UniProtKB - P39745 (MPK1_CAEEL)
Protein
Mitogen-activated protein kinase mpk-1
Gene
mpk-1
Organism
Caenorhabditis elegans
Status
Functioni
Function in let-60 Ras signaling pathway; acts downstream of lin-45 raf kinase, but before the lin-1 gene product in controlling vulval cell differentiation (PubMed:8299935, PubMed:8299936). Plays a negative role in proximal germline proliferation in the mitotic zone (PubMed:16319922). Required for progression of developing oocytes through the pachytene stage (PubMed:16319922, PubMed:19826475, PubMed:21901106). In oocytes, inhibits the activity of the chloride channel clh-3, likely by activating gck-3 (PubMed:21160027). Plays a role in response to M.nematophilum-mediated bacterial infection by promoting tail swelling and preventing constipation (PubMed:15268855). Involved in fluid homeostasis (PubMed:11689700). In addition, involved in the up-regulation of lysozyme ilys-3 expression in the intestine in responses to M.nematophilum-mediated bacterial infection (PubMed:27525822). By phosphorylating transcription factor skn-1 (isoform c) may play a role in increasing life span downstream of lin-45, let-60 and mek-2 (PubMed:20624915). By up-regulating cep-1 and down-regulating gld-1 expression in the late pachytene stage, plays a role in germline apoptosis in response to DNA damage (PubMed:21901106). Regulates egl-1 expression in response to DNA damage, probably upstream of cep-1 (PubMed:21901106).10 Publications
Suppresses germline tumor formation by preventing the dedifferentiation of secondary spermatocytes probably upstream of rskn-1.1 Publication
Catalytic activityi
Cofactori
Mg2+1 Publication
Activity regulationi
Activated by dual phosphorylation at Thr-256 and Tyr-258 (PubMed:20624915). May be inactivated by lip-1-mediated dephosphorylation (PubMed:21901106).2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 125 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 220 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 102 – 110 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- MAP kinase activity Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- protein serine/threonine kinase activity Source: WormBase
- protein serine kinase activity Source: RHEA
- protein threonine kinase activity Source: RHEA
GO - Biological processi
- cell surface receptor signaling pathway Source: GO_Central
- defense response to Gram-positive bacterium Source: UniProtKB
- determination of adult lifespan Source: UniProtKB
- intracellular signal transduction Source: GO_Central
- MAPK cascade Source: UniProtKB
- meiotic cell cycle Source: UniProtKB-KW
- oocyte maturation Source: WormBase
- peptidyl-serine phosphorylation Source: WormBase
- positive regulation of gene expression Source: UniProtKB
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
- protein phosphorylation Source: WormBase
- Ras protein signal transduction Source: WormBase
- regulation of gene expression Source: GO_Central
- vulval development Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Cell cycle, Differentiation, Meiosis, Oogenesis |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.24, 1045 |
Reactomei | R-CEL-110056, MAPK3 (ERK1) activation R-CEL-112409, RAF-independent MAPK1/3 activation R-CEL-112411, MAPK1 (ERK2) activation R-CEL-162658, Golgi Cisternae Pericentriolar Stack Reorganization R-CEL-170968, Frs2-mediated activation R-CEL-198753, ERK/MAPK targets R-CEL-202670, ERKs are inactivated R-CEL-2029482, Regulation of actin dynamics for phagocytic cup formation R-CEL-2559580, Oxidative Stress Induced Senescence R-CEL-2559582, Senescence-Associated Secretory Phenotype (SASP) R-CEL-2871796, FCERI mediated MAPK activation R-CEL-3371453, Regulation of HSF1-mediated heat shock response R-CEL-375165, NCAM signaling for neurite out-growth R-CEL-437239, Recycling pathway of L1 R-CEL-445144, Signal transduction by L1 R-CEL-450341, Activation of the AP-1 family of transcription factors R-CEL-456926, Thrombin signalling through proteinase activated receptors (PARs) R-CEL-5654726, Negative regulation of FGFR1 signaling R-CEL-5654733, Negative regulation of FGFR4 signaling R-CEL-5663213, RHO GTPases Activate WASPs and WAVEs R-CEL-5673001, RAF/MAP kinase cascade R-CEL-5674135, MAP2K and MAPK activation R-CEL-5674499, Negative feedback regulation of MAPK pathway R-CEL-5675221, Negative regulation of MAPK pathway R-CEL-6798695, Neutrophil degranulation R-CEL-881907, Gastrin-CREB signalling pathway via PKC and MAPK R-CEL-9634635, Estrogen-stimulated signaling through PRKCZ R-CEL-9634638, Estrogen-dependent nuclear events downstream of ESR-membrane signaling |
SignaLinki | P39745 |
Names & Taxonomyi
Protein namesi | Recommended name: Mitogen-activated protein kinase mpk-1 (EC:2.7.11.241 Publication)Alternative name(s): MAP kinase sur-1 |
Gene namesi | Name:mpk-1 Synonyms:sur-1 ORF Names:F43C1.2 |
Organismi | Caenorhabditis elegans |
Taxonomic identifieri | 6239 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Ecdysozoa › Nematoda › Chromadorea › Rhabditida › Rhabditina › Rhabditomorpha › Rhabditoidea › Rhabditidae › Peloderinae › Caenorhabditis |
Proteomesi |
|
Organism-specific databases
WormBasei | F43C1.2a ; CE01583 ; WBGene00003401 ; mpk-1 F43C1.2b ; CE24971 ; WBGene00003401 ; mpk-1 |
Subcellular locationi
Pathology & Biotechi
Disruption phenotypei
RNAi-mediated knockdown causes an increase in the number of germline cells in the mitotic zone, a lack of transition zone and a defect in pachytene progression resulting in a proximal gonad devoid of nuclei (PubMed:19826475, PubMed:16319922). Causes sterility (PubMed:19826475). RNAi-mediated knockdown in adults decreases lifespan (PubMed:20624915). RNAi-mediated knockdown of isoform b in lip-1 and puf-8 double mutant causes a decrease in number of germline tumors (PubMed:22820175). RNAi-mediated knockdown causes a reduction in intestinal ilys-3 expression in response to M.nematophilum-mediated bacterial infection (PubMed:27525822).5 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 106 | A → V in ku1; loss of function and ATP-binding. Lack of tail swelling, severe constipation and loss of ilys-3 expression up-regulation following M.nematophilium infection. 3 Publications | 1 | |
Mutagenesisi | 216 | V → G in ga111; at the restrictive temperature of 25 degrees Celsius, causes an increase in gld-1 expression and a loss of cep-1 expression in late pachytene germ cells. Loss of egl-1 mRNA expression in response to gamma irradiation. 70 percent of mutants have germ cells arrested at the pachytene stage. Partial phosphorylation at Thr-256 and Tyr-258. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000186306 | 1 – 444 | Mitogen-activated protein kinase mpk-1Add BLAST | 444 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 256 | Phosphothreonine4 Publications | 1 | |
Modified residuei | 258 | Phosphotyrosine4 Publications | 1 |
Post-translational modificationi
Isoform a is phosphorylated at the pachytene stage during oogenesis and is negatively regulated by gck-1. Isoform b is phosphorylated in proximal oocytes.1 Publication
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | P39745 |
PaxDbi | P39745 |
PeptideAtlasi | P39745 |
PTM databases
iPTMneti | P39745 |
Expressioni
Tissue specificityi
Expressed in cells lining the rectum (PubMed:15268855, PubMed:20624915). Isoform a is expressed in nervous system, body wall muscles and posterior intestine (PubMed:20624915). Isoform b expression may be restricted to germline (PubMed:22820175).3 Publications
Developmental stagei
The phosphorylated form is present in early to mid pachytene, is absent in late pachytene and diplotene/diakinesis stages and is again present in oocytes when they reach the spermatheca (PubMed:19826475, PubMed:21901106, PubMed:22820175). The phosphorylated form is also present in sperm (PubMed:22820175).3 Publications
Gene expression databases
Bgeei | WBGene00003401, Expressed in germ line (C elegans) and 6 other tissues |
Interactioni
Subunit structurei
Isoform a interacts with gck-1 (via N-terminus).
1 PublicationBinary interactionsi
P39745
With | #Exp. | IntAct |
---|---|---|
gla-3 [O02289] | 3 | EBI-321013,EBI-317795 |
Protein-protein interaction databases
BioGRIDi | 40782, 96 interactors |
DIPi | DIP-26227N |
IntActi | P39745, 52 interactors |
MINTi | P39745 |
STRINGi | 6239.F43C1.2b |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 96 – 384 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 289 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 256 – 258 | TXY | 3 |
Domaini
The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Sequence similaritiesi
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.Curated
Phylogenomic databases
eggNOGi | KOG0660, Eukaryota |
GeneTreei | ENSGT00940000156771 |
InParanoidi | P39745 |
OMAi | DIYIVQC |
OrthoDBi | 741207at2759 |
PhylomeDBi | P39745 |
Family and domain databases
InterProi | View protein in InterPro 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 |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
PRINTSi | PR01770, ERK1ERK2MAPK |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS01351, MAPK, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform b (identifier: P39745-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MPTWIPNNLC AQPTTRNAKP PSNGHPQATQ QQSAPGSLAY RNSSNIPNGA
60 70 80 90 100
TNHVRQQKWQ YTRSGHRKMA DGEAVISTVN NVEEVHGQLF EVAPRYVNLS
110 120 130 140 150
YIGEGAYGMV ASALDTITRD RVAIKKISPF EHQTFCQRTL REIKILNRFK
160 170 180 190 200
HENIINIQEI IRSETVDSLK DIYIVQCLME TDLYKLLKTQ KLSNDHVCYF
210 220 230 240 250
LYQILRGLKY IHSANVLHRD LKPSNLLLNT TCDLKICDFG LARVTDPQTD
260 270 280 290 300
HTGFLTEYVA TRWYRAPEIM LNSKGYTKSI DVWSVGCILA EMLSNRPLFP
310 320 330 340 350
GKHYLDQLNL ILAVVGSPSN ADLQCIINDK ARSYLISLPH KPKQPWARLY
360 370 380 390 400
PGADPRALDL LDKMLTFNPH NRIDIEQALA HPYLEQYYDP GDEPVCEEPF
410 420 430 440
TLEMEFDDLP KEKLKELIWE EAEAHHRRME AEAAARNNGG QNPV
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 9 – 10 | LC → FF in AAA18956 (PubMed:8299936).Curated | 2 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_004848 | 1 – 68 | Missing in isoform a. 1 PublicationAdd BLAST | 68 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U03879 mRNA Translation: AAA18956.1 U27124 mRNA Translation: AAA73482.1 Z46937 Genomic DNA Translation: CAA87057.1 Z46937 Genomic DNA Translation: CAB60996.1 |
PIRi | A36977 A36978 |
RefSeqi | NP_001022583.1, NM_001027412.3 NP_001022584.1, NM_001027413.2 [P39745-1] |
Genome annotation databases
EnsemblMetazoai | F43C1.2a.1; F43C1.2a.1; WBGene00003401 [P39745-2] F43C1.2b.1; F43C1.2b.1; WBGene00003401 [P39745-1] |
GeneIDi | 175545 |
KEGGi | cel:CELE_F43C1.2 |
UCSCi | F43C1.2a.1, c. elegans [P39745-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U03879 mRNA Translation: AAA18956.1 U27124 mRNA Translation: AAA73482.1 Z46937 Genomic DNA Translation: CAA87057.1 Z46937 Genomic DNA Translation: CAB60996.1 |
PIRi | A36977 A36978 |
RefSeqi | NP_001022583.1, NM_001027412.3 NP_001022584.1, NM_001027413.2 [P39745-1] |
3D structure databases
SMRi | P39745 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 40782, 96 interactors |
DIPi | DIP-26227N |
IntActi | P39745, 52 interactors |
MINTi | P39745 |
STRINGi | 6239.F43C1.2b |
PTM databases
iPTMneti | P39745 |
Proteomic databases
EPDi | P39745 |
PaxDbi | P39745 |
PeptideAtlasi | P39745 |
Genome annotation databases
EnsemblMetazoai | F43C1.2a.1; F43C1.2a.1; WBGene00003401 [P39745-2] F43C1.2b.1; F43C1.2b.1; WBGene00003401 [P39745-1] |
GeneIDi | 175545 |
KEGGi | cel:CELE_F43C1.2 |
UCSCi | F43C1.2a.1, c. elegans [P39745-1] |
Organism-specific databases
CTDi | 175545 |
WormBasei | F43C1.2a ; CE01583 ; WBGene00003401 ; mpk-1 F43C1.2b ; CE24971 ; WBGene00003401 ; mpk-1 |
Phylogenomic databases
eggNOGi | KOG0660, Eukaryota |
GeneTreei | ENSGT00940000156771 |
InParanoidi | P39745 |
OMAi | DIYIVQC |
OrthoDBi | 741207at2759 |
PhylomeDBi | P39745 |
Enzyme and pathway databases
BRENDAi | 2.7.11.24, 1045 |
Reactomei | R-CEL-110056, MAPK3 (ERK1) activation R-CEL-112409, RAF-independent MAPK1/3 activation R-CEL-112411, MAPK1 (ERK2) activation R-CEL-162658, Golgi Cisternae Pericentriolar Stack Reorganization R-CEL-170968, Frs2-mediated activation R-CEL-198753, ERK/MAPK targets R-CEL-202670, ERKs are inactivated R-CEL-2029482, Regulation of actin dynamics for phagocytic cup formation R-CEL-2559580, Oxidative Stress Induced Senescence R-CEL-2559582, Senescence-Associated Secretory Phenotype (SASP) R-CEL-2871796, FCERI mediated MAPK activation R-CEL-3371453, Regulation of HSF1-mediated heat shock response R-CEL-375165, NCAM signaling for neurite out-growth R-CEL-437239, Recycling pathway of L1 R-CEL-445144, Signal transduction by L1 R-CEL-450341, Activation of the AP-1 family of transcription factors R-CEL-456926, Thrombin signalling through proteinase activated receptors (PARs) R-CEL-5654726, Negative regulation of FGFR1 signaling R-CEL-5654733, Negative regulation of FGFR4 signaling R-CEL-5663213, RHO GTPases Activate WASPs and WAVEs R-CEL-5673001, RAF/MAP kinase cascade R-CEL-5674135, MAP2K and MAPK activation R-CEL-5674499, Negative feedback regulation of MAPK pathway R-CEL-5675221, Negative regulation of MAPK pathway R-CEL-6798695, Neutrophil degranulation R-CEL-881907, Gastrin-CREB signalling pathway via PKC and MAPK R-CEL-9634635, Estrogen-stimulated signaling through PRKCZ R-CEL-9634638, Estrogen-dependent nuclear events downstream of ESR-membrane signaling |
SignaLinki | P39745 |
Miscellaneous databases
PROi | PR:P39745 |
Gene expression databases
Bgeei | WBGene00003401, Expressed in germ line (C elegans) and 6 other tissues |
Family and domain databases
InterProi | View protein in InterPro 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 |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
PRINTSi | PR01770, ERK1ERK2MAPK |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS01351, MAPK, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MPK1_CAEEL | |
Accessioni | P39745Primary (citable) accession number: P39745 Secondary accession number(s): Q9U3F3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1995 |
Last sequence update: | November 25, 2002 | |
Last modified: | April 7, 2021 | |
This is version 186 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Caenorhabditis annotation project |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Caenorhabditis elegans
Caenorhabditis elegans: entries, gene names and cross-references to WormBase - SIMILARITY comments
Index of protein domains and families