Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2. Negative regulator of signaling cascades that mediate activation of MAP kinases via AKAP13. (updated: Jan. 31, 2018)

Protein identification was indicated in the following studies:

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: 100%

Model score: 100

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Variant	Description
	Found in a renal cell carcinoma sample; somatic mutation

Biological Process

Activation of MAPKK activity

Adaptive immune response

Apoptotic process

Axon guidance

Cytoplasmic sequestering of protein

Epidermal growth factor receptor signaling pathway

Fc-epsilon receptor signaling pathway

Fibroblast growth factor receptor signaling pathway

Gene expression

Hippo signaling

Innate immune response

Insulin receptor signaling pathway

Intrinsic apoptotic signaling pathway

MAPK cascade

Membrane organization

Negative regulation of G protein-coupled receptor signaling pathway

Negative regulation of protein dephosphorylation

Negative regulation of transcription, DNA-templated

Neurotrophin TRK receptor signaling pathway

Positive regulation of catalytic activity

Positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway

Protein heterooligomerization

Protein targeting

Ras protein signal transduction

Regulation of mRNA stability

Small GTPase mediated signal transduction

Vascular endothelial growth factor receptor signaling pathway

Viral process

Cellular Component

Cytoplasm

Cytoplasmic vesicle membrane

Cytosol

Extracellular exosome

Focal adhesion

Melanosome

Membrane

Mitochondrion

Nucleus

Perinuclear region of cytoplasm

Protein complex

Transcription repressor complex

Vacuolar membrane

Molecular Function

Cadherin binding

Enzyme binding

Histone deacetylase binding

Identical protein binding

Phosphoprotein binding

Phosphoserine residue binding

Protein C-terminus binding

Protein complex binding

Protein domain specific binding

Protein kinase inhibitor activity

Protein-containing complex binding

Transcription corepressor activity

The reference OMIM entry for this protein is 601289

Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta isoform; ywhab
Brain protein 14-3-3, beta isoform
14-3-3-beta

CLONING

The highly conserved 14-3-3 proteins are found in both plants and mammals; see YWHAH (113508) and YWHAZ (601288). Some have been shown to be involved in the activation of c-Raf (164760) by their participation in the protein kinase C signaling pathway (see 176960). Leffers et al. (1993) reported the cloning of 14-3-3 beta.

GENE FUNCTION

The 14-3-3 family of proteins mediates signal transduction by binding to phosphoserine-containing proteins. Using phosphoserine-oriented peptide libraries to probe all mammalian and yeast 14-3-3s, Yaffe et al. (1997) identified 2 different binding motifs, RSXpSXP and RXY/FXpSXP, present in nearly all known 14-3-3 binding proteins. The crystal structure of YWHAZ complexed with the phosphoserine motif in polyoma middle-T was determined to 2.6-angstrom resolution. The authors showed that the 14-3-3 dimer binds tightly to single molecules containing tandem repeats of phosphoserine motifs, implicating bidentate association as a signaling mechanism with molecules such as Raf, BAD (603167), and Cbl. Using 2-hybrid experiments, Han et al. (1997) demonstrated interaction between murine Ywhab and the RAS-binding domain of RIN1 (605965). Shumway et al. (2003) found that 14-3-3-beta interacts with the TSC1 (605284)-TSC2 (191092) dimer. The interaction required phosphorylation of TSC2 at ser1210. Binding of 14-3-3-beta to TSC2 did not alter the interaction between TSC1 and TSC2, but it reduced the ability of the complex to inhibit phosphorylation of ribosomal protein S6 kinase (608938), impairing the ability of the complex to inhibit cell growth. Yang et al. (2014) had previously found that mouse seipin (BSCL2; 606158) promotes adipogenesis to accommodate storage of excess nutrients in the form of lipids, whereas it inhibits lipid droplet production and accumulation in preadipocytes and other nonadipocyte lineages. Using mass spectrometry to identify proteins that interacted with seipin in adipose tissue lysates, Yang et al. (2014) identified the scaffold protein 14-3-3-beta. Interaction of seipin with 14-3-3-beta did not depend on insulin stimulation. In insulin (INS; 176730)-stimulated 3T3-L1 mouse adipocytes, 14-3-3-beta interacted with the actin-severing protein cofilin-1 (CFL1; 601442), and this interaction required serine phosphorylation of cofilin-1. Adipogenesis in 3T3-L1 cells was accompanied by remodeling of the actin cytoskeleton from central stress fibers to the cell cortex, concomitant with lipid droplet accumulation. Knockdown of seipin, 14-3-3-beta, or cofilin-1 in 3T3-L1 cells impaired adipocyte development and inhibited lipid drop accumulation, but stress fibers remained intact. Impaired adipogenesis was also present in 3T3-L1 cells expressing a severing-resistant actin mutant. Yang et al. (2014) concluded that the interaction of seipin with 14-3-3-beta recruits cofilin-1 to remodel the actin cytoskeleton for adipocyte differentiation.

MAPPING

Tommerup and Leffers (1996) mapped the YWHAB gene to 20q13.1 by fluorescence in situ hybridization. ... More on the omim web site

Subscribe to this protein entry history

Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

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

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

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 15, 2016: Protein entry updated
Automatic update: OMIM entry 601289 was added.

Jan. 27, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed

14-3-3 protein beta/alpha (YWHAB)