CIROP_DANRE
ID CIROP_DANRE Reviewed; 623 AA.
AC A0A1D5NSK0;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 03-AUG-2022, sequence version 2.
DT 03-AUG-2022, entry version 19.
DE RecName: Full=Ciliated left-right organizer metallopeptidase;
DE AltName: Full=Leishmanolysin-like peptidase 2;
DE EC=3.4.24.- {ECO:0000250|UniProtKB:Q9VH19};
DE Flags: Precursor;
GN Name=cirop; ORFNames=si:ch211-216p19.5;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP 249-HIS--HIS-253.
RX PubMed=34903892; DOI=10.1038/s41588-021-00970-4;
RA Szenker-Ravi E., Ott T., Khatoo M., de Bellaing A.M., Goh W.X., Chong Y.L.,
RA Beckers A., Kannesan D., Louvel G., Anujan P., Ravi V., Bonnard C.,
RA Moutton S., Schoen P., Fradin M., Colin E., Megarbane A., Daou L.,
RA Chehab G., Di Filippo S., Rooryck C., Deleuze J.F., Boland A., Arribard N.,
RA Eker R., Tohari S., Ng A.Y., Rio M., Lim C.T., Eisenhaber B.,
RA Eisenhaber F., Venkatesh B., Amiel J., Crollius H.R., Gordon C.T.,
RA Gossler A., Roy S., Attie-Bitach T., Blum M., Bouvagnet P., Reversade B.;
RT "Discovery of a genetic module essential for assigning left-right asymmetry
RT in humans and ancestral vertebrates.";
RL Nat. Genet. 54:62-72(2022).
CC -!- FUNCTION: Plays an essential role for patterning the left-right axis.
CC Requires solely on the left side, downstream of the leftward flow, but
CC upstream of dand5, a nodal inhibitor involved in left-right patterning.
CC {ECO:0000269|PubMed:34903892}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P08148};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P08148};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass type I
CC membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed specifically in dorsal forerunner cells
CC (DFCs) that form a ciliated Kupffer's vesicle later.
CC {ECO:0000269|PubMed:34903892}.
CC -!- DISRUPTION PHENOTYPE: Embryos with CRISPR-induced cirop null are
CC fertile but the developing heart at 48 h post-fertilization (hpf) show
CC cardiac looping randomization. Only 25% of cirop deficient embryos show
CC a normal positioning of brain, heart and pancreas at 72 hpf. No other
CC ciliopathy-related phenotypes such as body curvature, kidney cysts or
CC hydrocephalus are observed in cirop mutant embryos at 72 hpf. When
CC dand5 is depleted on the left side of cirop null zebrafish embryos, the
CC phenotype is rescued. {ECO:0000269|PubMed:34903892}.
CC -!- SIMILARITY: Belongs to the peptidase M8 family. {ECO:0000305}.
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DR EMBL; CR318603; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR Ensembl; ENSDART00000173472.2; ENSDARP00000142816.1; ENSDARG00000098915.3.
DR ZFIN; ZDB-GENE-160728-97; si:ch211-216p19.5.
DR GeneTree; ENSGT00940000163573; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 7.
DR Bgee; ENSDARG00000098915; Expressed in early embryo and 9 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008233; F:peptidase activity; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IEA:InterPro.
DR GO; GO:0061371; P:determination of heart left/right asymmetry; IMP:UniProtKB.
DR GO; GO:0061966; P:establishment of left/right asymmetry; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR001577; Peptidase_M8.
DR PANTHER; PTHR10942; PTHR10942; 2.
DR Pfam; PF01457; Peptidase_M8; 2.
PE 1: Evidence at protein level;
KW Developmental protein; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Protease; Reference proteome; Signal; Transmembrane; Transmembrane helix;
KW Zinc.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..623
FT /note="Ciliated left-right organizer metallopeptidase"
FT /id="PRO_0000455737"
FT TOPO_DOM 21..578
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 579..599
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 600..623
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT ACT_SITE 250
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 249
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 253
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 326
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT MUTAGEN 249..253
FT /note="HELFH->AALFA: Unable to rescue the heart looping
FT defects in cirop deficient larvae."
FT /evidence="ECO:0000269|PubMed:34903892"
SQ SEQUENCE 623 AA; 69342 MW; 4380C1E467FA4DAF CRC64;
MSFLLCIGIL LLPWFPCVCG KCIFDQIQRS VNVVSPPTAQ YASAYRFKTQ RSKRHIMPMD
NLQPIRIKIW IPSESPALSD WEREKLMSAV GEAVSEVSSL LSVKRVKDRL LLNRDVNKYC
KFIWRNSSTL NHMKCGRAHE NYRFESCLGV IIPDEHLDGC SVYPNPEHPV PTVLRPRGPG
VPDADFLLYV FTHNTEKCRA ESSVLAYTAH CQTGSDGRPL AGTMVICRET LKKERYTYQH
FVKVTTVIHE LFHVLGFSKE LLSNWKDFGV DCWSHGQVTS TDQTGQVRLY SPTVIRAMQK
HFNSTHTDLG APLENKDAAL DGLSSHWEAR VLQGSIMAAS LVEASLVRID AITLAALQDT
GWYSVNHSRA QSLVWGEGEG SDFGSVSACH NSSAFFCTGS GLGCHFLHLN KGECVTDQYL
DGCHIFKPLA NASECWIEDN ARSGMNEGGG EIFGSDSRCF ISNITRLNNV TAYTPVSGHC
YRHRCTGINK YHIQVKDSDW MDCPAGTSIE VSGYQGFIFC PENRLCKYSD LAPPTSTQRT
ESLFSDTTAQ SDLGMMEKDA AVQPSFTSLF LVSEAKISLA AVLSLMAVFA LLSAAVLLYR
KNLSVRVHAA SYRTPLPHIL YRN
