ID   CBPB2_MOUSE             Reviewed;         422 AA.
AC   Q9JHH6; Q5EBI3; Q9QZF0;
DT   26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   27-MAR-2024, entry version 156.
DE   RecName: Full=Carboxypeptidase B2;
DE            EC=3.4.17.20;
DE   AltName: Full=Carboxypeptidase R;
DE            Short=CPR;
DE   AltName: Full=Carboxypeptidase U;
DE            Short=CPU;
DE   AltName: Full=Thrombin-activable fibrinolysis inhibitor;
DE            Short=TAFI;
DE   Flags: Precursor;
GN   Name=Cpb2; Synonyms=Tafi;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=10878383; DOI=10.4049/jimmunol.165.2.1053;
RA   Sato T., Miwa T., Akatsu H., Matsukawa N., Obata K., Okada N., Campbell W.,
RA   Okada H.;
RT   "Pro-carboxypeptidase R is an acute phase protein in the mouse, whereas
RT   carboxypeptidase N is not.";
RL   J. Immunol. 165:1053-1058(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=10739389;
RA   Marx P.F., Wagenaar G.T.M., Reijerkerk A., Tiekstra M.J.,
RA   van Rossum A.G.S.H., Gebbink M.F.G.B., Meijers J.C.M.;
RT   "Characterization of mouse thrombin-activatable fibrinolysis inhibitor.";
RL   Thromb. Haemost. 83:297-303(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6 X CBA;
RA   He Y.C., Broze G.;
RT   "Isolation and characterization of mouse liver carboxypeptidase B gene.";
RL   Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Liver;
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   [6]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-72.
RC   STRAIN=C57BL/6J; TISSUE=Plasma;
RX   PubMed=16944957; DOI=10.1021/pr060186m;
RA   Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.;
RT   "Proteome-wide characterization of N-glycosylation events by diagonal
RT   chromatography.";
RL   J. Proteome Res. 5:2438-2447(2006).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Cleaves C-terminal arginine or lysine residues from
CC       biologically active peptides such as kinins or anaphylatoxins in the
CC       circulation thereby regulating their activities. Down-regulates
CC       fibrinolysis by removing C-terminal lysine residues from fibrin that
CC       has already been partially degraded by plasmin.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Release of C-terminal Arg and Lys from a polypeptide.;
CC         EC=3.4.17.20;
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:P15086};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P15086};
CC   -!- ACTIVITY REGULATION: TAFI/CPB2 is unique among carboxypeptidases in
CC       that it spontaneously inactivates with a short half-life, a property
CC       that is crucial for its role in controlling blood clot lysis. The
CC       zymogen is stabilized by interactions with the activation peptide.
CC       Release of the activation peptide increases a dynamic flap mobility and
CC       in time this leads to conformational changes that disrupt the catalytic
CC       site and expose a cryptic thrombin-cleavage site present at Arg-323 (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10739389}.
CC   -!- TISSUE SPECIFICITY: Plasma; synthesized in the liver.
CC       {ECO:0000269|PubMed:10739389}.
CC   -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}.
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DR   EMBL; AB021968; BAB03402.1; -; mRNA.
DR   EMBL; AF164524; AAF62385.1; -; mRNA.
DR   EMBL; AF186188; AAF00528.1; -; mRNA.
DR   EMBL; AK004045; BAB23141.1; -; mRNA.
DR   EMBL; BC089577; AAH89577.1; -; mRNA.
DR   CCDS; CCDS27277.1; -.
DR   RefSeq; NP_062749.2; NM_019775.3.
DR   AlphaFoldDB; Q9JHH6; -.
DR   SMR; Q9JHH6; -.
DR   BioGRID; 207935; 12.
DR   STRING; 10090.ENSMUSP00000022576; -.
DR   MEROPS; M14.009; -.
DR   GlyCosmos; Q9JHH6; 6 sites, No reported glycans.
DR   GlyGen; Q9JHH6; 6 sites.
DR   iPTMnet; Q9JHH6; -.
DR   PhosphoSitePlus; Q9JHH6; -.
DR   CPTAC; non-CPTAC-5582; -.
DR   CPTAC; non-CPTAC-5583; -.
DR   MaxQB; Q9JHH6; -.
DR   PaxDb; 10090-ENSMUSP00000022576; -.
DR   PeptideAtlas; Q9JHH6; -.
DR   ProteomicsDB; 265561; -.
DR   Antibodypedia; 1324; 668 antibodies from 35 providers.
DR   DNASU; 56373; -.
DR   Ensembl; ENSMUST00000022576.10; ENSMUSP00000022576.9; ENSMUSG00000021999.10.
DR   GeneID; 56373; -.
DR   KEGG; mmu:56373; -.
DR   UCSC; uc007uqq.2; mouse.
DR   AGR; MGI:1891837; -.
DR   CTD; 1361; -.
DR   MGI; MGI:1891837; Cpb2.
DR   VEuPathDB; HostDB:ENSMUSG00000021999; -.
DR   eggNOG; KOG2650; Eukaryota.
DR   GeneTree; ENSGT00940000159160; -.
DR   HOGENOM; CLU_019326_0_0_1; -.
DR   InParanoid; Q9JHH6; -.
DR   OMA; YDFTWKK; -.
DR   OrthoDB; 3540647at2759; -.
DR   PhylomeDB; Q9JHH6; -.
DR   TreeFam; TF317197; -.
DR   BRENDA; 3.4.17.20; 3474.
DR   Reactome; R-MMU-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR   Reactome; R-MMU-977606; Regulation of Complement cascade.
DR   BioGRID-ORCS; 56373; 1 hit in 76 CRISPR screens.
DR   ChiTaRS; Capzb; mouse.
DR   PRO; PR:Q9JHH6; -.
DR   Proteomes; UP000000589; Chromosome 14.
DR   RNAct; Q9JHH6; Protein.
DR   Bgee; ENSMUSG00000021999; Expressed in left lobe of liver and 75 other cell types or tissues.
DR   GO; GO:0005615; C:extracellular space; ISO:MGI.
DR   GO; GO:0004180; F:carboxypeptidase activity; IDA:MGI.
DR   GO; GO:0004181; F:metallocarboxypeptidase activity; IBA:GO_Central.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR   GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR   GO; GO:0042730; P:fibrinolysis; ISO:MGI.
DR   GO; GO:0097421; P:liver regeneration; IEA:Ensembl.
DR   GO; GO:0051918; P:negative regulation of fibrinolysis; ISO:MGI.
DR   GO; GO:2000346; P:negative regulation of hepatocyte proliferation; ISO:MGI.
DR   GO; GO:0010757; P:negative regulation of plasminogen activation; ISO:MGI.
DR   GO; GO:0003331; P:positive regulation of extracellular matrix constituent secretion; ISO:MGI.
DR   GO; GO:0030163; P:protein catabolic process; ISO:MGI.
DR   GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR   CDD; cd06246; M14_CPB2; 1.
DR   Gene3D; 3.30.70.340; Metallocarboxypeptidase-like; 1.
DR   Gene3D; 3.40.630.10; Zn peptidases; 1.
DR   InterPro; IPR033849; CPB2.
DR   InterPro; IPR036990; M14A-like_propep.
DR   InterPro; IPR003146; M14A_act_pep.
DR   InterPro; IPR000834; Peptidase_M14.
DR   PANTHER; PTHR11705:SF17; CARBOXYPEPTIDASE B2; 1.
DR   PANTHER; PTHR11705; PROTEASE FAMILY M14 CARBOXYPEPTIDASE A,B; 1.
DR   Pfam; PF00246; Peptidase_M14; 1.
DR   Pfam; PF02244; Propep_M14; 1.
DR   PRINTS; PR00765; CRBOXYPTASEA.
DR   SMART; SM00631; Zn_pept; 1.
DR   SUPFAM; SSF54897; Protease propeptides/inhibitors; 1.
DR   SUPFAM; SSF53187; Zn-dependent exopeptidases; 1.
DR   PROSITE; PS52035; PEPTIDASE_M14; 1.
DR   Genevisible; Q9JHH6; MM.
PE   1: Evidence at protein level;
KW   Blood coagulation; Carboxypeptidase; Disulfide bond; Fibrinolysis;
KW   Glycoprotein; Hemostasis; Hydrolase; Metal-binding; Metalloprotease;
KW   Protease; Reference proteome; Secreted; Signal; Zinc; Zymogen.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   PROPEP          22..113
FT                   /note="Activation peptide"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000004379"
FT   CHAIN           114..422
FT                   /note="Carboxypeptidase B2"
FT                   /id="PRO_0000004380"
FT   DOMAIN          121..418
FT                   /note="Peptidase M14"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   ACT_SITE        384
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   BINDING         180..183
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00730"
FT   BINDING         180
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   BINDING         183
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   BINDING         238
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00730"
FT   BINDING         255..256
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00730"
FT   BINDING         309
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   BINDING         310..311
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00730"
FT   BINDING         362
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00730"
FT   SITE            323..324
FT                   /note="Cleavage; by thrombin"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        43
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        72
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16944957"
FT   CARBOHYD        84
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        107
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        240
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        322
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        177..190
FT                   /evidence="ECO:0000250|UniProtKB:Q96IY4"
FT   DISULFID        249..273
FT                   /evidence="ECO:0000250|UniProtKB:Q96IY4"
FT   DISULFID        264..278
FT                   /evidence="ECO:0000250|UniProtKB:Q96IY4"
FT   CONFLICT        135
FT                   /note="I -> L (in Ref. 3; AAF00528)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        277
FT                   /note="Y -> C (in Ref. 5; AAH89577)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        344..346
FT                   /note="ESI -> GSF (in Ref. 3; AAF00528)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   422 AA;  48871 MW;  99113755669D55CB CRC64;
     MKLHGLGILV AIILYEQHGF AFQSGQVLSA LPRTSRQVQL LQNLTTTYEV VLWQPVTAEF
     IEKKKEVHFF VNASDVDSVK AHLNVSRIPF NVLMNNVEDL IEQQTFNDTV SPRASASYYE
     QYHSLNEIYS WIEVITEQHP DMLQKIYIGS SFEKYPLYVL KVSGKEQRIK NAIWIDCGIH
     AREWISPAFC LWFIGYVTQF HGKENLYTRL LRHVDFYIMP VMNVDGYDYT WKKNRMWRKN
     RSAHKNNRCV GTDLNRNFAS KHWCEKGASS SSCSETYCGL YPESEPEVKA VADFLRRNID
     HIKAYISMHS YSQQILFPYS YNRSKSKDHE ELSLVASEAV RAIESINKNT RYTHGSGSES
     LYLAPGGSDD WIYDLGIKYS FTIELRDTGR YGFLLPERYI KPTCAEALAA ISKIVWHVIR
     NT
//