U4PR86 · MELK_CAEEL
- ProteinMaternal embryonic leucine zipper kinase
- Genepig-1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids706 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Serine/threonine-protein kinase involved in cell autonomous neuroblast asymmetric divisions that generate one precursor cell and one apoptotic cell by controlling spindle positioning, myosin distribution and the segregation of cell fate determinants (PubMed:16774992, PubMed:20929735, PubMed:23267054, PubMed:23851392, PubMed:23946438, PubMed:28659600).
Plays a role in neural fate specification in several dopaminergic linages, acting in concert with ham-1 (PubMed:28659600).
Involved in phosphorylation of multiple proteins associated with key developmental processes, including the cell cycle, apoptosis, endocytosis, and asymmetric cell division (PubMed:28659600).
Promotes cell shedding during embryogenesis, probably through the endocytosis-mediated removal of cell adhesion molecules such as hmp-1 from the cell surface (PubMed:22801495).
May act downstream of par-4/strd-1/mop-25 to regulate cell shedding (PubMed:22801495).
Plays a role in neural fate specification in several dopaminergic linages, acting in concert with ham-1 (PubMed:28659600).
Involved in phosphorylation of multiple proteins associated with key developmental processes, including the cell cycle, apoptosis, endocytosis, and asymmetric cell division (PubMed:28659600).
Promotes cell shedding during embryogenesis, probably through the endocytosis-mediated removal of cell adhesion molecules such as hmp-1 from the cell surface (PubMed:22801495).
May act downstream of par-4/strd-1/mop-25 to regulate cell shedding (PubMed:22801495).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | centrosome | |
Cellular Component | cytoplasm | |
Molecular Function | ATP binding | |
Molecular Function | non-membrane spanning protein tyrosine kinase activity | |
Molecular Function | protein serine kinase activity | |
Molecular Function | protein serine/threonine kinase activity | |
Biological Process | apoptotic process | |
Biological Process | asymmetric neuroblast division | |
Biological Process | dopaminergic neuron differentiation | |
Biological Process | hemidesmosome assembly | |
Biological Process | negative regulation of apoptotic process involved in development | |
Biological Process | neuroblast development | |
Biological Process | positive regulation of apoptotic process | |
Biological Process | protein phosphorylation | |
Biological Process | regulation of cell adhesion |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMaternal embryonic leucine zipper kinase
- EC number
- Short namesMELK
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Ecdysozoa > Nematoda > Chromadorea > Rhabditida > Rhabditina > Rhabditomorpha > Rhabditoidea > Rhabditidae > Peloderinae > Caenorhabditis
Accessions
- Primary accessionU4PR86
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Cytoplasmic in undividing cells and co-localizes with centrosome in dividing cells.
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
During neuroblast differentiation, mutants produce an additional precursor cell for the HSN/PHB, I2, M4 and PLM/ALN and Q.a and Q.p lineages. The nucleus size of the 2 Q.p daughter cells is similar (PubMed:16774992).
Symmetrical distribution of myosin II during QR.a cell division (PubMed:20929735).
Abnormally high number of ADE neurons (PubMed:28659600).
Double knockouts of pig-1 and ced-3 have impaired cell shedding during embryogenesis which results in the generation of an ectopic excretory cell and an ERM-like neuron. In addition, mutants show a delay in clearance after engulfment of cell corpses which is associated with the abnormal expression of cell adhesion molecules (PubMed:22801495).
Symmetrical distribution of myosin II during QR.a cell division (PubMed:20929735).
Abnormally high number of ADE neurons (PubMed:28659600).
Double knockouts of pig-1 and ced-3 have impaired cell shedding during embryogenesis which results in the generation of an ectopic excretory cell and an ERM-like neuron. In addition, mutants show a delay in clearance after engulfment of cell corpses which is associated with the abnormal expression of cell adhesion molecules (PubMed:22801495).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 169 | May be inactive. Prevents cell shedding during embryogenesis. Additional production of PVM neuron. | ||||
Sequence: T → A | ||||||
Mutagenesis | 169 | May be constitutively active. Promotes cell shedding during embryogenesis. In some mutants, production of an additional PVM neuron. | ||||
Sequence: T → D | ||||||
Mutagenesis | 172 | In n4780; production of an additional M4 motor neuron. | ||||
Sequence: G → E | ||||||
Mutagenesis | 172 | In gm300; production of an additional HSN/PHB precursor cell. | ||||
Sequence: G → R | ||||||
Mutagenesis | 198 | In gm301; production of an additional HSN/PHB precursor cell and an additional PVM precursor cell. | ||||
Sequence: G → D |
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000432387 | 1-706 | Maternal embryonic leucine zipper kinase | |||
Sequence: MSKYEVLQGFYAVHDELGSGGFGKVRLATHLLTNQKVAIKIIDKKQLGHDLPRVQTEMDALRNLSHQNICRLYHYIETEDKFFIVMEYCSGGEMFDYIVRKERLEESEARHFFRQLVSAIAFVHSQGYAHRDLKPENLLLTEDLHLKLIDFGLCAKTEKGRIDKHNLDTCCGSPAYAAPELIQGLQYKGNEADVWSMGILLYTLLVGALPFEDDNMQIMYKKIQSGCFYEPEFLSPLSKQLLRAMLQVVPERRISVKKLLEHDWLNHKYTQPVKWNTIYDKNFIDRDVARVMSKYYGFESTDKMIEKIKEWNFDYMTSTYYALLHRKRNGMEIILPMVRNSTNTAPPNVQNILCSPTIHASLENNLDKSGLEDDDSDPSSISSSSDISARLKKNCVVSDESSSSRFVKPMSPAAEKDKKMSYVNAMLTMPSQFTGRSPLRIPESPMSVRSSDSASLGSAATPSRGGVKDNDKENASTGKNYRMGASTCKSRGPLKITGVEEGTMKSVYTTPNTRPTLRGLFSPGNAEHKKRQRARSSDRASIGMPPGSPVSIGSAHSANNELLADGRTPRSRIKTNRLPQRVFTSLERKKEKLITLLTPRKMQRDSPQVLKDVKNMVNVSMTASQDPEEVRNLLKKVFDDERMRYELNGWKFLATQETVHGWMTVELEIVRLQMFDKVGIRRKRLKGDAFMYKKVCEKILQMAKIE |
Post-translational modification
May be phosphorylated at Thr-169 by par-4 and/or autophosphorylated which likely results in its activation (PubMed:22801495).
Phosphorylation is not required for co-localization with the centrosome (PubMed:23267054).
Phosphorylation is not required for co-localization with the centrosome (PubMed:23267054).
Proteomic databases
Expression
Developmental stage
Ubiquitously expressed in early embryo with a more restricted expression in later embryonic stages and in young larvae. Expressed in dividing cells including ventral nerve cord neuroblasts, vulval precursors, hypodermal seam cells and in the Q lineage. No expression in adults.
Gene expression databases
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 11-265 | Protein kinase | ||||
Sequence: YAVHDELGSGGFGKVRLATHLLTNQKVAIKIIDKKQLGHDLPRVQTEMDALRNLSHQNICRLYHYIETEDKFFIVMEYCSGGEMFDYIVRKERLEESEARHFFRQLVSAIAFVHSQGYAHRDLKPENLLLTEDLHLKLIDFGLCAKTEKGRIDKHNLDTCCGSPAYAAPELIQGLQYKGNEADVWSMGILLYTLLVGALPFEDDNMQIMYKKIQSGCFYEPEFLSPLSKQLLRAMLQVVPERRISVKKLLEHDWL | ||||||
Region | 366-386 | Disordered | ||||
Sequence: LDKSGLEDDDSDPSSISSSSD | ||||||
Compositional bias | 433-460 | Polar residues | ||||
Sequence: FTGRSPLRIPESPMSVRSSDSASLGSAA | ||||||
Region | 433-493 | Disordered | ||||
Sequence: FTGRSPLRIPESPMSVRSSDSASLGSAATPSRGGVKDNDKENASTGKNYRMGASTCKSRGP | ||||||
Region | 506-555 | Disordered | ||||
Sequence: SVYTTPNTRPTLRGLFSPGNAEHKKRQRARSSDRASIGMPPGSPVSIGSA | ||||||
Domain | 656-705 | KA1 | ||||
Sequence: QETVHGWMTVELEIVRLQMFDKVGIRRKRLKGDAFMYKKVCEKILQMAKI |
Domain
The KA1 domain is required for the control of asymmetric neuroblast division.
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 8 isoforms produced by Alternative splicing.
U4PR86-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Namec
- Length706
- Mass (Da)80,340
- Last updated2013-12-11 v1
- Checksum7A6A330E2F5C4E2A
U4PR86-2
- Namea
- Differences from canonical
- 561-563: Missing
U4PR86-3
- Nameb
U4PR86-4
- Named
- Differences from canonical
- 679-706: GIRRKRLKGDAFMYKKVCEKILQMAKIE → RNLRRFFCCVNINIPSRKPTYIEL
U4PR86-5
- Namee
U4PR86-6
- Namef
U4PR86-7
- Nameg
- Differences from canonical
- 1-244: Missing
U4PR86-8
- Nameh
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_057506 | 1-244 | in isoform e, isoform f, isoform g and isoform h | |||
Sequence: Missing | ||||||
Compositional bias | 433-460 | Polar residues | ||||
Sequence: FTGRSPLRIPESPMSVRSSDSASLGSAA | ||||||
Alternative sequence | VSP_057507 | 561-563 | in isoform a, isoform b, isoform e and isoform f | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_057508 | 679-706 | in isoform b, isoform d, isoform f and isoform h | |||
Sequence: GIRRKRLKGDAFMYKKVCEKILQMAKIE → RNLRRFFCCVNINIPSRKPTYIEL |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
FO081096 EMBL· GenBank· DDBJ | CCD69087.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FO081096 EMBL· GenBank· DDBJ | CCD69088.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FO081096 EMBL· GenBank· DDBJ | CDH93078.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FO081096 EMBL· GenBank· DDBJ | CDH93079.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FO081096 EMBL· GenBank· DDBJ | CDH93080.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FO081096 EMBL· GenBank· DDBJ | CDH93081.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FO081096 EMBL· GenBank· DDBJ | CDH93082.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FO081096 EMBL· GenBank· DDBJ | CDH93083.1 EMBL· GenBank· DDBJ | Genomic DNA |