DYRK3

Functionⁱ

Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Negative regulator of EPO-dependent erythropoiesis, may place an upper limit on red cell production during stress erythropoiesis. Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells (PubMed:10779429). May act by regulating CREB/CRE signaling (By similarity). Stabilizes and prevents stress granule disassembly thereby regulating mTORC1 signaling during cellular stress. During stressful conditions, DYRK3 partitions to the stress granule from the cytosol, as well as mTORC1 components, which prevents mTORC1 signaling. When stress signals are gone, the kinase activity of DYRK3 is required for the dissolution of stress granule and mTORC1 relocation to the cytosol, and promotes the phosphorylation of the mTORC1 inhibitor, AKT1S1, allowing full reactivation of mTORC1 signaling (PubMed:23415227). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1. This in turn inhibits TP53 activity and apoptosis (PubMed:20167603).By similarity3 Publications

Catalytic activityⁱ

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactorⁱ

Mg²⁺By similarity

Activity regulationⁱ

Inhibited by harmine, leucettamine B and leucettine L41.

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Binding siteⁱ	238	ATPPROSITE-ProRule annotation1 Publication		1
Active siteⁱ	335	Proton acceptorPROSITE-ProRule annotation		1

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Nucleotide bindingⁱ	215 – 223	ATPPROSITE-ProRule annotation		9
Nucleotide bindingⁱ	288 – 291	ATPPROSITE-ProRule annotation		4

GO - Molecular functionⁱ

ATP binding
Source: UniProtKB
Inferred from direct assayⁱ
- 10779429
magnesium ion binding
Source: UniProtKB
Inferred from direct assayⁱ
- 10779429
protein kinase activity
Source: UniProtKB
Inferred from direct assayⁱ
- 10779429
protein serine/threonine/tyrosine kinase activity Source: UniProtKB-EC
protein serine/threonine kinase activity
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 23415227
protein tyrosine kinase activity Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

erythrocyte differentiation
Source: UniProtKB
Inferred from direct assayⁱ
- 10779429
negative regulation of apoptotic process Source: Ensembl
negative regulation of DNA damage response, signal transduction by p53 class mediator Source: Ensembl
protein phosphorylation
Source: UniProtKB
Inferred from direct assayⁱ
- 10779429
regulation of cellular response to stress
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 23415227
regulation of TORC1 signaling
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 23415227
stress granule disassembly
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 23415227

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase
Ligand	ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAⁱ	2.7.12.1 2681
SignaLinkⁱ	O43781
SIGNORⁱ	O43781

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Dual specificity tyrosine-phosphorylation-regulated kinase 3 (EC:2.7.12.11 Publication) Alternative name(s): Regulatory erythroid kinase1 Publication Short name: REDK1 Publication
Gene namesⁱ	Name:DYRK3
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 1

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000143479.15
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:3094 DYRK3
MIMⁱ	603497 gene
neXtProtⁱ	NX_O43781

Keywords - Cellular componentⁱ

Nucleus

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Mutagenesisⁱ	238	K → M: Kinase dead; Induces formation of stress granules-like in absence of stress. 1 Publication		1

Organism-specific databases

DisGeNET More...DisGeNETⁱ	8444
Open Targets More...OpenTargetsⁱ	ENSG00000143479
PharmGKBⁱ	PA27551

Chemistry databases

ChEMBLⁱ	CHEMBL4575
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	2012

Polymorphism and mutation databases

BioMutaⁱ	DYRK3

BioMutaⁱ

DYRK3

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000085938	1 – 588	Dual specificity tyrosine-phosphorylation-regulated kinase 3Add BLAST		588

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Modified residueⁱ	369	PhosphotyrosineBy similarity		1

Post-translational modificationⁱ

Autophosphorylated on tyrosine residues (PubMed:9748265).1 Publication

Keywords - PTMⁱ

Phosphoprotein

Proteomic databases

MaxQB - The MaxQuant DataBase More...MaxQBⁱ	O43781
PaxDbⁱ	O43781
PeptideAtlas More...PeptideAtlasⁱ	O43781
PRIDEⁱ	O43781
ProteomicsDBⁱ	49168 49169 [O43781-2]

PTM databases

iPTMnetⁱ	O43781
PhosphoSitePlusⁱ	O43781

Expressionⁱ

Tissue specificityⁱ

Isoform 1 and isoform 2 are highly expressed in testis and in hematopoietic tissue such as fetal liver, and bone marrow. Isoform 2 is the predominant form in testis. Isoform 1 is the predominant form in fetal liver and bone marrow. Isoform 1 and isoform 2 are present at low levels in heart, pancreas, lymph node, and thymus.1 Publication

Inductionⁱ

By EPO/erythropoietin.1 Publication

Gene expression databases

Bgeeⁱ	ENSG00000143479 Expressed in 163 organ(s), highest expression level in testis
CleanExⁱ	HS_DYRK3
ExpressionAtlasⁱ	O43781 baseline and differential
Genevisibleⁱ	O43781 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA075041

HPAⁱ

HPA075041

Interactionⁱ

Subunit structureⁱ

Interacts with SIRT1.By similarity

Protein-protein interaction databases

BioGridⁱ	114022, 6 interactors
IntActⁱ	O43781, 5 interactors
STRINGⁱ	9606.ENSP00000356076

Chemistry databases

BindingDBⁱ	O43781

BindingDBⁱ

O43781

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	143 – 149	Combined sources	7
Turnⁱ	150 – 153	Combined sources	4
Helixⁱ	156 – 161	Combined sources	6
Helixⁱ	162 – 164	Combined sources	3
Helixⁱ	185 – 188	Combined sources	4
Turnⁱ	206 – 208	Combined sources	3
Beta strandⁱ	209 – 218	Combined sources	10
Beta strandⁱ	221 – 228	Combined sources	8
Turnⁱ	229 – 232	Combined sources	4
Beta strandⁱ	233 – 240	Combined sources	8
Helixⁱ	244 – 263	Combined sources	20
Turnⁱ	266 – 269	Combined sources	4
Beta strandⁱ	274 – 280	Combined sources	7
Beta strandⁱ	283 – 288	Combined sources	6
Helixⁱ	295 – 301	Combined sources	7
Turnⁱ	302 – 304	Combined sources	3
Helixⁱ	309 – 328	Combined sources	20
Helixⁱ	338 – 340	Combined sources	3
Beta strandⁱ	341 – 345	Combined sources	5
Beta strandⁱ	351 – 353	Combined sources	3
Helixⁱ	356 – 358	Combined sources	3
Helixⁱ	373 – 375	Combined sources	3
Helixⁱ	378 – 382	Combined sources	5
Helixⁱ	389 – 404	Combined sources	16
Helixⁱ	414 – 425	Combined sources	12
Helixⁱ	430 – 434	Combined sources	5
Helixⁱ	439 – 441	Combined sources	3
Beta strandⁱ	452 – 456	Combined sources	5
Beta strandⁱ	462 – 465	Combined sources	4
Helixⁱ	483 – 486	Combined sources	4
Turnⁱ	487 – 489	Combined sources	3
Helixⁱ	493 – 502	Combined sources	10
Helixⁱ	507 – 509	Combined sources	3
Helixⁱ	513 – 518	Combined sources	6
Turnⁱ	520 – 522	Combined sources	3

Show more details

3D structure databases

ProteinModelPortalⁱ	O43781
SMRⁱ	O43781
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	209 – 522	Protein kinasePROSITE-ProRule annotationAdd BLAST		314

Domainⁱ

The N-terminal domain is required for stress granule localization (PubMed:23415227).

Sequence similaritiesⁱ

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.Curated

Phylogenomic databases

eggNOGⁱ	KOG0667 Eukaryota ENOG410XPET LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00760000119032
HOGENOMⁱ	HOG000220863
HOVERGENⁱ	HBG051426
InParanoidⁱ	O43781
KEGG Orthology (KO) More...KOⁱ	K18669
OMAⁱ	LKQYKHH
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0Q46
PhylomeDBⁱ	O43781
TreeFamⁱ	TF314624

Family and domain databases

InterProⁱ	View protein in InterPro IPR011009 Kinase-like_dom_sf IPR000719 Prot_kinase_dom IPR017441 Protein_kinase_ATP_BS IPR008271 Ser/Thr_kinase_AS
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00069 Pkinase, 1 hit
SMARTⁱ	View protein in SMART SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF56112 SSF56112, 1 hit
PROSITEⁱ	View protein in PROSITE PS00107 PROTEIN_KINASE_ATP, 1 hit PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2+)ⁱ

Sequence statusⁱ: Complete.

This entry describes 2 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.ⁱShow all

Isoform 1 (identifier: O43781-1) [UniParc]FASTA Add to basket

Also known as: Long

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.

« Hide

        10         20         30         40         50
MGGTARGPGR KDAGPPGAGL PPQQRRLGDG VYDTFMMIDE TKCPPCSNVL 
        60         70         80         90        100
CNPSEPPPPR RLNMTTEQFT GDHTQHFLDG GEMKVEQLFQ EFGNRKSNTI 
       110        120        130        140        150
QSDGISDSEK CSPTVSQGKS SDCLNTVKSN SSSKAPKVVP LTPEQALKQY 
       160        170        180        190        200
KHHLTAYEKL EIINYPEIYF VGPNAKKRHG VIGGPNNGGY DDADGAYIHV 
       210        220        230        240        250
PRDHLAYRYE VLKIIGKGSF GQVARVYDHK LRQYVALKMV RNEKRFHRQA 
       260        270        280        290        300
AEEIRILEHL KKQDKTGSMN VIHMLESFTF RNHVCMAFEL LSIDLYELIK 
       310        320        330        340        350
KNKFQGFSVQ LVRKFAQSIL QSLDALHKNK IIHCDLKPEN ILLKHHGRSS 
       360        370        380        390        400
TKVIDFGSSC FEYQKLYTYI QSRFYRAPEI ILGSRYSTPI DIWSFGCILA 
       410        420        430        440        450
ELLTGQPLFP GEDEGDQLAC MMELLGMPPP KLLEQSKRAK YFINSKGIPR 
       460        470        480        490        500
YCSVTTQADG RVVLVGGRSR RGKKRGPPGS KDWGTALKGC DDYLFIEFLK 
       510        520        530        540        550
RCLHWDPSAR LTPAQALRHP WISKSVPRPL TTIDKVSGKR VVNPASAFQG 
       560        570        580 
LGSKLPPVVG IANKLKANLM SETNGSIPLC SVLPKLIS

Length:588

Mass (Da):65,714

Last modified:June 26, 2007 - v3

Checksum:ⁱ9950F51C39AFED82

GO

Isoform 2 (identifier: O43781-2) [UniParc]FASTA Add to basket

Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
1-20: Missing.
21-26: PPQQRR → MKWKEK

« Hide

        10         20         30         40         50
MKWKEKLGDG VYDTFMMIDE TKCPPCSNVL CNPSEPPPPR RLNMTTEQFT 
        60         70         80         90        100
GDHTQHFLDG GEMKVEQLFQ EFGNRKSNTI QSDGISDSEK CSPTVSQGKS 
       110        120        130        140        150
SDCLNTVKSN SSSKAPKVVP LTPEQALKQY KHHLTAYEKL EIINYPEIYF 
       160        170        180        190        200
VGPNAKKRHG VIGGPNNGGY DDADGAYIHV PRDHLAYRYE VLKIIGKGSF 
       210        220        230        240        250
GQVARVYDHK LRQYVALKMV RNEKRFHRQA AEEIRILEHL KKQDKTGSMN 
       260        270        280        290        300
VIHMLESFTF RNHVCMAFEL LSIDLYELIK KNKFQGFSVQ LVRKFAQSIL 
       310        320        330        340        350
QSLDALHKNK IIHCDLKPEN ILLKHHGRSS TKVIDFGSSC FEYQKLYTYI 
       360        370        380        390        400
QSRFYRAPEI ILGSRYSTPI DIWSFGCILA ELLTGQPLFP GEDEGDQLAC 
       410        420        430        440        450
MMELLGMPPP KLLEQSKRAK YFINSKGIPR YCSVTTQADG RVVLVGGRSR 
       460        470        480        490        500
RGKKRGPPGS KDWGTALKGC DDYLFIEFLK RCLHWDPSAR LTPAQALRHP 
       510        520        530        540        550
WISKSVPRPL TTIDKVSGKR VVNPASAFQG LGSKLPPVVG IANKLKANLM 
       560 
SETNGSIPLC SVLPKLIS

Show »

Length:568

Mass (Da):63,977

Checksum:ⁱ9B710ECC413873F7

GO

Computationally mapped potential isoform sequencesⁱ

There is 1 potential isoform mapped to this entry.BLAST Align Show all Add to basket

	Entry	Entry name		Protein names	Gene names	Length	Annotation
	Q5SY34	Q5SY34_HUMAN		Dual-specificity tyrosine-phosphory... Dual-specificity tyrosine-phosphorylation-regulated kinase 3	DYRK3	243	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	313	R → H in AAH15501 (PubMed:15489334).Curated		1
Sequence conflictⁱ	396	G → R in CAA73266 (PubMed:9748265).Curated		1

Natural variant

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_040464	239	M → L1 Publication		1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_026178	1 – 20	Missing in isoform 2. 3 PublicationsAdd BLAST		20
Alternative sequenceⁱVSP_026179	21 – 26	PPQQRR → MKWKEK in isoform 2. 3 Publications		6

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	Y12735 mRNA Translation: CAA73266.2 AF186773 mRNA Translation: AAG17028.1 AF186774 mRNA Translation: AAG17029.1 AF327561 mRNA Translation: AAK16443.1 AY590695 mRNA Translation: AAT06103.1 AL591846 Genomic DNA No translation available. CH471100 Genomic DNA Translation: EAW93533.1 CH471100 Genomic DNA Translation: EAW93534.1 BC015501 mRNA Translation: AAH15501.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS30999.1 [O43781-1] CCDS31000.1 [O43781-2]
NCBI Reference Sequences More...RefSeqⁱ	NP_001004023.1, NM_001004023.1 [O43781-2] NP_003573.2, NM_003582.2 [O43781-1] XP_005273372.1, XM_005273315.4 [O43781-2]
UniGeneⁱ	Hs.164267

Genome annotation databases

Ensemblⁱ	ENST00000367106; ENSP00000356073; ENSG00000143479 [O43781-2] ENST00000367108; ENSP00000356075; ENSG00000143479 [O43781-2] ENST00000367109; ENSP00000356076; ENSG00000143479 [O43781-1]
GeneIDⁱ	8444
KEGGⁱ	hsa:8444
UCSC genome browser More...UCSCⁱ	uc001hei.4 human [O43781-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
O43781	Dual specificity tyrosine-phosphorylation-regulated kinase 3		RAT		586	UniRef90_O43781
Dual specificity tyrosine-phosphorylation-regulated kinase 3		MACFA		568
Dual specificity tyrosine phosphorylation regulated kinase 3		CERAT		588
Dual specificity tyrosine-phosphorylation-regulated kinase 3 isoform b (Fragment)		MACMU		376
Dual specificity tyrosine phosphorylation regulated kinase 3		Cebus capucinus imitator		588
+173

Protein	Similar proteins		Species	Score	Length	Source
O43781	Dual specificity tyrosine-phosphorylation-regulated kinase 3		RAT		586	UniRef50_O43781
Dual specificity tyrosine-phosphorylation-regulated kinase 3		MACFA		568
Dual specificity tyrosine-phosphorylation-regulated kinase 3		MOUSE		586
dual specificity tyrosine-phosphorylation-regulated kinase 3		TARSY		588
DYRK3 isoform 4		PANTR		588
+260

Entry informationⁱ

Entry nameⁱ	DYRK3_HUMAN
Accessionⁱ	O43781Primary (citable) accession number: O43781 Secondary accession number(s): D3DT79 , Q7Z752, Q9HBY6, Q9HBY7
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
	Last sequence update:	June 26, 2007
	Last modified:	September 12, 2018
	This is version 168 of the entry and version 3 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - O43781 (DYRK3_HUMAN)

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Dual specificity tyrosine-phosphorylation-regulated kinase 3

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Sites

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Nucleus

Other locations

Cytosol

Nucleus

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

Computationally mapped potential isoform sequencesi

Experimental Info

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Computationally mapped potential isoform sequencesⁱ

Keywords - Coding sequence diversityⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ