4UMU

Structure of MELK in complex with inhibitors

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d4umua_	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	automated matches	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	Protein kinase-like (PK-like)	8099168	3000066	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	UBA-like	8101058	3001235	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	UBA_MELK	e4umuA1	A: alpha arrays	X: RuvA-C	H: RuvA-C, UBA, CRAL/TRIO-N, HBS1 (From Topology)	T: RuvA-C, UBA, CRAL/TRIO-N, HBS1	F: UBA_MELK	ECOD (1.6)
A	Pkinase_Tyr	e4umuA2	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: Protein kinase	F: Pkinase_Tyr	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.10.510.10	Mainly Alpha	Orthogonal Bundle	Transferase(Phosphotransferase)	domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF21594	Maternal embryonic leucine zipper kinase, UBA domain (MELK_UBA)	Maternal embryonic leucine zipper kinase, UBA domain	This domain is found in Maternal embryonic leucine zipper kinase from humans (MELK) and similar proteins from animals. MELK is a member of the snf1/AMPK family of serine-threonine kinases that has been associated with various cellular processes, incl ...	This domain is found in Maternal embryonic leucine zipper kinase from humans (MELK) and similar proteins from animals. MELK is a member of the snf1/AMPK family of serine-threonine kinases that has been associated with various cellular processes, including stem cell renewal, cell cycle progression, and pre-mRNA splicing. It is upregulated in several types of tumour. MELK is organised into three domains: an N-terminal kinase domain (Pfam:PF00069), a ubiquitin associated (UBA) domain (this entry) and a C-terminal kinase associated domain (KA1, Pfam:PF02149). This domain adopts a compact configuration consisting of three alpha-helices organised in a "U"-shaped fold, with the first helix antiparallel to the third one [1-5].	Domain
A	PF00069	Protein kinase domain (Pkinase)	Protein kinase domain	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE	cation binding ion binding binding calcium ion binding metal ion binding small molecule binding catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity protein serine kinase activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups cation binding ion binding binding calcium ion binding metal ion binding small molecule binding catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity protein serine kinase activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding non-membrane spanning protein tyrosine kinase activity protein tyrosine kinase activity lipid binding protein serine/threonine kinase activity	cell population proliferation cellular process apoptotic process cell death programmed cell death regulation of biological process positive regulation of programmed cell death regulation of cellular process regulation of apoptotic process biological regulation positive regulation of biological process regulation of programmed cell death positive regulation of apoptotic process positive regulation of cellular process cell population proliferation cellular process apoptotic process cell death programmed cell death regulation of biological process positive regulation of programmed cell death regulation of cellular process regulation of apoptotic process biological regulation positive regulation of biological process regulation of programmed cell death positive regulation of apoptotic process positive regulation of cellular process developmental process cellular developmental process hemopoiesis cell differentiation anatomical structure development cell development protein phosphorylation protein autophosphorylation phosphorylation primary metabolic process macromolecule modification phosphate-containing compound metabolic process metabolic process protein metabolic process macromolecule metabolic process protein modification process phosphorus metabolic process neural precursor cell proliferation cell cycle G2/M phase transition mitotic cell cycle process G2/M transition of mitotic cell cycle cell cycle phase transition cell cycle mitotic cell cycle cell cycle process mitotic cell cycle phase transition cellular response to stimulus intrinsic apoptotic signaling pathway in response to oxidative stress response to stimulus signaling intracellular signal transduction cell communication apoptotic signaling pathway signal transduction intrinsic apoptotic signaling pathway	cellular anatomical structure membrane cell periphery cell cortex intracellular anatomical structure cytoplasm plasma membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR017441	Protein kinase, ATP binding site	Binding Site
A	IPR048637	Maternal embryonic leucine zipper kinase, UBA domain	Domain
A	IPR034673	Maternal embryonic leucine zipper kinase, catalytic domain	Domain
A	IPR001772	Kinase associated domain 1 (KA1)	Domain
A	IPR000719	Protein kinase domain	Domain
A	IPR028375	KA1 domain/Ssp2, C-terminal	Homologous Superfamily
A	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A	IPR008271	Serine/threonine-protein kinase, active site	Active Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: Q14680	non-small cell lung carcinoma malignant glioma medulloblastoma ovarian cancer pancreatic intraductal papillary-mucinous neoplasm adrenal cortex carcinoma breast cancer endometriosis idiopathic pulmonary fibrosis Interstitial fibrosis large cell medulloblastoma malignant colon neoplasm malignant mesothelioma nasopharyngeal carcinoma ovarian mucinous adenocarcinoma non-small cell lung carcinoma malignant glioma medulloblastoma ovarian cancer pancreatic intraductal papillary-mucinous neoplasm adrenal cortex carcinoma breast cancer endometriosis idiopathic pulmonary fibrosis Interstitial fibrosis large cell medulloblastoma malignant colon neoplasm malignant mesothelioma nasopharyngeal carcinoma ovarian mucinous adenocarcinoma primitive neuroectodermal tumor atopic eczema breast carcinoma glioblastoma IgA glomerulonephritis interstitial lung disease lung adenocarcinoma malignant ependymoma malignant pancreatic neoplasm pancreatic intraductal papillary-mucinous carcinoma psoriasis atypical teratoid rhabdoid tumor ductal breast carcinoma in situ hepatocellular carcinoma interstitial cystitis invasive ductal breast carcinoma lung cancer

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.