ID   CIROP_XENLA             Reviewed;         720 AA.
AC   A0A1L8HYT7;
DT   03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT   15-MAR-2017, sequence version 1.
DT   03-AUG-2022, entry version 16.
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;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=27762356; DOI=10.1038/nature19840;
RA   Session A.M., Uno Y., Kwon T., Chapman J.A., Toyoda A., Takahashi S.,
RA   Fukui A., Hikosaka A., Suzuki A., Kondo M., van Heeringen S.J., Quigley I.,
RA   Heinz S., Ogino H., Ochi H., Hellsten U., Lyons J.B., Simakov O.,
RA   Putnam N., Stites J., Kuroki Y., Tanaka T., Michiue T., Watanabe M.,
RA   Bogdanovic O., Lister R., Georgiou G., Paranjpe S.S., van Kruijsbergen I.,
RA   Shu S., Carlson J., Kinoshita T., Ohta Y., Mawaribuchi S., Jenkins J.,
RA   Grimwood J., Schmutz J., Mitros T., Mozaffari S.V., Suzuki Y., Haramoto Y.,
RA   Yamamoto T.S., Takagi C., Heald R., Miller K., Haudenschild C., Kitzman J.,
RA   Nakayama T., Izutsu Y., Robert J., Fortriede J., Burns K., Lotay V.,
RA   Karimi K., Yasuoka Y., Dichmann D.S., Flajnik M.F., Houston D.W.,
RA   Shendure J., DuPasquier L., Vize P.D., Zorn A.M., Ito M., Marcotte E.M.,
RA   Wallingford J.B., Ito Y., Asashima M., Ueno N., Matsuda Y., Veenstra G.J.,
RA   Fujiyama A., Harland R.M., Taira M., Rokhsar D.S.;
RT   "Genome evolution in the allotetraploid frog Xenopus laevis.";
RL   Nature 538:336-343(2016).
RN   [2]
RP   DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND FUNCTION.
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: Putative metalloprotease playing a role in the process of LR
CC       patterning. {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   -!- DEVELOPMENTAL STAGE: First expressed at stage 10.5 in the involuting
CC       marginal zone (IMZ) along a dorsal-high ventral-low gradient and, by
CC       stage 14 in cells of the circumblastoporal collar.
CC       {ECO:0000269|PubMed:34903892}.
CC   -!- DISRUPTION PHENOTYPE: Embryos with CRISPR-induced cirop null present
CC       heterotaxy phenotype (heart looping and intestine defects). No other
CC       ciliopathy-related phenotypes such as body curvature, kidney cysts or
CC       hydrocephalus are observed in cirop mutant embryos.
CC       {ECO:0000269|PubMed:34903892}.
CC   -!- SIMILARITY: Belongs to the peptidase M8 family. {ECO:0000305}.
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DR   EMBL; CM004466; OCU01276.1; -; Genomic_DNA.
DR   RefSeq; XP_018115074.1; XM_018259585.1.
DR   GeneID; 108714878; -.
DR   KEGG; xla:108714878; -.
DR   OrthoDB; 1310134at2759; -.
DR   Proteomes; UP000186698; Chromosome 1L.
DR   Bgee; 108714878; Expressed in kidney and 8 other tissues.
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: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; 1.
DR   Pfam; PF01457; Peptidase_M8; 2.
PE   2: Evidence at transcript level;
KW   Hydrolase; Membrane; Metal-binding; Metalloprotease; Protease;
KW   Reference proteome; Signal; Transmembrane; Transmembrane helix; Zinc.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   CHAIN           26..720
FT                   /note="Ciliated left-right organizer metallopeptidase"
FT                   /id="PRO_5023971209"
FT   TOPO_DOM        26..668
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        669..689
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        690..720
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   ACT_SITE        244
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         243
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         247
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         322
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
SQ   SEQUENCE   720 AA;  80584 MW;  E93441615BDDC346 CRC64;
     MTVSFSMFQI YRLVWLSFMT SMCLSACIHD SVLQETPVVS SNIISSRVPR LFPRSTSSDY
     FQPLRVTPWY LLGENAFISQ GQIRQLKIAL QEVTQMLSST LSVHRSEGSL LLNRDISRFC
     RSVWRAPNDN KCAYMQTSYQ GEKCLDVTIP DFHLQGVKVW SDLEKEPRTV IEDGAGVPDT
     DFLLYVQVAQ TQKCAAQPSV IAYASYCQQD PTGRPLAGVI VFCTDHLREE EYNQRHIIQV
     ALHELLHTLG FSSSLYASWL DCSLAEYGEA CSSRTRVTNT DENGQFRIYT PTVMQKMGEH
     LGVEGVGAPL ENKGFPNLAS SHWESRFFQG SIMTALLSPP HLTHLDPITL AAFTDMGWYK
     VNATIKSQLM WGKGAGRYFG LPTTCQDSST GFFCTGSKLG CHHLHLDKGN CSTDSYLEGC
     HIYSPLIHGG ECWRHQNSGD PDEIFHAQSR CFYSNLTKGA SPNQEFRGRC YLHQCLGENH
     FQVKVHESEW TDCPAGAWIQ VAGYEGFIQC PSGCLCLGFQ TPHVATLTPT YVTGQITTVK
     ENNVYPTEGI VQFRVQVEVS QRHKWTSEIK SFLLDEVLGV IAQKAGVQRC FLQSHMKEDL
     DLSFAIVGKW STDCPPTPEA DTAAFSLLTL NQDGAPYIIY NSSYFSTVSI RFIDSDPPAL
     YVSHMLYSYV IGGGCCAVCG AAIIFALFWY KLRRQFLRVG SSYPPETSNH ERPQIPADLV