Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Mitogen-activated protein kinase mpk-1

Gene

mpk-1

Organism
Caenorhabditis elegans
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 responses to M.nematophilum-mediated bacterial infection by promoting tail swelling and preventing constipation (PubMed:15268855). Involved in fluid homeostasis (PubMed:11689700). 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).9 Publications
Isoform b: Suppresses germline tumor formation by preventing the dedifferentiation of secondary spermatocytes probably upstream of rskn-1.1 Publication

Catalytic activityi

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

Cofactori

Mg2+1 Publication

Enzyme 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei125 – 1251ATPPROSITE-ProRule annotation
Active sitei220 – 2201Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi102 – 1109ATPPROSITE-ProRule annotation

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

GO - Biological processi

  • meiotic cell cycle Source: UniProtKB-KW
  • oocyte maturation Source: WormBase
  • peptidyl-serine phosphorylation Source: WormBase
  • Ras protein signal transduction Source: WormBase
  • vulval development Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, Differentiation, Meiosis, Oogenesis

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.24. 1045.
ReactomeiR-CEL-112409. RAF-independent MAPK1/3 activation.
R-CEL-112411. MAPK1 (ERK2) 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-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-CEL-375165. NCAM signaling for neurite out-growth.
R-CEL-442742. CREB phosphorylation through the activation of Ras.
R-CEL-444257. RSK activation.
R-CEL-445144. Signal transduction by L1.
R-CEL-456926. Thrombin signalling through proteinase activated receptors (PARs).
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-881907. Gastrin-CREB signalling pathway via PKC and MAPK.
SignaLinkiP39745.

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
OrganismiCaenorhabditis elegans
Taxonomic identifieri6239 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
Proteomesi
  • UP000001940 Componenti: Chromosome III

Organism-specific databases

WormBaseiF43C1.2a; CE01583; WBGene00003401; mpk-1.
F43C1.2b; CE24971; WBGene00003401; mpk-1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: WormBase
  • nucleus Source: WormBase
Complete GO annotation...

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).4 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi106 – 1061A → V in ku1; loss of function and ATP-binding. Lack of tail swelling and severe constipation following M.nematophilium infection. 2 Publications
Mutagenesisi216 – 2161V → 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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 444444Mitogen-activated protein kinase mpk-1PRO_0000186306Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei256 – 2561Phosphothreonine4 Publications
Modified residuei258 – 2581Phosphotyrosine4 Publications

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

Phosphoprotein

Proteomic databases

EPDiP39745.
PaxDbiP39745.
PRIDEiP39745.

PTM databases

iPTMnetiP39745.

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

Interactioni

Subunit structurei

Isoform a interacts with gck-1 (via N-terminus).1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
gla-3O022893EBI-321013,EBI-317795

Protein-protein interaction databases

BioGridi40782. 67 interactions.
DIPiDIP-26227N.
IntActiP39745. 51 interactions.
MINTiMINT-114245.
STRINGi6239.F43C1.2b.

Structurei

3D structure databases

ProteinModelPortaliP39745.
SMRiP39745. Positions 90-421.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini96 – 384289Protein kinasePROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi256 – 2583TXY

Domaini

The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074298.
HOGENOMiHOG000233024.
InParanoidiP39745.
KOiK04371.
OMAiKQQFAAR.
OrthoDBiEOG7M3J0K.
PhylomeDBiP39745.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008349. MAPK_ERK1/2.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01770. ERK1ERK2MAPK.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform b (identifier: P39745-1) [UniParc]FASTAAdd to basket

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
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
Length:444
Mass (Da):50,663
Last modified:November 25, 2002 - v2
Checksum:i11BA27D17641980D
GO
Isoform a (identifier: P39745-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-68: Missing.

Show »
Length:376
Mass (Da):43,102
Checksum:i9974B791EFE16838
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti9 – 102LC → FF in AAA18956 (PubMed:8299936).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 6868Missing in isoform a. 1 PublicationVSP_004848Add
BLAST

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.
PIRiA36977.
A36978.
RefSeqiNP_001022583.1. NM_001027412.3. [P39745-2]
NP_001022584.1. NM_001027413.2. [P39745-1]
UniGeneiCel.34032.

Genome annotation databases

EnsemblMetazoaiF43C1.2b; F43C1.2b; WBGene00003401. [P39745-1]
GeneIDi175545.
KEGGicel:CELE_F43C1.2.
UCSCiF43C1.2a.1. c. elegans. [P39745-1]

Keywords - Coding sequence diversityi

Alternative splicing

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.
PIRiA36977.
A36978.
RefSeqiNP_001022583.1. NM_001027412.3. [P39745-2]
NP_001022584.1. NM_001027413.2. [P39745-1]
UniGeneiCel.34032.

3D structure databases

ProteinModelPortaliP39745.
SMRiP39745. Positions 90-421.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi40782. 67 interactions.
DIPiDIP-26227N.
IntActiP39745. 51 interactions.
MINTiMINT-114245.
STRINGi6239.F43C1.2b.

PTM databases

iPTMnetiP39745.

Proteomic databases

EPDiP39745.
PaxDbiP39745.
PRIDEiP39745.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiF43C1.2b; F43C1.2b; WBGene00003401. [P39745-1]
GeneIDi175545.
KEGGicel:CELE_F43C1.2.
UCSCiF43C1.2a.1. c. elegans. [P39745-1]

Organism-specific databases

CTDi175545.
WormBaseiF43C1.2a; CE01583; WBGene00003401; mpk-1.
F43C1.2b; CE24971; WBGene00003401; mpk-1.

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074298.
HOGENOMiHOG000233024.
InParanoidiP39745.
KOiK04371.
OMAiKQQFAAR.
OrthoDBiEOG7M3J0K.
PhylomeDBiP39745.

Enzyme and pathway databases

BRENDAi2.7.11.24. 1045.
ReactomeiR-CEL-112409. RAF-independent MAPK1/3 activation.
R-CEL-112411. MAPK1 (ERK2) 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-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-CEL-375165. NCAM signaling for neurite out-growth.
R-CEL-442742. CREB phosphorylation through the activation of Ras.
R-CEL-444257. RSK activation.
R-CEL-445144. Signal transduction by L1.
R-CEL-456926. Thrombin signalling through proteinase activated receptors (PARs).
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-881907. Gastrin-CREB signalling pathway via PKC and MAPK.
SignaLinkiP39745.

Miscellaneous databases

PROiP39745.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008349. MAPK_ERK1/2.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01770. ERK1ERK2MAPK.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Suppression of activated Let-60 ras protein defines a role of Caenorhabditis elegans Sur-1 MAP kinase in vulval differentiation."
    Wu Y., Han M.
    Genes Dev. 8:147-159(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), MUTAGENESIS OF ALA-106.
    Strain: Bristol N2.
  2. "A MAP kinase homolog, mpk-1, is involved in ras-mediated induction of vulval cell fates in Caenorhabditis elegans."
    Lackner M.R., Kornfeld K., Miller L.M., Horvitz H.R., Kim S.K.
    Genes Dev. 8:160-173(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
    Strain: Bristol N2.
  3. "Genome sequence of the nematode C. elegans: a platform for investigating biology."
    The C. elegans sequencing consortium
    Science 282:2012-2018(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Bristol N2.
  4. "The Caenorhabditis elegans EGL-15 signaling pathway implicates a DOS-like multisubstrate adaptor protein in fibroblast growth factor signal transduction."
    Schutzman J.L., Borland C.Z., Newman J.C., Robinson M.K., Kokel M., Stern M.J.
    Mol. Cell. Biol. 21:8104-8116(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
    Strain: Bristol N2.
  5. "The ERK MAP kinase cascade mediates tail swelling and a protective response to rectal infection in C. elegans."
    Nicholas H.R., Hodgkin J.
    Curr. Biol. 14:1256-1261(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF ALA-106.
  6. "LIP-1 phosphatase controls the extent of germline proliferation in Caenorhabditis elegans."
    Lee M.H., Hook B., Lamont L.B., Wickens M., Kimble J.
    EMBO J. 25:88-96(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  7. "The germinal center kinase GCK-1 is a negative regulator of MAP kinase activation and apoptosis in the C. elegans germline."
    Schouest K.R., Kurasawa Y., Furuta T., Hisamoto N., Matsumoto K., Schumacher J.M.
    PLoS ONE 4:E7450-E7450(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH GCK-1, DEVELOPMENTAL STAGE, PHOSPHORYLATION AT THR-256 AND TYR-258, DISRUPTION PHENOTYPE.
  8. "The ERK-MAPK pathway regulates longevity through SKN-1 and insulin-like signaling in Caenorhabditis elegans."
    Okuyama T., Inoue H., Ookuma S., Satoh T., Kano K., Honjoh S., Hisamoto N., Matsumoto K., Nishida E.
    J. Biol. Chem. 285:30274-30281(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ENZYME REGULATION, TISSUE SPECIFICITY, PHOSPHORYLATION AT THR-256 AND TYR-258, DISRUPTION PHENOTYPE.
  9. "C. elegans STK39/SPAK ortholog-mediated inhibition of ClC anion channel activity is regulated by WNK-independent ERK kinase signaling."
    Falin R.A., Miyazaki H., Strange K.
    Am. J. Physiol. 300:C624-635(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "Regulation of Caenorhabditis elegans p53/CEP-1-dependent germ cell apoptosis by Ras/MAPK signaling."
    Rutkowski R., Dickinson R., Stewart G., Craig A., Schimpl M., Keyse S.M., Gartner A.
    PLoS Genet. 7:E1002238-E1002238(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ENZYME REGULATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, PHOSPHORYLATION AT THR-256 AND TYR-258, MUTAGENESIS OF VAL-216.
  11. "The Ras-ERK MAPK regulatory network controls dedifferentiation in Caenorhabditis elegans germline."
    Cha D.S., Datla U.S., Hollis S.E., Kimble J., Lee M.H.
    Biochim. Biophys. Acta 1823:1847-1855(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, PHOSPHORYLATION AT THR-256 AND TYR-258, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiMPK1_CAEEL
AccessioniPrimary (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: July 6, 2016
This is version 151 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Caenorhabditis elegans
    Caenorhabditis elegans: entries, gene names and cross-references to WormBase
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.