CBPQ_HUMAN
ID CBPQ_HUMAN Reviewed; 472 AA.
AC Q9Y646; B2RD88; Q8NBZ1; Q9UNM8; Q9Y5X6;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Carboxypeptidase Q;
DE EC=3.4.17.-;
DE AltName: Full=Lysosomal dipeptidase;
DE AltName: Full=Plasma glutamate carboxypeptidase;
DE Flags: Precursor;
GN Name=CPQ; Synonyms=LCH1, PGCP;
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], PROTEIN SEQUENCE OF 45-75, ENZYME ACTIVITY,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX PubMed=10206990; DOI=10.1074/jbc.274.17.11742;
RA Gingras R., Richard C., El-Alfy M., Morales C.R., Potier M.,
RA Pshezhetsky A.V.;
RT "Purification, cDNA cloning, and expression of a new human blood plasma
RT glutamate carboxypeptidase homologous to N-acetyl-aspartyl-alpha-glutamate
RT carboxypeptidase/prostate-specific membrane antigen.";
RL J. Biol. Chem. 274:11742-11750(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Liu C.H., Lin B.Y., Chang L.Y.;
RT "Cloning of the human aminopeptidase gene.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [7]
RP PROTEIN SEQUENCE OF 45-74, AND HOMODIMERIZATION.
RX PubMed=12675526; DOI=10.1515/bc.2003.036;
RA Dolenc I., Mihelic M.;
RT "Purification and primary structure determination of human lysosomal
RT dipeptidase.";
RL Biol. Chem. 384:317-320(2003).
RN [8]
RP INDUCTION.
RX PubMed=12591738;
RA Smith M.W., Yue Z.N., Geiss G.K., Sadovnikova N.Y., Carter V.S., Boix L.,
RA Lazaro C.A., Rosenberg G.B., Bumgarner R.E., Fausto N., Bruix J.,
RA Katze M.G.;
RT "Identification of novel tumor markers in hepatitis C virus-associated
RT hepatocellular carcinoma.";
RL Cancer Res. 63:859-864(2003).
RN [9]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-179; ASN-353 AND ASN-356.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [10]
RP HOMODIMERIZATION.
RX PubMed=17214548; DOI=10.1515/bc.2007.005;
RA Dolenc I., Pain R., Turk V.;
RT "Presence of the propeptide on recombinant lysosomal dipeptidase controls
RT both activation and dimerization.";
RL Biol. Chem. 388:47-51(2007).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-179.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
CC -!- FUNCTION: Carboxypeptidase that may play an important role in the
CC hydrolysis of circulating peptides. Catalyzes the hydrolysis of
CC dipeptides with unsubstituted terminals into amino acids. May play a
CC role in the liberation of thyroxine hormone from its thyroglobulin (Tg)
CC precursor.
CC -!- SUBUNIT: Homodimer. The monomeric form is inactive while the homodimer
CC is active.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:10206990}. Golgi apparatus
CC {ECO:0000269|PubMed:10206990}. Lysosome {ECO:0000250}. Secreted
CC {ECO:0000269|PubMed:10206990}. Note=Secretion is stimulated by
CC TSH/thyroid-stimulating hormone, INS/insulin and SST/somatostatin.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Mainly detected in blood plasma. Abundant in
CC placenta and kidney. Present at low level in muscles, liver and skin
CC fibroblasts. Not detected in brain or white blood cells (at protein
CC level). {ECO:0000269|PubMed:10206990}.
CC -!- INDUCTION: Up-regulated in the majority of hepatitis C virus-associated
CC hepatocellular carcinoma. {ECO:0000269|PubMed:12591738}.
CC -!- PTM: N-glycosylated. The secreted form is modified by hybrid or complex
CC type oligosaccharide chains (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase M28 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD31418.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF119386; AAD31418.1; ALT_FRAME; mRNA.
DR EMBL; AF107833; AAD43213.1; -; mRNA.
DR EMBL; AF107834; AAD43214.1; -; mRNA.
DR EMBL; AK075132; BAC11423.1; -; mRNA.
DR EMBL; AK315447; BAG37835.1; -; mRNA.
DR EMBL; CH471060; EAW91757.1; -; Genomic_DNA.
DR EMBL; BC020689; AAH20689.1; -; mRNA.
DR CCDS; CCDS6273.1; -.
DR RefSeq; NP_057218.1; NM_016134.3.
DR AlphaFoldDB; Q9Y646; -.
DR SMR; Q9Y646; -.
DR BioGRID; 115676; 27.
DR STRING; 9606.ENSP00000220763; -.
DR DrugBank; DB00142; Glutamic acid.
DR MEROPS; M28.014; -.
DR GlyConnect; 1069; 6 N-Linked glycans (1 site).
DR GlyGen; Q9Y646; 5 sites, 6 N-linked glycans (1 site).
DR iPTMnet; Q9Y646; -.
DR MetOSite; Q9Y646; -.
DR PhosphoSitePlus; Q9Y646; -.
DR BioMuta; CPQ; -.
DR DMDM; 74735298; -.
DR EPD; Q9Y646; -.
DR jPOST; Q9Y646; -.
DR MassIVE; Q9Y646; -.
DR MaxQB; Q9Y646; -.
DR PaxDb; Q9Y646; -.
DR PeptideAtlas; Q9Y646; -.
DR PRIDE; Q9Y646; -.
DR ProteomicsDB; 86599; -.
DR Antibodypedia; 12985; 121 antibodies from 26 providers.
DR DNASU; 10404; -.
DR Ensembl; ENST00000220763.10; ENSP00000220763.5; ENSG00000104324.16.
DR GeneID; 10404; -.
DR KEGG; hsa:10404; -.
DR MANE-Select; ENST00000220763.10; ENSP00000220763.5; NM_016134.4; NP_057218.1.
DR UCSC; uc003yhw.5; human.
DR CTD; 10404; -.
DR DisGeNET; 10404; -.
DR GeneCards; CPQ; -.
DR HGNC; HGNC:16910; CPQ.
DR HPA; ENSG00000104324; Tissue enhanced (thyroid).
DR MIM; 618754; gene.
DR neXtProt; NX_Q9Y646; -.
DR OpenTargets; ENSG00000104324; -.
DR VEuPathDB; HostDB:ENSG00000104324; -.
DR eggNOG; KOG2195; Eukaryota.
DR GeneTree; ENSGT00390000018110; -.
DR HOGENOM; CLU_033697_1_1_1; -.
DR InParanoid; Q9Y646; -.
DR OMA; LFMNEEN; -.
DR OrthoDB; 792624at2759; -.
DR PhylomeDB; Q9Y646; -.
DR TreeFam; TF323248; -.
DR PathwayCommons; Q9Y646; -.
DR BioGRID-ORCS; 10404; 19 hits in 1077 CRISPR screens.
DR ChiTaRS; CPQ; human.
DR GenomeRNAi; 10404; -.
DR Pharos; Q9Y646; Tbio.
DR PRO; PR:Q9Y646; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q9Y646; protein.
DR Bgee; ENSG00000104324; Expressed in left lobe of thyroid gland and 208 other tissues.
DR ExpressionAtlas; Q9Y646; baseline and differential.
DR Genevisible; Q9Y646; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0004180; F:carboxypeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070573; F:metallodipeptidase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0043171; P:peptide catabolic process; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0006590; P:thyroid hormone generation; ISS:UniProtKB.
DR GO; GO:0042246; P:tissue regeneration; ISS:UniProtKB.
DR InterPro; IPR039866; CPQ.
DR InterPro; IPR007484; Peptidase_M28.
DR PANTHER; PTHR12053; PTHR12053; 1.
DR Pfam; PF04389; Peptidase_M28; 1.
PE 1: Evidence at protein level;
KW Carboxypeptidase; Direct protein sequencing; Endoplasmic reticulum;
KW Glycoprotein; Golgi apparatus; Hydrolase; Lysosome; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Secreted; Signal; Zinc;
KW Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..44
FT /evidence="ECO:0000269|PubMed:10206990,
FT ECO:0000269|PubMed:12675526"
FT /id="PRO_5000055941"
FT CHAIN 45..472
FT /note="Carboxypeptidase Q"
FT /id="PRO_5000055942"
FT ACT_SITE 336
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 290
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 302
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 302
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 337
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 364
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 434
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT CARBOHYD 61
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 179
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT CARBOHYD 356
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT CARBOHYD 396
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 138
FT /note="S -> N (in dbSNP:rs34088584)"
FT /id="VAR_037466"
FT CONFLICT 37
FT /note="K -> E (in Ref. 4; BAC11423)"
FT /evidence="ECO:0000305"
FT CONFLICT 117
FT /note="E -> G (in Ref. 4; BAC11423)"
FT /evidence="ECO:0000305"
FT CONFLICT 385
FT /note="M -> V (in Ref. 4; BAC11423)"
FT /evidence="ECO:0000305"
FT CONFLICT 446
FT /note="K -> Q (in Ref. 1; AAD31418)"
FT /evidence="ECO:0000305"
FT CONFLICT 449
FT /note="N -> D (in Ref. 1; AAD31418)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 472 AA; 51888 MW; EB6CBD2149E042BF CRC64;
MKFLIFAFFG GVHLLSLCSG KAICKNGISK RTFEEIKEEI ASCGDVAKAI INLAVYGKAQ
NRSYERLALL VDTVGPRLSG SKNLEKAIQI MYQNLQQDGL EKVHLEPVRI PHWERGEESA
VMLEPRIHKI AILGLGSSIG TPPEGITAEV LVVTSFDELQ RRASEARGKI VVYNQPYINY
SRTVQYRTQG AVEAAKVGAL ASLIRSVASF SIYSPHTGIQ EYQDGVPKIP TACITVEDAE
MMSRMASHGI KIVIQLKMGA KTYPDTDSFN TVAEITGSKY PEQVVLVSGH LDSWDVGQGA
MDDGGGAFIS WEALSLIKDL GLRPKRTLRL VLWTAEEQGG VGAFQYYQLH KVNISNYSLV
MESDAGTFLP TGLQFTGSEK ARAIMEEVMS LLQPLNITQV LSHGEGTDIN FWIQAGVPGA
SLLDDLYKYF FFHHSHGDTM TVMDPKQMNV AAAVWAVVSY VVADMEEMLP RS
