Human Gene TAB2 (ENST00000367456.5) from GENCODE V41
  Description: Homo sapiens TGF-beta activated kinase 1 (MAP3K7) binding protein 2 (TAB2), transcript variant 1, mRNA. (from RefSeq NM_015093)
RefSeq Summary (NM_015093): The protein encoded by this gene is an activator of MAP3K7/TAK1, which is required for for the IL-1 induced activation of nuclear factor kappaB and MAPK8/JNK. This protein forms a kinase complex with TRAF6, MAP3K7 and TAB1, and it thus serves as an adaptor that links MAP3K7 and TRAF6. This protein, along with TAB1 and MAP3K7, also participates in the signal transduction induced by TNFSF11/RANKl through the activation of the receptor activator of NF-kappaB (TNFRSF11A/RANK), which may regulate the development and function of osteoclasts. Studies of the related mouse protein indicate that it functions to protect against liver damage caused by chemical stressors. Mutations in this gene cause congenital heart defects, multiple types, 2 (CHTD2). Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014].
Gencode Transcript: ENST00000367456.5
Gencode Gene: ENSG00000055208.20
Transcript (Including UTRs)
   Position: hg38 chr6:149,321,052-149,411,613 Size: 90,562 Total Exon Count: 8 Strand: +
Coding Region
   Position: hg38 chr6:149,369,998-149,409,719 Size: 39,722 Coding Exon Count: 6 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2022-05-14 09:57:26

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr6:149,321,052-149,411,613)mRNA (may differ from genome)Protein (693 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSCGAPEnsemblEntrez GeneExonPrimerGencode

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=TGF-beta-activated kinase 1 and MAP3K7-binding protein 2; AltName: Full=Mitogen-activated protein kinase kinase kinase 7-interacting protein 2; AltName: Full=TAK1-binding protein 2; Short=TAB-2; AltName: Full=TGF-beta-activated kinase 1-binding protein 2;
FUNCTION: 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.
SUBUNIT: 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.
INTERACTION: O43318:MAP3K7; NbExp=2; IntAct=EBI-358708, EBI-358684; Q05516:ZBTB16; NbExp=3; IntAct=EBI-358708, EBI-711925;
SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein. Cytoplasm, cytosol. Note=Following IL1 stimulation, translocation occurs from the membrane to cytosol.
TISSUE SPECIFICITY: 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.
DOMAIN: The RanBP2-type zinc finger (NZF) mediates binding to two consecutive 'Lys-63'-linked ubiquitins (By similarity).
PTM: Ubiquitinated; following IL1 stimulation or TRAF6 overexpression. Ubiquitination involves RBCK1 leading to proteasomal degradation.
PTM: Phosphorylated (Probable).
DISEASE: Defects in TAB2 are the cause of congenital heart disease non-syndromic type 2 (CHTD2) [MIM:612863]. It is a disease characterized by congenital developmental abnormalities involving structures of the heart. Clinical features include left ventricular outflow tract obstruction, subaortic stenosis, residual aortic regurgitation, atrial fibrillation, bicuspid aortic valve and aortic dilation. Note=A chromosomal aberration involving TAB2 has been found in a family with congenital heart disease. Translocation t(2;6)(q21;q25).
SIMILARITY: Contains 1 CUE domain.
SIMILARITY: Contains 1 RanBP2-type zinc finger.
SEQUENCE CAUTION: Sequence=BAA34453.2; Type=Erroneous initiation;

-  MalaCards Disease Associations
  MalaCards Gene Search: TAB2
Diseases sorted by gene-association score: congenital heart defects, nonsyndromic, 2* (1300), diabetes mellitus, insulin-dependent, 5 (12), frontometaphyseal dysplasia (10), left ventricular outflow tract obstruction (9), ectodermal dysplasia 10b, hypohidrotic/hair/tooth type, autosomal recessive (4), tetralogy of fallot (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 27.18 RPKM in Colon - Sigmoid
Total median expression: 755.12 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -138.90577-0.241 Picture PostScript Text
3' UTR -457.901894-0.242 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003892 - CUE
IPR001876 - Znf_RanBP2

Pfam Domains:
PF02845 - CUE domain
PF00641 - Zn-finger in Ran binding protein and others

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2DAE - NMR MuPIT 2WWZ - X-ray MuPIT 2WX0 - X-ray MuPIT 2WX1 - X-ray MuPIT

ModBase Predicted Comparative 3D Structure on Q9NYJ8
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein SequenceProtein Sequence   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0046872 metal ion binding
GO:0070530 K63-linked polyubiquitin binding

Biological Process:
GO:0000187 activation of MAPK activity
GO:0002223 stimulatory C-type lectin receptor signaling pathway
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007254 JNK cascade
GO:0007507 heart development
GO:0010507 negative regulation of autophagy
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045860 positive regulation of protein kinase activity
GO:0050852 T cell receptor signaling pathway
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0070423 nucleotide-binding oligomerization domain containing signaling pathway
GO:0070498 interleukin-1-mediated signaling pathway

Cellular Component:
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0010008 endosome membrane
GO:0016020 membrane

-  Descriptions from all associated GenBank mRNAs
  AK295750 - Homo sapiens cDNA FLJ57993 complete cds, highly similar to Mitogen-activated protein kinase kinase kinase7-interacting protein 2.
LF208694 - JP 2014500723-A/16197: Polycomb-Associated Non-Coding RNAs.
MA444271 - JP 2018138019-A/16197: Polycomb-Associated Non-Coding RNAs.
AB018276 - Homo sapiens KIAA0733 mRNA for KIAA0733 protein.
BC035910 - Homo sapiens mitogen-activated protein kinase kinase kinase 7 interacting protein 2, mRNA (cDNA clone MGC:45999 IMAGE:5492359), complete cds.
AK315038 - Homo sapiens cDNA, FLJ95984, Homo sapiens mitogen-activated protein kinase kinase kinase 7interacting protein 2 (MAP3K7IP2), transcript variant 2, mRNA.
AK307650 - Homo sapiens cDNA, FLJ97598.
AL117407 - Homo sapiens mRNA; cDNA DKFZp434D2050 (from clone DKFZp434D2050).
AF241230 - Homo sapiens TAK1-binding protein 2 mRNA, complete cds.
CR457387 - Homo sapiens full open reading frame cDNA clone RZPDo834D0621D for gene MAP3K7IP2, mitogen-activated protein kinase kinase kinase 7 interacting protein 2; complete cds, incl. stopcodon.
AB383968 - Synthetic construct DNA, clone: pF1KSDA0733, Homo sapiens MAP3K7IP2 gene for mitogen-activated protein kinase kinase kinase 7-interacting protein 2, complete cds, without stop codon, in Flexi system.
LF321619 - JP 2014500723-A/129122: Polycomb-Associated Non-Coding RNAs.
MA557196 - JP 2018138019-A/129122: Polycomb-Associated Non-Coding RNAs.
LF321617 - JP 2014500723-A/129120: Polycomb-Associated Non-Coding RNAs.
MA557194 - JP 2018138019-A/129120: Polycomb-Associated Non-Coding RNAs.
LF321616 - JP 2014500723-A/129119: Polycomb-Associated Non-Coding RNAs.
MA557193 - JP 2018138019-A/129119: Polycomb-Associated Non-Coding RNAs.
LF321615 - JP 2014500723-A/129118: Polycomb-Associated Non-Coding RNAs.
MA557192 - JP 2018138019-A/129118: Polycomb-Associated Non-Coding RNAs.
LF321614 - JP 2014500723-A/129117: Polycomb-Associated Non-Coding RNAs.
MA557191 - JP 2018138019-A/129117: Polycomb-Associated Non-Coding RNAs.
LF321611 - JP 2014500723-A/129114: Polycomb-Associated Non-Coding RNAs.
MA557188 - JP 2018138019-A/129114: Polycomb-Associated Non-Coding RNAs.
LF321610 - JP 2014500723-A/129113: Polycomb-Associated Non-Coding RNAs.
MA557187 - JP 2018138019-A/129113: Polycomb-Associated Non-Coding RNAs.
AK025538 - Homo sapiens cDNA: FLJ21885 fis, clone HEP02989.
JD209299 - Sequence 190323 from Patent EP1572962.
LF321606 - JP 2014500723-A/129109: Polycomb-Associated Non-Coding RNAs.
MA557183 - JP 2018138019-A/129109: Polycomb-Associated Non-Coding RNAs.
LF321605 - JP 2014500723-A/129108: Polycomb-Associated Non-Coding RNAs.
MA557182 - JP 2018138019-A/129108: Polycomb-Associated Non-Coding RNAs.
JD562757 - Sequence 543781 from Patent EP1572962.
LF321604 - JP 2014500723-A/129107: Polycomb-Associated Non-Coding RNAs.
MA557181 - JP 2018138019-A/129107: Polycomb-Associated Non-Coding RNAs.
JD046990 - Sequence 28014 from Patent EP1572962.
JD303843 - Sequence 284867 from Patent EP1572962.
JD533447 - Sequence 514471 from Patent EP1572962.
JD216011 - Sequence 197035 from Patent EP1572962.
LF321602 - JP 2014500723-A/129105: Polycomb-Associated Non-Coding RNAs.
MA557179 - JP 2018138019-A/129105: Polycomb-Associated Non-Coding RNAs.
JD115248 - Sequence 96272 from Patent EP1572962.
JD305596 - Sequence 286620 from Patent EP1572962.
JD504019 - Sequence 485043 from Patent EP1572962.
JD146386 - Sequence 127410 from Patent EP1572962.
LF321601 - JP 2014500723-A/129104: Polycomb-Associated Non-Coding RNAs.
MA557178 - JP 2018138019-A/129104: Polycomb-Associated Non-Coding RNAs.
AL050180 - Homo sapiens mRNA; cDNA DKFZp586A1023 (from clone DKFZp586A1023).
JD232135 - Sequence 213159 from Patent EP1572962.
LF321600 - JP 2014500723-A/129103: Polycomb-Associated Non-Coding RNAs.
MA557177 - JP 2018138019-A/129103: Polycomb-Associated Non-Coding RNAs.
JD091352 - Sequence 72376 from Patent EP1572962.
JD232834 - Sequence 213858 from Patent EP1572962.
JD098904 - Sequence 79928 from Patent EP1572962.
JD419973 - Sequence 400997 from Patent EP1572962.
JD051621 - Sequence 32645 from Patent EP1572962.
JD147445 - Sequence 128469 from Patent EP1572962.
JD154726 - Sequence 135750 from Patent EP1572962.
LF321599 - JP 2014500723-A/129102: Polycomb-Associated Non-Coding RNAs.
MA557176 - JP 2018138019-A/129102: Polycomb-Associated Non-Coding RNAs.
LF321598 - JP 2014500723-A/129101: Polycomb-Associated Non-Coding RNAs.
MA557175 - JP 2018138019-A/129101: Polycomb-Associated Non-Coding RNAs.
JD297130 - Sequence 278154 from Patent EP1572962.
MP330162 - Sequence 127 from Patent WO2019180153.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04010 - MAPK signaling pathway
hsa04620 - Toll-like receptor signaling pathway
hsa04621 - NOD-like receptor signaling pathway
hsa05140 - Leishmaniasis

Reactome (by CSHL, EBI, and GO)

Protein Q9NYJ8 (Reactome details) participates in the following event(s):

R-HSA-202510 Activation of TAK1-TAB2 complex
R-HSA-1253325 ERBB4s80 binds TAB2:NCOR1 complex
R-HSA-688985 K63 polyubiquitinated RIP2 associates with the TAK1 complex
R-HSA-446870 Polyubiquitinated TRAF6 binds the TAK1 complex
R-HSA-936960 Activated TRAF6:p-IRAK2 interacts with TAK1 complex
R-HSA-975097 Activated TRAF6:p-IRAK2 interacts with TAK1 complex upon TLR7/8 or 9 stimulation
R-HSA-177690 Activated TLR3:TRIF:K63pUb-TRAF6 recruits TAK1complex
R-HSA-936947 Activated TLR4:TICAM1:K63pUb-TRAF6 recruits TAK1complex
R-HSA-2730861 Recruitment of TAK1 kinase complex to oligo-K63-pUb-TRAF6
R-HSA-5357860 TNF:TNFR1:TRADD:TRAF2:K63polyUb-RIPK1:BIRC2/3 recruits TAK1 complex
R-HSA-5607759 TRIKA2 binds K63polyUb-TRAF6 oligomer
R-HSA-847070 Phosphorylated TAK1 dissociates from the TLR3 receptor complex
R-HSA-937075 Phosphorylated TAK1 leaves activated TLR receptor complex
R-HSA-936951 Activation of TAK1 complex bound to activated TLR4 complex
R-HSA-936991 Auto phosphorylation of TAK1 bound to p-IRAK2:pUb oligo-TRAF6: free K63 pUb:TAB1:TAB2/TAB3
R-HSA-177692 Activation of recruited TAK1 within the activated TLR3 complex
R-HSA-975103 Auto phosphorylation of TAK1 bound to p-IRAK2:pUb oligo-TRAF6: free K63 pUb:TAB1:TAB2/TAB3 upon TLR7/8 or 9 activation
R-HSA-1253319 ERBB4s80:TAB2:NCOR1 complex translocates to the nucleus
R-HSA-8954182 ERBB4s80:TAB2:NCOR1 complex binds S100B gene promoter
R-HSA-8954185 ERBB4s80:TAB2:NCOR1 complex binds GFAP gene promoter
R-HSA-202500 Activation of IKK complex
R-HSA-727819 TAK1 phosphorylates MKK6
R-HSA-5607732 K63polyUb-TAK1 autophosphorylates
R-HSA-2730876 Phosphorylation of IKK-beta by TAK1
R-HSA-168184 Activated TAK1 mediates phosphorylation of the IKK Complex
R-HSA-450337 Activated TAK1 phosphorylates MKK4/MKK7
R-HSA-450346 activated human TAK1 phosphorylates MKK3/MKK6
R-HSA-5607742 K63polyUb-p-3T,1S-TAK1 phosphorylates IKK-beta
R-HSA-202424 Downstream TCR signaling
R-HSA-1251985 Nuclear signaling by ERBB4
R-HSA-202403 TCR signaling
R-HSA-168638 NOD1/2 Signaling Pathway
R-HSA-9020702 Interleukin-1 signaling
R-HSA-937042 IRAK2 mediated activation of TAK1 complex
R-HSA-975163 IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation
R-HSA-9014325 TICAM1,TRAF6-dependent induction of TAK1 complex
R-HSA-937072 TRAF6-mediated induction of TAK1 complex within TLR4 complex
R-HSA-2871837 FCERI mediated NF-kB activation
R-HSA-5357956 TNFR1-induced NFkappaB signaling pathway
R-HSA-5607764 CLEC7A (Dectin-1) signaling
R-HSA-1236394 Signaling by ERBB4
R-HSA-1280218 Adaptive Immune System
R-HSA-168643 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
R-HSA-446652 Interleukin-1 family signaling
R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-975871 MyD88 cascade initiated on plasma membrane
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade
R-HSA-937061 TRIF(TICAM1)-mediated TLR4 signaling
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling
R-HSA-75893 TNF signaling
R-HSA-5621481 C-type lectin receptors (CLRs)
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-168256 Immune System
R-HSA-168249 Innate Immune System
R-HSA-449147 Signaling by Interleukins
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade
R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade
R-HSA-975155 MyD88 dependent cascade initiated on endosome
R-HSA-168898 Toll-Like Receptors Cascades
R-HSA-166166 MyD88-independent TLR4 cascade
R-HSA-73887 Death Receptor Signalling
R-HSA-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-450302 activated TAK1 mediates p38 MAPK activation
R-HSA-162582 Signal Transduction
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-450294 MAP kinase activation
R-HSA-448424 Interleukin-17 signaling

-  Other Names for This Gene
  Alternate Gene Symbols: B2RCC4, E1P5A0, ENST00000367456.1, ENST00000367456.2, ENST00000367456.3, ENST00000367456.4, KIAA0733, MAP3K7IP2, NM_015093, O94838, Q6I9W8, Q76N06, Q9NYJ8, Q9UFP7, TAB2_HUMAN, uc063sdy.1
UCSC ID: ENST00000367456.5
RefSeq Accession: NM_015093
Protein: Q9NYJ8 (aka TAB2_HUMAN)
CCDS: CCDS5214.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.