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Protein

Raf homolog serine/threonine-protein kinase

Gene

lin-45

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

Functioni

Protein kinase that participates in the induction of vulva and has roles in fertility and viability. Acts downstream of the Ras protein let-60 (PubMed:8483497, PubMed:11861555). Required for progression of developing oocytes through the pachytene stage (PubMed:19826475). Plays a role in responses to M.nematophilum -mediated bacterial infection by promoting tail swelling and preventing constipation (PubMed:15268855). Positively regulates lifespan upstream of mek-2 and mpk-1 (PubMed:20624915).4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Zn2+By similarityNote: Binds 2 Zn2+ ions per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi184 – 1841Zinc 2By similarity
Metal bindingi187 – 1871Zinc 2By similarity
Metal bindingi198 – 1981Zinc 1By similarity
Metal bindingi201 – 2011Zinc 1By similarity
Metal bindingi206 – 2061Zinc 2By similarity
Metal bindingi209 – 2091Zinc 2By similarity
Metal bindingi217 – 2171Zinc 1By similarity
Binding sitei507 – 5071ATPPROSITE-ProRule annotation
Active sitei602 – 6021Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri170 – 21748Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
BLAST
Nucleotide bindingi487 – 4959ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

  • cell fate specification Source: WormBase
  • meiotic cell cycle Source: UniProtKB-KW
  • nematode larval development Source: WormBase
  • oogenesis Source: UniProtKB-KW
  • Ras protein signal transduction Source: WormBase
  • reproduction Source: WormBase
  • vulval development Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Differentiation, Meiosis, Oogenesis

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

ReactomeiR-CEL-2672351. Stimuli-sensing channels.
R-CEL-392517. Rap1 signalling.
R-CEL-430116. GP1b-IX-V activation signalling.
R-CEL-442742. CREB phosphorylation through the activation of Ras.
R-CEL-5621575. CD209 (DC-SIGN) signaling.
R-CEL-5673000. RAF activation.
R-CEL-5674135. MAP2K and MAPK activation.
R-CEL-5674499. Negative feedback regulation of MAPK pathway.
R-CEL-5675221. Negative regulation of MAPK pathway.
SignaLinkiQ07292.

Names & Taxonomyi

Protein namesi
Recommended name:
Raf homolog serine/threonine-protein kinase (EC:2.7.11.1)
Alternative name(s):
Abnormal cell lineage protein 45
Gene namesi
Name:lin-45
Synonyms:raf-1
ORF Names:Y73B6A.5
OrganismiCaenorhabditis elegans
Taxonomic identifieri6239 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
Proteomesi
  • UP000001940 Componenti: Chromosome IV

Organism-specific databases

WormBaseiY73B6A.5a; CE25585; WBGene00003030; lin-45.
Y73B6A.5b; CE31742; WBGene00003030; lin-45.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Disruption phenotypei

RNAi-mediated knockdown causes a defect in pachytene progression resulting in a proximal gonad devoid of nuclei. The phenotype is more severe in gck-1 (km15) mutant (PubMed:19826475). RNAi-mediated knockdown in adults decreases lifespan (PubMed:20624915).2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi92 – 921P → S in n2018; 76% larval lethal, 24% abnormal vulval development. 1 Publication
Mutagenesisi108 – 1081R → W in n1925; no effect. 1 Publication
Mutagenesisi118 – 1181R → W in n2506; 86% larval lethal, 93% abnormal vulval development. 1 Publication
Mutagenesisi645 – 6451S → N in oz178 and oz201; 55% larval lethal, 100% abnormal vulval development. 1 Publication
Mutagenesisi726 – 7261I → F in n1924; 5% larval lethal, no effect on vulval development. 1 Publication
Mutagenesisi754 – 7541S → F in n2520 and n2523; no effect. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 813813Raf homolog serine/threonine-protein kinasePRO_0000086193Add
BLAST

Proteomic databases

EPDiQ07292.
PaxDbiQ07292.
PRIDEiQ07292.

PTM databases

iPTMnetiQ07292.

Expressioni

Gene expression databases

ExpressionAtlasiQ07292. baseline.

Interactioni

Subunit structurei

Interacts with cdf-1 in a zinc-dependent manner which promotes its activity.1 Publication

GO - Molecular functioni

  • Ras GTPase binding Source: WormBase

Protein-protein interaction databases

BioGridi42556. 18 interactions.
IntActiQ07292. 4 interactions.
MINTiMINT-1055674.
STRINGi6239.Y73B6A.5a.2.

Structurei

3D structure databases

ProteinModelPortaliQ07292.
SMRiQ07292. Positions 171-217, 473-792.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini85 – 16177RBDPROSITE-ProRule annotationAdd
BLAST
Domaini481 – 748268Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 phorbol-ester/DAG-type zinc finger.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 RBD (Ras-binding) domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri170 – 21748Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0193. Eukaryota.
ENOG410Y4UP. LUCA.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000252972.
InParanoidiQ07292.
OMAiPYSHINS.
OrthoDBiEOG7F5128.
PhylomeDBiQ07292.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR002219. PE/DAG-bd.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR003116. RBD_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamiPF00130. C1_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF02196. RBD. 1 hit.
[Graphical view]
SMARTiSM00109. C1. 1 hit.
SM00455. RBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50898. RBD. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform a (identifier: Q07292-1) [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
MSRINFKKSS ASTTPTSPHC PSPRLISLPR CASSSIDRKD QASPMASPST
60 70 80 90 100
PLYPKHSDSL HSLSGHHSAG GAGTSDKEPP KFKYKMIMVH LPFDQHSRVE
110 120 130 140 150
VRPGETARDA ISKLLKKRNI TPQLCHVNAS SDPKQESIEL SLTMEEIASR
160 170 180 190 200
LPGNELWVHS EYLNTVSSIK HAIVRRTFIP PKSCDVCNNP IWMMGFRCEF
210 220 230 240 250
CQFKFHQRCS SFAPLYCDLL QSVPKNEDLV KELFGIASQV EGPDRSVAEI
260 270 280 290 300
VLANLAPTSG QSPAATPDSS HPDLTSIKRT GGVKRHPMAV SPQNETSQLS
310 320 330 340 350
PSGPYPRDRS SSAPNINAIN DEATVQHNQR ILDALEAQRL EEESRDKTGS
360 370 380 390 400
LLSTQARHRP HFQSGHILSG ARMNRLHPLV DCTPLGSNSP SSTCSSPPGG
410 420 430 440 450
LIGQPTLGQS PNVSGSTTSS LVAAHLHTLP LTPPQSAPPQ KISPGFFRNR
460 470 480 490 500
SRSPGERLDA QRPRPPQKPH HEDWEILPNE FIIQYKVGSG SFGTVYRGEF
510 520 530 540 550
FGTVAIKKLN VVDPTPSQMA AFKNEVAVLK KTRHLNVLLF MGWVREPEIA
560 570 580 590 600
IITQWCEGSS LYRHIHVQEP RVEFEMGAII DILKQVSLGM NYLHSKNIIH
610 620 630 640 650
RDLKTNNIFL MDDMSTVKIG DFGLATVKTK WTVNGGQQQQ QPTGSILWMA
660 670 680 690 700
PEVIRMQDDN PYTPQSDVYS FGICMYEILS SHLPYSNINN RDQILFMVGR
710 720 730 740 750
GYLRPDRSKI RHDTPKSMLK LYDNCIMFDR NERPVFGEVL ERLRDIILPK
760 770 780 790 800
LTRSQSAPNV LHLDSQYSVM DAVMRSQMLS WSYIPPATAK TPQSAAAAAA
810
ANKKAYYNVY GLI
Length:813
Mass (Da):90,407
Last modified:July 11, 2002 - v2
Checksum:i6376E968D11A9E49
GO
Isoform b (identifier: Q07292-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MSAMAVLYSVCHFHGGWNRRKSAPKSPVTSSQTPSSSSTRRRM
     569-572: EPRV → GDLN
     573-813: Missing.

Note: No experimental confirmation available.
Show »
Length:614
Mass (Da):67,499
Checksum:i3AAD690DE18B966B
GO
Isoform c (identifier: Q07292-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-44: Missing.

Show »
Length:769
Mass (Da):85,681
Checksum:iCF8EF397C584F445
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti801 – 8011A → R in AAA28142 (PubMed:8483497).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4444Missing in isoform c. 1 PublicationVSP_020621Add
BLAST
Alternative sequencei1 – 11M → MSAMAVLYSVCHFHGGWNRR KSAPKSPVTSSQTPSSSSTR RRM in isoform b. CuratedVSP_020620
Alternative sequencei569 – 5724EPRV → GDLN in isoform b. CuratedVSP_020622
Alternative sequencei573 – 813241Missing in isoform b. CuratedVSP_020623Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L15347 mRNA. Translation: AAA28142.1.
AY455928 mRNA. Translation: AAR26307.1.
AY493413 mRNA. Translation: AAR86712.1.
AY493414 mRNA. Translation: AAR86713.1.
FO080249 Genomic DNA. Translation: CCD62343.1.
FO080249 Genomic DNA. Translation: CCD62344.1.
PIRiS33261.
RefSeqiNP_001293844.1. NM_001306915.1. [Q07292-3]
NP_741430.3. NM_171367.5. [Q07292-1]
NP_741431.2. NM_171368.2.
UniGeneiCel.18190.

Genome annotation databases

EnsemblMetazoaiY73B6A.5a.1; Y73B6A.5a.1; WBGene00003030. [Q07292-1]
Y73B6A.5a.2; Y73B6A.5a.2; WBGene00003030. [Q07292-1]
GeneIDi177436.
UCSCiY73B6A.5a.1. c. elegans. [Q07292-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L15347 mRNA. Translation: AAA28142.1.
AY455928 mRNA. Translation: AAR26307.1.
AY493413 mRNA. Translation: AAR86712.1.
AY493414 mRNA. Translation: AAR86713.1.
FO080249 Genomic DNA. Translation: CCD62343.1.
FO080249 Genomic DNA. Translation: CCD62344.1.
PIRiS33261.
RefSeqiNP_001293844.1. NM_001306915.1. [Q07292-3]
NP_741430.3. NM_171367.5. [Q07292-1]
NP_741431.2. NM_171368.2.
UniGeneiCel.18190.

3D structure databases

ProteinModelPortaliQ07292.
SMRiQ07292. Positions 171-217, 473-792.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi42556. 18 interactions.
IntActiQ07292. 4 interactions.
MINTiMINT-1055674.
STRINGi6239.Y73B6A.5a.2.

PTM databases

iPTMnetiQ07292.

Proteomic databases

EPDiQ07292.
PaxDbiQ07292.
PRIDEiQ07292.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiY73B6A.5a.1; Y73B6A.5a.1; WBGene00003030. [Q07292-1]
Y73B6A.5a.2; Y73B6A.5a.2; WBGene00003030. [Q07292-1]
GeneIDi177436.
UCSCiY73B6A.5a.1. c. elegans. [Q07292-1]

Organism-specific databases

CTDi177436.
WormBaseiY73B6A.5a; CE25585; WBGene00003030; lin-45.
Y73B6A.5b; CE31742; WBGene00003030; lin-45.

Phylogenomic databases

eggNOGiKOG0193. Eukaryota.
ENOG410Y4UP. LUCA.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000252972.
InParanoidiQ07292.
OMAiPYSHINS.
OrthoDBiEOG7F5128.
PhylomeDBiQ07292.

Enzyme and pathway databases

ReactomeiR-CEL-2672351. Stimuli-sensing channels.
R-CEL-392517. Rap1 signalling.
R-CEL-430116. GP1b-IX-V activation signalling.
R-CEL-442742. CREB phosphorylation through the activation of Ras.
R-CEL-5621575. CD209 (DC-SIGN) signaling.
R-CEL-5673000. RAF activation.
R-CEL-5674135. MAP2K and MAPK activation.
R-CEL-5674499. Negative feedback regulation of MAPK pathway.
R-CEL-5675221. Negative regulation of MAPK pathway.
SignaLinkiQ07292.

Miscellaneous databases

PROiQ07292.

Gene expression databases

ExpressionAtlasiQ07292. baseline.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR002219. PE/DAG-bd.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR003116. RBD_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamiPF00130. C1_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF02196. RBD. 1 hit.
[Graphical view]
SMARTiSM00109. C1. 1 hit.
SM00455. RBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50898. RBD. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "C. elegans lin-45 raf gene participates in let-60 ras-stimulated vulval differentiation."
    Han M., Golden A., Han Y., Sternberg P.W.
    Nature 363:133-140(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION.
    Strain: Bristol N2.
  2. "Translation repression by GLD-1 protects its mRNA targets from nonsense-mediated mRNA decay in C. elegans."
    Lee M.-H., Schedl T.
    Genes Dev. 18:1047-1059(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND C).
  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], ALTERNATIVE SPLICING.
    Strain: Bristol N2.
  4. "Caenorhabditis elegans lin-45 raf is essential for larval viability, fertility and the induction of vulval cell fates."
    Hsu V., Zobel C.L., Lambie E.J., Schedl T., Kornfeld K.
    Genetics 160:481-492(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF PRO-92; ARG-108; ARG-118; SER-645; ILE-726 AND SER-754.
  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.
  6. "Cation diffusion facilitator proteins modulate Raf-1 activity."
    Jirakulaporn T., Muslin A.J.
    J. Biol. Chem. 279:27807-27815(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CDF-1.
  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, 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, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiKRAF1_CAEEL
AccessioniPrimary (citable) accession number: Q07292
Secondary accession number(s): Q6RT23, Q8MXT8, Q9N4E3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: July 11, 2002
Last modified: July 6, 2016
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Miscellaneousi

Miscellaneous

Gld-1 binds to the 3'-UTR of lin-45 mRNA and is able to protect nonsense-containing lin-45 mRNA from nonsense mediated decay (NMD).

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.