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Protein

TGF-beta-activated kinase 1 and MAP3K7-binding protein 2

Gene

TAB2

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

Functioni

Adapter linking MAP3K7/TAK1 and TRAF6. Promotes MAP3K7 activation in the IL1 signaling pathway. The binding of 'Lys-63'-linked polyubiquitin chains to TAB2 promotes autophosphorylation of MAP3K7 at 'Thr-187'. Involved in heart development.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri663 – 693RanBP2-typePROSITE-ProRule annotationAdd BLAST31

GO - Molecular functioni

GO - Biological processi

Keywordsi

LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-1251985 Nuclear signaling by ERBB4
R-HSA-168638 NOD1/2 Signaling Pathway
R-HSA-202424 Downstream TCR signaling
R-HSA-2871837 FCERI mediated NF-kB activation
R-HSA-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-HSA-450302 activated TAK1 mediates p38 MAPK activation
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-5357956 TNFR1-induced NFkappaB signaling pathway
R-HSA-5607764 CLEC7A (Dectin-1) signaling
R-HSA-9014325 TICAM1,TRAF6-dependent induction of TAK1 complex
R-HSA-9020702 Interleukin-1 signaling
R-HSA-937042 IRAK2 mediated activation of TAK1 complex
R-HSA-937072 TRAF6-mediated induction of TAK1 complex within TLR4 complex
R-HSA-975163 IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation
SignaLinkiQ9NYJ8
SIGNORiQ9NYJ8

Names & Taxonomyi

Protein namesi
Recommended name:
TGF-beta-activated kinase 1 and MAP3K7-binding protein 2
Alternative name(s):
Mitogen-activated protein kinase kinase kinase 7-interacting protein 2
TAK1-binding protein 2
Short name:
TAB-2
TGF-beta-activated kinase 1-binding protein 2
Gene namesi
Name:TAB2
Synonyms:KIAA0733, MAP3K7IP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000055208.17
HGNCiHGNC:17075 TAB2
MIMi605101 gene
neXtProtiNX_Q9NYJ8

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, Membrane

Pathology & Biotechi

Involvement in diseasei

Congenital heart defects, multiple types, 2 (CHTD2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving TAB2 has been found in a family with congenital heart disease. Translocation t(2;6)(q21;q25).
Disease descriptionA disease characterized by congenital developmental abnormalities involving structures of the heart. CHTD2 patients have left ventricular outflow tract obstruction, subaortic stenosis, residual aortic regurgitation, atrial fibrillation, bicuspid aortic valve and aortic dilation.
See also OMIM:614980
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063774208P → S in CHTD2. 1 PublicationCorresponds to variant dbSNP:rs267607101Ensembl.1
Natural variantiVAR_063775230Q → K in CHTD2. 1 PublicationCorresponds to variant dbSNP:rs267607100Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi675F → A: Abolishes ubiquitin binding. 1 Publication1
Mutagenesisi678H → A: Abolishes ubiquitin binding. 1 Publication1
Mutagenesisi681L → A: Abolishes ubiquitin binding. 1 Publication1
Mutagenesisi685E → A: Abolishes ubiquitin binding. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi23118
MalaCardsiTAB2
MIMi614980 phenotype
OpenTargetsiENSG00000055208
PharmGKBiPA30605

Polymorphism and mutation databases

BioMutaiTAB2
DMDMi74753070

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002256951 – 693TGF-beta-activated kinase 1 and MAP3K7-binding protein 2Add BLAST693

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei173Asymmetric dimethylarginineCombined sources1
Modified residuei372PhosphoserineCombined sources1
Modified residuei450PhosphoserineCombined sources1
Modified residuei482PhosphoserineCombined sources1
Modified residuei524PhosphoserineCombined sources1
Modified residuei582PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated; following IL1 stimulation or TRAF6 overexpression. Ubiquitination involves RBCK1 leading to proteasomal degradation.2 Publications
Phosphorylated.1 Publication

Keywords - PTMi

Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9NYJ8
MaxQBiQ9NYJ8
PaxDbiQ9NYJ8
PeptideAtlasiQ9NYJ8
PRIDEiQ9NYJ8

PTM databases

iPTMnetiQ9NYJ8
PhosphoSitePlusiQ9NYJ8

Expressioni

Tissue specificityi

Widely expressed. In the embryo, expressed in the ventricular trabeculae, endothelial cells of the conotruncal cushions of the outflow tract and in the endothelial cells lining the developing aortic valves.2 Publications

Gene expression databases

BgeeiENSG00000055208
CleanExiHS_MAP3K7IP2
ExpressionAtlasiQ9NYJ8 baseline and differential
GenevisibleiQ9NYJ8 HS

Organism-specific databases

HPAiHPA071215

Interactioni

Subunit structurei

Interacts with MAP3K7 and TRAF6. Identified in the TRIKA2 complex composed of MAP3K7, TAB1 and TAB2. Binds 'Lys-63'-linked polyubiquitin chains. Interacts with NCOR1 and HDAC3 to form a ternary complex. Interacts (via C-terminal) with NUMBL (via PTB domain). Interacts (via the C-terminus) with WDR34 (via WD domains). Interacts with RBCK1. Interacts with TRIM5.8 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • K63-linked polyubiquitin modification-dependent protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi11674096 interactors.
CORUMiQ9NYJ8
DIPiDIP-27525N
IntActiQ9NYJ8 75 interactors.
MINTiQ9NYJ8
STRINGi9606.ENSP00000286332

Structurei

Secondary structure

1693
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi10 – 19Combined sources10
Beta strandi20 – 23Combined sources4
Helixi25 – 32Combined sources8
Turni33 – 36Combined sources4
Helixi40 – 53Combined sources14
Turni54 – 56Combined sources3
Turni671 – 673Combined sources3
Turni685 – 687Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DAENMR-A7-68[»]
2WWZX-ray1.40C662-693[»]
2WX0X-ray2.40C/G663-693[»]
2WX1X-ray3.00C663-693[»]
ProteinModelPortaliQ9NYJ8
SMRiQ9NYJ8
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9NYJ8

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini8 – 51CUEPROSITE-ProRule annotationAdd BLAST44

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni675 – 685Interaction with polyubiquitinAdd BLAST11

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili532 – 619Sequence analysisAdd BLAST88

Domaini

The RanBP2-type zinc finger (NZF) mediates binding to two consecutive 'Lys-63'-linked ubiquitins.By similarity

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri663 – 693RanBP2-typePROSITE-ProRule annotationAdd BLAST31

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IK8E Eukaryota
ENOG410XPAC LUCA
GeneTreeiENSGT00530000063642
HOVERGENiHBG056952
InParanoidiQ9NYJ8
KOiK04404
OMAiVYHHGRE
OrthoDBiEOG091G0AYA
PhylomeDBiQ9NYJ8
TreeFamiTF332021

Family and domain databases

InterProiView protein in InterPro
IPR003892 CUE
IPR001876 Znf_RanBP2
IPR036443 Znf_RanBP2_sf
PfamiView protein in Pfam
PF02845 CUE, 1 hit
SMARTiView protein in SMART
SM00546 CUE, 1 hit
SM00547 ZnF_RBZ, 1 hit
SUPFAMiSSF90209 SSF90209, 1 hit
PROSITEiView protein in PROSITE
PS51140 CUE, 1 hit
PS01358 ZF_RANBP2_1, 1 hit
PS50199 ZF_RANBP2_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9NYJ8-1) [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
MAQGSHQIDF QVLHDLRQKF PEVPEVVVSR CMLQNNNNLD ACCAVLSQES
60 70 80 90 100
TRYLYGEGDL NFSDDSGISG LRNHMTSLNL DLQSQNIYHH GREGSRMNGS
110 120 130 140 150
RTLTHSISDG QLQGGQSNSE LFQQEPQTAP AQVPQGFNVF GMSSSSGASN
160 170 180 190 200
SAPHLGFHLG SKGTSSLSQQ TPRFNPIMVT LAPNIQTGRN TPTSLHIHGV
210 220 230 240 250
PPPVLNSPQG NSIYIRPYIT TPGGTTRQTQ QHSGWVSQFN PMNPQQVYQP
260 270 280 290 300
SQPGPWTTCP ASNPLSHTSS QQPNQQGHQT SHVYMPISSP TTSQPPTIHS
310 320 330 340 350
SGSSQSSAHS QYNIQNISTG PRKNQIEIKL EPPQRNNSSK LRSSGPRTSS
360 370 380 390 400
TSSSVNSQTL NRNQPTVYIA ASPPNTDELM SRSQPKVYIS ANAATGDEQV
410 420 430 440 450
MRNQPTLFIS TNSGASAASR NMSGQVSMGP AFIHHHPPKS RAIGNNSATS
460 470 480 490 500
PRVVVTQPNT KYTFKITVSP NKPPAVSPGV VSPTFELTNL LNHPDHYVET
510 520 530 540 550
ENIQHLTDPT LAHVDRISET RKLSMGSDDA AYTQALLVHQ KARMERLQRE
560 570 580 590 600
LEIQKKKLDK LKSEVNEMEN NLTRRRLKRS NSISQIPSLE EMQQLRSCNR
610 620 630 640 650
QLQIDIDCLT KEIDLFQARG PHFNPSAIHN FYDNIGFVGP VPPKPKDQRS
660 670 680 690
IIKTPKTQDT EDDEGAQWNC TACTFLNHPA LIRCEQCEMP RHF
Length:693
Mass (Da):76,494
Last modified:October 1, 2000 - v1
Checksum:i47BB8709320084D7
GO
Isoform 2 (identifier: Q9NYJ8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     535-536: AL → DI
     537-693: Missing.

Show »
Length:536
Mass (Da):58,131
Checksum:iD74074A216D23425
GO

Sequence cautioni

The sequence BAA34453 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti196H → R in CAG33668 (Ref. 5) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063774208P → S in CHTD2. 1 PublicationCorresponds to variant dbSNP:rs267607101Ensembl.1
Natural variantiVAR_063775230Q → K in CHTD2. 1 PublicationCorresponds to variant dbSNP:rs267607100Ensembl.1
Natural variantiVAR_077348569E → K Found in an patient with a form of frontometaphyseal dysplasia; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs886039238Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_017419535 – 536AL → DI in isoform 2. 3 Publications2
Alternative sequenceiVSP_017420537 – 693Missing in isoform 2. 3 PublicationsAdd BLAST157

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF241230 mRNA Translation: AAF67176.1
AB018276 mRNA Translation: BAA34453.2 Different initiation.
AK315038 mRNA Translation: BAG37521.1
CR457387 mRNA Translation: CAG33668.1
DQ314877 Genomic DNA Translation: ABC40736.1
AL117407 mRNA Translation: CAB55907.1
AL031133 Genomic DNA No translation available.
AL139103 Genomic DNA No translation available.
AL138727 Genomic DNA No translation available.
CH471051 Genomic DNA Translation: EAW47805.1
CH471051 Genomic DNA Translation: EAW47806.1
CH471051 Genomic DNA Translation: EAW47807.1
BC035910 mRNA Translation: AAH35910.1
CCDSiCCDS5214.1 [Q9NYJ8-1]
PIRiT17217
RefSeqiNP_001278963.1, NM_001292034.2 [Q9NYJ8-1]
NP_001278964.1, NM_001292035.2
NP_055908.1, NM_015093.5 [Q9NYJ8-1]
XP_011533935.1, XM_011535633.2 [Q9NYJ8-1]
XP_016866080.1, XM_017010591.1 [Q9NYJ8-1]
XP_016866081.1, XM_017010592.1 [Q9NYJ8-1]
UniGeneiHs.269775
Hs.520477

Genome annotation databases

EnsembliENST00000367456; ENSP00000356426; ENSG00000055208 [Q9NYJ8-1]
ENST00000470466; ENSP00000432709; ENSG00000055208 [Q9NYJ8-2]
ENST00000538427; ENSP00000445752; ENSG00000055208 [Q9NYJ8-1]
ENST00000637181; ENSP00000490618; ENSG00000055208 [Q9NYJ8-1]
GeneIDi23118
KEGGihsa:23118
UCSCiuc063sdy.1 human [Q9NYJ8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement

Similar proteinsi

Entry informationi

Entry nameiTAB2_HUMAN
AccessioniPrimary (citable) accession number: Q9NYJ8
Secondary accession number(s): B2RCC4
, E1P5A0, O94838, Q6I9W8, Q76N06, Q9UFP7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: October 1, 2000
Last modified: March 28, 2018
This is version 166 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