O60343 (TBCD4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
TBC1 domain family member 4

Alternative name(s):
Akt substrate of 160 kDa
Short name=AS160

Gene names

Name:	TBC1D4
Synonyms:	AS160, KIAA0603

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1298 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1 Ref.10 Ref.23
Subcellular location	Cytoplasm. Note: Isoform 2 shows a cytoplasmic perinuclear localization in a myoblastic cell line in resting and insulin-stimulated cells. Ref.1
Tissue specificity	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. Ref.1 Ref.13 Ref.14
Post-translational modification	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. Ref.1 Ref.8 Ref.15
Sequence similarities	Contains 2 PID domains. Contains 1 Rab-GAP TBC domain.
Sequence caution	The sequence BAA25529.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Molecular function	GTPase activation
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to insulin stimulus Inferred from mutant phenotype Ref.23. Source: UniProtKB positive regulation of Rab GTPase activity Inferred from electronic annotation. Source: GOC vesicle-mediated transport Inferred from mutant phenotype Ref.23. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	Rab GTPase activator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O60343-1)

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.

Isoform 2 (identifier: O60343-2)

Also known as: AS160_tv2;

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

Note: Contains a phosphoserine at position 666. Contains a phosphoserine at position 672. Contains a phosphoserine at position 678.

Isoform 3 (identifier: O60343-3)

Also known as: AS160_tv3;

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

Isoform 4 (identifier: O60343-4)

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

Note: No experimental confirmation available.

Isoform 5 (identifier: O60343-5)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1298

1298

TBC1 domain family member 4

PRO_0000208026

Regions

Domain

53 – 209

157

PID 1

Domain

312 – 468

157

PID 2

Domain

918 – 1112

195

Rab-GAP TBC

Compositional bias

672 – 759

88

Ser-rich

Amino acid modifications

Modified residue

318

1

Phosphoserine; by PKB/AKT1 By similarity

Modified residue

341

1

Phosphoserine Ref.17 Ref.20 Ref.22

Modified residue

344

1

Phosphoserine Ref.11 Ref.22

Modified residue

477

1

N6-acetyllysine Ref.19

Modified residue

566

1

Phosphoserine Ref.17 Ref.18 Ref.20

Modified residue

568

1

Phosphothreonine Ref.18

Modified residue

570

1

Phosphoserine Ref.17 Ref.18

Modified residue

588

1

Phosphoserine; by PKB/AKT1 Ref.8 Ref.12 Ref.18 Ref.20 Ref.22

Modified residue

591

1

Phosphoserine Ref.12 Ref.22

Modified residue

642

1

Phosphothreonine; by PKB/AKT1 Ref.1 Ref.8

Modified residue

751

1

Phosphoserine; by PKB/AKT1 By similarity

Natural variations

Alternative sequence

1 – 783

783

Missing in isoform 4 and isoform 5.

VSP_036868

Alternative sequence

678 – 740

63

Missing in isoform 2.

VSP_036869

Alternative sequence

733 – 740

8

Missing in isoform 3.

VSP_036870

Alternative sequence

865 – 917

53

Missing in isoform 4.

VSP_036871

Natural variant

619

1

P → L.
Corresponds to variant rs56223054 [ dbSNP | Ensembl ].

VAR_061891

Natural variant

819

1

V → I. Ref.2 Ref.3 Ref.6 Ref.7 Ref.20
Corresponds to variant rs1062087 [ dbSNP | Ensembl ].

VAR_059855

Natural variant

1119

1

V → A.
Corresponds to variant rs58232698 [ dbSNP | Ensembl ].

VAR_061892

Natural variant

1147

1

T → M.
Corresponds to variant rs9600455 [ dbSNP | Ensembl ].

VAR_052534

Natural variant

1275

1

V → A. Ref.2 Ref.3 Ref.6
Corresponds to variant rs557337 [ dbSNP | Ensembl ].

VAR_052535

Natural variant

1284

1

L → I.
Corresponds to variant rs11616741 [ dbSNP | Ensembl ].

VAR_054862

Experimental info

Mutagenesis

318

1

S → A: 80% reduction of insulin-stimulated GLUT4 translocation; when associated with A-588; A-642 and A-751. Ref.9

Mutagenesis

588

1

S → A: 80% reduction of insulin-stimulated GLUT4 translocation; when associated with A-318; A-642 and A-751. Ref.9

Mutagenesis

642

1

T → A: 80% reduction of insulin-stimulated GLUT4 translocation; when associated with A-318; A-588 and A-751. Ref.9

Mutagenesis

751

1

S → A: 80% reduction of insulin-stimulated GLUT4 translocation; when associated with A-318; A-588 and A-642. Ref.9

Mutagenesis

972

1

R → 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. Ref.9 Ref.10

Sequence conflict

644

1

S → G in CAH18416. Ref.7

Sequence conflict

845

1

K → E in CAH18416. Ref.7

Sequence conflict

864

1

E → EG in BAH16628. Ref.2

Sequence conflict

864

1

E → EG in BAA25529. Ref.3

Sequence conflict

864

1

E → EG in AAI51240. Ref.6

Sequence conflict

867

1

R → G in CAH18416. Ref.7

Sequence conflict

1137

1

F → L in CAH18416. Ref.7

Sequence conflict

1178

1

E → G in BAG62187. Ref.4

Secondary structure

1

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1298

Helix Strand Turn

Details...

Turn

874 – 877

4

Helix

887 – 896

10

Helix

908 – 917

10

Turn

921 – 923

3

Helix

924 – 937

14

Beta strand

943 – 946

4

Helix

952 – 956

5

Helix

963 – 970

8

Helix

978 – 981

4

Helix

986 – 1001

16

Turn

1002 – 1005

4

Helix

1011 – 1019

9

Helix

1024 – 1035

12

Turn

1036 – 1039

4

Turn

1041 – 1044

4

Helix

1049 – 1063

15

Helix

1067 – 1075

9

Helix

1080 – 1083

4

Helix

1085 – 1090

6

Turn

1091 – 1095

5

Helix

1098 – 1108

11

Turn

1109 – 1111

3

Helix

1115 – 1124

10

Turn

1128 – 1133

6

Helix

1137 – 1144

8

Turn

1145 – 1149

5

Helix

1153 – 1164

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 7, 2005. Version 2. Checksum: 8DC70CE887C0B311	FASTA	1,298	146,563
	10 20 30 40 50 60 MEPPSCIQDE PFPHPLEPEP GVSAQPGPGK PSDKRFRLWY VGGSCLDHRT TLPMLPWLMA 70 80 90 100 110 120 EIRRRSQKPE AGGCGAPAAR EVILVLSAPF LRCVPAPGAG ASGGTSPSAT QPNPAVFIFE 130 140 150 160 170 180 HKAQHISRFI HNSHDLTYFA YLIKAQPDDP ESQMACHVFR ATDPSQVPDV ISSIRQLSKA 190 200 210 220 230 240 AMKEDAKPSK DNEDAFYNSQ KFEVLYCGKV TVTHKKAPSS LIDDCMEKFS LHEQQRLKIQ 250 260 270 280 290 300 GEQRGPDPGE DLADLEVVVP GSPGDCLPEE ADGTDTHLGL PAGASQPALT SSRVCFPERI 310 320 330 340 350 360 LEDSGFDEQQ EFRSRCSSVT GVQRRVHEGS QKSQPRRRHA SAPSHVQPSD SEKNRTMLFQ 370 380 390 400 410 420 VGRFEINLIS PDTKSVVLEK NFKDISSCSQ GIKHVDHFGF ICRESPEPGL SQYICYVFQC 430 440 450 460 470 480 ASESLVDEVM LTLKQAFSTA AALQSAKTQI KLCEACPMHS LHKLCERIEG LYPPRAKLVI 490 500 510 520 530 540 QRHLSSLTDN EQADIFERVQ KMKPVSDQEE NELVILHLRQ LCEAKQKTHV HIGEGPSTIS 550 560 570 580 590 600 NSTIPENATS SGRFKLDILK NKAKRSLTSS LENIFSRGAN RMRGRLGSVD SFERSNSLAS 610 620 630 640 650 660 EKDYSPGDSP PGTPPASPPS SAWQTFPEED SDSPQFRRRA HTFSHPPSST KRKLNLQDGR 670 680 690 700 710 720 AQGVRSPLLR QSSSEQCSNL SSVRRMYKES NSSSSLPSLH TSFSAPSFTA PSFLKSFYQN 730 740 750 760 770 780 SGRLSPQYEN EIRQDTASES SDGEGRKRTS STCSNESLSV GGTSVTPRRI SWRQRIFLRV 790 800 810 820 830 840 ASPMNKSPSA MQQQDGLDRN ELLPLSPLSP TMEEEPLVVF LSGEDDPEKI EERKKSKELR 850 860 870 880 890 900 SLWRKAIHQQ ILLLRMEKEN QKLEASRDEL QSRKVKLDYE EVGACQKEVL ITWDKKLLNC 910 920 930 940 950 960 RAKIRCDMED IHTLLKEGVP KSRRGEIWQF LALQYRLRHR LPNKQQPPDI SYKELLKQLT 970 980 990 1000 1010 1020 AQQHAILVDL GRTFPTHPYF SVQLGPGQLS LFNLLKAYSL LDKEVGYCQG ISFVAGVLLL 1030 1040 1050 1060 1070 1080 HMSEEQAFEM LKFLMYDLGF RKQYRPDMMS LQIQMYQLSR LLHDYHRDLY NHLEENEISP 1090 1100 1110 1120 1130 1140 SLYAAPWFLT LFASQFSLGF VARVFDIIFL QGTEVIFKVA LSLLSSQETL IMECESFENI 1150 1160 1170 1180 1190 1200 VEFLKNTLPD MNTSEMEKII TQVFEMDISK QLHAYEVEYH VLQDELQESS YSCEDSETLE 1210 1220 1230 1240 1250 1260 KLERANSQLK RQNMDLLEKL QVAHTKIQAL ESNLENLLTR ETKMKSLIRT LEQEKMAYQK 1270 1280 1290 TVEQLRKLLP ADALVNCDLL LRDLNCNPNN KAKIGNKP
	Isoform 2 (AS160_tv2) [UniParc]. Checksum: 2A688BE2C17FD422	FASTA	1,235	139,556
	10 20 30 40 50 60 MEPPSCIQDE PFPHPLEPEP GVSAQPGPGK PSDKRFRLWY VGGSCLDHRT TLPMLPWLMA 70 80 90 100 110 120 EIRRRSQKPE AGGCGAPAAR EVILVLSAPF LRCVPAPGAG ASGGTSPSAT QPNPAVFIFE 130 140 150 160 170 180 HKAQHISRFI HNSHDLTYFA YLIKAQPDDP ESQMACHVFR ATDPSQVPDV ISSIRQLSKA 190 200 210 220 230 240 AMKEDAKPSK DNEDAFYNSQ KFEVLYCGKV TVTHKKAPSS LIDDCMEKFS LHEQQRLKIQ 250 260 270 280 290 300 GEQRGPDPGE DLADLEVVVP GSPGDCLPEE ADGTDTHLGL PAGASQPALT SSRVCFPERI 310 320 330 340 350 360 LEDSGFDEQQ EFRSRCSSVT GVQRRVHEGS QKSQPRRRHA SAPSHVQPSD SEKNRTMLFQ 370 380 390 400 410 420 VGRFEINLIS PDTKSVVLEK NFKDISSCSQ GIKHVDHFGF ICRESPEPGL SQYICYVFQC 430 440 450 460 470 480 ASESLVDEVM LTLKQAFSTA AALQSAKTQI KLCEACPMHS LHKLCERIEG LYPPRAKLVI 490 500 510 520 530 540 QRHLSSLTDN EQADIFERVQ KMKPVSDQEE NELVILHLRQ LCEAKQKTHV HIGEGPSTIS 550 560 570 580 590 600 NSTIPENATS SGRFKLDILK NKAKRSLTSS LENIFSRGAN RMRGRLGSVD SFERSNSLAS 610 620 630 640 650 660 EKDYSPGDSP PGTPPASPPS SAWQTFPEED SDSPQFRRRA HTFSHPPSST KRKLNLQDGR 670 680 690 700 710 720 AQGVRSPLLR QSSSEQCSDG EGRKRTSSTC SNESLSVGGT SVTPRRISWR QRIFLRVASP 730 740 750 760 770 780 MNKSPSAMQQ QDGLDRNELL PLSPLSPTME EEPLVVFLSG EDDPEKIEER KKSKELRSLW 790 800 810 820 830 840 RKAIHQQILL LRMEKENQKL EASRDELQSR KVKLDYEEVG ACQKEVLITW DKKLLNCRAK 850 860 870 880 890 900 IRCDMEDIHT LLKEGVPKSR RGEIWQFLAL QYRLRHRLPN KQQPPDISYK ELLKQLTAQQ 910 920 930 940 950 960 HAILVDLGRT FPTHPYFSVQ LGPGQLSLFN LLKAYSLLDK EVGYCQGISF VAGVLLLHMS 970 980 990 1000 1010 1020 EEQAFEMLKF LMYDLGFRKQ YRPDMMSLQI QMYQLSRLLH DYHRDLYNHL EENEISPSLY 1030 1040 1050 1060 1070 1080 AAPWFLTLFA SQFSLGFVAR VFDIIFLQGT EVIFKVALSL LSSQETLIME CESFENIVEF 1090 1100 1110 1120 1130 1140 LKNTLPDMNT SEMEKIITQV FEMDISKQLH AYEVEYHVLQ DELQESSYSC EDSETLEKLE 1150 1160 1170 1180 1190 1200 RANSQLKRQN MDLLEKLQVA HTKIQALESN LENLLTRETK MKSLIRTLEQ EKMAYQKTVE 1210 1220 1230 QLRKLLPADA LVNCDLLLRD LNCNPNNKAK IGNKP
	Isoform 3 (AS160_tv3) [UniParc]. Checksum: 38A0D7A205A0D252	FASTA	1,290	145,689
	10 20 30 40 50 60 MEPPSCIQDE PFPHPLEPEP GVSAQPGPGK PSDKRFRLWY VGGSCLDHRT TLPMLPWLMA 70 80 90 100 110 120 EIRRRSQKPE AGGCGAPAAR EVILVLSAPF LRCVPAPGAG ASGGTSPSAT QPNPAVFIFE 130 140 150 160 170 180 HKAQHISRFI HNSHDLTYFA YLIKAQPDDP ESQMACHVFR ATDPSQVPDV ISSIRQLSKA 190 200 210 220 230 240 AMKEDAKPSK DNEDAFYNSQ KFEVLYCGKV TVTHKKAPSS LIDDCMEKFS LHEQQRLKIQ 250 260 270 280 290 300 GEQRGPDPGE DLADLEVVVP GSPGDCLPEE ADGTDTHLGL PAGASQPALT SSRVCFPERI 310 320 330 340 350 360 LEDSGFDEQQ EFRSRCSSVT GVQRRVHEGS QKSQPRRRHA SAPSHVQPSD SEKNRTMLFQ 370 380 390 400 410 420 VGRFEINLIS PDTKSVVLEK NFKDISSCSQ GIKHVDHFGF ICRESPEPGL SQYICYVFQC 430 440 450 460 470 480 ASESLVDEVM LTLKQAFSTA AALQSAKTQI KLCEACPMHS LHKLCERIEG LYPPRAKLVI 490 500 510 520 530 540 QRHLSSLTDN EQADIFERVQ KMKPVSDQEE NELVILHLRQ LCEAKQKTHV HIGEGPSTIS 550 560 570 580 590 600 NSTIPENATS SGRFKLDILK NKAKRSLTSS LENIFSRGAN RMRGRLGSVD SFERSNSLAS 610 620 630 640 650 660 EKDYSPGDSP PGTPPASPPS SAWQTFPEED SDSPQFRRRA HTFSHPPSST KRKLNLQDGR 670 680 690 700 710 720 AQGVRSPLLR QSSSEQCSNL SSVRRMYKES NSSSSLPSLH TSFSAPSFTA PSFLKSFYQN 730 740 750 760 770 780 SGRLSPQYEN EISDGEGRKR TSSTCSNESL SVGGTSVTPR RISWRQRIFL RVASPMNKSP 790 800 810 820 830 840 SAMQQQDGLD RNELLPLSPL SPTMEEEPLV VFLSGEDDPE KIEERKKSKE LRSLWRKAIH 850 860 870 880 890 900 QQILLLRMEK ENQKLEASRD ELQSRKVKLD YEEVGACQKE VLITWDKKLL NCRAKIRCDM 910 920 930 940 950 960 EDIHTLLKEG VPKSRRGEIW QFLALQYRLR HRLPNKQQPP DISYKELLKQ LTAQQHAILV 970 980 990 1000 1010 1020 DLGRTFPTHP YFSVQLGPGQ LSLFNLLKAY SLLDKEVGYC QGISFVAGVL LLHMSEEQAF 1030 1040 1050 1060 1070 1080 EMLKFLMYDL GFRKQYRPDM MSLQIQMYQL SRLLHDYHRD LYNHLEENEI SPSLYAAPWF 1090 1100 1110 1120 1130 1140 LTLFASQFSL GFVARVFDII FLQGTEVIFK VALSLLSSQE TLIMECESFE NIVEFLKNTL 1150 1160 1170 1180 1190 1200 PDMNTSEMEK IITQVFEMDI SKQLHAYEVE YHVLQDELQE SSYSCEDSET LEKLERANSQ 1210 1220 1230 1240 1250 1260 LKRQNMDLLE KLQVAHTKIQ ALESNLENLL TRETKMKSLI RTLEQEKMAY QKTVEQLRKL 1270 1280 1290 LPADALVNCD LLLRDLNCNP NNKAKIGNKP
	Isoform 4 [UniParc]. Checksum: B063DE6885C060DA	FASTA	462	53,850
	10 20 30 40 50 60 MNKSPSAMQQ QDGLDRNELL PLSPLSPTME EEPLVVFLSG EDDPEKIEER KKSKELRSLW 70 80 90 100 110 120 RKAIHQQILL LRMEKENQKL EGVPKSRRGE IWQFLALQYR LRHRLPNKQQ PPDISYKELL 130 140 150 160 170 180 KQLTAQQHAI LVDLGRTFPT HPYFSVQLGP GQLSLFNLLK AYSLLDKEVG YCQGISFVAG 190 200 210 220 230 240 VLLLHMSEEQ AFEMLKFLMY DLGFRKQYRP DMMSLQIQMY QLSRLLHDYH RDLYNHLEEN 250 260 270 280 290 300 EISPSLYAAP WFLTLFASQF SLGFVARVFD IIFLQGTEVI FKVALSLLSS QETLIMECES 310 320 330 340 350 360 FENIVEFLKN TLPDMNTSEM EKIITQVFEM DISKQLHAYE VEYHVLQDEL QESSYSCEDS 370 380 390 400 410 420 ETLEKLERAN SQLKRQNMDL LEKLQVAHTK IQALESNLEN LLTRETKMKS LIRTLEQEKM 430 440 450 460 AYQKTVEQLR KLLPADALVN CDLLLRDLNC NPNNKAKIGN KP
	Isoform 5 [UniParc]. Checksum: 18CDA70728CE1CBB	FASTA	515	60,095
	10 20 30 40 50 60 MNKSPSAMQQ QDGLDRNELL PLSPLSPTME EEPLVVFLSG EDDPEKIEER KKSKELRSLW 70 80 90 100 110 120 RKAIHQQILL LRMEKENQKL EASRDELQSR KVKLDYEEVG ACQKEVLITW DKKLLNCRAK 130 140 150 160 170 180 IRCDMEDIHT LLKEGVPKSR RGEIWQFLAL QYRLRHRLPN KQQPPDISYK ELLKQLTAQQ 190 200 210 220 230 240 HAILVDLGRT FPTHPYFSVQ LGPGQLSLFN LLKAYSLLDK EVGYCQGISF VAGVLLLHMS 250 260 270 280 290 300 EEQAFEMLKF LMYDLGFRKQ YRPDMMSLQI QMYQLSRLLH DYHRDLYNHL EENEISPSLY 310 320 330 340 350 360 AAPWFLTLFA SQFSLGFVAR VFDIIFLQGT EVIFKVALSL LSSQETLIME CESFENIVEF 370 380 390 400 410 420 LKNTLPDMNT SEMEKIITQV FEMDISKQLH AYEVEYHVLQ DELQESSYSC EDSETLEKLE 430 440 450 460 470 480 RANSQLKRQN MDLLEKLQVA HTKIQALESN LENLLTRETK MKSLIRTLEQ EKMAYQKTVE 490 500 510 QLRKLLPADA LVNCDLLLRD LNCNPNNKAK IGNKP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a novel AS160 splice variant that regulates GLUT4 translocation and glucose-uptake in rat muscle cells." Baus D., Heermeier K., De Hoop M., Metz-Weidmann C., Gassenhuber J., Dittrich W., Welte S., Tennagels N. Cell. Signal. 20:2237-2246(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PHOSPHORYLATION AT THR-642. Tissue: Testis.
[2]	"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 1), VARIANTS ILE-819 AND ALA-1275. Tissue: Brain.
[3]	"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS ILE-819 AND ALA-1275. Tissue: Brain.
[4]	"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 4 AND 5). Tissue: Placenta and Trachea.
[5]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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 ILE-819 AND ALA-1275.
[7]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 600-1298 (ISOFORM 3), VARIANT ILE-819. Tissue: Fetal liver.
[8]	"A method to identify serine kinase substrates. Akt phosphorylates a novel adipocyte protein with a Rab GTPase-activating protein (GAP) domain." Kane S., Sano H., Liu S.C.H., Asara J.M., Lane W.S., Garner C.C., Lienhard G.E. J. Biol. Chem. 277:22115-22118(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-588 AND THR-642.
[9]	"Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation." Sano H., Kane S., Sano E., Miinea C.P., Asara J.M., Lane W.S., Garner C.W., Lienhard G.E. J. Biol. Chem. 278:14599-14602(2003) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF SER-318; SER-588; THR-642; SER-751 AND ARG-972, EFFECT ON GLUT4 TRANSLOCATION.
[10]	"AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain." Miinea C.P., Sano H., Kane S., Sano E., Fukuda M., Peraenen J., Lane W.S., Lienhard G.E. Biochem. J. 391:87-93(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ARG-972.
[11]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-344, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588 AND SER-591, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Rab GTPase-activating protein AS160 is a major downstream effector of protein kinase B/Akt signaling in pancreatic beta-cells." Bouzakri K., Ribaux P., Tomas A., Parnaud G., Rickenbach K., Halban P.A. Diabetes 57:1195-1204(2008) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[14]	"Upregulation of the transcript level of GTPase activating protein KIAA0603 in T cells from patients with atopic dermatitis." Matsumoto Y., Imai Y., Lu Yoshida N., Sugita Y., Tanaka T., Tsujimoto G., Saito H., Oshida T. FEBS Lett. 572:135-140(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[15]	"Insulin-stimulated phosphorylation of the Akt substrate AS160 is impaired in skeletal muscle of type 2 diabetic subjects." Karlsson H.K.R., Zierath J.R., Kane S., Krook A., Lienhard G.E., Wallberg-Henriksson H. Diabetes 54:1692-1697(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION.
[16]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[17]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-341; SER-566 AND SER-570, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-666; SER-672 AND SER-678 (ISOFORM 2), MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-566; THR-568; SER-570 AND SER-588, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[19]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-477, MASS SPECTROMETRY.
[20]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-341; SER-566 AND SER-588, VARIANT [LARGE SCALE ANALYSIS] ILE-819, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[21]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-341; SER-344; SER-588 AND SER-591, MASS SPECTROMETRY.
[23]	"Rab10 and myosin-Va mediate insulin-stimulated GLUT4 storage vesicle translocation in adipocytes." Chen Y., Wang Y., Zhang J., Deng Y., Jiang L., Song E., Wu X.S., Hammer J.A., Xu T., Lippincott-Schwartz J. J. Cell Biol. 198:545-560(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[24]	"Crystal structures of human TBC1D1 and TBC1D4 (AS160) RabGTPase-activating protein (RabGAP) domains reveal critical elements for GLUT4 translocation." Park S.Y., Jin W., Woo J.R., Shoelson S.E. J. Biol. Chem. 286:18130-18138(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 874-1170.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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, AL162571 Genomic DNA. Translation: CAH70991.1.
AL162571, AL139230 Genomic DNA. Translation: CAI39591.1.
BC151239 mRNA. Translation: AAI51240.1.
CR749622 mRNA. Translation: CAH18416.1.

IPI

IPI00926241.
IPI00926460.
IPI00926756.
IPI00926985.
IPI00942269.

PIR

T00261.

RefSeq

NP_055647.2. NM_014832.2.

UniGene

Hs.210891.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3QYB	X-ray	3.50	A	874-1170	[»]

ProteinModelPortal

O60343.

ModBase

Search...

Protein-protein interaction databases

IntAct

O60343. 16 interactions.

MINT

MINT-5005871.

STRING

9606.ENSP00000366863.

PTM databases

PhosphoSite

O60343.

Proteomic databases

PaxDb

O60343.

PRIDE

O60343.

Protocols and materials databases

DNASU

9882.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000377625; ENSP00000366852; ENSG00000136111.
ENST00000377636; ENSP00000366863; ENSG00000136111.
ENST00000425511; ENSP00000390654; ENSG00000136111.
ENST00000431480; ENSP00000395986; ENSG00000136111.

GeneID

9882.

KEGG

hsa:9882.

UCSC

uc001vjl.1. human.
uc010aer.2. human.
uc010aes.2. human.
uc010tht.1. human.
uc010thu.1. human.

Organism-specific databases

CTD

9882.

GeneCards

GC13M075858.

H-InvDB

HIX0017963.

HGNC

HGNC:19165. TBC1D4.

HPA

CAB011623.

MIM

612465. gene.

neXtProt

NX_O60343.

PharmGKB

PA38807.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5210.

HOVERGEN

HBG059376.

InParanoid

O60343.

OMA

WYVGGSC.

OrthoDB

EOG498V01.

Enzyme and pathway databases

Pathway_Interaction_DB

pi3kciaktpathway. Class I PI3K signaling events mediated by Akt.
insulin_glucose_pathway. Insulin-mediated glucose transport.

Reactome

REACT_11123. Membrane Trafficking.

Gene expression databases

ArrayExpress

O60343.

Bgee

O60343.

CleanEx

HS_TBC1D4.

Genevestigator

O60343.

GermOnline

ENSG00000136111. Homo sapiens.

Family and domain databases

Gene3D

2.30.29.30. 3 hits.

InterPro

IPR021785. DUF3350.
IPR011993. PH_like_dom.
IPR006020. PTyr_interaction_dom.
IPR000195. Rab-GTPase-TBC_dom.
[Graphical view]

Pfam

PF11830. DUF3350. 1 hit.
PF00640. PID. 2 hits.
PF00566. RabGAP-TBC. 1 hit.
[Graphical view]

SMART

SM00462. PTB. 2 hits.
SM00164. TBC. 1 hit.
[Graphical view]

SUPFAM

SSF47923. RabGAP_TBC. 2 hits.

PROSITE

PS01179. PID. 1 hit.
PS50086. TBC_RABGAP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

TBC1D4. human.

EvolutionaryTrace

O60343.

GenomeRNAi

9882.

NextBio

37248.

PMAP-CutDB

O60343.

SOURCE

Search...

Entry information

Entry name

TBCD4_HUMAN

Accession

Primary (citable) accession number: O60343
Secondary accession number(s): A7E2X8 , B4DU25, B4E235, B6ETN8, B6ETN9, Q5W0B9, Q68D14

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 10, 2002
Last sequence update:	June 7, 2005
Last modified:	May 1, 2013
This is version 113 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.