DUSL_CAEEL
ID DUSL_CAEEL Reviewed; 381 AA.
AC V6CIV8; O44128;
DT 20-DEC-2017, integrated into UniProtKB/Swiss-Prot.
DT 19-FEB-2014, sequence version 1.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=Dual specificity protein phosphatase lip-1 {ECO:0000305};
DE EC=3.1.3.16 {ECO:0000305|PubMed:21901106};
DE EC=3.1.3.48 {ECO:0000305|PubMed:21901106};
DE AltName: Full=Lateral signaling-induced phosphatase 1 {ECO:0000312|WormBase:C05B10.1b};
DE AltName: Full=Mitogen-activated protein kinase phosphatase lip-1 {ECO:0000305};
DE Short=MAP kinase phosphatase lip-1 {ECO:0000250|UniProtKB:Q16828};
GN Name=lip-1 {ECO:0000312|WormBase:C05B10.1b};
GN ORFNames=C05B10.1 {ECO:0000312|WormBase:C05B10.1b};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=11161219; DOI=10.1126/science.1055642;
RA Berset T., Hoier E.F., Battu G., Canevascini S., Hajnal A.;
RT "Notch inhibition of RAS signaling through MAP kinase phosphatase LIP-1
RT during C. elegans vulval development.";
RL Science 291:1055-1058(2001).
RN [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF PRO-310.
RX PubMed=12169634; DOI=10.1093/emboj/cdf430;
RA Hajnal A., Berset T.;
RT "The C.elegans MAPK phosphatase LIP-1 is required for the G(2)/M meiotic
RT arrest of developing oocytes.";
RL EMBO J. 21:4317-4326(2002).
RN [4] {ECO:0000305}
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=16319922; DOI=10.1038/sj.emboj.7600901;
RA Lee M.H., Hook B., Lamont L.B., Wickens M., Kimble J.;
RT "LIP-1 phosphatase controls the extent of germline proliferation in
RT Caenorhabditis elegans.";
RL EMBO J. 25:88-96(2006).
RN [5] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=20624915; DOI=10.1074/jbc.m110.146274;
RA Okuyama T., Inoue H., Ookuma S., Satoh T., Kano K., Honjoh S., Hisamoto N.,
RA Matsumoto K., Nishida E.;
RT "The ERK-MAPK pathway regulates longevity through SKN-1 and insulin-like
RT signaling in Caenorhabditis elegans.";
RL J. Biol. Chem. 285:30274-30281(2010).
RN [6] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, DOMAIN, DISRUPTION PHENOTYPE, AND MUTAGENESIS
RP OF 59-ARG-ARG-60.
RX PubMed=21901106; DOI=10.1371/journal.pgen.1002238;
RA Rutkowski R., Dickinson R., Stewart G., Craig A., Schimpl M., Keyse S.M.,
RA Gartner A.;
RT "Regulation of Caenorhabditis elegans p53/CEP-1-dependent germ cell
RT apoptosis by Ras/MAPK signaling.";
RL PLoS Genet. 7:E1002238-E1002238(2011).
RN [7] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22820175; DOI=10.1016/j.bbamcr.2012.07.006;
RA Cha D.S., Datla U.S., Hollis S.E., Kimble J., Lee M.H.;
RT "The Ras-ERK MAPK regulatory network controls dedifferentiation in
RT Caenorhabditis elegans germline.";
RL Biochim. Biophys. Acta 1823:1847-1855(2012).
CC -!- FUNCTION: Dephosphorylates MAP kinase mpk-1.
CC {ECO:0000269|PubMed:11161219, ECO:0000269|PubMed:12169634,
CC ECO:0000269|PubMed:21901106, ECO:0000269|PubMed:22820175}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620; EC=3.1.3.48;
CC Evidence={ECO:0000305|PubMed:21901106};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] +
CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:83421; EC=3.1.3.16;
CC Evidence={ECO:0000305|PubMed:21901106};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:61977; EC=3.1.3.16;
CC Evidence={ECO:0000305|PubMed:21901106};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12169634,
CC ECO:0000269|PubMed:16319922}; Peripheral membrane protein
CC {ECO:0000269|PubMed:12169634, ECO:0000269|PubMed:16319922}.
CC Note=Localizes in rod-like structures at the plasma membrane of
CC pachytene germline cells. {ECO:0000269|PubMed:12169634,
CC ECO:0000269|PubMed:16319922}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=b {ECO:0000312|WormBase:C05B10.1b};
CC IsoId=V6CIV8-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:C05B10.1a};
CC IsoId=V6CIV8-2; Sequence=VSP_059250, VSP_059251;
CC -!- TISSUE SPECIFICITY: Expressed in vulva cell precursors. Expression is
CC increased in P5.p and P7.p and their descendants during vulva
CC induction. Expressed in syncytium hyp7 (PubMed:11161219). Expressed in
CC germline cells (PubMed:12169634, PubMed:16319922).
CC {ECO:0000269|PubMed:11161219, ECO:0000269|PubMed:12169634,
CC ECO:0000269|PubMed:16319922}.
CC -!- DEVELOPMENTAL STAGE: Expressed at low level in the proximal mitotic
CC region and transition zone of germline cells and at the pachytene stage
CC of meiotic prophase I. {ECO:0000269|PubMed:12169634,
CC ECO:0000269|PubMed:16319922}.
CC -!- DOMAIN: The KIM (kinase interacting motif) region may be involved in
CC the binding to MAP kinases. {ECO:0000305|PubMed:21901106}.
CC -!- DISRUPTION PHENOTYPE: Pachytene exit and oocyte development are
CC accelerated (PubMed:12169634, PubMed:21901106). These are associated
CC with the accumulation of smaller oocytes in the proximal gonadal arm,
CC the misalignment of oocytes in multiple rows, a premature nucleolus
CC breakdown and an abnormal mpk-1 phosphorylation after pachytene exit
CC and in diakinesis oocytes (PubMed:12169634, PubMed:21901106). 53
CC percent of mutants have endomitotic oocytes (PubMed:12169634). Embryo
CC development is arrested before morphogenesis resulting in 50 percent
CC embryonic lethality (PubMed:12169634). In adults, but not in larvae,
CC reduced number of germ cells in the mitotic region of the gonad
CC (PubMed:16319922). Moderate increase in the number of apoptotic corpses
CC in the germline which is further enhanced following gamma irradiation
CC (PubMed:21901106). Increased egl-1 mRNA expression in response to gamma
CC irradiation (PubMed:21901106). Increased cep-1 expression in early
CC pachytene germ cells (PubMed:21901106). Increased life span
CC (PubMed:20624915). Increased MAP kinase activity (PubMed:11161219).
CC Reduced levels of mpk-1 isoform b associated with an increase in mpk-1
CC isoform b phosphorylation (PubMed:21901106). In lip-1 and let-23, lip-1
CC and sem-5, and lip-1 and mpk-1 double mutants, normal vulva induction
CC is restored (PubMed:11161219). In lip-1 and mpk-1 double mutants,
CC normal oocyte development and fertility are restored (PubMed:12169634).
CC lip-1 and puf-8 double mutant produces only sperm and has abnormal mpk-
CC 1 phosphorylation in the transition zone at the permissive temperature
CC of 20 degrees Celsius. At the restrictive temperature of 25 degrees
CC Celsius, has proximal germline tumors with high levels of mpk-1
CC phosphorylation (PubMed:22820175). {ECO:0000269|PubMed:11161219,
CC ECO:0000269|PubMed:12169634, ECO:0000269|PubMed:16319922,
CC ECO:0000269|PubMed:20624915, ECO:0000269|PubMed:21901106,
CC ECO:0000269|PubMed:22820175}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class dual specificity subfamily. {ECO:0000305}.
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DR EMBL; BX284604; CCD63076.1; -; Genomic_DNA.
DR EMBL; BX284604; CDK13377.1; -; Genomic_DNA.
DR PIR; T32494; T32494.
DR RefSeq; NP_001293707.1; NM_001306778.1. [V6CIV8-1]
DR RefSeq; NP_501053.2; NM_068652.2. [V6CIV8-2]
DR AlphaFoldDB; V6CIV8; -.
DR SMR; V6CIV8; -.
DR IntAct; V6CIV8; 1.
DR STRING; 6239.C05B10.1; -.
DR EPD; V6CIV8; -.
DR EnsemblMetazoa; C05B10.1a.1; C05B10.1a.1; WBGene00003043. [V6CIV8-2]
DR EnsemblMetazoa; C05B10.1b.1; C05B10.1b.1; WBGene00003043. [V6CIV8-1]
DR GeneID; 191704; -.
DR KEGG; cel:CELE_C05B10.1; -.
DR UCSC; C05B10.1; c. elegans.
DR CTD; 191704; -.
DR WormBase; C05B10.1a; CE31151; WBGene00003043; lip-1. [V6CIV8-2]
DR WormBase; C05B10.1b; CE49310; WBGene00003043; lip-1. [V6CIV8-1]
DR eggNOG; KOG1717; Eukaryota.
DR GeneTree; ENSGT00940000169406; -.
DR OMA; HIMETEP; -.
DR OrthoDB; 911920at2759; -.
DR Reactome; R-CEL-112409; RAF-independent MAPK1/3 activation.
DR Reactome; R-CEL-202670; ERKs are inactivated.
DR Reactome; R-CEL-5675221; Negative regulation of MAPK pathway.
DR SignaLink; V6CIV8; -.
DR PRO; PR:V6CIV8; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00003043; Expressed in adult organism and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0017017; F:MAP kinase tyrosine/serine/threonine phosphatase activity; IBA:GO_Central.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IBA:GO_Central.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0008330; F:protein tyrosine/threonine phosphatase activity; IBA:GO_Central.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:WormBase.
DR GO; GO:0007281; P:germ cell development; IMP:WormBase.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IMP:WormBase.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0051447; P:negative regulation of meiotic cell cycle; IMP:WormBase.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IGI:WormBase.
DR GO; GO:0007219; P:Notch signaling pathway; IGI:WormBase.
DR GO; GO:0048599; P:oocyte development; IMP:WormBase.
DR GO; GO:0040026; P:positive regulation of vulval development; IGI:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:InterPro.
DR GO; GO:0042659; P:regulation of cell fate specification; IGI:WormBase.
DR GO; GO:0040028; P:regulation of vulval development; IGI:WormBase.
DR GO; GO:0072327; P:vulval cell fate specification; IGI:UniProtKB.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR000340; Dual-sp_phosphatase_cat-dom.
DR InterPro; IPR008343; MKP.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom.
DR Pfam; PF00782; DSPc; 1.
DR PRINTS; PR01764; MAPKPHPHTASE.
DR SMART; SM00195; DSPc; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR PROSITE; PS50054; TYR_PHOSPHATASE_DUAL; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Cell division; Cell membrane;
KW Differentiation; Hydrolase; Meiosis; Membrane; Mitosis; Oogenesis;
KW Protein phosphatase; Reference proteome.
FT CHAIN 1..381
FT /note="Dual specificity protein phosphatase lip-1"
FT /evidence="ECO:0000305"
FT /id="PRO_0000442494"
FT DOMAIN 184..327
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 56..68
FT /note="KIM"
FT /evidence="ECO:0000305|PubMed:21901106"
FT REGION 362..381
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 271
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT VAR_SEQ 334..369
FT /note="TYPSSAPRSPSCAIEAAAVSQVGGLLTPPPTSCSAS -> VSRQAVNFDVHF
FT FCIFKLKKKEENSPESRILAETAV (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_059250"
FT VAR_SEQ 370..381
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_059251"
FT MUTAGEN 59..60
FT /note="RR->AA: Loss of MAPK1/3 dephosphorylation."
FT /evidence="ECO:0000269|PubMed:21901106"
FT MUTAGEN 310
FT /note="P->L: In zh32; at the restrictive temperature of 25
FT degrees Celsius, 87 percent of mutants have endomitotic
FT oocytes."
FT /evidence="ECO:0000269|PubMed:12169634"
SQ SEQUENCE 381 AA; 42174 MW; C6AB1FBC4A2C47C5 CRC64;
MTTHLPSTSQ NGEEISAEQF NRIFHERNVI VLDCRSNGDS VKRANRFFCS LRLPALLQRR
LMGGSMRLST VPDLKDLNNS PDQCPEVLLI PGDSEQDEQL SAALARNLKS NHYRHFVLGE
PVKTLLSQFP TLRDAADENW NTTFQMNSMP GQASGQQASS GPLLNLNQLR LEGEDQGGKQ
RAEFPVKLTN FLYLGNAETA KNRDVLKKYS ISHVINVTSN LPNTFEEDPN MRYLRISADD
NASHNLTKFF PEAISFIDDA RRNDSACLVH CLAGISRSVT ICLAYLMKTE MCTLDSAYEW
VQKRNASIAP NFHFMGQLTD YEKMLGLNSN RVGTYPSSAP RSPSCAIEAA AVSQVGGLLT
PPPTSCSASP QSSNHSAKSF H
