CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-004013
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Nucleoprotein TPR 
Protein Synonyms/Alias
 Megator; NPC-associated intranuclear protein; Translocated promoter region protein 
Gene Name
 TPR 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
40QSEIDGLKGRHEKFKubiquitination[1]
59QQYFEIEKRLSHSQEubiquitination[1]
117QSQFTRTKEELEAEKmethylation[2]
124KEELEAEKRDLIRTNmethylation[2]
177QASDVSVKYREKRLEubiquitination[1]
252TSNEHLQKHVEDLLTacetylation[3, 4]
290IKLSNLYKSAADDSEubiquitination[1, 4, 5]
299AADDSEAKSNELTRAubiquitination[1]
312RAVEELHKLLKEAGEacetylation[3, 4, 6, 7]
312RAVEELHKLLKEAGEubiquitination[8, 9]
315EELHKLLKEAGEANKubiquitination[1]
322KEAGEANKAIQDHLLubiquitination[1]
335LLEVEQSKDQMEKEMubiquitination[1]
340QSKDQMEKEMLEKIGacetylation[7]
345MEKEMLEKIGRLEKEacetylation[3]
351EKIGRLEKELENANDacetylation[7]
351EKIGRLEKELENANDubiquitination[8, 9]
364NDLLSATKRKGAILSubiquitination[1, 5, 8, 9, 10, 11]
366LLSATKRKGAILSEEubiquitination[1, 11]
413QDQLLLEKLENKRINubiquitination[1]
421LENKRINKYLDEIVKubiquitination[1, 4, 8, 9, 10]
428KYLDEIVKEVEAKAPacetylation[3, 4, 7]
433IVKEVEAKAPILKRQubiquitination[1]
449EEYERAQKAVASLSVacetylation[4]
457AVASLSVKLEQAMKEacetylation[3, 4, 7]
463VKLEQAMKEIQRLQEubiquitination[1, 4, 5]
477EDTDKANKQSSVLERacetylation[4]
477EDTDKANKQSSVLERubiquitination[1, 4, 5, 11]
494RRMEIQVKDLSQQIRubiquitination[1, 4, 5, 8, 9, 10, 11, 12]
575EQETTSSKITELQLKubiquitination[1, 5, 8, 9, 12]
582KITELQLKLESALTEubiquitination[1, 5, 11]
673IEAKAALKQLQEIFEubiquitination[5, 8, 9]
691KEKAENEKIQNEQLEubiquitination[1]
699IQNEQLEKLQEQVTDubiquitination[1]
713DLRSQNTKISTQLDFacetylation[3, 4, 6, 7]
713DLRSQNTKISTQLDFubiquitination[1, 5]
723TQLDFASKRYEMLQDacetylation[3, 4, 6]
723TQLDFASKRYEMLQDubiquitination[8, 9]
748SLHERNQKLTATTQKacetylation[3, 4, 6, 7]
755KLTATTQKQEQIINTacetylation[3, 4, 6, 7]
755KLTATTQKQEQIINTubiquitination[1, 5, 11]
834ERSETETKQRLSSQIubiquitination[1]
843RLSSQIEKLEHEISHubiquitination[5]
852EHEISHLKKKLENEVubiquitination[5]
853HEISHLKKKLENEVEubiquitination[5]
854EISHLKKKLENEVEQacetylation[4]
877DVQLLDTKRQLDTETubiquitination[1]
952EEQVNDLKERLKTSTubiquitination[1, 4, 5]
956NDLKERLKTSTSNVEubiquitination[1]
1038QQLSELKKTLSSVQNubiquitination[8, 9]
1254EKVQVTAKTMAQHEEubiquitination[8, 9]
1265QHEELMKKTETMNVVacetylation[13]
1277NVVMETNKMLREEKEacetylation[13]
1296DLQQMQAKVRKLELDubiquitination[1, 8, 9]
1326GMLQAEKKLLEEDVKmethylation[2]
1400QNLIQSLKEDLNKVRubiquitination[1, 5, 8, 9, 10]
1427KIIDIQEKVKTITQVacetylation[4, 7]
1449KTQYEELKAQQDKVMubiquitination[1]
1491NQAETKSKSLESQVEubiquitination[8, 9]
1549LRQQITEKEEKTRKAacetylation[4]
1552QITEKEEKTRKAIVAacetylation[4]
1637EPQEPSNKVPEQQRQubiquitination[1, 4, 11]
1648QQRQITLKTTPASGEubiquitination[11]
1670DPPTANIKPTPVVSTacetylation[7]
1670DPPTANIKPTPVVSTubiquitination[1, 10]
1690AAAMAGNKSTPRASIubiquitination[1, 4, 5, 11]
Reference
 [1] 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]
 [2] Large-scale global identification of protein lysine methylation in vivo.
 Cao XJ, Arnaudo AM, Garcia BA.
 Epigenetics. 2013 May 1;8(5):477-85. [PMID: 23644510]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] 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]
 [7] 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]
 [8] 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]
 [9] 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]
 [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] 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]
 [12] 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]
 [13] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786] 
Functional Description
 Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs, plays a role in the establishment of nuclear-peripheral chromatin compartmentalization in interphase, and in the mitotic spindle checkpoint signaling during mitosis. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with NUP153, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Negatively regulates both the association of CTE-containing mRNA with large polyribosomes and translation initiation. Does not play any role in Rev response element (RRE)-mediated export of unspliced mRNAs. Implicated in nuclear export of mRNAs transcribed from heat shock gene promoters; associates both with chromatin in the HSP70 promoter and with mRNAs transcribed from this promoter under stress-induced conditions. Modulates the nucleocytoplasmic transport of activated MAPK1/ERK2 and huntingtin/HTT and may serve as a docking site for the XPO1/CRM1-mediated nuclear export complex. According to some authors, plays a limited role in the regulation of nuclear protein export (PubMed:22253824 and PubMed:11952838). Plays also a role as a structural and functional element of the perinuclear chromatin distribution; involved in the formation and/or maintenance of NPC-associated perinuclear heterochromatin exclusion zones (HEZs). Finally, acts as a spatial regulator of the spindle-assembly checkpoint (SAC) response ensuring a timely and effective recruitment of spindle checkpoint proteins like MAD1L1 and MAD2L1 to unattached kinetochore during the metaphase-anaphase transition before chromosome congression. Its N-terminus is involved in activation of oncogenic kinases. 
Sequence Annotation
 REGION 3 13 Sufficient for interaction with TPR.
 REGION 14 117 Necessary for interaction with HSF1.
 REGION 437 513 Necessary for association to the NPC.
 REGION 1218 1320 Necessary for interaction with HSF1.
 REGION 1812 1867 Sufficient and essential for mediating
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 252 252 N6-acetyllysine.
 MOD_RES 312 312 N6-acetyllysine.
 MOD_RES 345 345 N6-acetyllysine.
 MOD_RES 379 379 Phosphoserine.
 MOD_RES 428 428 N6-acetyllysine.
 MOD_RES 457 457 N6-acetyllysine.
 MOD_RES 713 713 N6-acetyllysine.
 MOD_RES 723 723 N6-acetyllysine.
 MOD_RES 748 748 N6-acetyllysine.
 MOD_RES 755 755 N6-acetyllysine.
 MOD_RES 1185 1185 Phosphoserine.
 MOD_RES 1692 1692 Phosphothreonine.
 MOD_RES 2048 2048 Phosphoserine.
 MOD_RES 2050 2050 Phosphoserine.
 MOD_RES 2073 2073 Phosphoserine.
 MOD_RES 2155 2155 Phosphoserine.  
Keyword
 Acetylation; Cell cycle; Cell division; Centromere; Chromosomal rearrangement; Chromosome; Coiled coil; Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing; Kinetochore; Membrane; Mitosis; mRNA transport; Nuclear pore complex; Nucleus; Phosphoprotein; Polymorphism; Protein transport; Proto-oncogene; Reference proteome; Translocation; Transport. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 2363 AA 
Protein Sequence
MAAVLQQVLE RTELNKLPKS VQNKLEKFLA DQQSEIDGLK GRHEKFKVES EQQYFEIEKR 60
LSHSQERLVN ETRECQSLRL ELEKLNNQLK ALTEKNKELE IAQDRNIAIQ SQFTRTKEEL 120
EAEKRDLIRT NERLSQELEY LTEDVKRLNE KLKESNTTKG ELQLKLDELQ ASDVSVKYRE 180
KRLEQEKELL HSQNTWLNTE LKTKTDELLA LGREKGNEIL ELKCNLENKK EEVSRLEEQM 240
NGLKTSNEHL QKHVEDLLTK LKEAKEQQAS MEEKFHNELN AHIKLSNLYK SAADDSEAKS 300
NELTRAVEEL HKLLKEAGEA NKAIQDHLLE VEQSKDQMEK EMLEKIGRLE KELENANDLL 360
SATKRKGAIL SEEELAAMSP TAAAVAKIVK PGMKLTELYN AYVETQDQLL LEKLENKRIN 420
KYLDEIVKEV EAKAPILKRQ REEYERAQKA VASLSVKLEQ AMKEIQRLQE DTDKANKQSS 480
VLERDNRRME IQVKDLSQQI RVLLMELEEA RGNHVIRDEE VSSADISSSS EVISQHLVSY 540
RNIEELQQQN QRLLVALREL GETREREEQE TTSSKITELQ LKLESALTEL EQLRKSRQHQ 600
MQLVDSIVRQ RDMYRILLSQ TTGVAIPLHA SSLDDVSLAS TPKRPSTSQT VSTPAPVPVI 660
ESTEAIEAKA ALKQLQEIFE NYKKEKAENE KIQNEQLEKL QEQVTDLRSQ NTKISTQLDF 720
ASKRYEMLQD NVEGYRREIT SLHERNQKLT ATTQKQEQII NTMTQDLRGA NEKLAVAEVR 780
AENLKKEKEM LKLSEVRLSQ QRESLLAEQR GQNLLLTNLQ TIQGILERSE TETKQRLSSQ 840
IEKLEHEISH LKKKLENEVE QRHTLTRNLD VQLLDTKRQL DTETNLHLNT KELLKNAQKE 900
IATLKQHLSN MEVQVASQSS QRTGKGQPSN KEDVDDLVSQ LRQTEEQVND LKERLKTSTS 960
NVEQYQAMVT SLEESLNKEK QVTEEVRKNI EVRLKESAEF QTQLEKKLME VEKEKQELQD 1020
DKRRAIESME QQLSELKKTL SSVQNEVQEA LQRASTALSN EQQARRDCQE QAKIAVEAQN 1080
KYERELMLHA ADVEALQAAK EQVSKMASVR QHLEETTQKA ESQLLECKAS WEERERMLKD 1140
EVSKCVCRCE DLEKQNRLLH DQIEKLSDKV VASVKEGVQG PLNVSLSEEG KSQEQILEIL 1200
RFIRREKEIA ETRFEVAQVE SLRYRQRVEL LERELQELQD SLNAEREKVQ VTAKTMAQHE 1260
ELMKKTETMN VVMETNKMLR EEKERLEQDL QQMQAKVRKL ELDILPLQEA NAELSEKSGM 1320
LQAEKKLLEE DVKRWKARNQ HLVSQQKDPD TEEYRKLLSE KEVHTKRIQQ LTEEIGRLKA 1380
EIARSNASLT NNQNLIQSLK EDLNKVRTEK ETIQKDLDAK IIDIQEKVKT ITQVKKIGRR 1440
YKTQYEELKA QQDKVMETSA QSSGDHQEQH VSVQEMQELK ETLNQAETKS KSLESQVENL 1500
QKTLSEKETE ARNLQEQTVQ LQSELSRLRQ DLQDRTTQEE QLRQQITEKE EKTRKAIVAA 1560
KSKIAHLAGV KDQLTKENEE LKQRNGALDQ QKDELDVRIT ALKSQYEGRI SRLERELREH 1620
QERHLEQRDE PQEPSNKVPE QQRQITLKTT PASGERGIAS TSDPPTANIK PTPVVSTPSK 1680
VTAAAMAGNK STPRASIRPM VTPATVTNPT TTPTATVMPT TQVESQEAMQ SEGPVEHVPV 1740
FGSTSGSVRS TSPNVQPSIS QPILTVQQQT QATAFVQPTQ QSHPQIEPAN QELSSNIVEV 1800
VQSSPVERPS TSTAVFGTVS ATPSSSLPKR TREEEEDSTI EASDQVSDDT VEMPLPKKLK 1860
SVTPVGTEEE VMAEESTDGE VETQVYNQDS QDSIGEGVTQ GDYTPMEDSE ETSQSLQIDL 1920
GPLQSDQQTT TSSQDGQGKG DDVIVIDSDD EEEDDDENDG EHEDYEEDEE DDDDDEDDTG 1980
MGDEGEDSNE GTGSADGNDG YEADDAEGGD GTDPGTETEE SMGGGEGNHR AADSQNSGEG 2040
NTGAAESSFS QEVSREQQPS SASERQAPRA PQSPRRPPHP LPPRLTIHAP PQELGPPVQR 2100
IQMTRRQSVG RGLQLTPGIG GMQQHFFDDE DRTVPSTPTL VVPHRTDGFA EAIHSPQVAG 2160
VPRFRFGPPE DMPQTSSSHS DLGQLASQGG LGMYETPLFL AHEEESGGRS VPTTPLQVAA 2220
PVTVFTESTT SDASEHASQS VPMVTTSTGT LSTTNETATG DDGDEVFVEA ESEGISSEAG 2280
LEIDSQQEEE PVQASDESDL PSTSQDPPSS SSVDTSSSQP KPFRRVRLQT TLRQGVRGRQ 2340
FNRQRGVSHA MGGRGGINRG NIN 2363 
Gene Ontology
 GO:0005868; C:cytoplasmic dynein complex; IDA:UniProtKB.
 GO:0019898; C:extrinsic to membrane; IDA:UniProtKB.
 GO:0000776; C:kinetochore; IDA:UniProtKB.
 GO:0072686; C:mitotic spindle; IDA:UniProtKB.
 GO:0042405; C:nuclear inclusion body; IDA:UniProtKB.
 GO:0031965; C:nuclear membrane; IDA:UniProtKB.
 GO:0034399; C:nuclear periphery; IDA:UniProtKB.
 GO:0044615; C:nuclear pore nuclear basket; IDA:UniProtKB.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005524; F:ATP binding; IEA:InterPro.
 GO:0003682; F:chromatin binding; IDA:UniProtKB.
 GO:0070840; F:dynein complex binding; IDA:UniProtKB.
 GO:0031072; F:heat shock protein binding; IDA:UniProtKB.
 GO:0051019; F:mitogen-activated protein kinase binding; IDA:UniProtKB.
 GO:0003729; F:mRNA binding; IDA:UniProtKB.
 GO:0005487; F:nucleocytoplasmic transporter activity; IDA:UniProtKB.
 GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
 GO:0004828; F:serine-tRNA ligase activity; IEA:InterPro.
 GO:0015631; F:tubulin binding; IDA:UniProtKB.
 GO:0005975; P:carbohydrate metabolic process; TAS:Reactome.
 GO:0051301; P:cell division; IEA:UniProtKB-KW.
 GO:0035457; P:cellular response to interferon-alpha; ISS:UniProtKB.
 GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
 GO:0015758; P:glucose transport; TAS:Reactome.
 GO:0000189; P:MAPK import into nucleus; IMP:UniProtKB.
 GO:0007067; P:mitosis; IEA:UniProtKB-KW.
 GO:0007094; P:mitotic spindle assembly checkpoint; IMP:UniProtKB.
 GO:0031990; P:mRNA export from nucleus in response to heat stress; IDA:UniProtKB.
 GO:0046832; P:negative regulation of RNA export from nucleus; IDA:UniProtKB.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
 GO:0045947; P:negative regulation of translational initiation; IMP:UniProtKB.
 GO:0006999; P:nuclear pore organization; IMP:UniProtKB.
 GO:0031453; P:positive regulation of heterochromatin assembly; IMP:UniProtKB.
 GO:0090267; P:positive regulation of mitotic cell cycle spindle assembly checkpoint; IMP:UniProtKB.
 GO:0046827; P:positive regulation of protein export from nucleus; ISS:UniProtKB.
 GO:0042307; P:positive regulation of protein import into nucleus; IMP:UniProtKB.
 GO:0010827; P:regulation of glucose transport; TAS:Reactome.
 GO:0010965; P:regulation of mitotic sister chromatid separation; IMP:UniProtKB.
 GO:1901673; P:regulation of spindle assembly involved in mitosis; IMP:UniProtKB.
 GO:0070849; P:response to epidermal growth factor stimulus; IDA:UniProtKB.
 GO:0006404; P:RNA import into nucleus; IDA:UniProtKB.
 GO:0006434; P:seryl-tRNA aminoacylation; IEA:InterPro.
 GO:0044281; P:small molecule metabolic process; TAS:Reactome.
 GO:0055085; P:transmembrane transport; TAS:Reactome.
 GO:0022415; P:viral reproductive process; TAS:Reactome. 
Interpro
 IPR009053; Prefoldin.
 IPR015866; Ser-tRNA-synth_1_N.
 IPR012929; TPR_MLP1_2. 
Pfam
 PF07926; TPR_MLP1_2 
SMART
  
PROSITE
  
PRINTS