CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007408
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Signal transducer and activator of transcription 3 
Protein Synonyms/Alias
 Acute-phase response factor 
Gene Name
 STAT3 
Gene Synonyms/Alias
 APRF 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
49DWAYAASKESHATLVacetylation[1, 2]
87QHNLRRIKQFLQSRYacetylation[1, 2]
87QHNLRRIKQFLQSRYubiquitination[3, 4, 5]
97LQSRYLEKPMEIARIubiquitination[3, 4, 5]
140TAAVVTEKQQMLEQHmethylation[6]
161RVQDLEQKMKVVENLubiquitination[4]
163QDLEQKMKVVENLQDubiquitination[4]
177DDFDFNYKTLKSQGDubiquitination[3, 4, 5, 7, 8]
180DFNYKTLKSQGDMQDubiquitination[4, 7, 9]
199NQSVTRQKMQQLEQMubiquitination[4, 7]
244DEELADWKRRQQIACubiquitination[3, 4, 5, 7, 10]
283QTRQQIKKLEELQQKubiquitination[4]
294LQQKVSYKGDPIVQHubiquitination[3, 4, 5, 7, 10]
318ELFRNLMKSAFVVERubiquitination[4, 10]
383AALRGSRKFNILGTNubiquitination[4]
409GSLSAEFKHLTLREQubiquitination[4]
574NIIDLVKKYILALWNubiquitination[7]
601ERAILSTKPPGTFLLubiquitination[4]
615LRFSESSKEGGVTFTubiquitination[4]
626VTFTWVEKDISGKTQubiquitination[4]
631VEKDISGKTQIQSVEubiquitination[4, 7]
679YLYPDIPKEEAFGKYacetylation[11]
685PKEEAFGKYCRPESQacetylation[12, 13]
707GSAAPYLKTKFICVTacetylation[11]
707GSAAPYLKTKFICVTubiquitination[4]
709AAPYLKTKFICVTPTacetylation[11]
709AAPYLKTKFICVTPTubiquitination[4]
Reference
 [1] STAT3 NH2-terminal acetylation is activated by the hepatic acute-phase response and required for IL-6 induction of angiotensinogen.
 Ray S, Boldogh I, Brasier AR.
 Gastroenterology. 2005 Nov;129(5):1616-32. [PMID: 16285960]
 [2] Requirement of histone deacetylase1 (HDAC1) in signal transducer and activator of transcription 3 (STAT3) nucleocytoplasmic distribution.
 Ray S, Lee C, Hou T, Boldogh I, Brasier AR.
 Nucleic Acids Res. 2008 Aug;36(13):4510-20. [PMID: 18611949]
 [3] 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]
 [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] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [6] Reversible methylation of promoter-bound STAT3 by histone-modifying enzymes.
 Yang J, Huang J, Dasgupta M, Sears N, Miyagi M, Wang B, Chance MR, Chen X, Du Y, Wang Y, An L, Wang Q, Lu T, Zhang X, Wang Z, Stark GR.
 Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21499-504. [PMID: 21098664]
 [7] 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]
 [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] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [10] 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]
 [11] STAT3 inhibition of gluconeogenesis is downregulated by SirT1.
 Nie Y, Erion DM, Yuan Z, Dietrich M, Shulman GI, Horvath TL, Gao Q.
 Nat Cell Biol. 2009 Apr;11(4):492-500. [PMID: 19295512]
 [12] Activation of Stat3 sequence-specific DNA binding and transcription by p300/CREB-binding protein-mediated acetylation.
 Wang R, Cherukuri P, Luo J.
 J Biol Chem. 2005 Mar 25;280(12):11528-34. [PMID: 15649887]
 [13] Stat3 dimerization regulated by reversible acetylation of a single lysine residue.
 Yuan ZL, Guan YJ, Chatterjee D, Chin YE.
 Science. 2005 Jan 14;307(5707):269-73. [PMID: 15653507] 
Functional Description
 Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF and other growth factors. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the interleukin-6 (IL-6)- responsive elements identified in the promoters of various acute- phase protein genes. Activated by IL31 through IL31RA. Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity. Plays an important role in host defense in methicillin-resistant S.aureus lung infection by regulating the expression of the antimicrobial lectin REG3G (By similarity). 
Sequence Annotation
 DOMAIN 580 670 SH2.
 MOTIF 150 162 Essential for nuclear import.
 MOD_RES 705 705 Phosphotyrosine; by FER and PTK6.
 MOD_RES 727 727 Phosphoserine; by DYRK2, NLK, NEK6,  
Keyword
 Activator; Alternative splicing; Complete proteome; Cytoplasm; Disease mutation; DNA-binding; Host-virus interaction; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; SH2 domain; Transcription; Transcription regulation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 770 AA 
Protein Sequence
MAQWNQLQQL DTRYLEQLHQ LYSDSFPMEL RQFLAPWIES QDWAYAASKE SHATLVFHNL 60
LGEIDQQYSR FLQESNVLYQ HNLRRIKQFL QSRYLEKPME IARIVARCLW EESRLLQTAA 120
TAAQQGGQAN HPTAAVVTEK QQMLEQHLQD VRKRVQDLEQ KMKVVENLQD DFDFNYKTLK 180
SQGDMQDLNG NNQSVTRQKM QQLEQMLTAL DQMRRSIVSE LAGLLSAMEY VQKTLTDEEL 240
ADWKRRQQIA CIGGPPNICL DRLENWITSL AESQLQTRQQ IKKLEELQQK VSYKGDPIVQ 300
HRPMLEERIV ELFRNLMKSA FVVERQPCMP MHPDRPLVIK TGVQFTTKVR LLVKFPELNY 360
QLKIKVCIDK DSGDVAALRG SRKFNILGTN TKVMNMEESN NGSLSAEFKH LTLREQRCGN 420
GGRANCDASL IVTEELHLIT FETEVYHQGL KIDLETHSLP VVVISNICQM PNAWASILWY 480
NMLTNNPKNV NFFTKPPIGT WDQVAEVLSW QFSSTTKRGL SIEQLTTLAE KLLGPGVNYS 540
GCQITWAKFC KENMAGKGFS FWVWLDNIID LVKKYILALW NEGYIMGFIS KERERAILST 600
KPPGTFLLRF SESSKEGGVT FTWVEKDISG KTQIQSVEPY TKQQLNNMSF AEIIMGYKIM 660
DATNILVSPL VYLYPDIPKE EAFGKYCRPE SQEHPEADPG SAAPYLKTKF ICVTPTTCSN 720
TIDLPMSPRT LDSLMQFGNN GEGAEPSAGG QFESLTFDME LTSECATSPM 770 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005886; C:plasma membrane; ISS:UniProtKB.
 GO:0005509; F:calcium ion binding; IEA:InterPro.
 GO:0004879; F:ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity; IDA:BHF-UCL.
 GO:0046983; F:protein dimerization activity; ISS:UniProtKB.
 GO:0019901; F:protein kinase binding; ISS:UniProtKB.
 GO:0043565; F:sequence-specific DNA binding; IEA:Compara.
 GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL.
 GO:0006953; P:acute-phase response; IEA:Compara.
 GO:0048708; P:astrocyte differentiation; ISS:UniProtKB.
 GO:0008283; P:cell proliferation; IEA:Compara.
 GO:0006928; P:cellular component movement; TAS:ProtInc.
 GO:0042755; P:eating behavior; ISS:UniProtKB.
 GO:0001754; P:eye photoreceptor cell differentiation; ISS:UniProtKB.
 GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
 GO:0070102; P:interleukin-6-mediated signaling pathway; IDA:BHF-UCL.
 GO:0060397; P:JAK-STAT cascade involved in growth hormone signaling pathway; ISS:UniProtKB.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; TAS:ProtInc.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0016310; P:phosphorylation; ISS:UniProtKB.
 GO:0045747; P:positive regulation of Notch signaling pathway; ISS:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
 GO:0006606; P:protein import into nucleus; IDA:UniProtKB.
 GO:0060019; P:radial glial cell differentiation; ISS:UniProtKB.
 GO:0040014; P:regulation of multicellular organism growth; IEA:Compara.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0032355; P:response to estradiol stimulus; IDA:BHF-UCL.
 GO:0045471; P:response to ethanol; IEA:Compara.
 GO:0019953; P:sexual reproduction; ISS:UniProtKB.
 GO:0019827; P:stem cell maintenance; IEA:Compara.
 GO:0001659; P:temperature homeostasis; ISS:UniProtKB.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
Interpro
 IPR011992; EF-hand-like_dom.
 IPR008967; p53-like_TF_DNA-bd.
 IPR000980; SH2.
 IPR013800; STAT_TF_alpha.
 IPR015988; STAT_TF_coiled-coil.
 IPR001217; STAT_TF_core.
 IPR013801; STAT_TF_DNA-bd.
 IPR012345; STAT_TF_DNA-bd_sub.
 IPR013799; STAT_TF_prot_interaction. 
Pfam
 PF00017; SH2
 PF01017; STAT_alpha
 PF02864; STAT_bind
 PF02865; STAT_int 
SMART
 SM00252; SH2
 SM00964; STAT_int 
PROSITE
 PS50001; SH2 
PRINTS