CIROP_HUMAN
ID CIROP_HUMAN Reviewed; 788 AA.
AC A0A1B0GTW7; A0A2R8Y3T5;
DT 12-SEP-2018, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2016, sequence version 1.
DT 03-AUG-2022, entry version 27.
DE RecName: Full=Ciliated left-right organizer metallopeptidase {ECO:0000303|PubMed:34903892};
DE AltName: Full=Leishmanolysin-like peptidase 2 {ECO:0000305};
DE EC=3.4.24.- {ECO:0000250|UniProtKB:Q9VH19};
DE Flags: Precursor;
GN Name=CIROP {ECO:0000312|HGNC:HGNC:53647};
GN Synonyms=LMLN2 {ECO:0000312|HGNC:HGNC:53647};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INVOLVEMENT IN HTX12, AND VARIANTS HTX12 PHE-31; 191-ARG--VAL-788 DEL;
RP SER-324; 346-TRP--VAL-788 DEL; LEU-384; ILE-389; PHE-456 DEL AND PRO-469.
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 metalloproteinase that plays a role in left-right
CC patterning process. {ECO:0000250|UniProtKB:A0A1D5NSK0}.
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=A0A1B0GTW7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A0A1B0GTW7-2; Sequence=VSP_061525;
CC Name=3;
CC IsoId=A0A1B0GTW7-3; Sequence=VSP_061523, VSP_061524, VSP_061526;
CC -!- DISEASE: Heterotaxy, visceral, 12, autosomal (HTX12) [MIM:619702]: A
CC form of visceral heterotaxy, a complex disorder due to disruption of
CC the normal left-right asymmetry of the thoracoabdominal organs.
CC Visceral heterotaxy or situs ambiguus results in randomization of the
CC placement of visceral organs, including the heart, lungs, liver,
CC spleen, and stomach. The organs are oriented randomly with respect to
CC the left-right axis and with respect to one another. It can be
CC associated with a variety of congenital defects including cardiac
CC malformations. Early death may occur. HTX12 inheritance is autosomal
CC recessive. {ECO:0000269|PubMed:34903892}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase M8 family. {ECO:0000305}.
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DR EMBL; AL117258; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC153822; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS86373.1; -.
DR SMR; A0A1B0GTW7; -.
DR GlyGen; A0A1B0GTW7; 5 sites.
DR BioMuta; ENSG00000283654; -.
DR MassIVE; A0A1B0GTW7; -.
DR PeptideAtlas; A0A1B0GTW7; -.
DR Ensembl; ENST00000637218.2; ENSP00000489869.1; ENSG00000283654.3.
DR MANE-Select; ENST00000637218.2; ENSP00000489869.1; NM_001354640.2; NP_001341569.1.
DR GeneCards; LMLN2; -.
DR HGNC; HGNC:53647; CIROP.
DR HPA; ENSG00000283654; Not detected.
DR MIM; 619702; phenotype.
DR MIM; 619703; gene.
DR neXtProt; NX_A0A1B0GTW7; -.
DR VEuPathDB; HostDB:ENSG00000283654; -.
DR GeneTree; ENSGT00940000163573; -.
DR OMA; PDTPNYH; -.
DR Pharos; A0A1B0GTW7; Tdark.
DR PRO; PR:A0A1B0GTW7; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; A0A1B0GTW7; protein.
DR Bgee; ENSG00000283654; Expressed in mucosa of stomach and 38 other tissues.
DR ExpressionAtlas; A0A1B0GTW7; baseline and differential.
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:InterPro.
DR GO; GO:0008233; F:peptidase activity; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IEA:InterPro.
DR GO; GO:0061966; P:establishment of left/right asymmetry; ISS: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; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Glycoprotein; Heterotaxy; Hydrolase;
KW Membrane; Metal-binding; Metalloprotease; Protease; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix; Zinc.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..788
FT /note="Ciliated left-right organizer metallopeptidase"
FT /evidence="ECO:0000255"
FT /id="PRO_5008408627"
FT TOPO_DOM 21..735
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 736..756
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 757..788
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 40..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 767..788
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 306
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 305
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 309
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 385
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 425
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 491
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 524
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 713
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VAR_SEQ 108
FT /note="V -> VPPV (in isoform 3)"
FT /id="VSP_061523"
FT VAR_SEQ 202..301
FT /note="Missing (in isoform 3)"
FT /id="VSP_061524"
FT VAR_SEQ 202..259
FT /note="Missing (in isoform 2)"
FT /id="VSP_061525"
FT VAR_SEQ 493..495
FT /note="SEC -> VSR (in isoform 3)"
FT /id="VSP_061526"
FT VARIANT 31
FT /note="S -> F (in HTX12; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:34903892"
FT /id="VAR_086199"
FT VARIANT 191..788
FT /note="Missing (in HTX12)"
FT /evidence="ECO:0000269|PubMed:34903892"
FT /id="VAR_086200"
FT VARIANT 324
FT /note="C -> S (in HTX12; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:34903892"
FT /id="VAR_086201"
FT VARIANT 346..788
FT /note="Missing (in HTX12)"
FT /evidence="ECO:0000269|PubMed:34903892"
FT /id="VAR_086202"
FT VARIANT 384
FT /note="S -> L (in HTX12; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:34903892"
FT /id="VAR_086203"
FT VARIANT 389
FT /note="R -> I (in HTX12; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:34903892"
FT /id="VAR_086204"
FT VARIANT 456
FT /note="Missing (in HTX12; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:34903892"
FT /id="VAR_086205"
FT VARIANT 469
FT /note="L -> P (in HTX12; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:34903892"
FT /id="VAR_086206"
FT CONFLICT 1..6
FT /note="MLLLLL -> MLLLP (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 339
FT /note="L -> Q (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 788 AA; 85397 MW; 8051E168BBD3EAF8 CRC64;
MLLLLLLLLL LPPLVLRVAA SRCLHDETQK SVSLLRPPFS QLPSKSRSSS LTLPSSRDPQ
PLRIQSCYLG DHISDGAWDP EGEGMRGGSR ALAAVREATQ RIQAVLAVQG PLLLSRDPAQ
YCHAVWGDPD SPNYHRCSLL NPGYKGESCL GAKIPDTHLR GYALWPEQGP PQLVQPDGPG
VQNTDFLLYV RVAHTSKCHQ ETVSLCCPGW STAAQSQLTA ALTSWAQRRG FVMLPRLCLK
LLGSSNLPTL ASQSIRITGP SVIAYAACCQ LDSEDRPLAG TIVYCAQHLT SPSLSHSDIV
MATLHELLHA LGFSGQLFKK WRDCPSGFSV RENCSTRQLV TRQDEWGQLL LTTPAVSLSL
AKHLGVSGAS LGVPLEEEEG LLSSHWEARL LQGSLMTATF DGAQRTRLDP ITLAAFKDSG
WYQVNHSAAE ELLWGQGSGP EFGLVTTCGT GSSDFFCTGS GLGCHYLHLD KGSCSSDPML
EGCRMYKPLA NGSECWKKEN GFPAGVDNPH GEIYHPQSRC FFANLTSQLL PGDKPRHPSL
TPHLKEAELM GRCYLHQCTG RGAYKVQVEG SPWVPCLPGK VIQIPGYYGL LFCPRGRLCQ
TNEDINAVTS PPVSLSTPDP LFQLSLELAG PPGHSLGKEQ QEGLAEAVLE ALASKGGTGR
CYFHGPSITT SLVFTVHMWK SPGCQGPSVA TLHKALTLTL QKKPLEVYHG GANFTTQPSK
LLVTSDHNPS MTHLRLSMGL CLMLLILVGV MGTTAYQKRA TLPVRPSASY HSPELHSTRV
PVRGIREV
