CleftGeneDB-Search

Gene: Mapk3

Basic information

Tag	Content
Uniprot ID	Q63844; Q61531; Q8K0X5; Q91YW5;
Entrez ID	26417
Genbank protein ID	AAB19973.1; CAA45889.1; AAH29712.1; AAH13754.1;
Genbank nucleotide ID	NM_011952.2
Ensembl protein ID	ENSMUSP00000051619
Ensembl nucleotide ID	ENSMUSG00000063065
Gene name	Mitogen-activated protein kinase 3
Gene symbol	Mapk3
Organism	Mus musculus
NCBI taxa ID	10090
Cleft type	CPO
Developmental stage	E13.5, E14.5, E15.5, E16.5
Data sources	Manually collected
Reference	18952847
Functional description	Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade.
Sequence	MAAAAAAPGG GGGEPRGTAG VVPVVPGEVE VVKGQPFDVG PRYTQLQYIG EGAYGMVSSA 60 YDHVRKTRVA IKKISPFEHQ TYCQRTLREI QILLRFRHEN VIGIRDILRA PTLEAMRDVY 120 IVQDLMETDL YKLLKSQQLS NDHICYFLYQ ILRGLKYIHS ANVLHRDLKP SNLLINTTCD 180 LKICDFGLAR IADPEHDHTG FLTEYVATRW YRAPEIMLNS KGYTKSIDIW SVGCILAEML 240 SNRPIFPGKH YLDQLNHILG ILGSPSQEDL NCIINMKARN YLQSLPSKTK VAWAKLFPKS 300 DSKALDLLDR MLTFNPNKRI TVEEALAHPY LEQYYDPTDE PVAEEPFTFD MELDDLPKER 360 LKELIFQETA RFQPGAPEGP

Abbreviation :
CLO : cleft lip only. CPO : cleft palate only. CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.

Gene expression information

Gene expression during embryonic days (E11.5~E18.5) ~ adult days (Ps) in the lip and palate tissues. (X-axis: days, Y-axis: tissues)

Protein structural annotations

3D structure in PDB database

There is no related protein structure for this gene.

Protein disorder information

Orthologous information

Relation	Gene symbol	Entrez ID	UniProt ID	Cleft type	Developmental stage	Species	Evidence	Details
1:1 ortholog	MAPK3	531391	A0A3Q1MNN7			Bos taurus	Prediction	More>>
1:1 ortholog	MAPK3		A0A452ETI1			Capra hircus	Prediction	More>>
1:1 ortholog	MAPK3	5595	P27361			Homo sapiens	Prediction	More>>
1:1 ortholog	Mapk3	26417	Q63844	CPO	E13.5, E14.5, E15.5, E16.5	Mus musculus	Publication	More>>
1:1 ortholog	MAPK3	454037	H2RA86			Pan troglodytes	Prediction	More>>
1:1 ortholog			A0A480NH74			Sus scrofa	Prediction	More>>
1:1 ortholog	Mapk3	50689	P21708			Rattus norvegicus	Prediction	More>>
1:1 ortholog	mapk3	399480	Q7ZVK8			Danio rerio	Prediction	More>>

Other genetic variants/mutations

ID	Variant	Type	Disease	Chromosome\Coordinate	Evidence
rs1134896630	p.Phe77Leu	missense variant	-	NC_000073.6:g.126760786T>C	UniProt

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO ID	GO Term	Evidence
GO:0001784	phosphotyrosine residue binding	IMP
GO:0004672	protein kinase activity	IDA
GO:0004707	MAP kinase activity	ISO
GO:0004707	MAP kinase activity	TAS
GO:0004707	MAP kinase activity	IMP
GO:0004707	MAP kinase activity	IDA
GO:0004707	MAP kinase activity	IBA
GO:0004708	MAP kinase kinase activity	IMP
GO:0005515	protein binding	IPI
GO:0005524	ATP binding	ISO
GO:0019902	phosphatase binding	ISO
GO:0042802	identical protein binding	ISO
GO:0097110	scaffold protein binding	ISO

GO:Biological Process

GO ID	GO Term	Evidence
GO:0000165	MAPK cascade	ISO
GO:0000187	activation of MAPK activity	IEA
GO:0001934	positive regulation of protein phosphorylation	ISO
GO:0002741	positive regulation of cytokine secretion involved in immune response	IMP
GO:0006351	transcription, DNA-templated	IMP
GO:0006468	protein phosphorylation	ISO
GO:0006468	protein phosphorylation	IDA
GO:0006915	apoptotic process	IEA
GO:0006974	cellular response to DNA damage stimulus	IDA
GO:0006975	DNA damage induced protein phosphorylation	ISO
GO:0007049	cell cycle	IEA
GO:0007165	signal transduction	TAS
GO:0007166	cell surface receptor signaling pathway	IBA
GO:0007568	aging	ISO
GO:0009636	response to toxic substance	ISO
GO:0009887	animal organ morphogenesis	IDA
GO:0010468	regulation of gene expression	IBA
GO:0010628	positive regulation of gene expression	ISO
GO:0010759	positive regulation of macrophage chemotaxis	IMP
GO:0014032	neural crest cell development	IGI
GO:0016310	phosphorylation	ISO
GO:0016310	phosphorylation	TAS
GO:0018105	peptidyl-serine phosphorylation	ISO
GO:0019233	sensory perception of pain	IMP
GO:0019369	arachidonic acid metabolic process	IEA
GO:0030278	regulation of ossification	IGI
GO:0030509	BMP signaling pathway	ISO
GO:0030641	regulation of cellular pH	IMP
GO:0030878	thyroid gland development	IGI
GO:0031281	positive regulation of cyclase activity	ISO
GO:0031663	lipopolysaccharide-mediated signaling pathway	IDA
GO:0032212	positive regulation of telomere maintenance via telomerase	ISO
GO:0032496	response to lipopolysaccharide	IDA
GO:0032872	regulation of stress-activated MAPK cascade	TAS
GO:0033129	positive regulation of histone phosphorylation	ISO
GO:0034198	cellular response to amino acid starvation	ISO
GO:0034614	cellular response to reactive oxygen species	ISO
GO:0035066	positive regulation of histone acetylation	ISO
GO:0035556	intracellular signal transduction	ISO
GO:0035556	intracellular signal transduction	IBA
GO:0038083	peptidyl-tyrosine autophosphorylation	ISO
GO:0042473	outer ear morphogenesis	IGI
GO:0043330	response to exogenous dsRNA	IDA
GO:0045727	positive regulation of translation	ISO
GO:0045944	positive regulation of transcription by RNA polymerase II	ISO
GO:0046697	decidualization	ISO
GO:0048538	thymus development	IGI
GO:0051090	regulation of DNA-binding transcription factor activity	IMP
GO:0051216	cartilage development	IDA
GO:0051403	stress-activated MAPK cascade	ISO
GO:0051493	regulation of cytoskeleton organization	TAS
GO:0051973	positive regulation of telomerase activity	ISO
GO:0060020	Bergmann glial cell differentiation	IGI
GO:0060324	face development	IGI
GO:0060425	lung morphogenesis	IGI
GO:0060440	trachea formation	IGI
GO:0061308	cardiac neural crest cell development involved in heart development	IGI
GO:0065003	protein-containing complex assembly	ISO
GO:0070371	ERK1 and ERK2 cascade	IMP
GO:0070371	ERK1 and ERK2 cascade	IGI
GO:0070374	positive regulation of ERK1 and ERK2 cascade	ISO
GO:0070498	interleukin-1-mediated signaling pathway	ISO
GO:0070849	response to epidermal growth factor	ISS
GO:0070849	response to epidermal growth factor	ISO
GO:0071260	cellular response to mechanical stimulus	IEA
GO:0071276	cellular response to cadmium ion	ISO
GO:0071310	cellular response to organic substance	IBA
GO:0071356	cellular response to tumor necrosis factor	IGI
GO:0072584	caveolin-mediated endocytosis	TAS
GO:0090170	regulation of Golgi inheritance	TAS
GO:1903351	cellular response to dopamine	ISO
GO:1904355	positive regulation of telomere capping	ISO
GO:1904417	positive regulation of xenophagy	IGI
GO:1905050	positive regulation of metallopeptidase activity	IMP
GO:2000641	regulation of early endosome to late endosome transport	TAS
GO:2000657	negative regulation of apolipoprotein binding	IMP

GO:Cellular Component

GO ID	GO Term	Evidence
GO:0005623	cell	IEA
GO:0005634	nucleus	ISO
GO:0005634	nucleus	IDA
GO:0005634	nucleus	TAS
GO:0005634	nucleus	IBA
GO:0005635	nuclear envelope	ISO
GO:0005654	nucleoplasm	ISO
GO:0005654	nucleoplasm	TAS
GO:0005737	cytoplasm	ISO
GO:0005737	cytoplasm	IDA
GO:0005737	cytoplasm	IBA
GO:0005739	mitochondrion	TAS
GO:0005769	early endosome	TAS
GO:0005770	late endosome	TAS
GO:0005794	Golgi apparatus	TAS
GO:0005829	cytosol	ISO
GO:0005829	cytosol	TAS
GO:0005829	cytosol	IDA
GO:0005856	cytoskeleton	TAS
GO:0005886	plasma membrane	ISS
GO:0005886	plasma membrane	ISO
GO:0005901	caveola	ISS
GO:0005901	caveola	ISO
GO:0005901	caveola	TAS
GO:0005925	focal adhesion	TAS
GO:0031143	pseudopodium	IDA
GO:0032991	protein-containing complex	ISO

Reactome Pathway

Reactome ID	Reactome Term	Evidence
R-MMU-109582	Hemostasis	IEA
R-MMU-110056	MAPK3 (ERK1) activation	IEA
R-MMU-112409	RAF-independent MAPK1/3 activation	IEA
R-MMU-1169408	ISG15 antiviral mechanism	IEA
R-MMU-1169410	Antiviral mechanism by IFN-stimulated genes	IEA
R-MMU-1257604	PIP3 activates AKT signaling	IEA
R-MMU-1266738	Developmental Biology	IEA
R-MMU-1280215	Cytokine Signaling in Immune system	IEA
R-MMU-1295596	Spry regulation of FGF signaling	IEA
R-MMU-162582	Signal Transduction	IEA
R-MMU-162658	Golgi Cisternae Pericentriolar Stack Reorganization	IEA
R-MMU-1640170	Cell Cycle	IEA
R-MMU-166016	Toll Like Receptor 4 (TLR4) Cascade	IEA
R-MMU-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane	IEA
R-MMU-166166	MyD88-independent TLR4 cascade	IEA
R-MMU-166520	Signaling by NTRKs	IEA
R-MMU-168138	Toll Like Receptor 9 (TLR9) Cascade	IEA
R-MMU-168142	Toll Like Receptor 10 (TLR10) Cascade	IEA
R-MMU-168164	Toll Like Receptor 3 (TLR3) Cascade	IEA
R-MMU-168176	Toll Like Receptor 5 (TLR5) Cascade	IEA
R-MMU-168179	Toll Like Receptor TLR1:TLR2 Cascade	IEA
R-MMU-168181	Toll Like Receptor 7/8 (TLR7/8) Cascade	IEA
R-MMU-168188	Toll Like Receptor TLR6:TLR2 Cascade	IEA
R-MMU-168249	Innate Immune System	IEA
R-MMU-168256	Immune System	IEA
R-MMU-168898	Toll-like Receptor Cascades	IEA
R-MMU-169893	Prolonged ERK activation events	IEA
R-MMU-170968	Frs2-mediated activation	IEA
R-MMU-181438	Toll Like Receptor 2 (TLR2) Cascade	IEA
R-MMU-187037	Signaling by NTRK1 (TRKA)	IEA
R-MMU-187687	Signalling to ERKs	IEA
R-MMU-190236	Signaling by FGFR	IEA
R-MMU-194315	Signaling by Rho GTPases	IEA
R-MMU-195258	RHO GTPase Effectors	IEA
R-MMU-198725	Nuclear Events (kinase and transcription factor activation)	IEA
R-MMU-198753	ERK/MAPK targets	IEA
R-MMU-199418	Negative regulation of the PI3K/AKT network	IEA
R-MMU-202670	ERKs are inactivated	IEA
R-MMU-2029480	Fcgamma receptor (FCGR) dependent phagocytosis	IEA
R-MMU-2029482	Regulation of actin dynamics for phagocytic cup formation	IEA
R-MMU-2262752	Cellular responses to stress	IEA
R-MMU-2454202	Fc epsilon receptor (FCERI) signaling	IEA
R-MMU-2559580	Oxidative Stress Induced Senescence	IEA
R-MMU-2559582	Senescence-Associated Secretory Phenotype (SASP)	IEA
R-MMU-2559583	Cellular Senescence	IEA
R-MMU-2559585	Oncogene Induced Senescence	IEA
R-MMU-2871796	FCERI mediated MAPK activation	IEA
R-MMU-3371453	Regulation of HSF1-mediated heat shock response	IEA
R-MMU-3371556	Cellular response to heat stress	IEA
R-MMU-372790	Signaling by GPCR	IEA
R-MMU-373760	L1CAM interactions	IEA
R-MMU-375165	NCAM signaling for neurite out-growth	IEA
R-MMU-388396	GPCR downstream signalling	IEA
R-MMU-416476	G alpha (q) signalling events	IEA
R-MMU-422475	Axon guidance	IEA
R-MMU-445144	Signal transduction by L1	IEA
R-MMU-448424	Interleukin-17 signaling	IEA
R-MMU-449147	Signaling by Interleukins	IEA
R-MMU-450282	MAPK targets/ Nuclear events mediated by MAP kinases	IEA
R-MMU-450294	MAP kinase activation	IEA
R-MMU-450341	Activation of the AP-1 family of transcription factors	IEA
R-MMU-456926	Thrombin signalling through proteinase activated receptors (PARs)	IEA
R-MMU-5654726	Negative regulation of FGFR1 signaling	IEA
R-MMU-5654727	Negative regulation of FGFR2 signaling	IEA
R-MMU-5654732	Negative regulation of FGFR3 signaling	IEA
R-MMU-5654733	Negative regulation of FGFR4 signaling	IEA
R-MMU-5654736	Signaling by FGFR1	IEA
R-MMU-5654738	Signaling by FGFR2	IEA
R-MMU-5654741	Signaling by FGFR3	IEA
R-MMU-5654743	Signaling by FGFR4	IEA
R-MMU-5663213	RHO GTPases Activate WASPs and WAVEs	IEA
R-MMU-5668599	RHO GTPases Activate NADPH Oxidases	IEA
R-MMU-5673001	RAF/MAP kinase cascade	IEA
R-MMU-5674135	MAP2K and MAPK activation	IEA
R-MMU-5674499	Negative feedback regulation of MAPK pathway	IEA
R-MMU-5675221	Negative regulation of MAPK pathway	IEA
R-MMU-5683057	MAPK family signaling cascades	IEA
R-MMU-5684996	MAPK1/MAPK3 signaling	IEA
R-MMU-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	IEA
R-MMU-68875	Mitotic Prophase	IEA
R-MMU-68886	M Phase	IEA
R-MMU-69278	Cell Cycle, Mitotic	IEA
R-MMU-73728	RNA Polymerase I Promoter Opening	IEA
R-MMU-73854	RNA Polymerase I Promoter Clearance	IEA
R-MMU-73864	RNA Polymerase I Transcription	IEA
R-MMU-74160	Gene expression (Transcription)	IEA
R-MMU-74749	Signal attenuation	IEA
R-MMU-74751	Insulin receptor signalling cascade	IEA
R-MMU-74752	Signaling by Insulin receptor	IEA
R-MMU-76002	Platelet activation, signaling and aggregation	IEA
R-MMU-881907	Gastrin-CREB signalling pathway via PKC and MAPK	IEA
R-MMU-8939211	ESR-mediated signaling	IEA
R-MMU-8953897	Cellular responses to external stimuli	IEA
R-MMU-9006925	Intracellular signaling by second messengers	IEA
R-MMU-9006931	Signaling by Nuclear Receptors	IEA
R-MMU-9006934	Signaling by Receptor Tyrosine Kinases	IEA
R-MMU-913531	Interferon Signaling	IEA
R-MMU-937061	TRIF(TICAM1)-mediated TLR4 signaling	IEA
R-MMU-9607240	FLT3 Signaling	IEA
R-MMU-975138	TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	IEA
R-MMU-975155	MyD88 dependent cascade initiated on endosome	IEA
R-MMU-975871	MyD88 cascade initiated on plasma membrane	IEA
R-MMU-982772	Growth hormone receptor signaling	IEA

Functional annotations

Keywords

Keyword ID	Keyword Term
KW-0007	Acetylation
KW-0053	Apoptosis
KW-0067	ATP-binding
KW-0131	Cell cycle
KW-0963	Cytoplasm
KW-0903	Direct protein sequencing
KW-0418	Kinase
KW-0472	Membrane
KW-0547	Nucleotide-binding
KW-0539	Nucleus
KW-0597	Phosphoprotein
KW-1185	Reference proteome
KW-0723	Serine/threonine-protein kinase
KW-0808	Transferase

Interpro

InterPro ID	InterPro Term
IPR011009	Kinase-like_dom_sf
IPR003527	MAP_kinase_CS
IPR008349	MAPK_ERK1/2
IPR000719	Prot_kinase_dom
IPR017441	Protein_kinase_ATP_BS
IPR008271	Ser/Thr_kinase_AS

PROSITE

PROSITE ID	PROSITE Term
PS01351	MAPK
PS00107	PROTEIN_KINASE_ATP
PS50011	PROTEIN_KINASE_DOM
PS00108	PROTEIN_KINASE_ST

Pfam

Pfam ID	Pfam Term
PF00069	Pkinase

Gene: Mapk3

Basic information

Gene expression information

Gene expression during embryonic days (E11.5~E18.5) ~ adult days (Ps) in the lip and palate tissues. (X-axis: days, Y-axis: tissues)

Protein structural annotations

3D structure in PDB database

There is no related protein structure for this gene.

Protein disorder information

Orthologous information

Other genetic variants/mutations

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO:Biological Process

GO:Cellular Component

Reactome Pathway

Functional annotations

Keywords

Interpro

PROSITE

Pfam

Protein-protein interaction

Protein-miRNA interaction