TBC17_HUMAN
ID TBC17_HUMAN Reviewed; 648 AA.
AC Q9HA65; B4DT12; B9A6L8; F5H1W7;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 3.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=TBC1 domain family member 17;
GN Name=TBC1D17 {ECO:0000312|HGNC:HGNC:25699};
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 3), AND VARIANT PRO-99.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP PRO-99.
RC TISSUE=Mammary gland;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-99.
RC TISSUE=Skin;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [6]
RP FUNCTION, INTERACTION WITH OPTN, AND MUTAGENESIS OF ARG-381.
RX PubMed=22854040; DOI=10.1242/jcs.102327;
RA Vaibhava V., Nagabhushana A., Chalasani M.L., Sudhakar C., Kumari A.,
RA Swarup G.;
RT "Optineurin mediates a negative regulation of Rab8 by the GTPase-activating
RT protein TBC1D17.";
RL J. Cell Sci. 125:5026-5039(2012).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-602; SER-604; THR-606;
RP SER-608 AND THR-615, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-381.
RX PubMed=24752605; DOI=10.1371/journal.pone.0095758;
RA Chalasani M.L., Kumari A., Radha V., Swarup G.;
RT "E50K-OPTN-induced retinal cell death involves the Rab GTPase-activating
RT protein, TBC1D17 mediated block in autophagy.";
RL PLoS ONE 9:E95758-E95758(2014).
CC -!- FUNCTION: Probable GTPase-activating protein for Rab8; its transient
CC association with Rab8 is mediated by OPTN. Inhibits Rab8-mediated
CC endocytic trafficking, such as of transferrin receptor (TfR) and
CC reduces Rab8 recruitnment to tubules emanating from the endocytic
CC recycling compartment (ERC). Involved in regulation of autophagy.
CC Mediates inhibition of autophagy caused by the OPTN variant GLC1E LYS-
CC 50; the function requires its catalytic activity, however, the involved
CC Rab is not known. {ECO:0000269|PubMed:22854040,
CC ECO:0000269|PubMed:24752605}.
CC -!- SUBUNIT: Interacts with OPTN. {ECO:0000269|PubMed:22854040}.
CC -!- INTERACTION:
CC Q9HA65; Q96CV9: OPTN; NbExp=7; IntAct=EBI-714625, EBI-748974;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, autophagosome
CC {ECO:0000269|PubMed:24752605}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9HA65-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9HA65-2; Sequence=VSP_047344;
CC Name=3;
CC IsoId=Q9HA65-3; Sequence=VSP_053997;
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}.
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DR EMBL; AB449903; BAH16646.1; -; mRNA.
DR EMBL; AK022230; BAB13991.1; -; mRNA.
DR EMBL; AK300007; BAG61824.1; -; mRNA.
DR EMBL; AC118341; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC118342; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003516; AAH03516.1; -; mRNA.
DR CCDS; CCDS12785.1; -. [Q9HA65-1]
DR CCDS; CCDS54294.1; -. [Q9HA65-2]
DR RefSeq; NP_001161694.1; NM_001168222.1.
DR RefSeq; NP_078958.2; NM_024682.2.
DR AlphaFoldDB; Q9HA65; -.
DR BioGRID; 122849; 43.
DR IntAct; Q9HA65; 23.
DR MINT; Q9HA65; -.
DR STRING; 9606.ENSP00000221543; -.
DR iPTMnet; Q9HA65; -.
DR PhosphoSitePlus; Q9HA65; -.
DR BioMuta; TBC1D17; -.
DR DMDM; 296452920; -.
DR EPD; Q9HA65; -.
DR jPOST; Q9HA65; -.
DR MassIVE; Q9HA65; -.
DR MaxQB; Q9HA65; -.
DR PaxDb; Q9HA65; -.
DR PeptideAtlas; Q9HA65; -.
DR PRIDE; Q9HA65; -.
DR ProteomicsDB; 25785; -.
DR ProteomicsDB; 81379; -. [Q9HA65-1]
DR Antibodypedia; 62898; 23 antibodies from 12 providers.
DR DNASU; 79735; -.
DR Ensembl; ENST00000221543.10; ENSP00000221543.4; ENSG00000104946.14. [Q9HA65-1]
DR Ensembl; ENST00000535102.6; ENSP00000446323.1; ENSG00000104946.14. [Q9HA65-2]
DR GeneID; 79735; -.
DR KEGG; hsa:79735; -.
DR MANE-Select; ENST00000221543.10; ENSP00000221543.4; NM_024682.3; NP_078958.2.
DR UCSC; uc002pqo.4; human. [Q9HA65-1]
DR CTD; 79735; -.
DR GeneCards; TBC1D17; -.
DR HGNC; HGNC:25699; TBC1D17.
DR HPA; ENSG00000104946; Tissue enhanced (skeletal).
DR MIM; 616659; gene.
DR neXtProt; NX_Q9HA65; -.
DR OpenTargets; ENSG00000104946; -.
DR PharmGKB; PA134922509; -.
DR VEuPathDB; HostDB:ENSG00000104946; -.
DR eggNOG; KOG2197; Eukaryota.
DR GeneTree; ENSGT00940000158989; -.
DR HOGENOM; CLU_004457_2_2_1; -.
DR InParanoid; Q9HA65; -.
DR OrthoDB; 1495285at2759; -.
DR PhylomeDB; Q9HA65; -.
DR TreeFam; TF314296; -.
DR PathwayCommons; Q9HA65; -.
DR Reactome; R-HSA-8854214; TBC/RABGAPs.
DR SignaLink; Q9HA65; -.
DR BioGRID-ORCS; 79735; 20 hits in 1075 CRISPR screens.
DR ChiTaRS; TBC1D17; human.
DR GenomeRNAi; 79735; -.
DR Pharos; Q9HA65; Tdark.
DR PRO; PR:Q9HA65; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9HA65; protein.
DR Bgee; ENSG00000104946; Expressed in gastrocnemius and 97 other tissues.
DR ExpressionAtlas; Q9HA65; baseline and differential.
DR Genevisible; Q9HA65; HS.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; TAS:Reactome.
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:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IMP:UniProtKB.
DR InterPro; IPR000195; Rab-GTPase-TBC_dom.
DR InterPro; IPR035969; Rab-GTPase_TBC_sf.
DR InterPro; IPR021935; SGSM1/2_RBD.
DR Pfam; PF12068; PH_RBD; 1.
DR Pfam; PF00566; RabGAP-TBC; 1.
DR SMART; SM00164; TBC; 1.
DR SUPFAM; SSF47923; SSF47923; 2.
DR PROSITE; PS50086; TBC_RABGAP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autophagy; Cytoplasmic vesicle; GTPase activation;
KW Phosphoprotein; Protein transport; Reference proteome; Transport.
FT CHAIN 1..648
FT /note="TBC1 domain family member 17"
FT /id="PRO_0000208045"
FT DOMAIN 310..520
FT /note="Rab-GAP TBC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00163"
FT REGION 218..309
FT /note="Required for interaction with OPTN"
FT /evidence="ECO:0000269|PubMed:22854040"
FT REGION 240..259
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 594..648
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 598..628
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 377
FT /note="Arginine finger"
FT /evidence="ECO:0000250"
FT SITE 418
FT /note="Glutamine finger"
FT /evidence="ECO:0000250"
FT MOD_RES 602
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 604
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 606
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 608
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 615
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 8..40
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_047344"
FT VAR_SEQ 584..637
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:19077034"
FT /id="VSP_053997"
FT VARIANT 84
FT /note="G -> D (in dbSNP:rs8109661)"
FT /id="VAR_060276"
FT VARIANT 99
FT /note="L -> P (in dbSNP:rs3745486)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:19077034"
FT /id="VAR_024655"
FT MUTAGEN 381
FT /note="R->A: Enhances Rab8 localization on ERC tubules and
FT Rab8 interaction with TfR; impairs inhibitory effect on
FT autophagy."
FT /evidence="ECO:0000269|PubMed:22854040,
FT ECO:0000269|PubMed:24752605"
SQ SEQUENCE 648 AA; 72670 MW; 312771272F420BB0 CRC64;
MEGAGYRVVF EKGGVYLHTS AKKYQDRDSL IAGVIRVVEK DNDVLLHWAP VEEAGDSTQI
LFSKKDSSGG DSCASEEEPT FDPGYEPDWA VISTVRPQLC HSEPTRGAEP SCPQGSWAFS
VSLGELKSIR RSKPGLSWAY LVLVTQAGGS LPALHFHRGG TRALLRVLSR YLLLASSPQD
SRLYLVFPHD SSALSNSFHH LQLFDQDSSN VVSRFLQDPY STTFSSFSRV TNFFRGALQP
QPEGAASDLP PPPDDEPEPG FEVISCVELG PRPTVERGPP VTEEEWARHV GPEGRLQQVP
ELKNRIFSGG LSPSLRREAW KFLLGYLSWE GTAEEHKAHI RKKTDEYFRM KLQWKSVSPE
QERRNSLLHG YRSLIERDVS RTDRTNKFYE GPENPGLGLL NDILLTYCMY HFDLGYVQGM
SDLLSPILYV IQNEVDAFWC FCGFMELVQG NFEESQETMK RQLGRLLLLL RVLDPLLCDF
LDSQDSGSLC FCFRWLLIWF KREFPFPDVL RLWEVLWTGL PGPNLHLLVA CAILDMERDT
LMLSGFGSNE ILKHINELTM KLSVEDVLTR AEALHRQLTA CPELPHNVQE ILGLAPPAEP
HSPSPTASPL PLSPTRAPPT PPPSTDTAPQ PDSSLEILPE EEDEGADS
