UniProtKB - Q61846 (MELK_MOUSE)
Maternal embryonic leucine zipper kinase
Melk
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 PublicationsCatalytic activityi
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 40 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 132 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 17 – 25 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- calcium ion binding Source: UniProtKB
- lipid binding Source: UniProtKB-KW
- non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
- protein kinase activity Source: MGI
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: RHEA
GO - Biological processi
- apoptotic process Source: UniProtKB
- cell cycle Source: UniProtKB-KW
- cell population proliferation Source: UniProtKB
- hemopoiesis Source: UniProtKB
- intracellular signal transduction Source: GO_Central
- intrinsic apoptotic signaling pathway in response to oxidative stress Source: MGI
- neural precursor cell proliferation Source: UniProtKB
- positive regulation of apoptotic process Source: UniProtKB
- protein autophosphorylation Source: UniProtKB
- protein phosphorylation Source: GO_Central
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Apoptosis, Cell cycle |
Ligand | ATP-binding, Calcium, Lipid-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.1, 3474 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:Melk Synonyms:Kiaa0175, Pk38 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:106924, Melk |
VEuPathDBi | HostDB:ENSMUSG00000035683 |
Subcellular locationi
Plasma membrane
- Cell membrane By similarity; Peripheral membrane protein By similarity
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- cell cortex Source: UniProtKB
- cytoplasm Source: MGI
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 40 | K → R: Loss of kinase activity. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086324 | 1 – 643 | Maternal embryonic leucine zipper kinaseAdd BLAST | 643 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 56 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 163 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 167 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 171 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 253 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 336 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 343 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 352 | PhosphoserineCombined sources | 1 | |
Modified residuei | 399 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 423 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 486 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 490 | PhosphoserineBy similarity | 1 | |
Modified residuei | 497 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 510 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 521 | Phosphoserine; by autocatalysisCombined sources | 1 | |
Modified residuei | 531 | Phosphothreonine; by autocatalysisBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q61846 |
jPOSTi | Q61846 |
MaxQBi | Q61846 |
PaxDbi | Q61846 |
PRIDEi | Q61846 |
ProteomicsDBi | 295853 |
PTM databases
iPTMneti | Q61846 |
PhosphoSitePlusi | Q61846 |
Expressioni
Tissue specificityi
Developmental stagei
Gene expression databases
Bgeei | ENSMUSG00000035683, Expressed in primary oocyte and 280 other tissues |
ExpressionAtlasi | Q61846, baseline and differential |
Genevisiblei | Q61846, MM |
Interactioni
Subunit structurei
Monomer.
Interacts with ZNF622 and PPP1R8 (By similarity).
By similarityProtein-protein interaction databases
BioGRIDi | 201390, 11 interactors |
STRINGi | 10090.ENSMUSP00000043806 |
Miscellaneous databases
RNActi | Q61846, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q61846 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 11 – 263 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 253 | |
Domaini | 594 – 643 | KA1PROSITE-ProRule annotationAdd BLAST | 50 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 282 – 321 | UBA-likeBy similarityAdd BLAST | 40 | |
Regioni | 326 – 643 | Autoinhibitory regionBy similarityAdd BLAST | 318 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0583, Eukaryota |
GeneTreei | ENSGT00940000154889 |
HOGENOMi | CLU_000288_157_8_1 |
InParanoidi | Q61846 |
OMAi | SEWKYDQ |
OrthoDBi | 1127668at2759 |
PhylomeDBi | Q61846 |
TreeFami | TF314032 |
Family and domain databases
CDDi | cd14078, STKc_MELK, 1 hit |
InterProi | View protein in InterPro IPR028375, KA1/Ssp2_C IPR001772, KA1_dom IPR011009, Kinase-like_dom_sf IPR034673, MELK IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF02149, KA1, 1 hit PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF103243, SSF103243, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50032, KA1, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA2ALQ9 | A2ALQ9_MOUSE | Maternal embryonic leucine zipper k... | Melk | 133 | Annotation score: | ||
A2ALR0 | A2ALR0_MOUSE | Maternal embryonic leucine zipper k... | Melk | 214 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 335 | L → P in CAA64641 (PubMed:9136115).Curated | 1 | |
Sequence conflicti | 335 | L → P in BAC97886 (PubMed:14621295).Curated | 1 |
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 Genomic DNA No translation available. AL807399 Genomic DNA No translation available. |
CCDSi | CCDS18124.1 |
RefSeqi | NP_034920.2, NM_010790.2 |
Genome annotation databases
Ensembli | ENSMUST00000045607; ENSMUSP00000043806; ENSMUSG00000035683 |
GeneIDi | 17279 |
KEGGi | mmu:17279 |
UCSCi | uc008srv.1, mouse |
Similar proteinsi
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 Genomic DNA No translation available. AL807399 Genomic DNA No translation available. |
CCDSi | CCDS18124.1 |
RefSeqi | NP_034920.2, NM_010790.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4BFM | X-ray | 2.35 | A | 1-326 | [»] | |
4CQG | X-ray | 2.57 | A | 1-326 | [»] | |
SMRi | Q61846 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 201390, 11 interactors |
STRINGi | 10090.ENSMUSP00000043806 |
PTM databases
iPTMneti | Q61846 |
PhosphoSitePlusi | Q61846 |
Proteomic databases
EPDi | Q61846 |
jPOSTi | Q61846 |
MaxQBi | Q61846 |
PaxDbi | Q61846 |
PRIDEi | Q61846 |
ProteomicsDBi | 295853 |
Protocols and materials databases
Antibodypediai | 2095, 463 antibodies from 40 providers |
DNASUi | 17279 |
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 |
VEuPathDBi | HostDB:ENSMUSG00000035683 |
Rougei | Search... |
Phylogenomic databases
eggNOGi | KOG0583, Eukaryota |
GeneTreei | ENSGT00940000154889 |
HOGENOMi | CLU_000288_157_8_1 |
InParanoidi | Q61846 |
OMAi | SEWKYDQ |
OrthoDBi | 1127668at2759 |
PhylomeDBi | Q61846 |
TreeFami | TF314032 |
Enzyme and pathway databases
BRENDAi | 2.7.11.1, 3474 |
Miscellaneous databases
BioGRID-ORCSi | 17279, 1 hit in 66 CRISPR screens |
ChiTaRSi | Melk, mouse |
PROi | PR:Q61846 |
RNActi | Q61846, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000035683, Expressed in primary oocyte and 280 other tissues |
ExpressionAtlasi | Q61846, baseline and differential |
Genevisiblei | Q61846, MM |
Family and domain databases
CDDi | cd14078, STKc_MELK, 1 hit |
InterProi | View protein in InterPro IPR028375, KA1/Ssp2_C IPR001772, KA1_dom IPR011009, Kinase-like_dom_sf IPR034673, MELK IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF02149, KA1, 1 hit PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF103243, SSF103243, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50032, KA1, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | MELK_MOUSE | |
Accessioni | Q61846Primary (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: | February 23, 2022 | |
This is version 178 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families