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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: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri663 – 69331RanBP2-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • K63-linked polyubiquitin binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

Metal-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-446652. Interleukin-1 signaling.
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-937042. IRAK2 mediated activation of TAK1 complex.
R-HSA-937072. TRAF6 mediated induction of TAK1 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

HGNCiHGNC:17075. TAB2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti208 – 2081P → S in CHTD2. 1 Publication
Corresponds to variant rs267607101 [ dbSNP | Ensembl ].
VAR_063774
Natural varianti230 – 2301Q → K in CHTD2. 1 Publication
Corresponds to variant rs267607100 [ dbSNP | Ensembl ].
VAR_063775

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi675 – 6751F → A: Abolishes ubiquitin binding. 1 Publication
Mutagenesisi678 – 6781H → A: Abolishes ubiquitin binding. 1 Publication
Mutagenesisi681 – 6811L → A: Abolishes ubiquitin binding. 1 Publication
Mutagenesisi685 – 6851E → A: Abolishes ubiquitin binding. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

MalaCardsiTAB2.
MIMi614980. phenotype.
PharmGKBiPA30605.

Polymorphism and mutation databases

BioMutaiTAB2.
DMDMi74753070.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 693693TGF-beta-activated kinase 1 and MAP3K7-binding protein 2PRO_0000225695Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei372 – 3721PhosphoserineCombined sources
Modified residuei450 – 4501PhosphoserineCombined sources
Modified residuei482 – 4821PhosphoserineCombined sources
Modified residuei524 – 5241PhosphoserineCombined sources
Modified residuei582 – 5821PhosphoserineCombined sources

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9NYJ8.
MaxQBiQ9NYJ8.
PaxDbiQ9NYJ8.
PeptideAtlasiQ9NYJ8.
PRIDEiQ9NYJ8.

PTM databases

iPTMnetiQ9NYJ8.
PhosphoSiteiQ9NYJ8.

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.

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

WithEntry#Exp.IntActNotes
BECN1Q1445711EBI-358708,EBI-949378
MAP3K7O433185EBI-358708,EBI-358684
MAP3K7O43318-22EBI-358708,EBI-358700
TAB1Q157505EBI-358708,EBI-358643
ZBTB16Q055163EBI-358708,EBI-711925

GO - Molecular functioni

  • K63-linked polyubiquitin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116740. 90 interactions.
DIPiDIP-27525N.
IntActiQ9NYJ8. 32 interactions.
MINTiMINT-1132340.
STRINGi9606.ENSP00000286332.

Structurei

Secondary structure

1
693
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi10 – 1910Combined sources
Beta strandi20 – 234Combined sources
Helixi25 – 328Combined sources
Turni33 – 364Combined sources
Helixi40 – 5314Combined sources
Turni54 – 563Combined sources
Turni671 – 6733Combined sources
Turni685 – 6873Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2DAENMR-A7-68[»]
2WWZX-ray1.40C662-693[»]
2WX0X-ray2.40C/G663-693[»]
2WX1X-ray3.00C663-693[»]
ProteinModelPortaliQ9NYJ8.
SMRiQ9NYJ8. Positions 5-70, 662-693.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9NYJ8.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini8 – 5144CUEPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni675 – 68511Interaction with polyubiquitinAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili532 – 61988Sequence analysisAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 CUE domain.PROSITE-ProRule annotation
Contains 1 RanBP2-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri663 – 69331RanBP2-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

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

Family and domain databases

InterProiIPR003892. CUE.
IPR001876. Znf_RanBP2.
[Graphical view]
PfamiPF02845. CUE. 1 hit.
[Graphical view]
SMARTiSM00546. CUE. 1 hit.
SM00547. ZnF_RBZ. 1 hit.
[Graphical view]
SUPFAMiSSF90209. SSF90209. 1 hit.
PROSITEiPS51140. CUE. 1 hit.
PS01358. ZF_RANBP2_1. 1 hit.
PS50199. ZF_RANBP2_2. 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: 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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti196 – 1961H → R in CAG33668 (Ref. 5) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti208 – 2081P → S in CHTD2. 1 Publication
Corresponds to variant rs267607101 [ dbSNP | Ensembl ].
VAR_063774
Natural varianti230 – 2301Q → K in CHTD2. 1 Publication
Corresponds to variant rs267607100 [ dbSNP | Ensembl ].
VAR_063775

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei535 – 5362AL → DI in isoform 2. 3 PublicationsVSP_017419
Alternative sequencei537 – 693157Missing in isoform 2. 3 PublicationsVSP_017420Add
BLAST

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, AL138727, AL139103 Genomic DNA. Translation: CAI20026.1.
AL139103, AL031133, AL138727 Genomic DNA. Translation: CAI20971.1.
AL138727, AL031133, AL139103 Genomic DNA. Translation: CAI19581.1.
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]
UniGeneiHs.269775.
Hs.520477.

Genome annotation databases

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

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement

Cross-referencesi

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, AL138727, AL139103 Genomic DNA. Translation: CAI20026.1.
AL139103, AL031133, AL138727 Genomic DNA. Translation: CAI20971.1.
AL138727, AL031133, AL139103 Genomic DNA. Translation: CAI19581.1.
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]
UniGeneiHs.269775.
Hs.520477.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2DAENMR-A7-68[»]
2WWZX-ray1.40C662-693[»]
2WX0X-ray2.40C/G663-693[»]
2WX1X-ray3.00C663-693[»]
ProteinModelPortaliQ9NYJ8.
SMRiQ9NYJ8. Positions 5-70, 662-693.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116740. 90 interactions.
DIPiDIP-27525N.
IntActiQ9NYJ8. 32 interactions.
MINTiMINT-1132340.
STRINGi9606.ENSP00000286332.

PTM databases

iPTMnetiQ9NYJ8.
PhosphoSiteiQ9NYJ8.

Polymorphism and mutation databases

BioMutaiTAB2.
DMDMi74753070.

Proteomic databases

EPDiQ9NYJ8.
MaxQBiQ9NYJ8.
PaxDbiQ9NYJ8.
PeptideAtlasiQ9NYJ8.
PRIDEiQ9NYJ8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi23118.
GeneCardsiTAB2.
HGNCiHGNC:17075. TAB2.
MalaCardsiTAB2.
MIMi605101. gene.
614980. phenotype.
neXtProtiNX_Q9NYJ8.
PharmGKBiPA30605.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

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

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-446652. Interleukin-1 signaling.
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-937042. IRAK2 mediated activation of TAK1 complex.
R-HSA-937072. TRAF6 mediated induction of TAK1 complex.
R-HSA-975163. IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
SignaLinkiQ9NYJ8.
SIGNORiQ9NYJ8.

Miscellaneous databases

ChiTaRSiTAB2. human.
EvolutionaryTraceiQ9NYJ8.
GeneWikiiMAP3K7IP2.
GenomeRNAii23118.
PROiQ9NYJ8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000055208.
CleanExiHS_MAP3K7IP2.
ExpressionAtlasiQ9NYJ8. baseline and differential.
GenevisibleiQ9NYJ8. HS.

Family and domain databases

InterProiIPR003892. CUE.
IPR001876. Znf_RanBP2.
[Graphical view]
PfamiPF02845. CUE. 1 hit.
[Graphical view]
SMARTiSM00546. CUE. 1 hit.
SM00547. ZnF_RBZ. 1 hit.
[Graphical view]
SUPFAMiSSF90209. SSF90209. 1 hit.
PROSITEiPS51140. CUE. 1 hit.
PS01358. ZF_RANBP2_1. 1 hit.
PS50199. ZF_RANBP2_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTAB2_HUMAN
AccessioniPrimary (citable) accession number: Q9NYJ8
Secondary accession number(s): B2RCC4
, E1P5A0, O94838, Q6I9W8, Q76N06, Q9UFP7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: October 1, 2000
Last modified: September 7, 2016
This is version 150 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: 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
  6. 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.