PTPR_CAEEL
ID PTPR_CAEEL Reviewed; 1409 AA.
AC H2KZM6; B2MZB0; H2KZM7; H2KZM8; O76282; Q9TZZ1;
DT 04-MAR-2015, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2012, sequence version 1.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=Receptor-type tyrosine-protein phosphatase {ECO:0000303|PubMed:9585503};
DE EC=3.1.3.48 {ECO:0000269|PubMed:9585503};
DE Flags: Precursor;
GN Name=clr-1 {ECO:0000312|WormBase:F56D1.4a};
GN ORFNames=F56D1.4 {ECO:0000312|WormBase:F56D1.4a};
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|EMBL:AAC27551.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND C), FUNCTION, CATALYTIC
RP ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF ALA-862; PRO-985; CYS-1013; ALA-1015 AND
RP GLY-1021.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAC27551.1};
RX PubMed=9585503; DOI=10.1101/gad.12.10.1425;
RA Kokel M., Borland C.Z., DeLong L., Horvitz H.R., Stern M.J.;
RT "clr-1 encodes a receptor tyrosine phosphatase that negatively regulates an
RT FGF receptor signaling pathway in Caenorhabditis elegans.";
RL Genes Dev. 12:1425-1437(1998).
RN [2] {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 [3] {ECO:0000305}
RP FUNCTION.
RX PubMed=14517244; DOI=10.1093/emboj/cdg472;
RA Szewczyk N.J., Jacobson L.A.;
RT "Activated EGL-15 FGF receptor promotes protein degradation in muscles of
RT Caenorhabditis elegans.";
RL EMBO J. 22:5058-5067(2003).
RN [4]
RP FUNCTION.
RX PubMed=15990870; DOI=10.1038/sj.emboj.7600741;
RA Gottschalk A., Almedom R.B., Schedletzky T., Anderson S.D., Yates J.R. III,
RA Schafer W.R.;
RT "Identification and characterization of novel nicotinic receptor-associated
RT proteins in Caenorhabditis elegans.";
RL EMBO J. 24:2566-2578(2005).
RN [5]
RP FUNCTION.
RX PubMed=16495308; DOI=10.1242/dev.02300;
RA Dixon S.J., Alexander M., Fernandes R., Ricker N., Roy P.J.;
RT "FGF negatively regulates muscle membrane extension in Caenorhabditis
RT elegans.";
RL Development 133:1263-1275(2006).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, DOMAIN, AND MUTAGENESIS OF CYS-1013 AND
RP 1072-TRP--ARG-1409.
RX PubMed=26968353; DOI=10.1016/j.ydbio.2016.03.001;
RA Liu X., Wang X., Shen K.;
RT "Receptor tyrosine phosphatase CLR-1 acts in skin cells to promote sensory
RT dendrite outgrowth.";
RL Dev. Biol. 413:60-69(2016).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN, AND MUTAGENESIS
RP OF CYS-1013 AND 1072-TRP--ARG-1409.
RX PubMed=29742100; DOI=10.1371/journal.pgen.1007312;
RA Varshney A., Benedetti K., Watters K., Shankar R., Tatarakis D.,
RA Coto Villa D., Magallanes K., Agenor V., Wung W., Farah F., Ali N., Le N.,
RA Pyle J., Farooqi A., Kieu Z., Bremer M., VanHoven M.;
RT "The receptor protein tyrosine phosphatase CLR-1 is required for synaptic
RT partner recognition.";
RL PLoS Genet. 14:E1007312-E1007312(2018).
CC -!- FUNCTION: Possesses an intrinsic protein tyrosine phosphatase (PTPase)
CC activity (PubMed:9585503). Regulates egl-15 activity which is required
CC for hypodermis-mediated fluid homeostasis and protein degradation in
CC muscle (PubMed:9585503). During the formation of neuromuscular
CC junctions at the larval stage, negatively regulates membrane protrusion
CC from body wall muscles (PubMed:16495308). Plays a role in nicotinic
CC acetylcholine receptor (nAChR)-mediated sensitivity to nicotine
CC (PubMed:15990870). Regulates synaptic levels of nAchR subunit lev-1 in
CC the nerve cord (PubMed:15990870). Promotes the outgrowth of the
CC quaternary dendritic branches of the PVD sensory neurons
CC (PubMed:26968353). In parallel to the sax-7/mnr-1 pathway, also
CC controls the extension of the PVD primary branches (PubMed:26968353).
CC Acts in the netrin/DCC pathway to mediate the formation of synapses
CC between the AVA interneurons and the PHB sensory neurons
CC (PubMed:29742100). Also required for the formation of synapses between
CC the AVA interneurons and the VA10 motor neurons (PubMed:29742100).
CC {ECO:0000269|PubMed:14517244, ECO:0000269|PubMed:15990870,
CC ECO:0000269|PubMed:16495308, ECO:0000269|PubMed:26968353,
CC ECO:0000269|PubMed:29742100, ECO:0000269|PubMed:9585503}.
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:0000269|PubMed:9585503};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:9585503};
CC Single-pass membrane protein {ECO:0000255}. Synapse
CC {ECO:0000269|PubMed:29742100}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=a; Synonyms=CLR-1 RTP1 {ECO:0000303|PubMed:9585503};
CC IsoId=H2KZM6-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:F56D1.4b};
CC IsoId=H2KZM6-2; Sequence=VSP_057500;
CC Name=c {ECO:0000312|WormBase:F56D1.4c};
CC IsoId=H2KZM6-3; Sequence=VSP_057501, VSP_057502;
CC Name=d {ECO:0000312|WormBase:F56D1.4d};
CC IsoId=H2KZM6-4; Sequence=VSP_057499;
CC -!- TISSUE SPECIFICITY: Expressed in muscles, hypodermis and a subset of
CC neurons (PubMed:9585503, PubMed:26968353). Expressed in the AVA
CC neurons, with high expression in the anterior half of the preanal
CC ganglion where AVA neurons contact the PHB neurons (PubMed:29742100).
CC {ECO:0000269|PubMed:26968353, ECO:0000269|PubMed:29742100,
CC ECO:0000269|PubMed:9585503}.
CC -!- DOMAIN: Tyrosine-protein phosphatase 1 domain has enzymatic activity
CC which is required for the negative regulation of egl-15
CC (PubMed:9585503). Tyrosine-protein phosphatase 1 domain is required for
CC correct PVD dendrite formation (PubMed:26968353). The second tyrosine-
CC protein phosphatase domain has no phosphatase activity and appears to
CC be dispensable for clr-1 function (PubMed:9585503). Isoform c lacks
CC both tyrosine-protein phosphatase domains and is likely to have no
CC catalytic activity (PubMed:9585503). {ECO:0000269|PubMed:26968353,
CC ECO:0000269|PubMed:9585503}.
CC -!- DOMAIN: The extracellular domain is required for the formation of
CC synapses between the AVA interneurons and the PHB sensory neurons.
CC {ECO:0000269|PubMed:29742100}.
CC -!- DISRUPTION PHENOTYPE: Mutants have a reduced size and a loss of both
CC motility and fertility. In addition the pharynx and the intestine
CC appear to float within the pseudocoelom resulting from the accumulation
CC of fluid. The majority die during larval development with hypodermal
CC ruptures. Simultaneous knockdown of clr-1 and egl-15 rescues the thin
CC body morphology of egl-15 mutants. {ECO:0000269|PubMed:9585503}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family.
CC Receptor class 2A subfamily. {ECO:0000305}.
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DR EMBL; AF047880; AAC27551.1; -; mRNA.
DR EMBL; AF047881; AAC27552.1; -; mRNA.
DR EMBL; FO081078; CCD68957.1; -; Genomic_DNA.
DR EMBL; FO081078; CCD68958.1; -; Genomic_DNA.
DR EMBL; FO081078; CCD68959.1; -; Genomic_DNA.
DR EMBL; FO081078; CCD68963.1; -; Genomic_DNA.
DR PIR; T42522; T42522.
DR RefSeq; NP_001022208.1; NM_001027037.2. [H2KZM6-1]
DR RefSeq; NP_001022209.1; NM_001027038.2. [H2KZM6-2]
DR RefSeq; NP_001129817.1; NM_001136345.2. [H2KZM6-4]
DR AlphaFoldDB; H2KZM6; -.
DR SMR; H2KZM6; -.
DR STRING; 6239.F56D1.4b; -.
DR EPD; H2KZM6; -.
DR PaxDb; H2KZM6; -.
DR PeptideAtlas; H2KZM6; -.
DR EnsemblMetazoa; F56D1.4a.1; F56D1.4a.1; WBGene00000548. [H2KZM6-1]
DR EnsemblMetazoa; F56D1.4b.1; F56D1.4b.1; WBGene00000548. [H2KZM6-2]
DR EnsemblMetazoa; F56D1.4d.1; F56D1.4d.1; WBGene00000548. [H2KZM6-4]
DR GeneID; 3565419; -.
DR KEGG; cel:CELE_F56D1.4; -.
DR UCSC; F56D1.4a; c. elegans.
DR CTD; 3565419; -.
DR WormBase; F56D1.4a; CE32051; WBGene00000548; clr-1. [H2KZM6-1]
DR WormBase; F56D1.4b; CE32052; WBGene00000548; clr-1. [H2KZM6-2]
DR WormBase; F56D1.4c; CE32053; WBGene00000548; clr-1. [H2KZM6-3]
DR WormBase; F56D1.4d; CE26369; WBGene00000548; clr-1. [H2KZM6-4]
DR eggNOG; KOG4228; Eukaryota.
DR GeneTree; ENSGT00940000174163; -.
DR OMA; EKNRQQC; -.
DR OrthoDB; 411281at2759; -.
DR SignaLink; H2KZM6; -.
DR PRO; PR:H2KZM6; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00000548; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR ExpressionAtlas; H2KZM6; baseline and differential.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0098794; C:postsynapse; IDA:UniProtKB.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IBA:GO_Central.
DR GO; GO:0005001; F:transmembrane receptor protein tyrosine phosphatase activity; IDA:WormBase.
DR GO; GO:0007635; P:chemosensory behavior; IMP:UniProtKB.
DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; IGI:WormBase.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0038007; P:netrin-activated signaling pathway; IGI:UniProtKB.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; IDA:WormBase.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IMP:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; IBA:GO_Central.
DR GO; GO:0007606; P:sensory perception of chemical stimulus; IMP:UniProtKB.
DR GO; GO:0099536; P:synaptic signaling; IMP:UniProtKB.
DR CDD; cd00063; FN3; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 3.90.190.10; -; 2.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000242; PTP_cat.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR Pfam; PF00102; Y_phosphatase; 2.
DR PRINTS; PR00700; PRTYPHPHTASE.
DR SMART; SM00060; FN3; 2.
DR SMART; SM00409; IG; 1.
DR SMART; SM00194; PTPc; 2.
DR SMART; SM00404; PTPc_motif; 2.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF49265; SSF49265; 1.
DR SUPFAM; SSF52799; SSF52799; 2.
DR PROSITE; PS50853; FN3; 2.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 2.
DR PROSITE; PS50055; TYR_PHOSPHATASE_PTP; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond; Hydrolase;
KW Immunoglobulin domain; Membrane; Neurogenesis; Protein phosphatase;
KW Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..1409
FT /note="Receptor-type tyrosine-protein phosphatase"
FT /id="PRO_0000432382"
FT TOPO_DOM 23..712
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 713..733
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 734..1409
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 159..267
FT /note="Ig-like C2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 276..366
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 372..502
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 793..1072
FT /note="Tyrosine-protein phosphatase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT DOMAIN 1135..1403
FT /note="Tyrosine-protein phosphatase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 32..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1013
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT ACT_SITE 1344
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT DISULFID 189..255
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 25..28
FT /note="FFRS -> LS (in isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_057499"
FT VAR_SEQ 276
FT /note="A -> EHARRTHSYWYKRPKKVMPPSSSSSLKTSDDDDDST (in
FT isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057500"
FT VAR_SEQ 941..942
FT /note="CG -> LM (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_057501"
FT VAR_SEQ 943..1409
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_057502"
FT MUTAGEN 862
FT /note="A->V: In n1649; slight fluid accumulation in the
FT pseudocoelom."
FT /evidence="ECO:0000269|PubMed:9585503"
FT MUTAGEN 985
FT /note="P->S: In n1635; fluid accumulation in the
FT pseudocoelom."
FT /evidence="ECO:0000269|PubMed:9585503"
FT MUTAGEN 1013
FT /note="C->G: Failure in quaternary dendritic arbor
FT formation of the PVD sensory neurons."
FT /evidence="ECO:0000269|PubMed:26968353"
FT MUTAGEN 1013
FT /note="C->S: Loss of activity. Reduced synapse formation
FT between the PHB and AVA neurons and defects in the
FT behavioral avoidance response towards sodium dodecyl
FT sulfate."
FT /evidence="ECO:0000269|PubMed:29742100,
FT ECO:0000269|PubMed:9585503"
FT MUTAGEN 1013
FT /note="C->Y: In gm30; fluid accumulation in the
FT pseudocoelom, reduced size and loss of both motility and
FT fertility."
FT /evidence="ECO:0000269|PubMed:9585503"
FT MUTAGEN 1015
FT /note="A->V: In n1641; fluid accumulation in the
FT pseudocoelom, reduced size and loss of both motility and
FT fertility."
FT /evidence="ECO:0000269|PubMed:9585503"
FT MUTAGEN 1021
FT /note="G->R: In n1660; fluid accumulation in the
FT pseudocoelom, reduced size and loss of both motility and
FT fertility."
FT /evidence="ECO:0000269|PubMed:9585503"
FT MUTAGEN 1072..1409
FT /note="Missing: In e1745; temperature sensitive. At the
FT restrictive temperature of 25 degrees Celsius, causes
FT reduction of the numbers and extensions of the quaternary
FT dendritic branches, reduced numbers of menorah and ectopic
FT branches from the primary and secondary dendrites of the
FT PVD sensory neurons. Reduced synapse formation between the
FT PHB and AVA neurons and defects in the behavioral avoidance
FT response towards sodium dodecyl sulfate. Defects in PVD
FT primary branch extensions when associated with sax-7(nj48),
FT dma-1(wy686) or mnr-1(wy758)."
FT /evidence="ECO:0000269|PubMed:26968353,
FT ECO:0000269|PubMed:29742100"
FT CONFLICT 586
FT /note="A -> V (in Ref. 1; AAC27551/AAC27552)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1409 AA; 159956 MW; 8082C43F33510C26 CRC64;
MRINRWIWWA TVILLYLRTG LAADFFRSSE ENDRKSSDDL DNFNSTKIEP DKPKTAKELG
VKSCESNQDC VHDGVCHRGN DGHGICMCPR SCPAITPKQC GYNYRTPSTC LLMDADYRSK
YDVKEPTCYS RKCVCPPQFD DVHVTANQKP LRLNSTLLPT KCDKRDLAVV ARAHPSTSVS
KGIDVTLFCC INVDPEGFID VASVFFIQNG TIMREATSHP FAPRNGLARR VHEKYSCWEL
EIKNAQTSDS GSYMCRVTAS ASDLDVTDTM QFEVKAPRQI KNLTVNPSER DAIVTWESEG
GEDMAIDLRL VRRTDTRGQV VFSKDNLTSP VSIKDLRAAT PYTLFVSGNN GQVPFEFTEH
FTTKQKRPFP PKEEDVRVLN SGSALSCEVE WKSPAEPNGR ITKYFVSVRG AMRKSDGSLT
PDDLPAAVEV DKRCANWDGD ENTSKHNGIN PIDFANEFYS CKFGPLKPNR NYTVTVWAEN
SAGRSLPAVF HKNCVTNYAQ PDMVETPQPL LSNNHSTFSL TFPQPPDDIN GPISCYYIAI
VPLPANVSLD ILPKSEEIVM HSFSKVFTNN LLPSSAEEKR FFAYIAESYV QLPEETTIGD
GVRVSDLKAC NVQYLSRYSS EDLALRRGLK YTGFLIVRVD KEEELNRKDV RNGADPNIFR
NLIDKSVSPT SRTRTASPMS RHLRQLHLSG PAYGYSAYFK PILLDTESSS SGFGIFMKII
LPFLLFLAFA TGVTMFFVNR KGHMLSTWCP LFTKMTSKDV VERTLLKQTF GAIPVDDLPT
EYVVRHRDTD FLFAQEYESL PHFQLDTVAS NRKENAIKNR YNDIRAFDDT RVKLKKINGD
DYSDYINANF IKSWKEKKLF IAAQAPVDAT IGDFWRMVWE QESYLIVMVA NLTEKNRQQC
AKYWPDEQIT RYGDIIVEPA SFSFHSDYAI RAFDIAHIGE CGPDVIPNGN GVEYANVPIV
KGQFANNSRR ILQYHFTNWN DYKAPECSTG LLRFMYRLRE LPQFNNSPVV IHCSAGVGRT
GTFISIDSML DQCLAEDKAN IFEFVCNLRR QRNLMVQSLE QYVFIYKALA EWHMYGDTDE
DVRDFEDHYQ RLCASNRDRA VSFNQQSSTN GSISPRVAIV SSRESMTTSN GETGLEEEFK
KLERNLTTPL SSNFAAKDEN LLKNRYEAAV PFDKYRVILP PTIGHADSSY INASHIKGYF
FDYIAAQDPV SEGTAFDFWR MIADQNVTTV VMLSDETDWS DVEKYWPIDG SGTECHFGSE
RNSVNVTCVS EEHHQDFIIR NLSYSMKDNE SMPANQEVVQ YSYTGWPSDS IVPKSANSLM
NLIEMVLQRQ SSLMGSQAPI VVHCRNGSSE SGIFICISLL WLRQKAEQRI DVFQTVKGLQ
SHRPMMFTRF EQYSFCYRAL ADYISKTYR
