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Q14680 (MELK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Maternal embryonic leucine zipper kinase

Short name=hMELK
EC=2.7.11.1
Alternative name(s):
Protein kinase Eg3
Short name=pEg3 kinase
Protein kinase PK38
Short name=hPK38
Tyrosine-protein kinase MELK
EC=2.7.10.2
Gene names
Name:MELK
Synonyms:KIAA0175
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length651 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.8 Ref.9 Ref.12 Ref.15 Ref.17

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.15

ATP + a protein = ADP + a phosphoprotein. Ref.15

Enzyme regulation

Activated by autophosphorylation of the T-loop at Thr-167 and Ser-171: in contrast to other members of the SNF1 subfamily, phosphorylation at Thr-167 is not mediated by STK11/LKB1 but via autophosphorylation instead. Inhibited by calcium-binding. Kinase activity is also regulated by reducing agents: dithiothreitol (DTT) or reduced glutathione are required for kinase activity in vitro; such dependence is however not due to the presence of disulfide bonds. Ref.15

Subunit structure

Monomer. Interacts with ZNF622 and PPP1R8. Ref.7 Ref.9

Subcellular location

Cell membrane; Peripheral membrane protein Ref.16 Ref.26.

Tissue specificity

Expressed in placenta, kidney, thymus, testis, ovary and intestine. Ref.2

Developmental stage

Increases during G2/M phase compared to interphase. Protein level decreases when cells exit mitosis, probably due to degradation. Ref.27

Induction

Up-regulated in many cancers cells. Up-regulated upon treatment with radiation or 5-fluorouracil (5-FU) in colorectal cancer cells, suggesting that it might be associated with increased resistance of colorectal cells against radiation and 5-FU. Down-regulated upon siomycin A, a thiazole antibiotic, treatment, leading to inhibit tumor growth in vivo. Ref.15 Ref.28 Ref.29

Domain

The KA1 domain mediates binding to phospholipids and targeting to membranes By similarity.

Post-translational modification

Autophosphorylated: autophosphorylation of the T-loop at Thr-167 and Ser-171 is required for activation. Thr-478 phosphorylation during mitosis promotes interaction with PPP1R8 Probable. Ref.9 Ref.10 Ref.14 Ref.15 Ref.27

Involvement in disease

Defects in MELK are associated with some cancers, such as brain or breast cancers. Expression is dramatically increased in aggressive undifferentiated tumors, correlating with poor patient outcome in breast and brain cancers, suggesting a role in tumor-initiating cells and proliferation via its function in cell proliferation regulation.

Miscellaneous

Potential therapeutic target for treatment of somatic tumors, such as brain and breast cancers, down-regulation of MELK inhibiting tumorigenesis (Ref.18, Ref.25).

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Contains 1 KA1 (kinase-associated) domain.

Contains 1 protein kinase domain.

Sequence caution

The sequence BAA11492.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processApoptosis
Cell cycle
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Calcium
Lipid-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG2/M transition of mitotic cell cycle

Traceable author statement Ref.8. Source: UniProtKB

apoptotic process

Inferred from direct assay Ref.17. Source: UniProtKB

cell proliferation

Inferred from direct assay Ref.17. Source: UniProtKB

hemopoiesis

Inferred from sequence or structural similarity. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to oxidative stress

Inferred from electronic annotation. Source: Ensembl

neural precursor cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.15. Source: GOC

positive regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay Ref.15. Source: UniProtKB

   Cellular_componentcell cortex

Inferred from direct assay Ref.16. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.26. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

calcium ion binding

Inferred from direct assay Ref.15. Source: UniProtKB

lipid binding

Inferred from electronic annotation. Source: UniProtKB-KW

non-membrane spanning protein tyrosine kinase activity

Inferred from direct assay Ref.15. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.8Ref.12Ref.17. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.8Ref.12Ref.15Ref.17. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

BCL2L14Q9BZR84EBI-1046702,EBI-1385773

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q14680-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q14680-2)

The sequence of this isoform differs from the canonical sequence as follows:
     88-158: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q14680-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-194: Missing.
Isoform 4 (identifier: Q14680-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-135: MKDYDELLKY...QGYAHRDLKP → MVLE
Isoform 5 (identifier: Q14680-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-87: MKDYDELLKY...TANKIFMVLE → MMNFSNIMNYMKLLGQ
Isoform 6 (identifier: Q14680-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-48: MKDYDELLKYYELHETIGTGGFAKVKLACHILTGEMVAIKIMDKNTLG → MMNFSNIMNYMKLLGQ
Isoform 7 (identifier: Q14680-7)

The sequence of this isoform differs from the canonical sequence as follows:
     352-392: Missing.
Note: No experimental confirmation available.
Isoform 8 (identifier: Q14680-8)

The sequence of this isoform differs from the canonical sequence as follows:
     88-135: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 651651Maternal embryonic leucine zipper kinase
PRO_0000086323

Regions

Domain11 – 263253Protein kinase
Domain602 – 65150KA1
Nucleotide binding17 – 259ATP By similarity
Region282 – 32140UBA-like
Region326 – 651326Autoinhibitory region

Sites

Active site1321Proton acceptor By similarity
Binding site401ATP By similarity

Amino acid modifications

Modified residue561Phosphothreonine; by autocatalysis Ref.15
Modified residue1631Phosphotyrosine; by autocatalysis Ref.15
Modified residue1671Phosphothreonine; by autocatalysis Ref.10 Ref.14 Ref.15
Modified residue1711Phosphoserine; by autocatalysis Ref.15
Modified residue2531Phosphoserine; by autocatalysis Ref.15
Modified residue3361Phosphoserine; by autocatalysis Ref.15
Modified residue3431Phosphoserine; by autocatalysis Ref.14 Ref.15
Modified residue3561Phosphoserine; by autocatalysis Ref.14 Ref.15 Ref.20 Ref.23 Ref.24
Modified residue3671Phosphotyrosine Ref.14
Modified residue3911Phosphoserine; by autocatalysis Ref.15
Modified residue3981Phosphothreonine; by autocatalysis Ref.14 Ref.15
Modified residue4071Phosphoserine; by autocatalysis Ref.15
Modified residue4091Phosphothreonine Ref.14
Modified residue4311Phosphoserine; by autocatalysis Ref.14 Ref.15 Ref.21
Modified residue4781Phosphothreonine Ref.9
Modified residue4941Phosphothreonine; by autocatalysis Ref.14 Ref.15
Modified residue4981Phosphoserine Ref.20 Ref.23
Modified residue5051Phosphoserine; by autocatalysis Ref.13 Ref.14 Ref.15 Ref.20 Ref.21 Ref.23
Modified residue5181Phosphothreonine Ref.20
Modified residue5291Phosphoserine; alternate Ref.14 Ref.15 Ref.20 Ref.23
Modified residue5291Phosphoserine; by autocatalysis; alternate Ref.14 Ref.15 Ref.20 Ref.23
Modified residue5391Phosphothreonine; by autocatalysis Ref.15

Natural variations

Alternative sequence1 – 194194Missing in isoform 3.
VSP_045208
Alternative sequence1 – 135135MKDYD…RDLKP → MVLE in isoform 4.
VSP_045209
Alternative sequence1 – 8787MKDYD…FMVLE → MMNFSNIMNYMKLLGQ in isoform 5.
VSP_045430
Alternative sequence1 – 4848MKDYD…KNTLG → MMNFSNIMNYMKLLGQ in isoform 6.
VSP_045431
Alternative sequence88 – 15871Missing in isoform 2.
VSP_044715
Alternative sequence88 – 13548Missing in isoform 8.
VSP_046759
Alternative sequence352 – 39241Missing in isoform 7.
VSP_046760
Natural variant561T → M. Ref.30
Corresponds to variant rs35233455 [ dbSNP | Ensembl ].
VAR_040794
Natural variant2191K → R. Ref.30
Corresponds to variant rs35142210 [ dbSNP | Ensembl ].
VAR_040795
Natural variant3331R → K. Ref.30
Corresponds to variant rs34655121 [ dbSNP | Ensembl ].
VAR_040796
Natural variant3481T → I. Ref.30
Corresponds to variant rs55845414 [ dbSNP | Ensembl ].
VAR_040797
Natural variant4601T → M in an ovarian mucinous carcinoma sample; somatic mutation. Ref.30
VAR_040798

Experimental info

Mutagenesis291C → V: Abolishes dependence to reducing agents; when associated with V-70; A-89; A-154; A-168; A-169; A-204; A-286 and A-339. Ref.15
Mutagenesis701C → V: Abolishes dependence to reducing agents; when associated with V-29; A-89; A-154; A-168; A-169; A-204; A-286 and A-339. Ref.15
Mutagenesis891C → A: Abolishes dependence to reducing agents; when associated with V-29; V-70; A-154; A-168; A-169; A-204; A-286 and A-339. Ref.15
Mutagenesis1501D → A: Abolishes enzymatic activity. Ref.9 Ref.15 Ref.17
Mutagenesis1541C → A: Abolishes dependence to reducing agents; when associated with V-29; V-70; A-89; A-168; A-169; A-204; A-286 and A-339. Ref.15
Mutagenesis1631Y → F: Abolishes autophosphorylation on tyrosine but still active on exogenous substrates. Ref.15
Mutagenesis1671T → A: Abolishes activation of serine/threonine-protein kinase activity and has only weak activity. Ref.10
Mutagenesis1671T → D or E: Phosphomimetic mutant that has similar kinase activity as wild-type. Ref.10
Mutagenesis1681C → A: Abolishes dependence to reducing agents; when associated with V-29; V-70; A-89; A-154; A-169; A-204; A-286 and A-339. Ref.15
Mutagenesis1691C → A: Abolishes dependence to reducing agents; when associated with V-29; V-70; A-89; A-154; A-168; A-204; A-286 and A-339. Ref.15
Mutagenesis1711S → A: Abolishes activation of serine/threonine-protein kinase activity and has only weak activity. Ref.15
Mutagenesis1711S → D: Inactive. Ref.15
Mutagenesis2041C → A: Abolishes dependence to reducing agents; when associated with V-29; V-70; A-89; A-154; A-168; A-169; A-286 and A-339. Ref.15
Mutagenesis283 – 2853DDD → KKK: Inactive. Ref.15
Mutagenesis2861C → A: Abolishes dependence to reducing agents; when associated with V-29; V-70; A-89; A-154; A-168; A-169; A-204; and A-339. Ref.15
Mutagenesis3391C → A: Abolishes dependence to reducing agents; when associated with V-29; V-70; A-89; A-154; A-168; A-169; A-204 and A-286. Ref.15
Mutagenesis3451T → A: No effect on interaction with PPP1R8. Ref.9
Mutagenesis3871T → A: No effect on interaction with PPP1R8. Ref.9
Mutagenesis4091T → A: No effect on interaction with PPP1R8. Ref.9
Mutagenesis4151T → A: No effect on interaction with PPP1R8. Ref.9
Mutagenesis4281T → A: No effect on interaction with PPP1R8. Ref.9
Mutagenesis4461T → A: Inhibits interaction with PPP1R8. Ref.9
Mutagenesis4601T → A: Inhibits interaction with PPP1R8. Ref.9
Mutagenesis4661T → A: Inhibits interaction with PPP1R8. Ref.9
Mutagenesis4781T → A: Strongly inhibits interaction with PPP1R8. Enhances enzymatic activity. Ref.9
Mutagenesis5181T → A: No effect on interaction with PPP1R8. Ref.9
Sequence conflict691I → M in BAH12961. Ref.3
Sequence conflict3981T → A in BAH12961. Ref.3
Sequence conflict4281T → A in BAH11482. Ref.3
Sequence conflict4741C → R in BAH13343. Ref.3
Sequence conflict4831P → L in BAH13354. Ref.3

Secondary structure

........................................................ 651
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 19, 2004. Version 3.
Checksum: 57F05CDC6122E570

FASTA65174,642
        10         20         30         40         50         60 
MKDYDELLKY YELHETIGTG GFAKVKLACH ILTGEMVAIK IMDKNTLGSD LPRIKTEIEA 

        70         80         90        100        110        120 
LKNLRHQHIC QLYHVLETAN KIFMVLEYCP GGELFDYIIS QDRLSEEETR VVFRQIVSAV 

       130        140        150        160        170        180 
AYVHSQGYAH RDLKPENLLF DEYHKLKLID FGLCAKPKGN KDYHLQTCCG SLAYAAPELI 

       190        200        210        220        230        240 
QGKSYLGSEA DVWSMGILLY VLMCGFLPFD DDNVMALYKK IMRGKYDVPK WLSPSSILLL 

       250        260        270        280        290        300 
QQMLQVDPKK RISMKNLLNH PWIMQDYNYP VEWQSKNPFI HLDDDCVTEL SVHHRNNRQT 

       310        320        330        340        350        360 
MEDLISLWQY DHLTATYLLL LAKKARGKPV RLRLSSFSCG QASATPFTDI KSNNWSLEDV 

       370        380        390        400        410        420 
TASDKNYVAG LIDYDWCEDD LSTGAATPRT SQFTKYWTES NGVESKSLTP ALCRTPANKL 

       430        440        450        460        470        480 
KNKENVYTPK SAVKNEEYFM FPEPKTPVNK NQHKREILTT PNRYTTPSKA RNQCLKETPI 

       490        500        510        520        530        540 
KIPVNSTGTD KLMTGVISPE RRCRSVELDL NQAHMEETPK RKGAKVFGSL ERGLDKVITV 

       550        560        570        580        590        600 
LTRSKRKGSA RDGPRRLKLH YNVTTTRLVN PDQLLNEIMS ILPKKHVDFV QKGYTLKCQT 

       610        620        630        640        650 
QSDFGKVTMQ FELEVCQLQK PDVVGIRRQR LKGDAWVYKR LVEDILSSCK V 

« Hide

Isoform 2 [UniParc].

Checksum: B91D7CA0BA90C2C1
Show »

FASTA58066,399
Isoform 3 [UniParc].

Checksum: 8E6CB0758D50AC49
Show »

FASTA45752,528
Isoform 4 [UniParc].

Checksum: F56647A88C371BBF
Show »

FASTA52059,576
Isoform 5 [UniParc].

Checksum: 1A6547694E09401B
Show »

FASTA58066,547
Isoform 6 [UniParc].

Checksum: AF6938BF6FFB3CE4
Show »

FASTA61971,174
Isoform 7 [UniParc].

Checksum: 2A9A1C90DF1F63B9
Show »

FASTA61070,150
Isoform 8 [UniParc].

Checksum: E1FEF6AD1C03F796
Show »

FASTA60369,116

References

« Hide 'large scale' references
[1]"Identification of MELK whose expression was highly up-regulated in breast cancers."
Katagiri T., Lin M.
Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5 AND 6).
[2]"Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1."
Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N.
DNA Res. 3:17-24(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Bone marrow.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4; 5; 7 AND 8).
Tissue: Spleen and Testis.
[4]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Colon.
[7]"Phosphorylation of a novel zinc-finger-like protein, ZPR9, by murine protein serine/threonine kinase 38 (MPK38)."
Seong H.-A., Gil M., Kim K.-T., Kim S.-J., Ha H.
Biochem. J. 361:597-604(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZNF622, FUNCTION IN PHOSPHORYLATION OF ZNF622.
Tissue: Keratinocyte.
[8]"Human pEg3 kinase associates with and phosphorylates CDC25B phosphatase: a potential role for pEg3 in cell cycle regulation."
Davezac N., Baldin V., Blot J., Ducommun B., Tassan J.P.
Oncogene 21:7630-7641(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CDC25B.
[9]"Inhibition of spliceosome assembly by the cell cycle-regulated protein kinase MELK and involvement of splicing factor NIPP1."
Vulsteke V., Beullens M., Boudrez A., Keppens S., Van Eynde A., Rider M.H., Stalmans W., Bollen M.
J. Biol. Chem. 279:8642-8647(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PPP1R8, AUTOPHOSPHORYLATION, MUTAGENESIS OF ASP-150; THR-345; THR-387; THR-409; THR-415; THR-428; THR-446; THR-460; THR-466; THR-478 AND THR-518, PHOSPHORYLATION AT THR-478, FUNCTION.
[10]"LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1."
Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R.
EMBO J. 23:833-843(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-167, AUTOPHOSPHORYLATION, MUTAGENESIS OF THR-167.
[11]"Maternal embryonic leucine zipper kinase/murine protein serine-threonine kinase 38 is a promising therapeutic target for multiple cancers."
Gray D., Jubb A.M., Hogue D., Dowd P., Kljavin N., Yi S., Bai W., Frantz G., Zhang Z., Koeppen H., de Sauvage F.J., Davis D.P.
Cancer Res. 65:9751-9761(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CANCER.
[12]"CDC25B phosphorylated by pEg3 localizes to the centrosome and the spindle poles at mitosis."
Mirey G., Chartrain I., Froment C., Quaranta M., Bouche J.P., Monsarrat B., Tassan J.P., Ducommun B.
Cell Cycle 4:806-811(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CDC25B.
[13]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-505, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"M-phase MELK activity is regulated by MPF and MAPK."
Badouel C., Korner R., Frank-Vaillant M., Couturier A., Nigg E.A., Tassan J.P.
Cell Cycle 5:883-889(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-167; SER-343; SER-356; TYR-367; THR-398; THR-409; SER-431; THR-494; SER-505 AND SER-529.
[15]"Substrate specificity and activity regulation of protein kinase MELK."
Beullens M., Vancauwenbergh S., Morrice N., Derua R., Ceulemans H., Waelkens E., Bollen M.
J. Biol. Chem. 280:40003-40011(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, AUTOPHOSPHORYLATION, CALCIUM-BINDING, PHOSPHORYLATION AT THR-56; TYR-163; THR-167; SER-171; SER-253; SER-336; SER-343; SER-356; SER-391; THR-398; SER-407; SER-431; THR-494; SER-505; SER-529 AND THR-539, MUTAGENESIS OF CYS-29; CYS-70; CYS-89; ASP-150; CYS-154; TYR-163; CYS-168; CYS-169; SER-171; CYS-204; 283-ASP--ASP-285; CYS-286 AND CYS-339.
[16]"Cell-cycle-dependent cortical localization of pEg3 protein kinase in Xenopus and human cells."
Chartrain I., Couturier A., Tassan J.P.
Biol. Cell 98:253-263(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[17]"Involvement of maternal embryonic leucine zipper kinase (MELK) in mammary carcinogenesis through interaction with Bcl-G, a pro-apoptotic member of the Bcl-2 family."
Lin M.L., Park J.H., Nishidate T., Nakamura Y., Katagiri T.
Breast Cancer Res. 9:R17-R17(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF BCL2L14, MUTAGENESIS OF ASP-150.
[18]"Maternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in human astrocytomas."
Marie S.K., Okamoto O.K., Uno M., Hasegawa A.P., Oba-Shinjo S.M., Cohen T., Camargo A.A., Kosoy A., Carlotti C.G. Jr., Toledo S., Moreira-Filho C.A., Zago M.A., Simpson A.J., Caballero O.L.
Int. J. Cancer 122:807-815(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CANCER.
[19]"Maternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cells."
Nakano I., Masterman-Smith M., Saigusa K., Paucar A.A., Horvath S., Shoemaker L., Watanabe M., Negro A., Bajpai R., Howes A., Lelievre V., Waschek J.A., Lazareff J.A., Freije W.A., Liau L.M., Gilbertson R.J., Cloughesy T.F., Geschwind D.H. expand/collapse author list , Nelson S.F., Mischel P.S., Terskikh A.V., Kornblum H.I.
J. Neurosci. Res. 86:48-60(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CANCER.
[20]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356; SER-498; SER-505; THR-518 AND SER-529, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[21]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-431 AND SER-505, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[22]"Dysregulated expression of Fau and MELK is associated with poor prognosis in breast cancer."
Pickard M.R., Green A.R., Ellis I.O., Caldas C., Hedge V.L., Mourtada-Maarabouni M., Williams G.T.
Breast Cancer Res. 11:R60-R60(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CANCER.
[23]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356; SER-498; SER-505 AND SER-529, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[25]"Maternal embryonic leucine zipper kinase is upregulated and required in mammary tumor-initiating cells in vivo."
Hebbard L.W., Maurer J., Miller A., Lesperance J., Hassell J., Oshima R.G., Terskikh A.V.
Cancer Res. 70:8863-8873(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CANCER.
[26]"Kinase associated-1 domains drive MARK/PAR1 kinases to membrane targets by binding acidic phospholipids."
Moravcevic K., Mendrola J.M., Schmitz K.R., Wang Y.H., Slochower D., Janmey P.A., Lemmon M.A.
Cell 143:966-977(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[27]"Maternal embryonic leucine zipper kinase is stabilized in mitosis by phosphorylation and is partially degraded upon mitotic exit."
Badouel C., Chartrain I., Blot J., Tassan J.P.
Exp. Cell Res. 316:2166-2173(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE, PHOSPHORYLATION.
[28]"Resistance of colorectal cancer cells to radiation and 5-FU is associated with MELK expression."
Choi S., Ku J.L.
Biochem. Biophys. Res. Commun. 412:207-213(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[29]"Siomycin A targets brain tumor stem cells partially through a MELK-mediated pathway."
Nakano I., Joshi K., Visnyei K., Hu B., Watanabe M., Lam D., Wexler E., Saigusa K., Nakamura Y., Laks D.R., Mischel P.S., Viapiano M., Kornblum H.I.
Neuro-oncol. 13:622-634(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[30]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] MET-56; ARG-219; LYS-333; ILE-348 AND MET-460.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB183427 mRNA. Translation: BAF73615.1.
AB183428 mRNA. Translation: BAF73616.1.
D79997 mRNA. Translation: BAA11492.2. Different initiation.
AK293284 mRNA. Translation: BAH11482.1.
AK293447 mRNA. Translation: BAH11508.1.
AK299164 mRNA. Translation: BAH12961.1.
AK300761 mRNA. Translation: BAH13343.1.
AK300821 mRNA. Translation: BAH13354.1.
AK301131 mRNA. Translation: BAH13416.1.
AK302374 mRNA. Translation: BAH13687.1.
AL354932, AL442063 Genomic DNA. Translation: CAI11034.2.
AL442063, AL354932 Genomic DNA. Translation: CAI16995.2.
CH471071 Genomic DNA. Translation: EAW58303.1.
CH471071 Genomic DNA. Translation: EAW58304.1.
BC014039 mRNA. Translation: AAH14039.1.
CCDSCCDS59123.1. [Q14680-7]
CCDS59124.1. [Q14680-8]
CCDS59125.1. [Q14680-2]
CCDS59126.1. [Q14680-6]
CCDS59127.1. [Q14680-5]
CCDS59128.1. [Q14680-4]
CCDS59129.1. [Q14680-3]
CCDS6606.1. [Q14680-1]
RefSeqNP_001243614.1. NM_001256685.1. [Q14680-7]
NP_001243616.1. NM_001256687.1. [Q14680-8]
NP_001243617.1. NM_001256688.1. [Q14680-2]
NP_001243618.1. NM_001256689.1. [Q14680-6]
NP_001243619.1. NM_001256690.1. [Q14680-5]
NP_001243621.1. NM_001256692.1. [Q14680-4]
NP_001243622.1. NM_001256693.1. [Q14680-3]
NP_055606.1. NM_014791.3. [Q14680-1]
UniGeneHs.184339.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4BKYX-ray1.83A2-340[»]
4BKZX-ray2.20A2-340[»]
4BL1X-ray2.60A2-340[»]
4IXPX-ray2.75A1-340[»]
ProteinModelPortalQ14680.
SMRQ14680. Positions 2-335, 554-651.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115171. 10 interactions.
IntActQ14680. 3 interactions.
MINTMINT-7944803.
STRING9606.ENSP00000298048.

Chemistry

BindingDBQ14680.
ChEMBLCHEMBL4578.
GuidetoPHARMACOLOGY2102.

PTM databases

PhosphoSiteQ14680.

Polymorphism databases

DMDM50400857.

Proteomic databases

MaxQBQ14680.
PaxDbQ14680.
PRIDEQ14680.

Protocols and materials databases

DNASU9833.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000298048; ENSP00000298048; ENSG00000165304. [Q14680-1]
ENST00000536329; ENSP00000443550; ENSG00000165304. [Q14680-5]
ENST00000536860; ENSP00000439792; ENSG00000165304. [Q14680-8]
ENST00000536987; ENSP00000439184; ENSG00000165304. [Q14680-4]
ENST00000538311; ENSP00000438226; ENSG00000165304. [Q14680-3]
ENST00000541717; ENSP00000437804; ENSG00000165304. [Q14680-7]
ENST00000543751; ENSP00000441596; ENSG00000165304. [Q14680-6]
ENST00000545008; ENSP00000445452; ENSG00000165304. [Q14680-2]
GeneID9833.
KEGGhsa:9833.
UCSCuc003zzn.4. human. [Q14680-1]
uc011lpm.3. human.

Organism-specific databases

CTD9833.
GeneCardsGC09P036562.
HGNCHGNC:16870. MELK.
HPAHPA017214.
MIM607025. gene.
neXtProtNX_Q14680.
PharmGKBPA134902874.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233023.
HOVERGENHBG106273.
InParanoidQ14680.
KOK08799.
OMAWQSKNPF.
OrthoDBEOG7CK36C.
PhylomeDBQ14680.
TreeFamTF314032.

Enzyme and pathway databases

SignaLinkQ14680.

Gene expression databases

ArrayExpressQ14680.
BgeeQ14680.
CleanExHS_MELK.
GenevestigatorQ14680.

Family and domain databases

Gene3D3.30.310.80. 1 hit.
InterProIPR028375. KA1/Ssp2_C.
IPR001772. KA1_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF02149. KA1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50032. KA1. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMELK.
GenomeRNAi9833.
NextBio35480044.
PROQ14680.
SOURCESearch...

Entry information

Entry nameMELK_HUMAN
AccessionPrimary (citable) accession number: Q14680
Secondary accession number(s): A6P3A7 expand/collapse secondary AC list , A6P3A8, B1AMQ6, B7Z1E6, B7Z5M5, B7Z6Q7, B7Z6R8, B7Z6Y0, B7Z7Q1, D3DRP8, F5H0Y0, F5H2R4, F5H689, Q7L3C3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: July 19, 2004
Last modified: July 9, 2014
This is version 136 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM