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Protein

Maternal embryonic leucine zipper kinase

Gene

Melk

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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.PROSITE-ProRule annotation
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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei40ATPPROSITE-ProRule annotation1
Active sitei132Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi17 – 25ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

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

Enzyme and pathway databases

BRENDAi2.7.11.1. 3474.

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
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:106924. Melk.

Subcellular locationi

GO - Cellular componenti

  • cell cortex Source: UniProtKB
  • cytoplasm Source: MGI
  • membrane Source: MGI
  • nucleus Source: GO_Central
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi40K → R: Loss of kinase activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863241 – 643Maternal embryonic leucine zipper kinaseAdd BLAST643

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei56Phosphothreonine; by autocatalysisBy similarity1
Modified residuei163Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei167Phosphothreonine; by autocatalysisBy similarity1
Modified residuei171Phosphoserine; by autocatalysisBy similarity1
Modified residuei253Phosphoserine; by autocatalysisBy similarity1
Modified residuei336Phosphoserine; by autocatalysisBy similarity1
Modified residuei343Phosphoserine; by autocatalysisBy similarity1
Modified residuei352PhosphoserineCombined sources1
Modified residuei399Phosphoserine; by autocatalysisBy similarity1
Modified residuei423Phosphoserine; by autocatalysisBy similarity1
Modified residuei486Phosphothreonine; by autocatalysisBy similarity1
Modified residuei490PhosphoserineBy similarity1
Modified residuei497Phosphoserine; by autocatalysisBy similarity1
Modified residuei510PhosphothreonineBy similarity1
Modified residuei521Phosphoserine; by autocatalysisCombined sources1
Modified residuei531Phosphothreonine; by autocatalysisBy similarity1

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

EPDiQ61846.
MaxQBiQ61846.
PaxDbiQ61846.
PRIDEiQ61846.

PTM databases

iPTMnetiQ61846.
PhosphoSitePlusiQ61846.

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

BgeeiENSMUSG00000035683.
CleanExiMM_MELK.
ExpressionAtlasiQ61846. baseline and differential.
GenevisibleiQ61846. MM.

Interactioni

Subunit structurei

Monomer. Interacts with ZNF622 and PPP1R8 (By similarity).By similarity

Protein-protein interaction databases

BioGridi201390. 9 interactors.
STRINGi10090.ENSMUSP00000043806.

Structurei

Secondary structure

1643
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 7Combined sources5
Turni8 – 10Combined sources3
Beta strandi11 – 19Combined sources9
Beta strandi21 – 30Combined sources10
Turni31 – 33Combined sources3
Beta strandi36 – 43Combined sources8
Helixi44 – 47Combined sources4
Helixi48 – 51Combined sources4
Helixi52 – 62Combined sources11
Beta strandi72 – 77Combined sources6
Beta strandi79 – 87Combined sources9
Helixi94 – 101Combined sources8
Helixi106 – 125Combined sources20
Helixi135 – 137Combined sources3
Beta strandi138 – 140Combined sources3
Beta strandi146 – 148Combined sources3
Helixi172 – 174Combined sources3
Helixi177 – 179Combined sources3
Helixi188 – 204Combined sources17
Helixi214 – 223Combined sources10
Helixi234 – 243Combined sources10
Turni248 – 250Combined sources3
Helixi254 – 258Combined sources5
Helixi261 – 264Combined sources4
Helixi284 – 294Combined sources11
Helixi298 – 305Combined sources8
Helixi312 – 326Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BFMX-ray2.35A1-326[»]
4CQGX-ray2.57A1-326[»]
ProteinModelPortaliQ61846.
SMRiQ61846.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini11 – 263Protein kinasePROSITE-ProRule annotationAdd BLAST253
Domaini594 – 643KA1PROSITE-ProRule annotationAdd BLAST50

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni282 – 321UBA-likeBy similarityAdd BLAST40
Regioni326 – 643Autoinhibitory regionBy similarityAdd BLAST318

Domaini

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

Sequence similaritiesi

Contains 1 KA1 (kinase-associated) domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0583. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00860000133728.
HOGENOMiHOG000233023.
HOVERGENiHBG106273.
InParanoidiQ61846.
KOiK08799.
OMAiYELHETI.
OrthoDBiEOG091G05V9.
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.
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

        10         20         30         40         50
MKDYDELLKY YELYETIGTG GFAKVKLACH VLTGEMVAIK IMDKNALGSD
60 70 80 90 100
LPRVKTEIDA LKSLRHQHIC QLYHVLETKN KIFMVLEYCP GGELFDYIIS
110 120 130 140 150
QDRLSEEETR VVFRQILSAV AYVHSQGYAH RDLKPENLLF DENHKLKLID
160 170 180 190 200
FGLCAKPKGN KDYHLQTCCG SLAYAAPELI QGKSYLGSEA DVWSMGILLY
210 220 230 240 250
VLMCGFLPFD DDNVMALYKK IMRGKYEVPK WLSPSSILLL QQMLQVDPKK
260 270 280 290 300
RISMRNLLNH PWVMQDYSCP VEWQSKTPLT HLDEDCVTEL SVHHRSSRQT
310 320 330 340 350
MEDLISSWQY DHLTATYLLL LAKKARGKPA RLQLLSFSCG TASTTPKSKN
360 370 380 390 400
LSLEDMSTSD DNCVAGLIDY ELCEDKLLAP KTPQVTKHLA ESNHAASKSP
410 420 430 440 450
APGVRRAVAN KLMDKENVCT PKSSVKNEEQ FVFSEPKIPV SKNQYKREIP
460 470 480 490 500
ASPTRFPTPA KARAQCLREA PVRTPGNSAG ADTLTTGVIS PERRCRSMDV
510 520 530 540 550
DLNQAHMEDT PKKKGTNVFG SLERGLDKVL TALTRNKKKG SARDGPRKRK
560 570 580 590 600
LHYNVTTTRL VNPDQLLSEI MAILPKKNVD FVQKGYTLKC QTQSDFGKVT
610 620 630 640
MQFELEVCQL QRPDVVGIRR QRLKGDAWVY KRLVEDILSG CKM
Length:643
Mass (Da):72,729
Last modified:July 27, 2011 - v2
Checksum:i5637D2A4E8CFA216
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti335L → P in CAA64641 (PubMed:9136115).Curated1
Sequence conflicti335L → P in BAC97886 (PubMed:14621295).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BFMX-ray2.35A1-326[»]
4CQGX-ray2.57A1-326[»]
ProteinModelPortaliQ61846.
SMRiQ61846.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201390. 9 interactors.
STRINGi10090.ENSMUSP00000043806.

PTM databases

iPTMnetiQ61846.
PhosphoSitePlusiQ61846.

Proteomic databases

EPDiQ61846.
MaxQBiQ61846.
PaxDbiQ61846.
PRIDEiQ61846.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi9833.
MGIiMGI:106924. Melk.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG0583. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00860000133728.
HOGENOMiHOG000233023.
HOVERGENiHBG106273.
InParanoidiQ61846.
KOiK08799.
OMAiYELHETI.
OrthoDBiEOG091G05V9.
TreeFamiTF314032.

Enzyme and pathway databases

BRENDAi2.7.11.1. 3474.

Miscellaneous databases

PROiQ61846.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000035683.
CleanExiMM_MELK.
ExpressionAtlasiQ61846. baseline and differential.
GenevisibleiQ61846. MM.

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.
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]
ProtoNetiSearch...

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: November 30, 2016
This is version 148 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.