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Q61846 (MELK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Maternal embryonic leucine zipper kinase

EC=2.7.11.1
Alternative name(s):
Protein kinase PK38
Short name=mPK38
Tyrosine-protein kinase MELK
EC=2.7.10.2
Gene names
Name:Melk
Synonyms:Kiaa0175, Pk38
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length643 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. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits 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.6 Ref.8

Catalytic activity

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

ATP + a protein = ADP + a phosphoprotein.

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 By similarity.

Subunit structure

Monomer. Interacts with ZNF622 and PPP1R8 By similarity.

Subcellular location

Cell membrane; Peripheral membrane protein By similarity.

Tissue specificity

Expressed in testis, ovary, thymus, spleen and T-cell. Expressed by neural progenitors: highly enriched in cultures containing multipotent progenitors. Ref.1 Ref.2 Ref.6

Developmental stage

Expressed in the 2-cell-stage embryo, followed by a strong expression at 8-cell-stage. Ref.2

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 By similarity.

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.

Ontologies

Keywords
   Biological processApoptosis
Cell cycle
   Cellular componentCell membrane
Membrane
   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_processapoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

cell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

hemopoiesis

Inferred from sequence or structural similarity. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to oxidative stress

Inferred from direct assay Ref.8. Source: MGI

neural precursor cell proliferation

Inferred from direct assay Ref.6. Source: UniProtKB

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: GOC

positive regulation of apoptotic process

Inferred from direct assay Ref.8. Source: UniProtKB

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcell cortex

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from direct assay PubMed 10417823. Source: MGI

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

calcium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

lipid binding

Inferred from electronic annotation. Source: UniProtKB-KW

non-membrane spanning protein tyrosine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.8. Source: UniProtKB

protein kinase activity

Inferred from direct assay Ref.1. Source: MGI

protein serine/threonine kinase activity

Inferred from direct assay Ref.8. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 643643Maternal embryonic leucine zipper kinase
PRO_0000086324

Regions

Domain11 – 263253Protein kinase
Domain594 – 64350KA1
Nucleotide binding17 – 259ATP By similarity
Region282 – 32140UBA-like By similarity
Region326 – 643318Autoinhibitory region By similarity

Sites

Active site1321Proton acceptor By similarity
Binding site401ATP By similarity

Amino acid modifications

Modified residue561Phosphothreonine; by autocatalysis By similarity
Modified residue1631Phosphotyrosine; by autocatalysis By similarity
Modified residue1671Phosphothreonine; by autocatalysis By similarity
Modified residue1711Phosphoserine; by autocatalysis By similarity
Modified residue2531Phosphoserine; by autocatalysis By similarity
Modified residue3361Phosphoserine; by autocatalysis By similarity
Modified residue3431Phosphoserine; by autocatalysis By similarity
Modified residue3521Phosphoserine; by autocatalysis By similarity
Modified residue3991Phosphoserine; by autocatalysis By similarity
Modified residue4231Phosphoserine; by autocatalysis By similarity
Modified residue4861Phosphothreonine; by autocatalysis By similarity
Modified residue4901Phosphoserine By similarity
Modified residue4971Phosphoserine; by autocatalysis By similarity
Modified residue5101Phosphothreonine By similarity
Modified residue5211Phosphoserine; alternate Ref.7 Ref.9
Modified residue5211Phosphoserine; by autocatalysis; alternate Probable
Modified residue5311Phosphothreonine; by autocatalysis By similarity

Experimental info

Mutagenesis401K → R: Loss of kinase activity. Ref.8
Sequence conflict3351L → P in CAA64641. Ref.2
Sequence conflict3351L → P in BAC97886. Ref.4

Secondary structure

................................................ 643
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q61846 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 5637D2A4E8CFA216

FASTA64372,729
        10         20         30         40         50         60 
MKDYDELLKY YELYETIGTG GFAKVKLACH VLTGEMVAIK IMDKNALGSD LPRVKTEIDA 

        70         80         90        100        110        120 
LKSLRHQHIC QLYHVLETKN KIFMVLEYCP GGELFDYIIS QDRLSEEETR VVFRQILSAV 

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

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

       250        260        270        280        290        300 
QQMLQVDPKK RISMRNLLNH PWVMQDYSCP VEWQSKTPLT HLDEDCVTEL SVHHRSSRQT 

       310        320        330        340        350        360 
MEDLISSWQY DHLTATYLLL LAKKARGKPA RLQLLSFSCG TASTTPKSKN LSLEDMSTSD 

       370        380        390        400        410        420 
DNCVAGLIDY ELCEDKLLAP KTPQVTKHLA ESNHAASKSP APGVRRAVAN KLMDKENVCT 

       430        440        450        460        470        480 
PKSSVKNEEQ FVFSEPKIPV SKNQYKREIP ASPTRFPTPA KARAQCLREA PVRTPGNSAG 

       490        500        510        520        530        540 
ADTLTTGVIS PERRCRSMDV DLNQAHMEDT PKKKGTNVFG SLERGLDKVL TALTRNKKKG 

       550        560        570        580        590        600 
SARDGPRKRK LHYNVTTTRL VNPDQLLSEI MAILPKKNVD FVQKGYTLKC QTQSDFGKVT 

       610        620        630        640 
MQFELEVCQL QRPDVVGIRR QRLKGDAWVY KRLVEDILSG CKM 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and expression of a cDNA encoding a novel protein serine/threonine kinase predominantly expressed in hematopoietic cells."
Gil M., Yang Y., Lee Y., Choi I., Ha H.
Gene 195:295-301(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Keratinocyte.
[2]"New member of the Snf1/AMPK kinase family, Melk, is expressed in the mouse egg and preimplantation embryo."
Heyer B.S., Warsowe J., Solter D., Knowles B.B., Ackerman S.L.
Mol. Reprod. Dev. 47:148-156(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
Strain: C57BL/6 X DBA/2.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Embryo and Spinal cord.
[4]"Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H.
DNA Res. 10:167-180(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Embryonic tail.
[5]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[6]"Maternal embryonic leucine zipper kinase (MELK) regulates multipotent neural progenitor proliferation."
Nakano I., Paucar A.A., Bajpai R., Dougherty J.D., Zewail A., Kelly T.K., Kim K.J., Ou J., Groszer M., Imura T., Freije W.A., Nelson S.F., Sofroniew M.V., Wu H., Liu X., Terskikh A.V., Geschwind D.H., Kornblum H.I.
J. Cell Biol. 170:413-427(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[7]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-521, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[8]"Murine protein serine/threonine kinase 38 activates apoptosis signal-regulating kinase 1 via Thr 838 phosphorylation."
Jung H., Seong H.A., Ha H.
J. Biol. Chem. 283:34541-34553(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF MAP3K5, MUTAGENESIS OF LYS-40.
[9]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-521, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L76158 mRNA. Translation: AAB72030.1.
X95351 mRNA. Translation: CAA64641.1.
AK011932 mRNA. Translation: BAB27923.1.
AK145316 mRNA. Translation: BAE26362.1.
AK164138 mRNA. Translation: BAE37644.1.
AK129076 mRNA. Translation: BAC97886.1.
AL805952, AL807399 Genomic DNA. Translation: CAM14393.1.
AL807399, AL805952 Genomic DNA. Translation: CAM22652.1.
CCDSCCDS18124.1.
RefSeqNP_034920.2. NM_010790.2.
UniGeneMm.268668.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4BFMX-ray2.35A1-326[»]
ProteinModelPortalQ61846.
SMRQ61846. Positions 2-312, 546-643.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201390. 9 interactions.

PTM databases

PhosphoSiteQ61846.

Proteomic databases

PaxDbQ61846.
PRIDEQ61846.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000045607; ENSMUSP00000043806; ENSMUSG00000035683.
GeneID17279.
KEGGmmu:17279.
UCSCuc008srv.1. mouse.

Organism-specific databases

CTD9833.
MGIMGI:106924. Melk.
RougeSearch...

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000115114.
HOGENOMHOG000233023.
HOVERGENHBG106273.
InParanoidQ3TPU1.
KOK08799.
OMAWQSKNPF.
OrthoDBEOG7CK36C.
TreeFamTF314032.

Gene expression databases

ArrayExpressQ61846.
BgeeQ61846.
CleanExMM_MELK.
GenevestigatorQ61846.

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

NextBio291778.
PROQ61846.
SOURCESearch...

Entry information

Entry nameMELK_MOUSE
AccessionPrimary (citable) accession number: Q61846
Secondary accession number(s): Q3TPU1, Q61804, Q6ZQH6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 123 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot