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Protein

TBC1 domain family member 5

Gene

TBC1D5

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

Functioni

May act as a GTPase-activating protein (GAP) for Rab family protein(s). May act as a GAP for RAB7A. Can displace RAB7A and retromer CSC subcomplex from the endosomal membrane to the cytosol; at least retromer displacement seems to require its catalytic activity (PubMed:19531583, PubMed:20923837). Required for retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN); the function seems to require its catalytic activity. Involved in regulation of autophagy (PubMed:22354992). May act as a molecular switch between endosomal and autophagosomal transport and is involved in reprogramming vesicle trafficking upon autophagy induction. Involved in the trafficking of ATG9A upon activation of autophagy. May regulate the recruitment of ATG9A-AP2-containing vesicles to autophagic membranes (PubMed:24603492).3 Publications4 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei169 – 1691Arginine fingerBy similarity
Sitei204 – 2041Glutamine fingerBy similarity

GO - Molecular functioni

  • AP-2 adaptor complex binding Source: UniProtKB
  • GTPase activator activity Source: GO_Central
  • Rab GTPase binding Source: GO_Central

GO - Biological processi

  • activation of GTPase activity Source: GO_Central
  • intracellular protein transport Source: GO_Central
  • mitophagy in response to mitochondrial depolarization Source: ParkinsonsUK-UCL
  • positive regulation of autophagy Source: UniProtKB
  • positive regulation of receptor internalization Source: UniProtKB
  • regulation of vesicle fusion Source: GO_Central
  • response to starvation Source: UniProtKB
  • 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 5
Gene namesi
Name:TBC1D5
Synonyms:KIAA0210
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:19166. TBC1D5.

Subcellular locationi

  • Endosome membrane 1 Publication
  • Cytoplasmic vesicleautophagosome 1 Publication

  • Note: During starvation induced autophagy is relocalized from endosomal localization to LC3-positive autophagosomes.1 Publication

GO - Cellular componenti

  • autophagosome Source: UniProtKB
  • cytoplasmic vesicle Source: UniProtKB-KW
  • cytosol Source: GOC
  • endosome membrane Source: UniProtKB
  • retromer complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi59 – 591W → A: Disrupts interaction with VPS29. 1 Publication
Mutagenesisi169 – 1691R → A: Abolishes retromer displacement from endosome membrane; no effect on interaction with VPS29; when associated with A-204. 1 Publication
Mutagenesisi204 – 2041Q → A: Abolishes retromer displacement from endosome membrane; no effect on interaction with VPS29; when associated with A-169. 1 Publication

Organism-specific databases

PharmGKBiPA38808.

Polymorphism and mutation databases

BioMutaiTBC1D5.
DMDMi2495720.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 795795TBC1 domain family member 5PRO_0000208028Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei42 – 421PhosphothreonineCombined sources
Modified residuei43 – 431PhosphoserineCombined sources
Modified residuei44 – 441PhosphoserineCombined sources
Modified residuei460 – 4601PhosphoserineCombined sources
Modified residuei522 – 5221PhosphoserineCombined sources
Modified residuei539 – 5391PhosphoserineCombined sources
Modified residuei541 – 5411PhosphoserineCombined sources
Modified residuei544 – 5441PhosphoserineCombined sources
Modified residuei554 – 5541PhosphoserineCombined sources
Modified residuei570 – 5701PhosphoserineCombined sources
Modified residuei584 – 5841PhosphoserineBy similarity
Modified residuei730 – 7301PhosphoserineCombined sources
Modified residuei791 – 7911PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ92609.
MaxQBiQ92609.
PaxDbiQ92609.
PeptideAtlasiQ92609.
PRIDEiQ92609.

PTM databases

iPTMnetiQ92609.
PhosphoSiteiQ92609.

Expressioni

Gene expression databases

BgeeiENSG00000131374.
CleanExiHS_TBC1D5.
ExpressionAtlasiQ92609. baseline and differential.
GenevisibleiQ92609. HS.

Organism-specific databases

HPAiHPA035125.
HPA035126.

Interactioni

Subunit structurei

Interacts with MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAP, GABARAPL1, GABARAPL2. Interacts with VPS29 and VPS35; indicative for an association with retromer CSC subcomplex. MAP1LC3A and VPS29 compete for binding to TBC1D5 (PubMed:20923837, PubMed:22354992). Interacts with AP2M1; indicative for an association with the AP2 complex. Interacts with ULK1 and ATG13 (phosphorylated); indicative for an association with the activated ULK1-ATG13-FIP200 complex. Interacts with ATG9A; the interactions seems to be restricted to the AP2-clathrin-associated fraction of ATG9A (PubMed:24603492).1 Publication3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AP2M1Q96CW13EBI-742381,EBI-297683
ATXN1P542532EBI-742381,EBI-930964
VPS29Q9UBQ03EBI-742381,EBI-718596

GO - Molecular functioni

  • AP-2 adaptor complex binding Source: UniProtKB
  • Rab GTPase binding Source: GO_Central

Protein-protein interaction databases

BioGridi115123. 16 interactions.
IntActiQ92609. 17 interactions.
MINTiMINT-1457212.
STRINGi9606.ENSP00000402935.

Structurei

3D structure databases

ProteinModelPortaliQ92609.
SMRiQ92609. Positions 163-396.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini81 – 359279Rab-GAP TBCPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni56 – 649Required for interaction with retromer; involved in interaction with ATG8 family proteins1 Publication
Regioni786 – 7916Required for interaction with ATG8 family proteins1 Publication

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi57 – 626LIR 12 Publications
Motifi785 – 7895LIR 22 Publications

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
The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins. LIR 1 is also implicated in interaction with retromer; LIR 2 is only implicated in interaction with ATG8 family proteins.1 Publication1 Publication

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG1091. Eukaryota.
ENOG410YX8Z. LUCA.
GeneTreeiENSGT00840000129860.
HOGENOMiHOG000067839.
HOVERGENiHBG062913.
InParanoidiQ92609.
KOiK18469.
OMAiNFQTCLG.
OrthoDBiEOG091G0DU7.
PhylomeDBiQ92609.
TreeFamiTF105784.

Family and domain databases

InterProiIPR000195. Rab-GTPase-TBC_dom.
[Graphical view]
PfamiPF00566. RabGAP-TBC. 1 hit.
[Graphical view]
SMARTiSM00164. TBC. 1 hit.
[Graphical view]
SUPFAMiSSF47923. SSF47923. 3 hits.
PROSITEiPS50086. TBC_RABGAP. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q92609-1) [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
MYHSLSETRH PLQPEEQEVG IDPLSSYSNK SGGDSNKNGR RTSSTLDSEG
60 70 80 90 100
TFNSYRKEWE ELFVNNNYLA TIRQKGINGQ LRSSRFRSIC WKLFLCVLPQ
110 120 130 140 150
DKSQWISRIE ELRAWYSNIK EIHITNPRKV VGQQDLMINN PLSQDEGSLW
160 170 180 190 200
NKFFQDKELR SMIEQDVKRT FPEMQFFQQE NVRKILTDVL FCYARENEQL
210 220 230 240 250
LYKQGMHELL APIVFVLHCD HQAFLHASES AQPSEEMKTV LNPEYLEHDA
260 270 280 290 300
YAVFSQLMET AEPWFSTFEH DGQKGKETLM TPIPFARPQD LGPTIAIVTK
310 320 330 340 350
VNQIQDHLLK KHDIELYMHL NRLEIAPQIY GLRWVRLLFG REFPLQDLLV
360 370 380 390 400
VWDALFADGL SLGLVDYIFV AMLLYIRDAL ISSNYQTCLG LLMHYPFIGD
410 420 430 440 450
VHSLILKALF LRDPKRNPRP VTYQFHPNLD YYKARGADLM NKSRTNAKGA
460 470 480 490 500
PLNINKVSNS LINFGRKLIS PAMAPGSAGG PVPGGNSSSS SSVVIPTRTS
510 520 530 540 550
AEAPSHHLQQ QQQQQRLMKS ESMPVQLNKG LSSKNISSSP SVESLPGGRE
560 570 580 590 600
FTGSPPSSAT KKDSFFSNIS RSRSHSKTMG RKESEEELEA QISFLQGQLN
610 620 630 640 650
DLDAMCKYCA KVMDTHLVNI QDVILQENLE KEDQILVSLA GLKQIKDILK
660 670 680 690 700
GSLRFNQSQL EAEENEQITI ADNHYCSSGQ GQGRGQGQSV QMSGAIKQAS
710 720 730 740 750
SETPGCTDRG NSDDFILISK DDDGSSARGS FSGQAQPLRT LRSTSGKSQA
760 770 780 790
PVCSPLVFSD PLMGPASASS SNPSSSPDDD SSKDSGFTIV SPLDI
Length:795
Mass (Da):89,004
Last modified:February 1, 1997 - v1
Checksum:i598CE3B436835E1D
GO
Isoform 2 (identifier: Q92609-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     529-529: K → KGDVVTGSDAQVSVPVQTLTDLQ

Note: No experimental confirmation available.
Show »
Length:817
Mass (Da):91,216
Checksum:iC59C43FB263398BD
GO

Sequence cautioni

The sequence BAA13201 differs from that shown. Reason: Erroneous initiation. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti696 – 6961I → V.
Corresponds to variant rs1138454 [ dbSNP | Ensembl ].
VAR_052536

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei529 – 5291K → KGDVVTGSDAQVSVPVQTLT DLQ in isoform 2. 1 PublicationVSP_045039

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D86965 mRNA. Translation: BAA13201.2. Different initiation.
AK310539 mRNA. No translation available.
AC090644 Genomic DNA. No translation available.
AC090960 Genomic DNA. No translation available.
AC099543 Genomic DNA. No translation available.
AC104297 Genomic DNA. No translation available.
AC104451 Genomic DNA. No translation available.
AC132807 Genomic DNA. No translation available.
AC137672 Genomic DNA. No translation available.
AC139618 Genomic DNA. No translation available.
AC140076 Genomic DNA. No translation available.
AC144521 Genomic DNA. No translation available.
AC144531 Genomic DNA. No translation available.
BC013145 mRNA. Translation: AAH13145.1.
CCDSiCCDS33714.1. [Q92609-1]
CCDS46770.1. [Q92609-2]
RefSeqiNP_001127853.1. NM_001134381.1. [Q92609-2]
NP_055559.1. NM_014744.2. [Q92609-1]
XP_005265668.1. XM_005265611.1. [Q92609-2]
XP_005265669.1. XM_005265612.1. [Q92609-2]
XP_005265671.1. XM_005265614.1. [Q92609-1]
XP_006713493.1. XM_006713430.1. [Q92609-2]
XP_011532583.1. XM_011534281.1. [Q92609-2]
XP_011532585.1. XM_011534283.2. [Q92609-2]
XP_011532586.1. XM_011534284.2. [Q92609-2]
XP_011532588.1. XM_011534286.1. [Q92609-2]
UniGeneiHs.475629.

Genome annotation databases

EnsembliENST00000253692; ENSP00000253692; ENSG00000131374. [Q92609-1]
ENST00000429383; ENSP00000398127; ENSG00000131374. [Q92609-1]
ENST00000446818; ENSP00000402935; ENSG00000131374. [Q92609-2]
GeneIDi9779.
KEGGihsa:9779.
UCSCiuc003cbf.3. human. [Q92609-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D86965 mRNA. Translation: BAA13201.2. Different initiation.
AK310539 mRNA. No translation available.
AC090644 Genomic DNA. No translation available.
AC090960 Genomic DNA. No translation available.
AC099543 Genomic DNA. No translation available.
AC104297 Genomic DNA. No translation available.
AC104451 Genomic DNA. No translation available.
AC132807 Genomic DNA. No translation available.
AC137672 Genomic DNA. No translation available.
AC139618 Genomic DNA. No translation available.
AC140076 Genomic DNA. No translation available.
AC144521 Genomic DNA. No translation available.
AC144531 Genomic DNA. No translation available.
BC013145 mRNA. Translation: AAH13145.1.
CCDSiCCDS33714.1. [Q92609-1]
CCDS46770.1. [Q92609-2]
RefSeqiNP_001127853.1. NM_001134381.1. [Q92609-2]
NP_055559.1. NM_014744.2. [Q92609-1]
XP_005265668.1. XM_005265611.1. [Q92609-2]
XP_005265669.1. XM_005265612.1. [Q92609-2]
XP_005265671.1. XM_005265614.1. [Q92609-1]
XP_006713493.1. XM_006713430.1. [Q92609-2]
XP_011532583.1. XM_011534281.1. [Q92609-2]
XP_011532585.1. XM_011534283.2. [Q92609-2]
XP_011532586.1. XM_011534284.2. [Q92609-2]
XP_011532588.1. XM_011534286.1. [Q92609-2]
UniGeneiHs.475629.

3D structure databases

ProteinModelPortaliQ92609.
SMRiQ92609. Positions 163-396.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115123. 16 interactions.
IntActiQ92609. 17 interactions.
MINTiMINT-1457212.
STRINGi9606.ENSP00000402935.

PTM databases

iPTMnetiQ92609.
PhosphoSiteiQ92609.

Polymorphism and mutation databases

BioMutaiTBC1D5.
DMDMi2495720.

Proteomic databases

EPDiQ92609.
MaxQBiQ92609.
PaxDbiQ92609.
PeptideAtlasiQ92609.
PRIDEiQ92609.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000253692; ENSP00000253692; ENSG00000131374. [Q92609-1]
ENST00000429383; ENSP00000398127; ENSG00000131374. [Q92609-1]
ENST00000446818; ENSP00000402935; ENSG00000131374. [Q92609-2]
GeneIDi9779.
KEGGihsa:9779.
UCSCiuc003cbf.3. human. [Q92609-1]

Organism-specific databases

CTDi9779.
GeneCardsiTBC1D5.
HGNCiHGNC:19166. TBC1D5.
HPAiHPA035125.
HPA035126.
MIMi615740. gene.
neXtProtiNX_Q92609.
PharmGKBiPA38808.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1091. Eukaryota.
ENOG410YX8Z. LUCA.
GeneTreeiENSGT00840000129860.
HOGENOMiHOG000067839.
HOVERGENiHBG062913.
InParanoidiQ92609.
KOiK18469.
OMAiNFQTCLG.
OrthoDBiEOG091G0DU7.
PhylomeDBiQ92609.
TreeFamiTF105784.

Miscellaneous databases

ChiTaRSiTBC1D5. human.
GenomeRNAii9779.
PROiQ92609.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000131374.
CleanExiHS_TBC1D5.
ExpressionAtlasiQ92609. baseline and differential.
GenevisibleiQ92609. HS.

Family and domain databases

InterProiIPR000195. Rab-GTPase-TBC_dom.
[Graphical view]
PfamiPF00566. RabGAP-TBC. 1 hit.
[Graphical view]
SMARTiSM00164. TBC. 1 hit.
[Graphical view]
SUPFAMiSSF47923. SSF47923. 3 hits.
PROSITEiPS50086. TBC_RABGAP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTBCD5_HUMAN
AccessioniPrimary (citable) accession number: Q92609
Secondary accession number(s): A6NP25, C9JP52
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 1997
Last modified: September 7, 2016
This is version 137 of the entry and version 1 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 3
    Human chromosome 3: 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.