InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MELK

Summary

InnateDB Protein

IDBP-65358.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MELK

Protein Name

maternal embryonic leucine zipper kinase

Synonyms

HPK38;

Species

Homo sapiens

Ensembl Protein

ENSP00000298048

InnateDB Gene

IDBG-65356 (MELK)

Protein Structure

UniProt Annotation

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 and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of 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. {ECO:0000269PubMed:11802789, ECO:0000269PubMed:12400006, ECO:0000269PubMed:14699119, ECO:0000269PubMed:15908796, ECO:0000269PubMed:16216881, ECO:0000269PubMed:17280616}.

Subcellular Localization

Cell membrane {ECO:0000269PubMed:16159311, ECO:0000269PubMed:21145462}; Peripheral membrane protein {ECO:0000269PubMed:16159311, ECO:0000269PubMed:21145462}.

Disease Associations

Note=Defects in MELK are associated with some cancers, such as brain or breast cancers. Expression is dramatically increased in aggressive undifferentiated tumors, correlating with poor patient outcome in breast and brain cancers, suggesting a role in tumor-initiating cells and proliferation via its function in cell proliferation regulation.

Tissue Specificity

Expressed in placenta, kidney, thymus, testis, ovary and intestine. {ECO:0000269PubMed:8724849}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 12 experimentally validated interaction(s) in this database.

Experimentally validated
Total	12 [view]
Protein-Protein	10 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008289	lipid binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor

Biological Process

GO:0000086	G2/M transition of mitotic cell cycle
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0008283	cell proliferation
GO:0008631	intrinsic apoptotic signaling pathway in response to oxidative stress
GO:0009103	lipopolysaccharide biosynthetic process
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0030097	hemopoiesis
GO:0043065	positive regulation of apoptotic process
GO:0046777	protein autophosphorylation
GO:0061351	neural precursor cell proliferation

Cellular Component

GO:0005737	cytoplasm
GO:0005886	plasma membrane
GO:0005938	cell cortex
GO:0016020	membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001772 Kinase associated domain 1 (KA1)
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR010440 Lipopolysaccharide kinase
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR028375 KA1 domain/Ssp2 C-terminal domain

PFAM

PF00069
PF07714
PF02149
PF06293

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt