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UniProtKB - Q92609 (TBCD5_HUMAN)

Protein

TBC1 domain family member 5

Gene

TBC1D5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Sitei169Arginine fingerBy similarity1
Sitei204Glutamine fingerBy similarity1

GO - Molecular functioni

  • AP-2 adaptor complex binding Source: UniProtKB
  • GTPase activator activity Source: GO_Central
  • Rab GTPase binding Source: GO_Central
  • retromer complex binding Source: ParkinsonsUK-UCL
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionGTPase activation
Biological processAutophagy, 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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000131374.14
HGNCiHGNC:19166 TBC1D5
MIMi615740 gene
neXtProtiNX_Q92609

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasmic vesicle, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi59W → A: Disrupts interaction with VPS29. 1 Publication1
Mutagenesisi169R → A: Abolishes retromer displacement from endosome membrane; no effect on interaction with VPS29; when associated with A-204. 1 Publication1
Mutagenesisi204Q → A: Abolishes retromer displacement from endosome membrane; no effect on interaction with VPS29; when associated with A-169. 1 Publication1

Organism-specific databases

DisGeNETi9779
OpenTargetsiENSG00000131374
PharmGKBiPA38808

Polymorphism and mutation databases

BioMutaiTBC1D5
DMDMi2495720

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002080281 – 795TBC1 domain family member 5Add BLAST795

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei42PhosphothreonineCombined sources1
Modified residuei43PhosphoserineCombined sources1
Modified residuei44PhosphoserineCombined sources1
Modified residuei460PhosphoserineCombined sources1
Modified residuei522PhosphoserineCombined sources1
Modified residuei539PhosphoserineCombined sources1
Modified residuei541PhosphoserineCombined sources1
Modified residuei544PhosphoserineCombined sources1
Modified residuei554PhosphoserineCombined sources1
Modified residuei570PhosphoserineCombined sources1
Modified residuei584PhosphoserineBy similarity1
Modified residuei730PhosphoserineCombined sources1
Modified residuei791PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ92609
MaxQBiQ92609
PaxDbiQ92609
PeptideAtlasiQ92609
PRIDEiQ92609
ProteomicsDBi75354

PTM databases

iPTMnetiQ92609
PhosphoSitePlusiQ92609

Expressioni

Gene expression databases

BgeeiENSG00000131374 Expressed in 230 organ(s), highest expression level in corpus callosum
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

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi115123, 23 interactors
ELMiQ92609
IntActiQ92609, 27 interactors
MINTiQ92609
STRINGi9606.ENSP00000402935

Structurei

Secondary structure

1795
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ92609
SMRiQ92609
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini81 – 359Rab-GAP TBCPROSITE-ProRule annotationAdd BLAST279

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni56 – 64Required for interaction with retromer; involved in interaction with ATG8 family proteins1 Publication9
Regioni786 – 791Required for interaction with ATG8 family proteins1 Publication6

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi57 – 62LIR 12 Publications6
Motifi785 – 789LIR 22 Publications5

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

Phylogenomic databases

eggNOGiKOG1091 Eukaryota
ENOG410YX8Z LUCA
GeneTreeiENSGT00860000133795
HOGENOMiHOG000067839
HOVERGENiHBG062913
InParanoidiQ92609
KOiK18469
OMAiLEAMCKY
OrthoDBiEOG091G0DU7
PhylomeDBiQ92609
TreeFamiTF105784

Family and domain databases

InterProiView protein in InterPro
IPR000195 Rab-GTPase-TBC_dom
IPR035969 Rab-GTPase_TBC_sf
PfamiView protein in Pfam
PF00566 RabGAP-TBC, 1 hit
SMARTiView protein in SMART
SM00164 TBC, 1 hit
SUPFAMiSSF47923 SSF47923, 2 hits
PROSITEiView protein in PROSITE
PS50086 TBC_RABGAP, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 12 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9J3F6C9J3F6_HUMAN
TBC1 domain family member 5
TBC1D5
593Annotation score:
C9JDR8C9JDR8_HUMAN
TBC1 domain family member 5
TBC1D5
183Annotation score:
C9JMP7C9JMP7_HUMAN
TBC1 domain family member 5
TBC1D5
30Annotation score:
C9JWX0C9JWX0_HUMAN
TBC1 domain family member 5
TBC1D5
140Annotation score:
C9J397C9J397_HUMAN
TBC1 domain family member 5
TBC1D5
129Annotation score:
C9JNM0C9JNM0_HUMAN
TBC1 domain family member 5
TBC1D5
74Annotation score:
F2Z3C3F2Z3C3_HUMAN
TBC1 domain family member 5
TBC1D5
88Annotation score:
C9K0P2C9K0P2_HUMAN
TBC1 domain family member 5
TBC1D5
110Annotation score:
C9JIU4C9JIU4_HUMAN
TBC1 domain family member 5
TBC1D5
32Annotation score:
C9JED7C9JED7_HUMAN
TBC1 domain family member 5
TBC1D5
79Annotation score:
There are more potential isoformsShow all

Sequence cautioni

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052536696I → V. Corresponds to variant dbSNP:rs1138454Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_045039529K → KGDVVTGSDAQVSVPVQTLT DLQ in isoform 2. 1 Publication1

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_006713493.1, XM_006713430.1
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_016863041.1, XM_017007552.1 [Q92609-2]
XP_016863042.1, XM_017007553.1 [Q92609-2]
XP_016863043.1, XM_017007554.1 [Q92609-2]
XP_016863044.1, XM_017007555.1 [Q92609-2]
XP_016863045.1, XM_017007556.1 [Q92609-2]
XP_016863046.1, XM_017007557.1 [Q92609-1]
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

Similar proteinsi

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_006713493.1, XM_006713430.1
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_016863041.1, XM_017007552.1 [Q92609-2]
XP_016863042.1, XM_017007553.1 [Q92609-2]
XP_016863043.1, XM_017007554.1 [Q92609-2]
XP_016863044.1, XM_017007555.1 [Q92609-2]
XP_016863045.1, XM_017007556.1 [Q92609-2]
XP_016863046.1, XM_017007557.1 [Q92609-1]
UniGeneiHs.475629

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5GTUX-ray1.50B132-158[»]
ProteinModelPortaliQ92609
SMRiQ92609
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115123, 23 interactors
ELMiQ92609
IntActiQ92609, 27 interactors
MINTiQ92609
STRINGi9606.ENSP00000402935

PTM databases

iPTMnetiQ92609
PhosphoSitePlusiQ92609

Polymorphism and mutation databases

BioMutaiTBC1D5
DMDMi2495720

Proteomic databases

EPDiQ92609
MaxQBiQ92609
PaxDbiQ92609
PeptideAtlasiQ92609
PRIDEiQ92609
ProteomicsDBi75354

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
DisGeNETi9779
EuPathDBiHostDB:ENSG00000131374.14
GeneCardsiTBC1D5
HGNCiHGNC:19166 TBC1D5
HPAiHPA035125
HPA035126
MIMi615740 gene
neXtProtiNX_Q92609
OpenTargetsiENSG00000131374
PharmGKBiPA38808
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1091 Eukaryota
ENOG410YX8Z LUCA
GeneTreeiENSGT00860000133795
HOGENOMiHOG000067839
HOVERGENiHBG062913
InParanoidiQ92609
KOiK18469
OMAiLEAMCKY
OrthoDBiEOG091G0DU7
PhylomeDBiQ92609
TreeFamiTF105784

Miscellaneous databases

ChiTaRSiTBC1D5 human
GenomeRNAii9779
PROiPR:Q92609
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000131374 Expressed in 230 organ(s), highest expression level in corpus callosum
CleanExiHS_TBC1D5
ExpressionAtlasiQ92609 baseline and differential
GenevisibleiQ92609 HS

Family and domain databases

InterProiView protein in InterPro
IPR000195 Rab-GTPase-TBC_dom
IPR035969 Rab-GTPase_TBC_sf
PfamiView protein in Pfam
PF00566 RabGAP-TBC, 1 hit
SMARTiView protein in SMART
SM00164 TBC, 1 hit
SUPFAMiSSF47923 SSF47923, 2 hits
PROSITEiView protein in PROSITE
PS50086 TBC_RABGAP, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTBCD5_HUMAN
AccessioniPrimary (citable) accession number: Q92609
Secondary accession number(s): A6NP25, C9JP52
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 1997
Last modified: November 7, 2018
This is version 156 of the entry and version 1 of the sequence. See 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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