MAP3K7IP2

Last updated
TAB2
Protein MAP3K7IP2 PDB 2dae.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TAB2 , CHTD2, MAP3K7IP2, TAB-2, TGF-beta activated kinase 1/MAP3K7 binding protein 2, TGF-beta activated kinase 1 (MAP3K7) binding protein 2
External IDs OMIM: 605101 MGI: 1915902 HomoloGene: 9019 GeneCards: TAB2
Orthologs
SpeciesHumanMouse
Entrez

23118

68652

Ensembl

ENSG00000055208

ENSMUSG00000015755

UniProt

Q9NYJ8

Q99K90

RefSeq (mRNA)

NM_001292034
NM_001292035
NM_015093
NM_145342
NM_001369506

Contents

NM_138667
NM_001359534

RefSeq (protein)

NP_001278963
NP_001278964
NP_055908
NP_001356435

NP_619608
NP_001346463

Location (UCSC) Chr 6: 149.22 – 149.41 Mb Chr 10: 7.91 – 7.96 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Mitogen-activated protein kinase kinase kinase 7-interacting protein 2 is an enzyme that in humans is encoded by the MAP3K7IP2 gene. [5] [6] [7]

The protein encoded by this gene is an activator of MAP3K7/TAK1, which is required for the IL-1 induced activation of nuclear factor kappaB and MAPK8/JNK. This protein forms a kinase complex with TRAF6, MAP3K7 and TAB1, thus serves as an adaptor linking MAP3K7 and TRAF6. This protein, TAB1, and MAP3K7 also participate in the signal transduction induced by TNFSF11/RANKL through the activation of the receptor activator of NF-kappB (TNFRSF11A/RANK), which may regulate the development and function of osteoclasts. [7] Mutations in MAP3K7IP2 have been associated with human congenital heart defects. [8]

Interactions

MAP3K7IP2 has been shown to interact with:

Related Research Articles

<span class="mw-page-title-main">Signal transducing adaptor protein</span>

Signal transducing adaptor proteins (STAPs) are proteins that are accessory to main proteins in a signal transduction pathway. Adaptor proteins contain a variety of protein-binding modules that link protein-binding partners together and facilitate the creation of larger signaling complexes. These proteins tend to lack any intrinsic enzymatic activity themselves, instead mediating specific protein–protein interactions that drive the formation of protein complexes. Examples of adaptor proteins include MYD88, Grb2 and SHC1.

<span class="mw-page-title-main">RANK</span> Mammalian protein found in Homo sapiens

Receptor activator of nuclear factor κ B (RANK), also known as TRANCE receptor or TNFRSF11A, is a member of the tumor necrosis factor receptor (TNFR) molecular sub-family. RANK is the receptor for RANK-Ligand (RANKL) and part of the RANK/RANKL/OPG signaling pathway that regulates osteoclast differentiation and activation. It is associated with bone remodeling and repair, immune cell function, lymph node development, thermal regulation, and mammary gland development. Osteoprotegerin (OPG) is a decoy receptor for RANKL, and regulates the stimulation of the RANK signaling pathway by competing for RANKL. The cytoplasmic domain of RANK binds TRAFs 1, 2, 3, 5, and 6 which transmit signals to downstream targets such as NF-κB and JNK.

<span class="mw-page-title-main">TRAF6</span> Protein-coding gene in the species Homo sapiens

TRAF6 is a TRAF human protein.

<span class="mw-page-title-main">TRAF2</span> Protein-coding gene in humans

TNF receptor-associated factor 2 is a protein that in humans is encoded by the TRAF2 gene.

<span class="mw-page-title-main">ASK1</span> Protein-coding gene in the species Homo sapiens

Apoptosis signal-regulating kinase 1 (ASK1) also known as mitogen-activated protein kinase 5 (MAP3K5) is a member of MAP kinase family and as such a part of mitogen-activated protein kinase pathway. It activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases in a Raf-independent fashion in response to an array of stresses such as oxidative stress, endoplasmic reticulum stress and calcium influx. ASK1 has been found to be involved in cancer, diabetes, rheumatoid arthritis, cardiovascular and neurodegenerative diseases.

<span class="mw-page-title-main">MAPK8</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase 8 is a ubiquitous enzyme that in humans is encoded by the MAPK8 gene.

<span class="mw-page-title-main">CHUK</span> Protein-coding gene in humans

Inhibitor of nuclear factor kappa-B kinase subunit alpha (IKK-α) also known as IKK1 or conserved helix-loop-helix ubiquitous kinase (CHUK) is a protein kinase that in humans is encoded by the CHUK gene. IKK-α is part of the IκB kinase complex that plays an important role in regulating the NF-κB transcription factor. However, IKK-α has many additional cellular targets, and is thought to function independently of the NF-κB pathway to regulate epidermal differentiation.

<span class="mw-page-title-main">MAP3K7</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase kinase kinase 7 (MAP3K7), also known as TAK1, is an enzyme that in humans is encoded by the MAP3K7 gene.

<span class="mw-page-title-main">TRAF1</span> Protein-coding gene in the species Homo sapiens

TNF receptor-associated factor 1 is a protein that in humans is encoded by the TRAF1 gene.

<span class="mw-page-title-main">MAP2K6</span> Protein-coding gene in the species Homo sapiens

Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 or MAPK/ERK kinase 6 is an enzyme that in humans is encoded by the MAP2K6 gene, on chromosome 17.

<span class="mw-page-title-main">IRAK1</span> Protein-coding gene in the species Homo sapiens

Interleukin-1 receptor-associated kinase 1 (IRAK-1) is an enzyme in humans encoded by the IRAK1 gene. IRAK-1 plays an important role in the regulation of the expression of inflammatory genes by immune cells, such as monocytes and macrophages, which in turn help the immune system in eliminating bacteria, viruses, and other pathogens. IRAK-1 is part of the IRAK family consisting of IRAK-1, IRAK-2, IRAK-3, and IRAK-4, and is activated by inflammatory molecules released by signaling pathways during pathogenic attack. IRAK-1 is classified as a kinase enzyme, which regulates pathways in both innate and adaptive immune systems.

<span class="mw-page-title-main">Testicular receptor 4</span> Protein-coding gene in the species Homo sapiens

Testicular receptor 4 also known as NR2C2 is a protein that in humans is encoded by the NR2C2 gene.

<span class="mw-page-title-main">MAP3K14</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase kinase kinase 14 also known as NF-kappa-B-inducing kinase (NIK) is an enzyme that in humans is encoded by the MAP3K14 gene.

<span class="mw-page-title-main">TAB1</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase kinase kinase 7-interacting protein 1 is an enzyme that in humans is encoded by the TAB1 gene.

<span class="mw-page-title-main">CARD11</span> Protein-coding gene in the species Homo sapiens

Caspase recruitment domain-containing protein 11 also known as CARD-containing MAGUK protein 1 is a protein in the CARD-CC protein family that in humans is encoded by the CARD11 gene. CARD 11 is a membrane associated protein that is found in various human tissues, including the thymus, spleen, liver, and peripheral blood leukocytes. Similarly, CARD 11 is also found in abundance in various lines of cancer cells.

<span class="mw-page-title-main">NLK</span> Mammalian protein found in Homo sapiens

Serine/threonine protein kinase NLK is an enzyme that in humans is encoded by the NLK gene. Its name is an abbreviation for Nemo-Like Kinase, Nemo (nmo) being the Drosophila ortholog of the mammalian NLK gene. This enzyme is a member of the Mitogen-activated protein kinase (MAPK) family, although not explicitly designated as such. It is a highly divergent, atypical member of the MAPK group, lacking most features so characteristic of most mitogen-activated protein kinases. Its activation mechanism and downstream targets are still not well characterized.

<span class="mw-page-title-main">PPM1B</span> Protein-coding gene in the species Homo sapiens

Protein phosphatase 1B is an enzyme that in humans is encoded by the PPM1B gene.

<span class="mw-page-title-main">MAP3K7IP3</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase kinase kinase 7-interacting protein 3 is an enzyme that in humans is encoded by the MAP3K7IP3 gene.

The interleukin-1 receptor (IL-1R) associated kinase (IRAK) family plays a crucial role in the protective response to pathogens introduced into the human body by inducing acute inflammation followed by additional adaptive immune responses. IRAKs are essential components of the Interleukin-1 receptor signaling pathway and some Toll-like receptor signaling pathways. Toll-like receptors (TLRs) detect microorganisms by recognizing specific pathogen-associated molecular patterns (PAMPs) and IL-1R family members respond the interleukin-1 (IL-1) family cytokines. These receptors initiate an intracellular signaling cascade through adaptor proteins, primarily, MyD88. This is followed by the activation of IRAKs. TLRs and IL-1R members have a highly conserved amino acid sequence in their cytoplasmic domain called the Toll/Interleukin-1 (TIR) domain. The elicitation of different TLRs/IL-1Rs results in similar signaling cascades due to their homologous TIR motif leading to the activation of mitogen-activated protein kinases (MAPKs) and the IκB kinase (IKK) complex, which initiates a nuclear factor-κB (NF-κB) and AP-1-dependent transcriptional response of pro-inflammatory genes. Understanding the key players and their roles in the TLR/IL-1R pathway is important because the presence of mutations causing the abnormal regulation of Toll/IL-1R signaling leading to a variety of acute inflammatory and autoimmune diseases.

<span class="mw-page-title-main">Act 1 adaptor protein</span> Act 1 adaptor protein

Act 1 adaptor protein is an essential intermediate in the interleukin-17 pathway. The IL-17 protein is a pro-inflammatory cytokine important for tissue inflammation in host defense against infection and in autoimmune disease. It is produced by the CD4 + T cells, in particular the Th17 cells. There are 6 subtypes of IL-17, from IL-17A to IL17-F, these subtypes have nearly identical structures. We know that the cytokines are interacting homotypically, but IL-17A and IL-17F are capable do perform heterotypic interaction too.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000055208 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000015755 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Apr 1999). "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 5 (5): 277–86. doi: 10.1093/dnares/5.5.277 . PMID   9872452.
  6. 1 2 3 4 5 Takaesu G, Kishida S, Hiyama A, Yamaguchi K, Shibuya H, Irie K, Ninomiya-Tsuji J, Matsumoto K (Jul 2000). "TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway". Mol Cell. 5 (4): 649–58. doi: 10.1016/S1097-2765(00)80244-0 . PMID   10882101.
  7. 1 2 "Entrez Gene: MAP3K7IP2 mitogen-activated protein kinase kinase kinase 7 interacting protein 2".
  8. ↑ Thienpont B, Zhang L, Postma AV, Breckpot J, Tranchevent LC, Van Loo P, Møllgård K, Tommerup N, Bache I, Tümer Z, van Engelen K, Menten B, Mortier G, Waggoner D, Gewillig M, Moreau Y, Devriendt K, Larsen LA (2010). "Haploinsufficiency of TAB2 causes congenital heart defects in humans". Am J Hum Genet. 86 (6): 839–49. doi:10.1016/j.ajhg.2010.04.011. PMC   3032066 . PMID   20493459.
  9. 1 2 3 Baek SH, Ohgi KA, Rose DW, Koo EH, Glass CK, Rosenfeld MG (Jul 2002). "Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein". Cell. 110 (1): 55–67. doi: 10.1016/S0092-8674(02)00809-7 . PMID   12150997. S2CID   17679498.
  10. ↑ Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (Feb 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID   14743216. S2CID   11683986.
  11. 1 2 Cheung PC, Nebreda AR, Cohen P (Feb 2004). "TAB3, a new binding partner of the protein kinase TAK1". Biochem. J. 378 (Pt 1): 27–34. doi:10.1042/BJ20031794. PMC   1223947 . PMID   14670075.
  12. 1 2 Ishitani T, Takaesu G, Ninomiya-Tsuji J, Shibuya H, Gaynor RB, Matsumoto K (Dec 2003). "Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling". EMBO J. 22 (23): 6277–88. doi:10.1093/emboj/cdg605. PMC   291846 . PMID   14633987.
  13. 1 2 Takaesu G, Ninomiya-Tsuji J, Kishida S, Li X, Stark GR, Matsumoto K (Apr 2001). "Interleukin-1 (IL-1) receptor-associated kinase leads to activation of TAK1 by inducing TAB2 translocation in the IL-1 signaling pathway". Mol. Cell. Biol. 21 (7): 2475–84. doi:10.1128/MCB.21.7.2475-2484.2001. PMC   86880 . PMID   11259596.
  14. 1 2 Ma Q, Zhou L, Shi H, Huo K (Jun 2008). "NUMBL interacts with TAB2 and inhibits TNFalpha and IL-1beta-induced NF-kappaB activation". Cell. Signal. 20 (6): 1044–51. doi:10.1016/j.cellsig.2008.01.015. PMID   18299187.
  15. ↑ Li S, Wang L, Dorf ME (Jan 2009). "PKC phosphorylation of TRAF2 mediates IKKalpha/beta recruitment and K63-linked polyubiquitination". Mol. Cell. 33 (1): 30–42. doi:10.1016/j.molcel.2008.11.023. PMC   2643372 . PMID   19150425.
  16. ↑ Walsh MC, Kim GK, Maurizio PL, Molnar EE, Choi Y (2008). Unutmaz D (ed.). "TRAF6 autoubiquitination-independent activation of the NFkappaB and MAPK pathways in response to IL-1 and RANKL". PLOS ONE. 3 (12): e4064. Bibcode:2008PLoSO...3.4064W. doi: 10.1371/journal.pone.0004064 . PMC   2603309 . PMID   19112497.
  17. ↑ Windheim M, Stafford M, Peggie M, Cohen P (Mar 2008). "Interleukin-1 (IL-1) induces the Lys63-linked polyubiquitination of IL-1 receptor-associated kinase 1 to facilitate NEMO binding and the activation of IkappaBalpha kinase". Mol. Cell. Biol. 28 (5): 1783–91. doi:10.1128/MCB.02380-06. PMC   2258775 . PMID   18180283.

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