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UniProtKB - O60343 (TBCD4_HUMAN)

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Protein

TBC1 domain family member 4

Gene

TBC1D4

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

Functioni

May act as a GTPase-activating protein for RAB2A, RAB8A, RAB10 and RAB14. Isoform 2 promotes insulin-induced glucose transporter SLC2A4/GLUT4 translocation at the plasma membrane, thus increasing glucose uptake.3 Publications

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

  • activation of GTPase activity Source: GO_Central
  • cellular response to insulin stimulus Source: UniProtKB
  • intracellular protein transport Source: GO_Central
  • negative regulation of vesicle fusion Source: Ensembl
  • regulation of vesicle fusion Source: GO_Central
  • vesicle-mediated transport Source: UniProtKB
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionGTPase activation

Enzyme and pathway databases

ReactomeiR-HSA-1445148 Translocation of GLUT4 to the plasma membrane
SIGNORiO60343

Protein family/group databases

TCDBi8.A.87.1.1 the tbc1 domain (tbc1) family

Names & Taxonomyi

Protein namesi
Recommended name:
TBC1 domain family member 4
Alternative name(s):
Akt substrate of 160 kDa
Short name:
AS160
Gene namesi
Name:TBC1D4
Synonyms:AS160, KIAA0603
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 13

Organism-specific databases

EuPathDBiHostDB:ENSG00000136111.12
HGNCiHGNC:19165 TBC1D4
MIMi612465 gene
neXtProtiNX_O60343

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

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Diabetes mellitus, non-insulin-dependent, 5 (NIDDM5)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
See also OMIM:616087

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi318S → A: 80% reduction of insulin-stimulated GLUT4 translocation; when associated with A-588; A-642 and A-751. 1 Publication1
Mutagenesisi588S → A: 80% reduction of insulin-stimulated GLUT4 translocation; when associated with A-318; A-642 and A-751. 1 Publication1
Mutagenesisi642T → A: 80% reduction of insulin-stimulated GLUT4 translocation; when associated with A-318; A-588 and A-751. 1 Publication1
Mutagenesisi751S → A: 80% reduction of insulin-stimulated GLUT4 translocation; when associated with A-318; A-588 and A-642. 1 Publication1
Mutagenesisi972R → K: Loss of Rab GTPase activation. Only 20% reduction of GLUT4 translocation; even when associated with A-318; A-588; A-642 and A-751. 2 Publications1

Keywords - Diseasei

Diabetes mellitus

Organism-specific databases

DisGeNETi9882
MalaCardsiTBC1D4
MIMi616087 phenotype
OpenTargetsiENSG00000136111
PharmGKBiPA38807

Polymorphism and mutation databases

BioMutaiTBC1D4

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002080261 – 1298TBC1 domain family member 4Add BLAST1298

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei262PhosphoserineCombined sources1
Modified residuei314PhosphoserineCombined sources1
Modified residuei318Phosphoserine; by PKB/AKT1By similarity1
Modified residuei341PhosphoserineCombined sources1
Modified residuei344PhosphoserineCombined sources1
Modified residuei477N6-acetyllysineCombined sources1
Modified residuei566PhosphoserineCombined sources1
Modified residuei568PhosphothreonineCombined sources1
Modified residuei570PhosphoserineCombined sources1
Modified residuei577Omega-N-methylarginineBy similarity1
Modified residuei588Phosphoserine; by PKB/AKT1Combined sources1 Publication1
Modified residuei591PhosphoserineCombined sources1
Modified residuei609PhosphoserineBy similarity1
Modified residuei613PhosphothreonineBy similarity1
Modified residuei617PhosphoserineBy similarity1
Modified residuei642Phosphothreonine; by PKB/AKT12 Publications1
Modified residuei666PhosphoserineCombined sources1
Modified residuei751Phosphoserine; by PKB/AKT1By similarity1
Modified residuei754PhosphoserineCombined sources1
Modified residuei757PhosphoserineBy similarity1
Modified residuei763PhosphothreonineBy similarity1
Isoform 2 (identifier: O60343-2)
Modified residuei666PhosphoserineCombined sources1
Modified residuei672PhosphoserineCombined sources1
Modified residuei678PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by AKT1; insulin-induced. Also phosphorylated by AMPK in response to insulin. Insulin-stimulated phosphorylation is required for SLC2A4/GLUT4 translocation. Has no effect on SLC2A4/GLUT4 internalization. Physiological hyperinsulinemia increases phosphorylation in skeletal muscle. Insulin-stimulated phosphorylation is reduced by 39% in type 2 diabetic patients.3 Publications

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiO60343
MaxQBiO60343
PaxDbiO60343
PeptideAtlasiO60343
PRIDEiO60343
ProteomicsDBi49366
49367 [O60343-2]
49368 [O60343-3]
49369 [O60343-4]
49370 [O60343-5]

PTM databases

iPTMnetiO60343
PhosphoSitePlusiO60343

Miscellaneous databases

PMAP-CutDBiO60343

Expressioni

Tissue specificityi

Widely expressed. Isoform 2 is the highest overexpressed in most tissues. Isoform 1 is highly expressed in skeletal muscle and heart, but was not detectable in the liver nor in adipose tissue. Isoform 2 is strongly expressed in adrenal and thyroid gland, and also in lung, kidney, colon, brain and adipose tissue. Isoform 2 is moderately expressed in skeletal muscle. Expressed in pancreatic Langerhans islets, including beta cells (at protein level). Expression is decreased by twofold in pancreatic islets in type 2 diabetes patients compared to control subjects. Up-regulated in T-cells from patients with atopic dermatitis.3 Publications

Gene expression databases

BgeeiENSG00000136111
CleanExiHS_TBC1D4
ExpressionAtlasiO60343 baseline and differential
GenevisibleiO60343 HS

Organism-specific databases

HPAiHPA040145
HPA059885

Interactioni

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi115213, 62 interactors
IntActiO60343, 31 interactors
MINTiO60343
STRINGi9606.ENSP00000366863

Structurei

Secondary structure

11298
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni874 – 877Combined sources4
Helixi887 – 896Combined sources10
Helixi908 – 917Combined sources10
Turni921 – 923Combined sources3
Helixi924 – 937Combined sources14
Beta strandi943 – 946Combined sources4
Helixi952 – 956Combined sources5
Helixi963 – 970Combined sources8
Helixi978 – 981Combined sources4
Helixi986 – 1001Combined sources16
Turni1002 – 1005Combined sources4
Helixi1011 – 1019Combined sources9
Helixi1024 – 1035Combined sources12
Turni1036 – 1039Combined sources4
Turni1041 – 1044Combined sources4
Helixi1049 – 1063Combined sources15
Helixi1067 – 1075Combined sources9
Helixi1080 – 1083Combined sources4
Helixi1085 – 1090Combined sources6
Turni1091 – 1095Combined sources5
Helixi1098 – 1108Combined sources11
Turni1109 – 1111Combined sources3
Helixi1115 – 1124Combined sources10
Turni1128 – 1133Combined sources6
Helixi1137 – 1144Combined sources8
Turni1145 – 1149Combined sources5
Helixi1153 – 1164Combined sources12

3D structure databases

ProteinModelPortaliO60343
SMRiO60343
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60343

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini53 – 209PID 1PROSITE-ProRule annotationAdd BLAST157
Domaini312 – 468PID 2PROSITE-ProRule annotationAdd BLAST157
Domaini918 – 1112Rab-GAP TBCPROSITE-ProRule annotationAdd BLAST195

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi672 – 759Ser-richAdd BLAST88

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG4436 Eukaryota
ENOG410YWJY LUCA
GeneTreeiENSGT00750000117238
HOVERGENiHBG059376
InParanoidiO60343
KOiK17902
OMAiFPHPLEP
OrthoDBiEOG091G01QW
PhylomeDBiO60343
TreeFamiTF317184

Family and domain databases

Gene3Di2.30.29.30, 2 hits
InterProiView protein in InterPro
IPR021785 DUF3350
IPR011993 PH-like_dom_sf
IPR006020 PTB/PI_dom
IPR000195 Rab-GTPase-TBC_dom
IPR035969 Rab-GTPase_TBC_sf
IPR033564 TBC1D4
PANTHERiPTHR22957:SF195 PTHR22957:SF195, 1 hit
PfamiView protein in Pfam
PF11830 DUF3350, 1 hit
PF00640 PID, 2 hits
PF00566 RabGAP-TBC, 1 hit
SMARTiView protein in SMART
SM00462 PTB, 2 hits
SM00164 TBC, 1 hit
SUPFAMiSSF47923 SSF47923, 2 hits
PROSITEiView protein in PROSITE
PS01179 PID, 1 hit
PS50086 TBC_RABGAP, 1 hit

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O60343-1) [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
MEPPSCIQDE PFPHPLEPEP GVSAQPGPGK PSDKRFRLWY VGGSCLDHRT 
        60         70         80         90        100
TLPMLPWLMA EIRRRSQKPE AGGCGAPAAR EVILVLSAPF LRCVPAPGAG 
       110        120        130        140        150
ASGGTSPSAT QPNPAVFIFE HKAQHISRFI HNSHDLTYFA YLIKAQPDDP 
       160        170        180        190        200
ESQMACHVFR ATDPSQVPDV ISSIRQLSKA AMKEDAKPSK DNEDAFYNSQ 
       210        220        230        240        250
KFEVLYCGKV TVTHKKAPSS LIDDCMEKFS LHEQQRLKIQ GEQRGPDPGE 
       260        270        280        290        300
DLADLEVVVP GSPGDCLPEE ADGTDTHLGL PAGASQPALT SSRVCFPERI 
       310        320        330        340        350
LEDSGFDEQQ EFRSRCSSVT GVQRRVHEGS QKSQPRRRHA SAPSHVQPSD 
       360        370        380        390        400
SEKNRTMLFQ VGRFEINLIS PDTKSVVLEK NFKDISSCSQ GIKHVDHFGF 
       410        420        430        440        450
ICRESPEPGL SQYICYVFQC ASESLVDEVM LTLKQAFSTA AALQSAKTQI 
       460        470        480        490        500
KLCEACPMHS LHKLCERIEG LYPPRAKLVI QRHLSSLTDN EQADIFERVQ 
       510        520        530        540        550
KMKPVSDQEE NELVILHLRQ LCEAKQKTHV HIGEGPSTIS NSTIPENATS 
       560        570        580        590        600
SGRFKLDILK NKAKRSLTSS LENIFSRGAN RMRGRLGSVD SFERSNSLAS 
       610        620        630        640        650
EKDYSPGDSP PGTPPASPPS SAWQTFPEED SDSPQFRRRA HTFSHPPSST 
       660        670        680        690        700
KRKLNLQDGR AQGVRSPLLR QSSSEQCSNL SSVRRMYKES NSSSSLPSLH 
       710        720        730        740        750
TSFSAPSFTA PSFLKSFYQN SGRLSPQYEN EIRQDTASES SDGEGRKRTS 
       760        770        780        790        800
STCSNESLSV GGTSVTPRRI SWRQRIFLRV ASPMNKSPSA MQQQDGLDRN 
       810        820        830        840        850
ELLPLSPLSP TMEEEPLVVF LSGEDDPEKI EERKKSKELR SLWRKAIHQQ 
       860        870        880        890        900
ILLLRMEKEN QKLEASRDEL QSRKVKLDYE EVGACQKEVL ITWDKKLLNC 
       910        920        930        940        950
RAKIRCDMED IHTLLKEGVP KSRRGEIWQF LALQYRLRHR LPNKQQPPDI 
       960        970        980        990       1000
SYKELLKQLT AQQHAILVDL GRTFPTHPYF SVQLGPGQLS LFNLLKAYSL 
      1010       1020       1030       1040       1050
LDKEVGYCQG ISFVAGVLLL HMSEEQAFEM LKFLMYDLGF RKQYRPDMMS 
      1060       1070       1080       1090       1100
LQIQMYQLSR LLHDYHRDLY NHLEENEISP SLYAAPWFLT LFASQFSLGF 
      1110       1120       1130       1140       1150
VARVFDIIFL QGTEVIFKVA LSLLSSQETL IMECESFENI VEFLKNTLPD 
      1160       1170       1180       1190       1200
MNTSEMEKII TQVFEMDISK QLHAYEVEYH VLQDELQESS YSCEDSETLE 
      1210       1220       1230       1240       1250
KLERANSQLK RQNMDLLEKL QVAHTKIQAL ESNLENLLTR ETKMKSLIRT 
      1260       1270       1280       1290 
LEQEKMAYQK TVEQLRKLLP ADALVNCDLL LRDLNCNPNN KAKIGNKP
Length:1,298
Mass (Da):146,563
Last modified:June 7, 2005 - v2
Checksum:i8DC70CE887C0B311
GO
Isoform 2 (identifier: O60343-2) [UniParc]FASTAAdd to basket
Also known as: AS160_tv2

The sequence of this isoform differs from the canonical sequence as follows:
     678-740: Missing.

Show »
Length:1,235
Mass (Da):139,556
Checksum:i2A688BE2C17FD422
GO
Isoform 3 (identifier: O60343-3) [UniParc]FASTAAdd to basket
Also known as: AS160_tv3

The sequence of this isoform differs from the canonical sequence as follows:
     733-740: Missing.

Show »
Length:1,290
Mass (Da):145,689
Checksum:i38A0D7A205A0D252
GO
Isoform 4 (identifier: O60343-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-783: Missing.
     865-917: Missing.

Note: No experimental confirmation available.
Show »
Length:462
Mass (Da):53,850
Checksum:iB063DE6885C060DA
GO
Isoform 5 (identifier: O60343-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-783: Missing.

Note: No experimental confirmation available.
Show »
Length:515
Mass (Da):60,095
Checksum:i18CDA70728CE1CBB
GO

Sequence cautioni

The sequence BAA25529 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti644S → G in CAH18416 (PubMed:17974005).Curated1
Sequence conflicti845K → E in CAH18416 (PubMed:17974005).Curated1
Sequence conflicti864E → EG in BAH16628 (PubMed:19077034).Curated1
Sequence conflicti864E → EG in BAA25529 (PubMed:9628581).Curated1
Sequence conflicti864E → EG in AAI51240 (PubMed:15489334).Curated1
Sequence conflicti867R → G in CAH18416 (PubMed:17974005).Curated1
Sequence conflicti1137F → L in CAH18416 (PubMed:17974005).Curated1
Sequence conflicti1178E → G in BAG62187 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_061891619P → L. Corresponds to variant dbSNP:rs56223054EnsemblClinVar.1
Natural variantiVAR_059855819V → ICombined sources4 PublicationsCorresponds to variant dbSNP:rs1062087EnsemblClinVar.1
Natural variantiVAR_0618921119V → A. Corresponds to variant dbSNP:rs58232698EnsemblClinVar.1
Natural variantiVAR_0525341147T → M. Corresponds to variant dbSNP:rs9600455EnsemblClinVar.1
Natural variantiVAR_0525351275V → A3 PublicationsCorresponds to variant dbSNP:rs557337EnsemblClinVar.1
Natural variantiVAR_0548621284L → I. Corresponds to variant dbSNP:rs11616741Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0368681 – 783Missing in isoform 4 and isoform 5. 1 PublicationAdd BLAST783
Alternative sequenceiVSP_036869678 – 740Missing in isoform 2. 1 PublicationAdd BLAST63
Alternative sequenceiVSP_036870733 – 740Missing in isoform 3. 2 Publications8
Alternative sequenceiVSP_036871865 – 917Missing in isoform 4. 1 PublicationAdd BLAST53

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FM207106 mRNA Translation: CAR62509.1
FM207107 mRNA Translation: CAR62510.1
AB449885 mRNA Translation: BAH16628.1
AB011175 mRNA Translation: BAA25529.2 Different initiation.
AK300468 mRNA Translation: BAG62187.1
AK304091 mRNA Translation: BAG64997.1
AL139230 Genomic DNA No translation available.
AL162571 Genomic DNA No translation available.
BC151239 mRNA Translation: AAI51240.1
CR749622 mRNA Translation: CAH18416.1
CCDSiCCDS41901.1 [O60343-1]
CCDS66563.1 [O60343-2]
CCDS66564.1 [O60343-3]
PIRiT00261
RefSeqiNP_001273587.1, NM_001286658.2 [O60343-3]
NP_001273588.1, NM_001286659.2 [O60343-2]
NP_055647.2, NM_014832.4 [O60343-1]
UniGeneiHs.210891

Genome annotation databases

EnsembliENST00000377625; ENSP00000366852; ENSG00000136111 [O60343-2]
ENST00000377636; ENSP00000366863; ENSG00000136111 [O60343-1]
ENST00000431480; ENSP00000395986; ENSG00000136111 [O60343-3]
GeneIDi9882
KEGGihsa:9882
UCSCiuc001vjl.3 human [O60343-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTBCD4_HUMAN
AccessioniPrimary (citable) accession number: O60343
Secondary accession number(s): A7E2X8
, B4DU25, B4E235, B6ETN8, B6ETN9, Q5W0B9, Q68D14
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 10, 2002
Last sequence update: June 7, 2005
Last modified: July 18, 2018
This is version 164 of the entry and version 2 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 13
    Human chromosome 13: 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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