May be an important signaling intermediate between TGFB receptors and MAP3K7/TAK1. May play an important role in mammalian embryogenesis. (updated: April 1, 2015)

Protein identification was indicated in the following studies:

Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

Publication	Identification ¹	Uniprot mapping ²	Not mapped / Obsolete	TrEMBL	Swiss-Prot
Goodman (2013)	2289 (gene list)	2278	53	20599	2269
Lange (2014)	1234	1234	7	28	1224
Hegedus (2015)	2638	2622	0	235	2387
Wilson (2016)	1658	1528	170	291	1068
d'Alessandro (2017)	1826	1817	2	0	1815
Bryk (2017)	2090	2060	10	108	1942
Chu (2018)	1853	1804	55	362	1387

¹ as available in the article and/or in supplementary material
² uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Protein sequence (FASTA)

Protein coevolution profile (FreeContact)

Multiple Sequence Alignment (Muscle)

Total structural coverage: 88%

Model score: 100

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Variant	Description
	dbSNP:rs17001096

Biological Process

Activation of MAPK activity

Activation of MAPKKK activity

Aorta development

Cardiac septum development

Coronary vasculature development

Cytoplasmic pattern recognition receptor signaling pathway

Fc-epsilon receptor signaling pathway

Heart morphogenesis

I-kappaB kinase/NF-kappaB signaling

In utero embryonic development

Innate immune response

Interleukin-1-mediated signaling pathway

JNK cascade

Lung development

MyD88-dependent toll-like receptor signaling pathway

MyD88-independent toll-like receptor signaling pathway

Negative regulation of protein kinase activity

Nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway

Nucleotide-binding oligomerization domain containing signaling pathway

Positive regulation of NF-kappaB transcription factor activity

Protein dephosphorylation

Protein deubiquitination

Stimulatory C-type lectin receptor signaling pathway

Stress-activated MAPK cascade

Toll-like receptor 10 signaling pathway

Toll-like receptor 2 signaling pathway

Toll-like receptor 3 signaling pathway

Toll-like receptor 4 signaling pathway

Toll-like receptor 5 signaling pathway

Toll-like receptor 9 signaling pathway

Toll-like receptor signaling pathway

Toll-like receptor TLR1:TLR2 signaling pathway

Toll-like receptor TLR6:TLR2 signaling pathway

Transforming growth factor beta receptor signaling pathway

TRIF-dependent toll-like receptor signaling pathway

Cellular Component

Cytoplasm

Cytosol

Endosome membrane

Nuclear speck

Nucleoplasm

Nucleus

Protein complex

Protein-containing complex

Molecular Function

Catalytic activity

Enzyme activator activity

Kinase activator activity

Magnesium-dependent protein serine/threonine phosphatase activity

Mitogen-activated protein kinase p38 binding

Phosphatase activity

Protein complex binding

Protein kinase activator activity

Protein serine/threonine phosphatase activity

Protein-containing complex binding

The reference OMIM entry for this protein is 602615

Mitogen-activated protein kinase kinase kinase 7-interacting protein 1; map3k7ip1
Tak1-binding protein 1; tab1

CLONING

Shibuya et al. (1996) used the yeast 2-hybrid system to identify brain cDNAs encoding proteins that interacted with TAK1 (602614). They recovered a gene encoding a predicted 504-amino acid protein that they named TAB1 (TAK1-binding protein-1). On Northern blots, TAB1 was expressed as a 3.5-kb mRNA in all tissues tested.

GENE FUNCTION

Shibuya et al. (1996) found that in both yeast and mammalian cells, TAB1 activated the kinase activity of TAK1 by direct interaction. They showed that the C-terminal 68 amino acids of TAB1 are sufficient for binding and activation of TAK1 in mammalian cells, while the N-terminal 418 amino acids act as a dominant-negative inhibitor of transforming growth factor-beta (TGFB; 190180)-induced gene expression. Since TAK1 functions as an MAPKKK in the TGFB signaling pathway, Shibuya et al. (1996) suggested that TAB1 may be an important signaling intermediate between TGFB receptors and TAK1. Using a yeast 2-hybrid screen of gastrointestinal tract tissue with p38-alpha (MAPK14; 600289) as the bait, Ge et al. (2002) isolated multiple clones encoding TAB1. Immunoprecipitation and GST pull-down analyses indicated that TAB1 interacts with p38-alpha, but not with other MAPKs, with or without treatment with TNF (191160). Immunoblot analysis showed that coexpression of TAB1 and p38-alpha enhanced autophosphorylation of p38-alpha even in the presence of dominant-negative forms of MAP2Ks (e.g., MAP2K3; 602315) and TAK1. The amino acids between positions 373 and 418 of TAB1 were found to be required for phosphorylation of p38-alpha. Expression of TLR2 (603028) caused p38-alpha phosphorylation in the presence or absence of inhibitors, whereas p38-alpha phosphorylation after stimulation of TLR4 (603030) could be inhibited by mutant TAB1, suggesting that activation of p38-alpha can be TAB1 dependent or independent. Immunoblot analysis detected the formation of TRAF6 (602355)-TAB1-p38-alpha complexes. Formation of these complexes could be enhanced by stimulation with lipopolysaccharide. Ge et al. (2002) concluded that activation of p38-alpha by a nonenzymatic adaptor protein such as TAB1 may be an important alternative activation pathway operating in parallel with kinase cascades in regulating intracellular signaling.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the TAB1 gene to chromosome 22 (TMAP WI-18691). ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602615 was added.

TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 (TAB1)