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Protein

TBC1 domain family member 17

Gene

TBC1D17

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Probable GTPase-activating protein for Rab8; its transient association with Rab8 is mediated by OPTN. Inhibits Rab8-mediated endocytic trafficking, such as of transferrin receptor (TfR) and reduces Rab8 recruitnment to tubules emanating from the endocytic recycling compartment (ERC). Involved in regulation of autophagy. Mediates inhibition of autophagy caused by the OPTN variant GLC1E LYS-50; the function requires its catalytic activity, however, the involved Rab is not known.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei377 – 3771Arginine fingerBy similarity
Sitei418 – 4181Glutamine fingerBy similarity

GO - Molecular functioni

GO - Biological processi

  • autophagy Source: UniProtKB-KW
  • protein transport Source: UniProtKB-KW
  • retrograde transport, endosome to Golgi Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

GTPase activation

Keywords - Biological processi

Autophagy, Protein transport, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
TBC1 domain family member 17
Gene namesi
Name:TBC1D17
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:25699. TBC1D17.

Subcellular locationi

GO - Cellular componenti

  • autophagosome Source: UniProtKB-SubCell
  • cytoplasmic vesicle Source: UniProtKB-KW
  • cytosol Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi381 – 3811R → A: Enhances Rab8 localization on ERC tubules and Rab8 interaction with TfR; impairs inhibitory effect on autophagy. 2 Publications

Organism-specific databases

PharmGKBiPA134922509.

Polymorphism and mutation databases

BioMutaiTBC1D17.
DMDMi296452920.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 648648TBC1 domain family member 17PRO_0000208045Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei602 – 6021PhosphoserineCombined sources
Modified residuei604 – 6041PhosphoserineCombined sources
Modified residuei606 – 6061PhosphothreonineCombined sources
Modified residuei608 – 6081PhosphoserineCombined sources
Modified residuei615 – 6151PhosphothreonineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9HA65.
MaxQBiQ9HA65.
PaxDbiQ9HA65.
PRIDEiQ9HA65.

PTM databases

iPTMnetiQ9HA65.
PhosphoSiteiQ9HA65.

Expressioni

Gene expression databases

BgeeiQ9HA65.
CleanExiHS_TBC1D17.
ExpressionAtlasiQ9HA65. baseline and differential.
GenevisibleiQ9HA65. HS.

Interactioni

Subunit structurei

Interacts with OPTN.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
OPTNQ96CV97EBI-714625,EBI-748974

Protein-protein interaction databases

BioGridi122849. 28 interactions.
IntActiQ9HA65. 16 interactions.
MINTiMINT-1409083.
STRINGi9606.ENSP00000221543.

Structurei

3D structure databases

ProteinModelPortaliQ9HA65.
SMRiQ9HA65. Positions 313-546.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini310 – 520211Rab-GAP TBCPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni218 – 30992Required for interaction with OPTNAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi596 – 63136Pro-richAdd
BLAST

Domaini

The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site.By similarity

Sequence similaritiesi

Contains 1 Rab-GAP TBC domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2197. Eukaryota.
COG5210. LUCA.
HOGENOMiHOG000012710.
HOVERGENiHBG057668.
InParanoidiQ9HA65.
KOiK19945.
OrthoDBiEOG7HTHHR.
PhylomeDBiQ9HA65.
TreeFamiTF314296.

Family and domain databases

InterProiIPR021935. DUF3548.
IPR000195. Rab-GTPase-TBC_dom.
[Graphical view]
PfamiPF12068. DUF3548. 1 hit.
PF00566. RabGAP-TBC. 1 hit.
[Graphical view]
SMARTiSM00164. TBC. 1 hit.
[Graphical view]
SUPFAMiSSF47923. SSF47923. 2 hits.
PROSITEiPS50086. TBC_RABGAP. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9HA65-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEGAGYRVVF EKGGVYLHTS AKKYQDRDSL IAGVIRVVEK DNDVLLHWAP
60 70 80 90 100
VEEAGDSTQI LFSKKDSSGG DSCASEEEPT FDPDYEPDWA VISTVRPQLC
110 120 130 140 150
HSEPTRGAEP SCPQGSWAFS VSLGELKSIR RSKPGLSWAY LVLVTQAGGS
160 170 180 190 200
LPALHFHRGG TRALLRVLSR YLLLASSPQD SRLYLVFPHD SSALSNSFHH
210 220 230 240 250
LQLFDQDSSN VVSRFLQDPY STTFSSFSRV TNFFRGALQP QPEGAASDLP
260 270 280 290 300
PPPDDEPEPG FEVISCVELG PRPTVERGPP VTEEEWARHV GPEGRLQQVP
310 320 330 340 350
ELKNRIFSGG LSPSLRREAW KFLLGYLSWE GTAEEHKAHI RKKTDEYFRM
360 370 380 390 400
KLQWKSVSPE QERRNSLLHG YRSLIERDVS RTDRTNKFYE GPENPGLGLL
410 420 430 440 450
NDILLTYCMY HFDLGYVQGM SDLLSPILYV IQNEVDAFWC FCGFMELVQG
460 470 480 490 500
NFEESQETMK RQLGRLLLLL RVLDPLLCDF LDSQDSGSLC FCFRWLLIWF
510 520 530 540 550
KREFPFPDVL RLWEVLWTGL PGPNLHLLVA CAILDMERDT LMLSGFGSNE
560 570 580 590 600
ILKHINELTM KLSVEDVLTR AEALHRQLTA CPELPHNVQE ILGLAPPAEP
610 620 630 640
HSPSPTASPL PLSPTRAPPT PPPSTDTAPQ PDSSLEILPE EEDEGADS
Length:648
Mass (Da):72,728
Last modified:May 18, 2010 - v2
Checksum:i1C09D2272FA95496
GO
Isoform 2 (identifier: Q9HA65-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     8-40: Missing.

Note: No experimental confirmation available.
Show »
Length:615
Mass (Da):69,040
Checksum:i7E14E985970763AF
GO
Isoform 3 (identifier: Q9HA65-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     584-637: Missing.

Show »
Length:594
Mass (Da):67,224
Checksum:i649CBD723039579B
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti84 – 841D → G.3 Publications
Corresponds to variant rs8109661 [ dbSNP | Ensembl ].
VAR_060276
Natural varianti99 – 991L → P.3 Publications
Corresponds to variant rs3745486 [ dbSNP | Ensembl ].
VAR_024655

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei8 – 4033Missing in isoform 2. 1 PublicationVSP_047344Add
BLAST
Alternative sequencei584 – 63754Missing in isoform 3. 1 PublicationVSP_053997Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB449903 mRNA. Translation: BAH16646.1.
AK022230 mRNA. Translation: BAB13991.1.
AK300007 mRNA. Translation: BAG61824.1.
AC118341 Genomic DNA. No translation available.
AC118342 Genomic DNA. No translation available.
BC003516 mRNA. Translation: AAH03516.1.
CCDSiCCDS12785.1. [Q9HA65-1]
CCDS54294.1. [Q9HA65-2]
RefSeqiNP_001161694.1. NM_001168222.1.
NP_078958.2. NM_024682.2.
UniGeneiHs.631587.

Genome annotation databases

EnsembliENST00000221543; ENSP00000221543; ENSG00000104946.
ENST00000535102; ENSP00000446323; ENSG00000104946.
GeneIDi79735.
KEGGihsa:79735.
UCSCiuc002pqo.4. human. [Q9HA65-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB449903 mRNA. Translation: BAH16646.1.
AK022230 mRNA. Translation: BAB13991.1.
AK300007 mRNA. Translation: BAG61824.1.
AC118341 Genomic DNA. No translation available.
AC118342 Genomic DNA. No translation available.
BC003516 mRNA. Translation: AAH03516.1.
CCDSiCCDS12785.1. [Q9HA65-1]
CCDS54294.1. [Q9HA65-2]
RefSeqiNP_001161694.1. NM_001168222.1.
NP_078958.2. NM_024682.2.
UniGeneiHs.631587.

3D structure databases

ProteinModelPortaliQ9HA65.
SMRiQ9HA65. Positions 313-546.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122849. 28 interactions.
IntActiQ9HA65. 16 interactions.
MINTiMINT-1409083.
STRINGi9606.ENSP00000221543.

PTM databases

iPTMnetiQ9HA65.
PhosphoSiteiQ9HA65.

Polymorphism and mutation databases

BioMutaiTBC1D17.
DMDMi296452920.

Proteomic databases

EPDiQ9HA65.
MaxQBiQ9HA65.
PaxDbiQ9HA65.
PRIDEiQ9HA65.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000221543; ENSP00000221543; ENSG00000104946.
ENST00000535102; ENSP00000446323; ENSG00000104946.
GeneIDi79735.
KEGGihsa:79735.
UCSCiuc002pqo.4. human. [Q9HA65-1]

Organism-specific databases

CTDi79735.
GeneCardsiTBC1D17.
HGNCiHGNC:25699. TBC1D17.
MIMi616659. gene.
neXtProtiNX_Q9HA65.
PharmGKBiPA134922509.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2197. Eukaryota.
COG5210. LUCA.
HOGENOMiHOG000012710.
HOVERGENiHBG057668.
InParanoidiQ9HA65.
KOiK19945.
OrthoDBiEOG7HTHHR.
PhylomeDBiQ9HA65.
TreeFamiTF314296.

Miscellaneous databases

ChiTaRSiTBC1D17. human.
GenomeRNAii79735.
NextBioi35481910.
PROiQ9HA65.
SOURCEiSearch...

Gene expression databases

BgeeiQ9HA65.
CleanExiHS_TBC1D17.
ExpressionAtlasiQ9HA65. baseline and differential.
GenevisibleiQ9HA65. HS.

Family and domain databases

InterProiIPR021935. DUF3548.
IPR000195. Rab-GTPase-TBC_dom.
[Graphical view]
PfamiPF12068. DUF3548. 1 hit.
PF00566. RabGAP-TBC. 1 hit.
[Graphical view]
SMARTiSM00164. TBC. 1 hit.
[Graphical view]
SUPFAMiSSF47923. SSF47923. 2 hits.
PROSITEiPS50086. TBC_RABGAP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification and characterization of a novel Tre-2/Bub2/Cdc16 (TBC) protein that possesses Rab3A-GAP activity."
    Ishibashi K., Kanno E., Itoh T., Fukuda M.
    Genes Cells 14:41-52(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), VARIANTS GLY-84 AND PRO-99.
    Tissue: Brain.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANTS GLY-84 AND PRO-99.
    Tissue: Mammary gland.
  3. "The DNA sequence and biology of human chromosome 19."
    Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
    , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
    Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS GLY-84 AND PRO-99.
    Tissue: Skin.
  5. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  6. "Optineurin mediates a negative regulation of Rab8 by the GTPase-activating protein TBC1D17."
    Vaibhava V., Nagabhushana A., Chalasani M.L., Sudhakar C., Kumari A., Swarup G.
    J. Cell Sci. 125:5026-5039(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH OPTN, MUTAGENESIS OF ARG-381.
  7. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-602; SER-604; THR-606; SER-608 AND THR-615, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  8. "E50K-OPTN-induced retinal cell death involves the Rab GTPase-activating protein, TBC1D17 mediated block in autophagy."
    Chalasani M.L., Kumari A., Radha V., Swarup G.
    PLoS ONE 9:E95758-E95758(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-381.

Entry informationi

Entry nameiTBC17_HUMAN
AccessioniPrimary (citable) accession number: Q9HA65
Secondary accession number(s): B4DT12, B9A6L8, F5H1W7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 15, 2005
Last sequence update: May 18, 2010
Last modified: May 11, 2016
This is version 110 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.