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Q61846

- MELK_MOUSE

UniProt

Q61846 - MELK_MOUSE

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Protein

Maternal embryonic leucine zipper kinase

Gene
Melk, Kiaa0175, Pk38
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

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

Enzyme regulationi

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei40 – 401ATP By similarity
Active sitei132 – 1321Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi17 – 259ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. calcium ion binding Source: UniProtKB
  3. lipid binding Source: UniProtKB-KW
  4. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
  5. protein binding Source: UniProtKB
  6. protein kinase activity Source: MGI
  7. protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  1. apoptotic process Source: UniProtKB
  2. cell cycle Source: UniProtKB-KW
  3. cell proliferation Source: UniProtKB
  4. hemopoiesis Source: UniProtKB
  5. intrinsic apoptotic signaling pathway in response to oxidative stress Source: MGI
  6. neural precursor cell proliferation Source: UniProtKB
  7. peptidyl-tyrosine phosphorylation Source: GOC
  8. positive regulation of apoptotic process Source: UniProtKB
  9. protein autophosphorylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Cell cycle

Keywords - Ligandi

ATP-binding, Calcium, Lipid-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Melk
Synonyms:Kiaa0175, Pk38
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 4

Organism-specific databases

MGIiMGI:106924. Melk.

Subcellular locationi

GO - Cellular componenti

  1. cell cortex Source: UniProtKB
  2. cytoplasm Source: MGI
  3. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi40 – 401K → R: Loss of kinase activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 643643Maternal embryonic leucine zipper kinasePRO_0000086324Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei56 – 561Phosphothreonine; by autocatalysis By similarity
Modified residuei163 – 1631Phosphotyrosine; by autocatalysis By similarity
Modified residuei167 – 1671Phosphothreonine; by autocatalysis By similarity
Modified residuei171 – 1711Phosphoserine; by autocatalysis By similarity
Modified residuei253 – 2531Phosphoserine; by autocatalysis By similarity
Modified residuei336 – 3361Phosphoserine; by autocatalysis By similarity
Modified residuei343 – 3431Phosphoserine; by autocatalysis By similarity
Modified residuei352 – 3521Phosphoserine; by autocatalysis By similarity
Modified residuei399 – 3991Phosphoserine; by autocatalysis By similarity
Modified residuei423 – 4231Phosphoserine; by autocatalysis By similarity
Modified residuei486 – 4861Phosphothreonine; by autocatalysis By similarity
Modified residuei490 – 4901Phosphoserine By similarity
Modified residuei497 – 4971Phosphoserine; by autocatalysis By similarity
Modified residuei510 – 5101Phosphothreonine By similarity
Modified residuei521 – 5211Phosphoserine; alternate2 Publications
Modified residuei521 – 5211Phosphoserine; by autocatalysis; alternate Inferred
Modified residuei531 – 5311Phosphothreonine; by autocatalysis By similarity

Post-translational modificationi

Autophosphorylated: autophosphorylation of the T-loop at Thr-167 and Ser-171 is required for activation By similarity.

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ61846.
PRIDEiQ61846.

PTM databases

PhosphoSiteiQ61846.

Expressioni

Tissue specificityi

Expressed in testis, ovary, thymus, spleen and T-cell. Expressed by neural progenitors: highly enriched in cultures containing multipotent progenitors.3 Publications

Developmental stagei

Expressed in the 2-cell-stage embryo, followed by a strong expression at 8-cell-stage.1 Publication

Gene expression databases

ArrayExpressiQ61846.
BgeeiQ61846.
CleanExiMM_MELK.
GenevestigatoriQ61846.

Interactioni

Subunit structurei

Monomer. Interacts with ZNF622 and PPP1R8 By similarity.

Protein-protein interaction databases

BioGridi201390. 9 interactions.

Structurei

Secondary structure

1
643
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi3 – 75
Turni8 – 103
Beta strandi11 – 199
Beta strandi21 – 3010
Turni31 – 333
Beta strandi36 – 438
Helixi44 – 474
Helixi48 – 514
Helixi52 – 6211
Beta strandi72 – 776
Beta strandi79 – 879
Helixi94 – 1018
Helixi106 – 12520
Helixi135 – 1373
Beta strandi138 – 1403
Beta strandi146 – 1483
Helixi172 – 1743
Helixi177 – 1793
Helixi188 – 20417
Helixi214 – 22310
Helixi234 – 24310
Turni248 – 2503
Helixi254 – 2585
Helixi261 – 2644
Helixi284 – 29411
Helixi298 – 3058
Helixi312 – 32615

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4BFMX-ray2.35A1-326[»]
ProteinModelPortaliQ61846.
SMRiQ61846. Positions 2-312, 546-643.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini11 – 263253Protein kinaseAdd
BLAST
Domaini594 – 64350KA1Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni282 – 32140UBA-like By similarityAdd
BLAST
Regioni326 – 643318Autoinhibitory region By similarityAdd
BLAST

Domaini

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00740000115114.
HOGENOMiHOG000233023.
HOVERGENiHBG106273.
InParanoidiQ3TPU1.
KOiK08799.
OMAiWQSKNPF.
OrthoDBiEOG7CK36C.
TreeFamiTF314032.

Family and domain databases

Gene3Di3.30.310.80. 1 hit.
InterProiIPR028375. 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]
PfamiPF02149. KA1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50032. KA1. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q61846-1 [UniParc]FASTAAdd to Basket

« Hide

MKDYDELLKY YELYETIGTG GFAKVKLACH VLTGEMVAIK IMDKNALGSD    50
LPRVKTEIDA LKSLRHQHIC QLYHVLETKN KIFMVLEYCP GGELFDYIIS 100
QDRLSEEETR VVFRQILSAV AYVHSQGYAH RDLKPENLLF DENHKLKLID 150
FGLCAKPKGN KDYHLQTCCG SLAYAAPELI QGKSYLGSEA DVWSMGILLY 200
VLMCGFLPFD DDNVMALYKK IMRGKYEVPK WLSPSSILLL QQMLQVDPKK 250
RISMRNLLNH PWVMQDYSCP VEWQSKTPLT HLDEDCVTEL SVHHRSSRQT 300
MEDLISSWQY DHLTATYLLL LAKKARGKPA RLQLLSFSCG TASTTPKSKN 350
LSLEDMSTSD DNCVAGLIDY ELCEDKLLAP KTPQVTKHLA ESNHAASKSP 400
APGVRRAVAN KLMDKENVCT PKSSVKNEEQ FVFSEPKIPV SKNQYKREIP 450
ASPTRFPTPA KARAQCLREA PVRTPGNSAG ADTLTTGVIS PERRCRSMDV 500
DLNQAHMEDT PKKKGTNVFG SLERGLDKVL TALTRNKKKG SARDGPRKRK 550
LHYNVTTTRL VNPDQLLSEI MAILPKKNVD FVQKGYTLKC QTQSDFGKVT 600
MQFELEVCQL QRPDVVGIRR QRLKGDAWVY KRLVEDILSG CKM 643
Length:643
Mass (Da):72,729
Last modified:July 27, 2011 - v2
Checksum:i5637D2A4E8CFA216
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti335 – 3351L → P in CAA64641. 1 Publication
Sequence conflicti335 – 3351L → P in BAC97886. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS18124.1.
RefSeqiNP_034920.2. NM_010790.2.
UniGeneiMm.268668.

Genome annotation databases

EnsembliENSMUST00000045607; ENSMUSP00000043806; ENSMUSG00000035683.
GeneIDi17279.
KEGGimmu:17279.
UCSCiuc008srv.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS18124.1.
RefSeqi NP_034920.2. NM_010790.2.
UniGenei Mm.268668.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4BFM X-ray 2.35 A 1-326 [» ]
ProteinModelPortali Q61846.
SMRi Q61846. Positions 2-312, 546-643.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 201390. 9 interactions.

PTM databases

PhosphoSitei Q61846.

Proteomic databases

PaxDbi Q61846.
PRIDEi Q61846.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000045607 ; ENSMUSP00000043806 ; ENSMUSG00000035683 .
GeneIDi 17279.
KEGGi mmu:17279.
UCSCi uc008srv.1. mouse.

Organism-specific databases

CTDi 9833.
MGIi MGI:106924. Melk.
Rougei Search...

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00740000115114.
HOGENOMi HOG000233023.
HOVERGENi HBG106273.
InParanoidi Q3TPU1.
KOi K08799.
OMAi WQSKNPF.
OrthoDBi EOG7CK36C.
TreeFami TF314032.

Miscellaneous databases

NextBioi 291778.
PROi Q61846.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q61846.
Bgeei Q61846.
CleanExi MM_MELK.
Genevestigatori Q61846.

Family and domain databases

Gene3Di 3.30.310.80. 1 hit.
InterProi IPR028375. 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 ]
Pfami PF02149. KA1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi PS50032. KA1. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  6. Cited for: FUNCTION, TISSUE SPECIFICITY.
  7. 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].

Entry informationi

Entry nameiMELK_MOUSE
AccessioniPrimary (citable) accession number: Q61846
Secondary accession number(s): Q3TPU1, Q61804, Q6ZQH6
Entry historyi
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 statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi