVTDI SDLIRDSYEK FGDQSVEQIE
HLRYKHRIRV LQGHEDTTKQ NVLRVVIPEV SILPEDLEEL YDLFKREHMM SCYWEQPRPM
ASRHDPSRPY AEQYRIDARQ FAHLFQLVSP WTCGAHTEIL AERTFRLLDD NMDQLIEFKA
FVSCLDIMYN GEMNEKIKLL YRLHIPPALT ENDRDSQSPL RNPLLSTSRP LVFGKPNGDA
VDYQKQLKQM IKDLAKEKDK TEKELPKMSQ REFIQFCKTL YSMFHEDPEE NDLYQAIATV
TTLLLQIGEV GQRGSSSGSC SQECGEELRA SAPSPEDSVF ADTGKTPQDS QAFPEAAERD
WTVSLEHILA SLLTEQSLVN FFEKPLDMKS KLENAKINQY NLKTFEMSHQ SQSELKLSNL
