CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-015734
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Serine/threonine-protein kinase MARK2 
Protein Synonyms/Alias
 ELKL motif kinase 1; EMK-1; MAP/microtubule affinity-regulating kinase 2; PAR1 homolog; PAR1 homolog b; Par-1b; Par1b 
Gene Name
 MARK2 
Gene Synonyms/Alias
 EMK1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
637ASGSIFSKFTSKFVRubiquitination[1, 2, 3]
Reference
 [1] 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]
 [2] 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]
 [3] 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] 
Functional Description
 Serine/threonine-protein kinase involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4, MAPT/TAU, and RAB11FIP2. Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule- dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells. 
Sequence Annotation
 DOMAIN 53 304 Protein kinase.
 DOMAIN 323 362 UBA.
 DOMAIN 739 788 KA1.
 NP_BIND 59 67 ATP (By similarity).
 ACT_SITE 175 175 Proton acceptor (By similarity).
 BINDING 82 82 ATP (By similarity).
 MOD_RES 40 40 Phosphoserine.
 MOD_RES 58 58 Phosphothreonine; by autocatalysis (By
 MOD_RES 91 91 Phosphoserine; by CaMK1 (By similarity).
 MOD_RES 92 92 Phosphoserine; by CaMK1 (By similarity).
 MOD_RES 93 93 Phosphoserine; by CaMK1 (By similarity).
 MOD_RES 208 208 Phosphothreonine; by LKB1 and TAOK1.
 MOD_RES 212 212 Phosphoserine; by GSK3-beta (By
 MOD_RES 274 274 Phosphoserine; by autocatalysis (By
 MOD_RES 275 275 Phosphothreonine; by autocatalysis (By
 MOD_RES 294 294 Phosphothreonine; by CaMK1 (By
 MOD_RES 409 409 Phosphoserine.
 MOD_RES 456 456 Phosphoserine.
 MOD_RES 486 486 Phosphoserine.
 MOD_RES 493 493 Phosphoserine.
 MOD_RES 569 569 Phosphoserine.
 MOD_RES 571 571 Phosphoserine (By similarity).
 MOD_RES 595 595 Phosphoserine (By similarity).
 MOD_RES 596 596 Phosphothreonine; by PKC/PRKCZ.
 MOD_RES 619 619 Phosphoserine.
 MOD_RES 722 722 Phosphoserine.  
Keyword
 3D-structure; Alternative promoter usage; Alternative splicing; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Developmental protein; Differentiation; Kinase; Lipid-binding; Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase; Wnt signaling pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 788 AA 
Protein Sequence
MSSARTPLPT LNERDTEQPT LGHLDSKPSS KSNMIRGRNS ATSADEQPHI GNYRLLKTIG 60
KGNFAKVKLA RHILTGKEVA VKIIDKTQLN SSSLQKLFRE VRIMKVLNHP NIVKLFEVIE 120
TEKTLYLVME YASGGEVFDY LVAHGRMKEK EARAKFRQIV SAVQYCHQKF IVHRDLKAEN 180
LLLDADMNIK IADFGFSNEF TFGNKLDTFC GSPPYAAPEL FQGKKYDGPE VDVWSLGVIL 240
YTLVSGSLPF DGQNLKELRE RVLRGKYRIP FYMSTDCENL LKKFLILNPS KRGTLEQIMK 300
DRWMNVGHED DELKPYVEPL PDYKDPRRTE LMVSMGYTRE EIQDSLVGQR YNEVMATYLL 360
LGYKSSELEG DTITLKPRPS ADLTNSSAPS PSHKVQRSVS ANPKQRRFSD QAAGPAIPTS 420
NSYSKKTQSN NAENKRPEED RESGRKASST AKVPASPLPG LERKKTTPTP STNSVLSTST 480
NRSRNSPLLE RASLGQASIQ NGKDSLTMPG SRASTASASA AVSAARPRQH QKSMSASVHP 540
NKASGLPPTE SNCEVPRPST APQRVPVASP SAHNISSSGG APDRTNFPRG VSSRSTFHAG 600
QLRQVRDQQN LPYGVTPASP SGHSQGRRGA SGSIFSKFTS KFVRRNLSFR FARRNLNEPE 660
SKDRVETLRP HVVGSGGNDK EKEEFREAKP RSLRFTWSMK TTSSMEPNEM MREIRKVLDA 720
NSCQSELHEK YMLLCMHGTP GHEDFVQWEM EVCKLPRLSL NGVRFKRISG TSMAFKNIAS 780
KIANELKL 788 
Gene Ontology
 GO:0045180; C:basal cortex; IEA:Compara.
 GO:0016020; C:membrane; IMP:UniProtKB.
 GO:0005634; C:nucleus; IEA:Compara.
 GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; IDA:UniProtKB.
 GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
 GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0050321; F:tau-protein kinase activity; ISS:UniProtKB.
 GO:0030010; P:establishment of cell polarity; IDA:UniProtKB.
 GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; IDA:UniProtKB.
 GO:0007243; P:intracellular protein kinase cascade; IDA:UniProtKB.
 GO:0001764; P:neuron migration; ISS:UniProtKB.
 GO:0010976; P:positive regulation of neuron projection development; IDA:UniProtKB.
 GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
 GO:0050770; P:regulation of axonogenesis; IMP:UniProtKB.
 GO:0051493; P:regulation of cytoskeleton organization; ISS:UniProtKB.
 GO:0006979; P:response to oxidative stress; IEP:BHF-UCL.
 GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW. 
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.
 IPR015940; UBA/transl_elong_EF1B_N_euk. 
Pfam
 PF02149; KA1
 PF00069; Pkinase 
SMART
 SM00220; S_TKc
 SM00165; UBA 
PROSITE
 PS50032; KA1
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST
 PS50030; UBA 
PRINTS