CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012367
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Maternal embryonic leucine zipper kinase 
Protein Synonyms/Alias
 hMELK; Protein kinase Eg3; pEg3 kinase; Protein kinase PK38; hPK38; Tyrosine-protein kinase MELK 
Gene Name
 MELK 
Gene Synonyms/Alias
 KIAA0175 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
2******MKDYDELLKubiquitination[1]
44VAIKIMDKNTLGSDLubiquitination[1, 2, 3]
55GSDLPRIKTEIEALKubiquitination[1, 2, 4, 5]
62KTEIEALKNLRHQHIubiquitination[1, 2, 3, 5]
134GYAHRDLKPENLLFDubiquitination[1, 2]
145LLFDEYHKLKLIDFGubiquitination[1, 2, 3]
147FDEYHKLKLIDFGLCubiquitination[1, 3]
156IDFGLCAKPKGNKDYubiquitination[1]
161CAKPKGNKDYHLQTCubiquitination[1]
225YKKIMRGKYDVPKWLubiquitination[1, 2]
249QMLQVDPKKRISMKNubiquitination[1]
250MLQVDPKKRISMKNLubiquitination[1]
255PKKRISMKNLLNHPWubiquitination[1]
395PRTSQFTKYWTESNGubiquitination[1, 2, 4, 5, 6, 7, 8, 9]
406ESNGVESKSLTPALCubiquitination[1, 3, 4, 7]
423PANKLKNKENVYTPKubiquitination[1]
434YTPKSAVKNEEYFMFubiquitination[2]
481CLKETPIKIPVNSTGubiquitination[1, 2]
491VNSTGTDKLMTGVISubiquitination[1, 2]
520AHMEETPKRKGAKVFubiquitination[1]
522MEETPKRKGAKVFGSubiquitination[1]
525TPKRKGAKVFGSLERubiquitination[1]
536SLERGLDKVITVLTRubiquitination[1, 3, 6, 8, 9]
558RDGPRRLKLHYNVTTubiquitination[1]
585IMSILPKKHVDFVQKubiquitination[1]
592KHVDFVQKGYTLKCQubiquitination[1]
597VQKGYTLKCQTQSDFubiquitination[1]
632GIRRQRLKGDAWVYKubiquitination[1, 2, 4]
639KGDAWVYKRLVEDILmethylation[10]
639KGDAWVYKRLVEDILubiquitination[1]
650EDILSSCKV******methylation[10]
650EDILSSCKV******ubiquitination[1, 3, 4]
Reference
 [1] 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]
 [2] 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]
 [3] 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]
 [4] 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]
 [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] 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]
 [7] 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]
 [8] 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]
 [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] 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] 
Functional Description
 Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis. 
Sequence Annotation
 DOMAIN 11 263 Protein kinase.
 DOMAIN 602 651 KA1.
 NP_BIND 17 25 ATP (By similarity).
 REGION 282 321 UBA-like.
 REGION 326 651 Autoinhibitory region.
 ACT_SITE 132 132 Proton acceptor (By similarity).
 BINDING 40 40 ATP (By similarity).
 MOD_RES 56 56 Phosphothreonine; by autocatalysis.
 MOD_RES 163 163 Phosphotyrosine; by autocatalysis.
 MOD_RES 167 167 Phosphothreonine; by autocatalysis.
 MOD_RES 171 171 Phosphoserine; by autocatalysis.
 MOD_RES 253 253 Phosphoserine; by autocatalysis.
 MOD_RES 336 336 Phosphoserine; by autocatalysis.
 MOD_RES 343 343 Phosphoserine; by autocatalysis.
 MOD_RES 356 356 Phosphoserine; by autocatalysis.
 MOD_RES 367 367 Phosphotyrosine.
 MOD_RES 391 391 Phosphoserine; by autocatalysis.
 MOD_RES 398 398 Phosphothreonine; by autocatalysis.
 MOD_RES 407 407 Phosphoserine; by autocatalysis.
 MOD_RES 409 409 Phosphothreonine.
 MOD_RES 431 431 Phosphoserine; by autocatalysis.
 MOD_RES 478 478 Phosphothreonine.
 MOD_RES 494 494 Phosphothreonine; by autocatalysis.
 MOD_RES 498 498 Phosphoserine.
 MOD_RES 505 505 Phosphoserine; by autocatalysis.
 MOD_RES 518 518 Phosphothreonine.
 MOD_RES 529 529 Phosphoserine; alternate.
 MOD_RES 529 529 Phosphoserine; by autocatalysis;
 MOD_RES 539 539 Phosphothreonine; by autocatalysis.  
Keyword
 3D-structure; Alternative splicing; Apoptosis; ATP-binding; Calcium; Cell cycle; Cell membrane; Complete proteome; Kinase; Lipid-binding; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 651 AA 
Protein Sequence
MKDYDELLKY YELHETIGTG GFAKVKLACH ILTGEMVAIK IMDKNTLGSD LPRIKTEIEA 60
LKNLRHQHIC QLYHVLETAN KIFMVLEYCP GGELFDYIIS QDRLSEEETR VVFRQIVSAV 120
AYVHSQGYAH RDLKPENLLF DEYHKLKLID FGLCAKPKGN KDYHLQTCCG SLAYAAPELI 180
QGKSYLGSEA DVWSMGILLY VLMCGFLPFD DDNVMALYKK IMRGKYDVPK WLSPSSILLL 240
QQMLQVDPKK RISMKNLLNH PWIMQDYNYP VEWQSKNPFI HLDDDCVTEL SVHHRNNRQT 300
MEDLISLWQY DHLTATYLLL LAKKARGKPV RLRLSSFSCG QASATPFTDI KSNNWSLEDV 360
TASDKNYVAG LIDYDWCEDD LSTGAATPRT SQFTKYWTES NGVESKSLTP ALCRTPANKL 420
KNKENVYTPK SAVKNEEYFM FPEPKTPVNK NQHKREILTT PNRYTTPSKA RNQCLKETPI 480
KIPVNSTGTD KLMTGVISPE RRCRSVELDL NQAHMEETPK RKGAKVFGSL ERGLDKVITV 540
LTRSKRKGSA RDGPRRLKLH YNVTTTRLVN PDQLLNEIMS ILPKKHVDFV QKGYTLKCQT 600
QSDFGKVTMQ FELEVCQLQK PDVVGIRRQR LKGDAWVYKR LVEDILSSCK V 651 
Gene Ontology
 GO:0005938; C:cell cortex; IDA:UniProtKB.
 GO:0005886; C:plasma membrane; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0005509; F:calcium ion binding; IDA:UniProtKB.
 GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0006915; P:apoptotic process; IDA:UniProtKB.
 GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:UniProtKB.
 GO:0030097; P:hemopoiesis; ISS:UniProtKB.
 GO:0061351; P:neural precursor cell proliferation; ISS:UniProtKB.
 GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. 
Interpro
 IPR001772; KA1_dom.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF02149; KA1
 PF00069; Pkinase 
SMART
 SM00220; S_TKc 
PROSITE
 PS50032; KA1
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS