CBPO_HUMAN
ID CBPO_HUMAN Reviewed; 374 AA.
AC Q8IVL8; Q2M277; Q7RTW7;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Carboxypeptidase O {ECO:0000312|HGNC:HGNC:21011};
DE Short=CPO {ECO:0000312|HGNC:HGNC:21011};
DE EC=3.4.17.- {ECO:0000269|PubMed:21921028};
DE Flags: Precursor;
GN Name=CPO {ECO:0000312|HGNC:HGNC:21011};
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 [MRNA].
RC TISSUE=Ovary;
RA Obaya A.J., Lopez-Otin C.;
RT "A new Zn-carboxypeptidase highly expressed in ovary.";
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ILE-85 AND ARG-134.
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 [4]
RP IDENTIFICATION.
RX PubMed=11836249; DOI=10.1074/jbc.m112254200;
RA Wei S., Segura S., Vendrell J., Aviles F.X., Lanoue E., Day R., Feng Y.,
RA Fricker L.D.;
RT "Identification and characterization of three members of the human
RT metallocarboxypeptidase gene family.";
RL J. Biol. Chem. 277:14954-14964(2002).
RN [5]
RP PROTEIN SEQUENCE OF 21-25, FUNCTION, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND GLYCOSYLATION.
RX PubMed=21921028; DOI=10.1074/jbc.m111.265819;
RA Lyons P.J., Fricker L.D.;
RT "Carboxypeptidase O is a glycosylphosphatidylinositol-anchored intestinal
RT peptidase with acidic amino acid specificity.";
RL J. Biol. Chem. 286:39023-39032(2011).
RN [6]
RP VARIANT [LARGE SCALE ANALYSIS] ASN-273.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Carboxypeptidase which preferentially cleaves C-terminal
CC acidic residues from peptides and proteins. Can also cleave C-terminal
CC hydrophobic amino acids, with a preference for small residues over
CC large residues. {ECO:0000269|PubMed:21921028}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P00730};
CC -!- ACTIVITY REGULATION: Strongly inhibited by potato carboxypeptidase
CC inhibitor, and the chelating agents EDTA and 1,10-phenanthroline. Also
CC inhibited by compounds with multiple carboxylic acid groups such as
CC citrate and succinate, and to a lesser exent the amino acids aspartate
CC and glutamate. Not significantly inhibited by benzylsuccinic acid.
CC {ECO:0000269|PubMed:21921028}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=325 uM for 3-(2-furyl)acryloyl-Glu-Glu (at pH 7.5)
CC {ECO:0000269|PubMed:21921028};
CC KM=284 uM for 3-(2-furyl)acryloyl-Phe-Phe (at pH 7.5)
CC {ECO:0000269|PubMed:21921028};
CC KM=549 uM for 3-(2-furyl)acryloyl-Phe-Ala (at pH 7.5)
CC {ECO:0000269|PubMed:21921028};
CC KM=614 uM for 3-(2-furyl)acryloyl-Lys-Ala (at pH 7.5)
CC {ECO:0000269|PubMed:21921028};
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:21921028}; Lipid-anchor, GPI-anchor
CC {ECO:0000269|PubMed:21921028}.
CC -!- TISSUE SPECIFICITY: Detected in enterocytes of the ileum.
CC {ECO:0000269|PubMed:21921028}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:21921028}.
CC -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}.
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DR EMBL; AJ422118; CAD19478.1; -; mRNA.
DR EMBL; AC019052; AAX93277.1; -; Genomic_DNA.
DR EMBL; BC112076; AAI12077.1; -; mRNA.
DR EMBL; BC112078; AAI12079.1; -; mRNA.
DR EMBL; BK000189; DAA00036.1; -; mRNA.
DR CCDS; CCDS2372.1; -.
DR RefSeq; NP_775100.1; NM_173077.2.
DR RefSeq; XP_016858861.1; XM_017003372.1.
DR PDB; 5MRV; X-ray; 1.85 A; A/B=21-349.
DR PDBsum; 5MRV; -.
DR AlphaFoldDB; Q8IVL8; -.
DR SMR; Q8IVL8; -.
DR STRING; 9606.ENSP00000272852; -.
DR MEROPS; M14.021; -.
DR GlyGen; Q8IVL8; 4 sites.
DR iPTMnet; Q8IVL8; -.
DR PhosphoSitePlus; Q8IVL8; -.
DR BioMuta; CPO; -.
DR DMDM; 74723635; -.
DR MassIVE; Q8IVL8; -.
DR PaxDb; Q8IVL8; -.
DR PeptideAtlas; Q8IVL8; -.
DR PRIDE; Q8IVL8; -.
DR ProteomicsDB; 70740; -.
DR Antibodypedia; 52118; 189 antibodies from 21 providers.
DR DNASU; 130749; -.
DR Ensembl; ENST00000272852.4; ENSP00000272852.2; ENSG00000144410.5.
DR GeneID; 130749; -.
DR KEGG; hsa:130749; -.
DR MANE-Select; ENST00000272852.4; ENSP00000272852.2; NM_173077.3; NP_775100.1.
DR UCSC; uc002vby.2; human.
DR CTD; 130749; -.
DR DisGeNET; 130749; -.
DR GeneCards; CPO; -.
DR HGNC; HGNC:21011; CPO.
DR HPA; ENSG00000144410; Tissue enriched (intestine).
DR MIM; 609563; gene.
DR neXtProt; NX_Q8IVL8; -.
DR OpenTargets; ENSG00000144410; -.
DR PharmGKB; PA164741367; -.
DR VEuPathDB; HostDB:ENSG00000144410; -.
DR eggNOG; KOG2650; Eukaryota.
DR GeneTree; ENSGT00940000161508; -.
DR HOGENOM; CLU_019326_4_1_1; -.
DR InParanoid; Q8IVL8; -.
DR OMA; TKKIIWM; -.
DR OrthoDB; 524270at2759; -.
DR PhylomeDB; Q8IVL8; -.
DR TreeFam; TF317197; -.
DR PathwayCommons; Q8IVL8; -.
DR BioGRID-ORCS; 130749; 9 hits in 1071 CRISPR screens.
DR ChiTaRS; CPO; human.
DR GenomeRNAi; 130749; -.
DR Pharos; Q8IVL8; Tdark.
DR PRO; PR:Q8IVL8; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q8IVL8; protein.
DR Bgee; ENSG00000144410; Expressed in small intestine Peyer's patch and 90 other tissues.
DR Genevisible; Q8IVL8; HS.
DR GO; GO:0046658; C:anchored component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR CDD; cd06247; M14_CPO; 1.
DR InterPro; IPR033850; Carboxypeptidase_O.
DR InterPro; IPR000834; Peptidase_M14.
DR Pfam; PF00246; Peptidase_M14; 1.
DR PRINTS; PR00765; CRBOXYPTASEA.
DR SMART; SM00631; Zn_pept; 1.
DR PROSITE; PS00132; CARBOXYPEPT_ZN_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Carboxypeptidase; Cell membrane; Direct protein sequencing;
KW Glycoprotein; GPI-anchor; Hydrolase; Lipoprotein; Membrane; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Signal; Zinc.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:21921028"
FT CHAIN 21..352
FT /note="Carboxypeptidase O"
FT /evidence="ECO:0000305"
FT /id="PRO_0000252401"
FT PROPEP 353..374
FT /note="Removed in mature form"
FT /evidence="ECO:0000305"
FT /id="PRO_0000437881"
FT ACT_SITE 310
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 108
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 111
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 236
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT LIPID 352
FT /note="GPI-anchor amidated aspartate"
FT /evidence="ECO:0000255"
FT CARBOHYD 132
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 174
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 187
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 251
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 85
FT /note="M -> I (in dbSNP:rs13420911)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_027850"
FT VARIANT 134
FT /note="S -> R (in dbSNP:rs11903403)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_027851"
FT VARIANT 273
FT /note="K -> N (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs896000260)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036012"
FT HELIX 53..66
FT /evidence="ECO:0007829|PDB:5MRV"
FT TURN 67..70
FT /evidence="ECO:0007829|PDB:5MRV"
FT STRAND 71..78
FT /evidence="ECO:0007829|PDB:5MRV"
FT STRAND 84..90
FT /evidence="ECO:0007829|PDB:5MRV"
FT STRAND 99..105
FT /evidence="ECO:0007829|PDB:5MRV"
FT HELIX 113..128
FT /evidence="ECO:0007829|PDB:5MRV"
FT TURN 129..131
FT /evidence="ECO:0007829|PDB:5MRV"
FT HELIX 133..141
FT /evidence="ECO:0007829|PDB:5MRV"
FT STRAND 142..148
FT /evidence="ECO:0007829|PDB:5MRV"
FT HELIX 152..160
FT /evidence="ECO:0007829|PDB:5MRV"
FT TURN 173..176
FT /evidence="ECO:0007829|PDB:5MRV"
FT HELIX 182..184
FT /evidence="ECO:0007829|PDB:5MRV"
FT STRAND 186..189
FT /evidence="ECO:0007829|PDB:5MRV"
FT STRAND 192..194
FT /evidence="ECO:0007829|PDB:5MRV"
FT HELIX 213..225
FT /evidence="ECO:0007829|PDB:5MRV"
FT HELIX 226..228
FT /evidence="ECO:0007829|PDB:5MRV"
FT STRAND 229..236
FT /evidence="ECO:0007829|PDB:5MRV"
FT STRAND 241..245
FT /evidence="ECO:0007829|PDB:5MRV"
FT HELIX 256..274
FT /evidence="ECO:0007829|PDB:5MRV"
FT STRAND 279..282
FT /evidence="ECO:0007829|PDB:5MRV"
FT HELIX 283..286
FT /evidence="ECO:0007829|PDB:5MRV"
FT HELIX 294..300
FT /evidence="ECO:0007829|PDB:5MRV"
FT STRAND 304..310
FT /evidence="ECO:0007829|PDB:5MRV"
FT STRAND 314..317
FT /evidence="ECO:0007829|PDB:5MRV"
FT HELIX 323..325
FT /evidence="ECO:0007829|PDB:5MRV"
FT HELIX 326..346
FT /evidence="ECO:0007829|PDB:5MRV"
SQ SEQUENCE 374 AA; 42529 MW; 404C373BB841AAD2 CRC64;
MKPLLETLYL LGMLVPGGLG YDRSLAQHRQ EIVDKSVSPW SLETYSYNIY HPMGEIYEWM
REISEKYKEV VTQHFLGVTY ETHPMYYLKI SQPSGNPKKI IWMDCGIHAR EWIAPAFCQW
FVKEILQNHK DNSSIRKLLR NLDFYVLPVL NIDGYIYTWT TDRLWRKSRS PHNNGTCFGT
DLNRNFNASW CSIGASRNCQ DQTFCGTGPV SEPETKAVAS FIESKKDDIL CFLTMHSYGQ
LILTPYGYTK NKSSNHPEMI QVGQKAANAL KAKYGTNYRV GSSADILYAS SGSSRDWARD
IGIPFSYTFE LRDSGTYGFV LPEAQIQPTC EETMEAVLSV LDDVYAKHWH SDSAGRVTSA
TMLLGLLVSC MSLL
