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Protein

Mitogen-activated protein kinase mpk-1

Gene

mpk-1

Organism
Caenorhabditis elegans
Status
Reviewed-Annotation score: -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 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
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)DescriptionActionsGraphical viewLength
Binding sitei125ATPPROSITE-ProRule annotation1
Active sitei220Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi102 – 110ATPPROSITE-ProRule annotation9

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

  • cell surface receptor signaling pathway Source: GO_Central
  • cellular response to organic substance Source: GO_Central
  • defense response to Gram-positive bacterium Source: UniProtKB
  • 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
  • protein phosphorylation Source: WormBase
  • Ras protein signal transduction Source: WormBase
  • regulation of gene expression Source: GO_Central
  • vulval development Source: UniProtKB

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle, Differentiation, Meiosis, Oogenesis
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.24 1045
ReactomeiR-CEL-110056 MAPK3 (ERK1) activation
R-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-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-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-5654726 Negative regulation of FGFR1 signaling
R-CEL-5654727 Negative regulation of FGFR2 signaling
R-CEL-5654732 Negative regulation of FGFR3 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
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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi106A → 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 Publications1
Mutagenesisi216V → 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 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001863061 – 444Mitogen-activated protein kinase mpk-1Add BLAST444

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei256Phosphothreonine4 Publications1
Modified residuei258Phosphotyrosine4 Publications1

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
PeptideAtlasiP39745

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

Gene expression databases

BgeeiWBGene00003401

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 interactors
DIPiDIP-26227N
IntActiP39745, 52 interactors
MINTiP39745
STRINGi6239.F43C1.2b

Structurei

3D structure databases

ProteinModelPortaliP39745
SMRiP39745
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini96 – 384Protein kinasePROSITE-ProRule annotationAdd BLAST289

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi256 – 258TXY3

Domaini

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0660 Eukaryota
ENOG410XNY0 LUCA
GeneTreeiENSGT00910000144035
HOGENOMiHOG000233024
InParanoidiP39745
KOiK04371
OMAiMEKCLTF
OrthoDBiEOG091G08QL
PhylomeDBiP39745

Family and domain databases

InterProiView 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
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PRINTSiPR01770 ERK1ERK2MAPK
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView 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

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)DescriptionActionsGraphical viewLength
Sequence conflicti9 – 10LC → FF in AAA18956 (PubMed:8299936).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0048481 – 68Missing in isoform a. 1 PublicationAdd BLAST68

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
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

Similar proteinsi

Entry informationi

Entry nameiMPK1_CAEEL
AccessioniPrimary (citable) accession number: P39745
Secondary accession number(s): Q9U3F3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: November 25, 2002
Last modified: May 23, 2018
This is version 165 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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