CBPZ_HUMAN
ID CBPZ_HUMAN Reviewed; 652 AA.
AC Q66K79; O00520; Q96MX2;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Carboxypeptidase Z;
DE Short=CPZ;
DE EC=3.4.17.-;
DE Flags: Precursor;
GN Name=CPZ;
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] (ISOFORM 2), FUNCTION, ENZYME ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, TISSUE SPECIFICITY, AND
RP VARIANTS PRO-5; LEU-6 AND THR-486.
RX PubMed=9099699; DOI=10.1074/jbc.272.16.10543;
RA Song L., Fricker L.D.;
RT "Cloning and expression of human carboxypeptidase Z, a novel
RT metallocarboxypeptidase.";
RL J. Biol. Chem. 272:10543-10550(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Teratocarcinoma;
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANTS
RP PRO-5 AND THR-486.
RC TISSUE=Muscle;
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 [5]
RP ENZYME ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10080937; DOI=10.1006/bbrc.1999.0378;
RA Novikova E.G., Fricker L.D.;
RT "Purification and characterization of human metallocarboxypeptidase Z.";
RL Biochem. Biophys. Res. Commun. 256:564-568(1999).
RN [6]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10671522; DOI=10.1074/jbc.275.7.4865;
RA Novikova E.G., Reznik S.E., Varlamov O., Fricker L.D.;
RT "Carboxypeptidase Z is present in the regulated secretory pathway and
RT extracellular matrix in cultured cells and in human tissues.";
RL J. Biol. Chem. 275:4865-4870(2000).
RN [7]
RP FUNCTION.
RX PubMed=11766880; DOI=10.1007/pl00000819;
RA Reznik S.E., Fricker L.D.;
RT "Carboxypeptidases from A to Z: implications in embryonic development and
RT Wnt binding.";
RL Cell. Mol. Life Sci. 58:1790-1804(2001).
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12417617; DOI=10.1177/002215540205001111;
RA Fan X., Olson S.J., Blevins L.S., Allen G.S., Johnson M.D.;
RT "Immunohistochemical localization of carboxypeptidases D, E, and Z in
RT pituitary adenomas and normal human pituitary.";
RL J. Histochem. Cytochem. 50:1509-1516(2002).
CC -!- FUNCTION: Cleaves substrates with C-terminal arginine residues.
CC Probably modulates the Wnt signaling pathway, by cleaving some
CC undefined protein. May play a role in cleavage during prohormone
CC processing. {ECO:0000269|PubMed:11766880, ECO:0000269|PubMed:12417617,
CC ECO:0000269|PubMed:9099699}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P00730};
CC -!- ACTIVITY REGULATION: Inhibited by 2-mercaptomethyl-3-
CC guanidinoethylthiopropanoic acid (MGTA) and
CC guanidinoethylmercaptosuccinic acid (GEMSA). Inhibited by chelating
CC agents such as EDTA and EGTA. {ECO:0000269|PubMed:9099699}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2 mM for dansyl-Phe-Ala-Arg {ECO:0000269|PubMed:10080937,
CC ECO:0000269|PubMed:9099699};
CC KM=2 mM for dansyl-Pro-Ala-Arg {ECO:0000269|PubMed:10080937,
CC ECO:0000269|PubMed:9099699};
CC pH dependence:
CC Optimum pH is 7.8. {ECO:0000269|PubMed:10080937,
CC ECO:0000269|PubMed:9099699};
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:10671522}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q66K79-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q66K79-2; Sequence=VSP_020983;
CC Name=3;
CC IsoId=Q66K79-3; Sequence=VSP_040356;
CC -!- TISSUE SPECIFICITY: In placenta, it is present within invasive
CC trophoblasts and in the surrounding extracellular space. Also present
CC in amnion cells, but is not readily apparent in the extracellular
CC matrix of this cell type. Present in normal pituitary gland and
CC neoplastic pituitary gland (especially POMC-, GH- and PRL-producing
CC adenomas) (at protein level). Widely expressed.
CC {ECO:0000269|PubMed:10671522, ECO:0000269|PubMed:12417617,
CC ECO:0000269|PubMed:9099699}.
CC -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB71147.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U83411; AAB58911.1; -; mRNA.
DR EMBL; AK056317; BAB71147.1; ALT_FRAME; mRNA.
DR EMBL; AC105345; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006393; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC080539; AAH80539.1; -; mRNA.
DR CCDS; CCDS33953.1; -. [Q66K79-1]
DR CCDS; CCDS3404.1; -. [Q66K79-2]
DR CCDS; CCDS43212.1; -. [Q66K79-3]
DR RefSeq; NP_001014447.1; NM_001014447.2. [Q66K79-1]
DR RefSeq; NP_001014448.1; NM_001014448.2. [Q66K79-3]
DR RefSeq; NP_003643.2; NM_003652.3. [Q66K79-2]
DR AlphaFoldDB; Q66K79; -.
DR SMR; Q66K79; -.
DR BioGRID; 114102; 23.
DR IntAct; Q66K79; 3.
DR STRING; 9606.ENSP00000354255; -.
DR MEROPS; M14.012; -.
DR GlyGen; Q66K79; 1 site.
DR iPTMnet; Q66K79; -.
DR PhosphoSitePlus; Q66K79; -.
DR BioMuta; CPZ; -.
DR DMDM; 296434423; -.
DR EPD; Q66K79; -.
DR jPOST; Q66K79; -.
DR MassIVE; Q66K79; -.
DR PaxDb; Q66K79; -.
DR PeptideAtlas; Q66K79; -.
DR PRIDE; Q66K79; -.
DR ProteomicsDB; 65958; -. [Q66K79-1]
DR ProteomicsDB; 65959; -. [Q66K79-2]
DR ProteomicsDB; 65960; -. [Q66K79-3]
DR Antibodypedia; 22804; 64 antibodies from 22 providers.
DR DNASU; 8532; -.
DR Ensembl; ENST00000315782.6; ENSP00000315074.6; ENSG00000109625.19. [Q66K79-2]
DR Ensembl; ENST00000360986.9; ENSP00000354255.4; ENSG00000109625.19. [Q66K79-1]
DR Ensembl; ENST00000382480.6; ENSP00000371920.2; ENSG00000109625.19. [Q66K79-3]
DR GeneID; 8532; -.
DR KEGG; hsa:8532; -.
DR MANE-Select; ENST00000360986.9; ENSP00000354255.4; NM_001014447.3; NP_001014447.2.
DR UCSC; uc003glm.4; human. [Q66K79-1]
DR CTD; 8532; -.
DR DisGeNET; 8532; -.
DR GeneCards; CPZ; -.
DR HGNC; HGNC:2333; CPZ.
DR HPA; ENSG00000109625; Tissue enhanced (ovary).
DR MIM; 603105; gene.
DR neXtProt; NX_Q66K79; -.
DR OpenTargets; ENSG00000109625; -.
DR PharmGKB; PA26854; -.
DR VEuPathDB; HostDB:ENSG00000109625; -.
DR eggNOG; KOG2649; Eukaryota.
DR GeneTree; ENSGT00940000156391; -.
DR HOGENOM; CLU_006722_5_1_1; -.
DR InParanoid; Q66K79; -.
DR OMA; RCAHIAK; -.
DR OrthoDB; 101221at2759; -.
DR PhylomeDB; Q66K79; -.
DR TreeFam; TF315592; -.
DR PathwayCommons; Q66K79; -.
DR SignaLink; Q66K79; -.
DR BioGRID-ORCS; 8532; 10 hits in 1064 CRISPR screens.
DR GeneWiki; CPZ_(gene); -.
DR GenomeRNAi; 8532; -.
DR Pharos; Q66K79; Tbio.
DR PRO; PR:Q66K79; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q66K79; protein.
DR Bgee; ENSG00000109625; Expressed in left ovary and 98 other tissues.
DR ExpressionAtlas; Q66K79; baseline and differential.
DR Genevisible; Q66K79; HS.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006518; P:peptide metabolic process; IBA:GO_Central.
DR GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd03867; M14_CPZ; 1.
DR Gene3D; 1.10.2000.10; -; 1.
DR InterPro; IPR008969; CarboxyPept-like_regulatory.
DR InterPro; IPR020067; Frizzled_dom.
DR InterPro; IPR036790; Frizzled_dom_sf.
DR InterPro; IPR034239; M14_CPZ_CPD.
DR InterPro; IPR000834; Peptidase_M14.
DR Pfam; PF01392; Fz; 1.
DR Pfam; PF00246; Peptidase_M14; 1.
DR PRINTS; PR00765; CRBOXYPTASEA.
DR SMART; SM00063; FRI; 1.
DR SMART; SM00631; Zn_pept; 1.
DR SUPFAM; SSF49464; SSF49464; 1.
DR SUPFAM; SSF63501; SSF63501; 1.
DR PROSITE; PS00133; CARBOXYPEPT_ZN_2; 1.
DR PROSITE; PS50038; FZ; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Carboxypeptidase; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Secreted; Signal;
KW Wnt signaling pathway; Zinc.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..652
FT /note="Carboxypeptidase Z"
FT /evidence="ECO:0000250"
FT /id="PRO_0000252456"
FT DOMAIN 27..160
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT REGION 595..629
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 472
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P14384"
FT BINDING 248
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 251
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 380
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT CARBOHYD 281
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 43..109
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 51..102
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 93..129
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 118..157
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 122..146
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT VAR_SEQ 1..137
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040356"
FT VAR_SEQ 30..40
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9099699"
FT /id="VSP_020983"
FT VARIANT 5
FT /note="L -> P (in dbSNP:rs2302583)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9099699"
FT /id="VAR_027883"
FT VARIANT 6
FT /note="P -> L (in dbSNP:rs34964084)"
FT /evidence="ECO:0000269|PubMed:9099699"
FT /id="VAR_047244"
FT VARIANT 130
FT /note="Q -> L (in dbSNP:rs35993494)"
FT /id="VAR_047245"
FT VARIANT 486
FT /note="I -> T (in dbSNP:rs7378066)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9099699"
FT /id="VAR_047246"
FT VARIANT 501
FT /note="T -> M (in dbSNP:rs9991535)"
FT /id="VAR_027884"
FT CONFLICT 200
FT /note="T -> M (in Ref. 4; BC006393)"
FT /evidence="ECO:0000305"
FT CONFLICT 291
FT /note="M -> I (in Ref. 1; AAB58911)"
FT /evidence="ECO:0000305"
FT CONFLICT 523
FT /note="I -> T (in Ref. 2; BAB71147)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 652 AA; 73655 MW; BFA1EA7753E63F98 CRC64;
MPPPLPLLLL TVLVVAAARP GCEFERNPAG ECHRPPAADS ATCVDLQLRT CSDAAYNHTT
FPNLLQHRSW EVVEASSEYI LLSVLHQLLE GQCNPDLRLL GCAVLAPRCE GGWVRRPCRH
ICEGLREVCQ PAFDAIDMAW PYFLDCHRYF TREDEGCYDP LEKLRGGLEA DEALPSGLPP
TFIRFSHHSY AQMVRVLRRT ASRCAHVART YSIGRSFDGR ELLVIEFSSR PGQHELMEPE
VKLIGNIHGN EVAGREMLIY LAQYLCSEYL LGNPRIQRLL NTTRIHLLPS MNPDGYEVAA
AEGAGYNGWT SGRQNAQNLD LNRNFPDLTS EYYRLAETRG ARSDHIPIPQ HYWWGKVAPE
TKAIMKWMQT IPFVLSASLH GGDLVVSYPF DFSKHPQEEK MFSPTPDEKM FKLLSRAYAD
VHPMMMDRSE NRCGGNFLKR GSIINGADWY SFTGGMSDFN YLHTNCFEIT VELGCVKFPP
EEALYILWQH NKESLLNFVE TVHRGIKGVV TDKFGKPVKN ARISVKGIRH DITTAPDGDY
WRLLPPGIHI VIAQAPGYAK VIKKVIIPAR MKRAGRVDFI LQPLGMGPKN FIHGLRRTGP
HDPLGGASSL GEATEPDPLR ARRQPSADGS KPWWWSYFTS LSTHRPRWLL KY
