UniProt Accession

 1433B_HUMAN; P31946; A8K9K2; E1P616 

Genbank Protein ID

 X57346; AK292717; AL008725; CH471077; CH471077; CH471077; BC001359 

Genbank Nucleotide ID

 CAA40621.1; BAF85406.1; CAA15497.1; EAW75893.1; EAW75894.1; EAW75896.1; AAH01359.1 

Protein Name

 14-3-3 protein beta/alpha 

Protein Synonyms/Alias

 Protein 1054; Protein kinase C inhibitor protein 1; KCIP-1; 14-3-3 protein beta/alpha, N-terminally processed 

Gene Name

 YWHAB 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
5	***MTMDKSELVQKA	acetylation	[1, 2]
5	***MTMDKSELVQKA	ubiquitination	[2, 3, 4]
11	DKSELVQKAKLAEQA	ubiquitination	[2, 3, 4, 5, 6, 7, 8, 9]
13	SELVQKAKLAEQAER	ubiquitination	[3, 4, 10]
51	NLLSVAYKNVVGARR	acetylation	[11]
51	NLLSVAYKNVVGARR	ubiquitination	[3, 12]
70	VISSIEQKTERNEKK	acetylation	[1, 2, 11, 13]
70	VISSIEQKTERNEKK	ubiquitination	[2, 3, 4, 5, 6, 7, 9, 14]
82	EKKQQMGKEYREKIE	acetylation	[1]
117	NATQPESKVFYLKMK	acetylation	[11]
117	NATQPESKVFYLKMK	ubiquitination	[2, 3, 5]
122	ESKVFYLKMKGDYFR	ubiquitination	[3]
140	EVASGDNKQTTVSNS	ubiquitination	[2, 4, 5, 6, 7, 8, 9]
159	QEAFEISKKEMQPTH	acetylation	[13]
159	QEAFEISKKEMQPTH	ubiquitination	[4, 6]
160	EAFEISKKEMQPTHP	ubiquitination	[4]
195	EKACSLAKTAFDEAI	ubiquitination	[14]

Reference

 [1] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [2] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [3] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [5] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [6] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [7] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [8] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [9] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [10] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [11] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [12] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [13] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [14] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931] 

Functional Description

 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. 

Sequence Annotation

 MOD_RES 1 1 N-acetylmethionine; in 14-3-3 protein
 MOD_RES 2 2 N-acetylthreonine; in 14-3-3 protein
 MOD_RES 60 60 Phosphoserine (By similarity).
 MOD_RES 70 70 N6-acetyllysine.
 MOD_RES 84 84 Nitrated tyrosine (By similarity).
 MOD_RES 106 106 Nitrated tyrosine (By similarity).
 MOD_RES 117 117 N6-acetyllysine.
 MOD_RES 186 186 Phosphoserine (By similarity).  

Keyword

 3D-structure; Acetylation; Alternative initiation; Complete proteome; Cytoplasm; Direct protein sequencing; Nitration; Phosphoprotein; Polymorphism; Reference proteome. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 246 AA 

Protein Sequence

Gene Ontology

 GO:0030659; C:cytoplasmic vesicle membrane; TAS:Reactome.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
 GO:0017053; C:transcriptional repressor complex; IEA:Compara.
 GO:0003714; F:transcription corepressor activity; IEA:Compara.
 GO:0000186; P:activation of MAPKK activity; TAS:Reactome.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0016044; P:cellular membrane organization; TAS:Reactome.
 GO:0051220; P:cytoplasmic sequestering of protein; IDA:BHF-UCL.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0010467; P:gene expression; TAS:Reactome.
 GO:0035329; P:hippo signaling cascade; TAS:Reactome.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
 GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:Reactome.
 GO:0000165; P:MAPK cascade; TAS:Reactome.
 GO:0016071; P:mRNA metabolic process; TAS:Reactome.
 GO:0035308; P:negative regulation of protein dephosphorylation; IDA:BHF-UCL.
 GO:0045892; P:negative regulation of transcription, DNA-dependent; IEA:Compara.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:1900740; P:positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; TAS:Reactome.
 GO:0051291; P:protein heterooligomerization; IEA:Compara.
 GO:0006605; P:protein targeting; IEA:Compara.
 GO:0007265; P:Ras protein signal transduction; TAS:Reactome. 

Interpro

 IPR000308; 14-3-3.
 IPR023409; 14-3-3_CS.
 IPR023410; 14-3-3_domain. 

Pfam

 PF00244; 14-3-3 

SMART

 SM00101; 14_3_3 

PROSITE

 PS00796; 1433_1
 PS00797; 1433_2 

PRINTS

 PR00305; 1433ZETA.