Q14680 (MELK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	651 AA.
Sequence status	Complete.
Protein existence	Evidence 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.5 Ref.6 Ref.7 Ref.10 Ref.12 Ref.15
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.12 ATP + a protein = ADP + a phosphoprotein. Ref.12
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.12
Subunit structure	Monomer. Interacts with ZNF622 and PPP1R8. Ref.5 Ref.7
Subcellular location	Cell membrane; Peripheral membrane protein Ref.13 Ref.24.
Tissue specificity	Expressed in placenta, kidney, thymus, testis, ovary and intestine. Ref.1
Developmental stage	Increases during G2/M phase compared to interphase. Protein level decreases when cells exit mitosis, probably due to degradation. Ref.25
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.12 Ref.26 Ref.27
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.5 Ref.6 Ref.7 Ref.8 Ref.10 Ref.11 Ref.12 Ref.14 Ref.15 Ref.18 Ref.19 Ref.21 Ref.22 Ref.25
Involvement in disease	Note=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.16, Ref.23).
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 process	Apoptosis Cell cycle
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Calcium Lipid-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	G2/M transition of mitotic cell cycle Traceable author statement Ref.6. Source: UniProtKB apoptotic process Inferred from direct assay Ref.15. Source: UniProtKB hemopoiesis Inferred from sequence or structural similarity. Source: UniProtKB neural precursor cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from direct assay Ref.12. Source: UniProtKB
Cellular component	cell cortex Inferred from direct assay Ref.13. Source: UniProtKB plasma membrane Inferred from direct assay Ref.24. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from direct assay Ref.12. Source: UniProtKB lipid binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from direct assay Ref.12. Source: UniProtKB protein binding Inferred from physical interaction Ref.6Ref.10. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.6Ref.10Ref.12Ref.15. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCL2L14	Q9BZR8	4	EBI-1046702,EBI-1385773

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 651	651	Maternal embryonic leucine zipper kinase		PRO_0000086323
Regions
	Domain	11 – 263	253	Protein kinase
	Domain	602 – 651	50	KA1
	Nucleotide binding	17 – 25	9	ATP By similarity
	Region	282 – 321	40	UBA-like
	Region	326 – 651	326	Autoinhibitory region
Sites
	Active site	132	1	Proton acceptor By similarity
	Binding site	40	1	ATP By similarity
Amino acid modifications
	Modified residue	56	1	Phosphothreonine; by autocatalysis Ref.12
	Modified residue	163	1	Phosphotyrosine; by autocatalysis Ref.12
	Modified residue	167	1	Phosphothreonine; by autocatalysis Ref.8 Ref.11 Ref.12
	Modified residue	171	1	Phosphoserine; by autocatalysis Ref.12
	Modified residue	253	1	Phosphoserine; by autocatalysis Ref.12
	Modified residue	335	1	Phosphoserine Ref.21
	Modified residue	336	1	Phosphoserine; by autocatalysis Ref.12
	Modified residue	343	1	Phosphoserine; by autocatalysis Ref.11 Ref.12
	Modified residue	356	1	Phosphoserine; by autocatalysis Ref.11 Ref.12 Ref.18 Ref.21 Ref.22
	Modified residue	367	1	Phosphotyrosine Ref.11
	Modified residue	391	1	Phosphoserine; by autocatalysis Ref.12
	Modified residue	398	1	Phosphothreonine; by autocatalysis Ref.11 Ref.12
	Modified residue	407	1	Phosphoserine; by autocatalysis Ref.12
	Modified residue	409	1	Phosphothreonine Ref.11
	Modified residue	431	1	Phosphoserine; by autocatalysis Ref.11 Ref.12 Ref.19
	Modified residue	446	1	Phosphothreonine Ref.18
	Modified residue	460	1	Phosphothreonine Ref.18 Ref.21
	Modified residue	478	1	Phosphothreonine Ref.7 Ref.18
	Modified residue	494	1	Phosphothreonine; by autocatalysis Ref.11 Ref.12 Ref.18
	Modified residue	498	1	Phosphoserine Ref.18 Ref.21
	Modified residue	505	1	Phosphoserine; by autocatalysis Ref.11 Ref.12 Ref.14 Ref.18 Ref.19 Ref.21
	Modified residue	518	1	Phosphothreonine Ref.18 Ref.21
	Modified residue	529	1	Phosphoserine Ref.11 Ref.12 Ref.18 Ref.21
	Modified residue	529	1	Phosphoserine; by autocatalysis Ref.11 Ref.12 Ref.18 Ref.21
	Modified residue	539	1	Phosphothreonine; by autocatalysis Ref.12
Natural variations
	Natural variant	56	1	T → M. Ref.28 Corresponds to variant rs35233455 [ dbSNP | Ensembl ].		VAR_040794
	Natural variant	219	1	K → R. Ref.28 Corresponds to variant rs35142210 [ dbSNP | Ensembl ].		VAR_040795
	Natural variant	333	1	R → K. Ref.28 Corresponds to variant rs34655121 [ dbSNP | Ensembl ].		VAR_040796
	Natural variant	348	1	T → I. Ref.28 Corresponds to variant rs55845414 [ dbSNP | Ensembl ].		VAR_040797
	Natural variant	460	1	T → M in an ovarian mucinous carcinoma sample; somatic mutation. Ref.28		VAR_040798
Experimental info
	Mutagenesis	29	1	C → 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.12
	Mutagenesis	70	1	C → 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.12
	Mutagenesis	89	1	C → 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.12
	Mutagenesis	150	1	D → A: Abolishes enzymatic activity. Ref.7 Ref.12 Ref.15
	Mutagenesis	154	1	C → 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.12
	Mutagenesis	163	1	Y → F: Abolishes autophosphorylation on tyrosine but still active on exogenous substrates. Ref.12
	Mutagenesis	167	1	T → A: Abolishes activation of serine/threonine-protein kinase activity and has only weak activity. Ref.8
	Mutagenesis	167	1	T → D or E: Phosphomimetic mutant that has similar kinase activity as wild-type. Ref.8
	Mutagenesis	168	1	C → 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.12
	Mutagenesis	169	1	C → 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.12
	Mutagenesis	171	1	S → A: Abolishes activation of serine/threonine-protein kinase activity and has only weak activity. Ref.12
	Mutagenesis	171	1	S → D: Inactive. Ref.12
	Mutagenesis	204	1	C → 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.12
	Mutagenesis	283 – 285	3	DDD → KKK: Inactive. Ref.12
	Mutagenesis	286	1	C → 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.12
	Mutagenesis	339	1	C → 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.12
	Mutagenesis	345	1	T → A: No effect on interaction with PPP1R8. Ref.7
	Mutagenesis	387	1	T → A: No effect on interaction with PPP1R8. Ref.7
	Mutagenesis	409	1	T → A: No effect on interaction with PPP1R8. Ref.7
	Mutagenesis	415	1	T → A: No effect on interaction with PPP1R8. Ref.7
	Mutagenesis	428	1	T → A: No effect on interaction with PPP1R8. Ref.7
	Mutagenesis	446	1	T → A: Inhibits interaction with PPP1R8. Ref.7
	Mutagenesis	460	1	T → A: Inhibits interaction with PPP1R8. Ref.7
	Mutagenesis	466	1	T → A: Inhibits interaction with PPP1R8. Ref.7
	Mutagenesis	478	1	T → A: Strongly inhibits interaction with PPP1R8. Enhances enzymatic activity. Ref.7
	Mutagenesis	518	1	T → A: No effect on interaction with PPP1R8. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Q14680 [UniParc]. Last modified July 19, 2004. Version 3. Checksum: 57F05CDC6122E570	FASTA	651	74,642
	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

References

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[1]	"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: 8724849] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], TISSUE SPECIFICITY. Tissue: Bone marrow.
[2]	"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. , 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: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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. , 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].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon.
[5]	"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: 11802789] [Abstract] Cited for: INTERACTION WITH ZNF622, FUNCTION IN PHOSPHORYLATION OF ZNF622. Tissue: Keratinocyte.
[6]	"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: 12400006] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CDC25B.
[7]	"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: 14699119] [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.
[8]	"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: 14976552] [Abstract] Cited for: PHOSPHORYLATION AT THR-167, AUTOPHOSPHORYLATION, MUTAGENESIS OF THR-167.
[9]	"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: 16266996] [Abstract] Cited for: INVOLVEMENT IN CANCER.
[10]	"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: 15908796] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CDC25B.
[11]	"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: 16628004] [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.
[12]	"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: 16216881] [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.
[13]	"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: 16159311] [Abstract] Cited for: SUBCELLULAR LOCATION.
[14]	"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: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-505, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"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: 17280616] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF BCL2L14, MUTAGENESIS OF ASP-150.
[16]	"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: 17960622] [Abstract] Cited for: INVOLVEMENT IN CANCER.
[17]	"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. , Nelson S.F., Mischel P.S., Terskikh A.V., Kornblum H.I. J. Neurosci. Res. 86:48-60(2008) [PubMed: 17722061] [Abstract] Cited for: INVOLVEMENT IN CANCER.
[18]	"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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356; THR-446; THR-460; THR-478; THR-494; SER-498; SER-505; THR-518 AND SER-529, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-431 AND SER-505, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[20]	"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: 19671159] [Abstract] Cited for: INVOLVEMENT IN CANCER.
[21]	"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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-335; SER-356; THR-460; SER-498; SER-505; THR-518 AND SER-529, MASS SPECTROMETRY.
[22]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[23]	"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: 20861186] [Abstract] Cited for: INVOLVEMENT IN CANCER.
[24]	"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: 21145462] [Abstract] Cited for: SUBCELLULAR LOCATION.
[25]	"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: 20420823] [Abstract] Cited for: DEVELOPMENTAL STAGE, PHOSPHORYLATION.
[26]	"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: 21806965] [Abstract] Cited for: INDUCTION.
[27]	"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: 21558073] [Abstract] Cited for: INDUCTION.
[28]	"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. , 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: 17344846] [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	D79997 mRNA. Translation: BAA11492.2. Different initiation. 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.
IPI	IPI00006471.
RefSeq	NP_055606.1. NM_014791.2.
UniGene	Hs.184339.
3D structure databases
ProteinModelPortal	Q14680.
SMR	Q14680. Positions 4-323, 548-651.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q14680. 2 interactions.
STRING	Q14680.
PTM databases
PhosphoSite	Q14680.
Polymorphism databases
DMDM	50400857.
Proteomic databases
PRIDE	Q14680.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000298048; ENSP00000298048; ENSG00000165304.
GeneID	9833.
KEGG	hsa:9833.
UCSC	uc003zzn.1. human.
Organism-specific databases
CTD	9833.
GeneCards	GC09P036562.
H-InvDB	HIX0008033.
HGNC	HGNC:16870. MELK.
HPA	HPA017214.
MIM	607025. gene.
neXtProt	NX_Q14680.
PharmGKB	PA134902874.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13861.
HOGENOM	HBG383890.
HOVERGEN	HBG106273.
InParanoid	Q14680.
OMA	QTMEDLI.
OrthoDB	EOG4BCDMQ.
PhylomeDB	Q14680.
Gene expression databases
ArrayExpress	Q14680.
Bgee	Q14680.
CleanEx	HS_MELK.
Genevestigator	Q14680.
GermOnline	ENSG00000165304. Homo sapiens.
Family and domain databases
InterPro	IPR001772. Kinase-assoc_KA1. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
Gene3D	G3DSA:3.30.310.80. Kinase-assoc_KA1. 1 hit.
KO	K08799.
Pfam	PF02149. KA1. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF103243. Kinase-assoc_KA1. 1 hit. SSF56112. Kinase_like. 1 hit.
PROSITE	PS50032. KA1. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	37054.
SOURCE	Search...

Entry information

Entry name

MELK_HUMAN

Accession

Primary (citable) accession number: Q14680
Secondary accession number(s): B1AMQ6, D3DRP8, Q7L3C3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	July 19, 2004
Last modified:	December 14, 2011
This is version 108 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.