ID   CBPC3_HUMAN             Reviewed;        1001 AA.
AC   Q8NEM8; B7Z827; Q9H965;
DT   03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2007, sequence version 2.
DT   27-MAR-2024, entry version 144.
DE   RecName: Full=Cytosolic carboxypeptidase 3 {ECO:0000250|UniProtKB:Q8CDP0};
DE            EC=3.4.17.- {ECO:0000250|UniProtKB:Q8CDP0};
DE   AltName: Full=ATP/GTP-binding protein-like 3;
DE   AltName: Full=Protein deglutamylase CCP3 {ECO:0000305};
GN   Name=AGBL3 {ECO:0000312|HGNC:HGNC:27981};
GN   Synonyms=CCP3 {ECO:0000250|UniProtKB:Q8CDP0};
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 MRNA] (ISOFORMS 3 AND 4), AND VARIANT
RP   GLN-122.
RC   TISSUE=Testis;
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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA   Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA   Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA   Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA   Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA   Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA   Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA   Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA   Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA   Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA   Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA   Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA   Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA   Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA   Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA   McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA   Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLN-122.
RC   TISSUE=Testis;
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   SIMILARITY WITH M14 FAMILY.
RX   PubMed=17244817; DOI=10.1096/fj.06-7330com;
RA   Rodriguez de la Vega M., Sevilla R.G., Hermoso A., Lorenzo J., Tanco S.,
RA   Diez A., Fricker L.D., Bautista J.M., Aviles F.X.;
RT   "Nna1-like proteins are active metallocarboxypeptidases of a new and
RT   diverse M14 subfamily.";
RL   FASEB J. 21:851-865(2007).
RN   [5]
RP   FUNCTION (ISOFORM 2).
RX   PubMed=25103237; DOI=10.1091/mbc.e14-06-1072;
RA   Tort O., Tanco S., Rocha C., Bieche I., Seixas C., Bosc C., Andrieux A.,
RA   Moutin M.J., Aviles F.X., Lorenzo J., Janke C.;
RT   "The cytosolic carboxypeptidases CCP2 and CCP3 catalyze posttranslational
RT   removal of acidic amino acids.";
RL   Mol. Biol. Cell 25:3017-3027(2014).
CC   -!- FUNCTION: Metallocarboxypeptidase that mediates deglutamylation of
CC       tubulin and non-tubulin target proteins. Catalyzes the removal of
CC       polyglutamate side chains present on the gamma-carboxyl group of
CC       glutamate residues within the C-terminal tail of tubulin protein.
CC       Specifically cleaves tubulin long-side-chains, while it is not able to
CC       remove the branching point glutamate. Also catalyzes the removal of
CC       polyglutamate residues from the carboxy-terminus of non-tubulin
CC       proteins such as MYLK. May catalyze the hydrolysis of aspartate from
CC       the carboxy-terminus of target proteins. Does not show detyrosinase or
CC       deglycylase activities from the carboxy-terminus of target proteins.
CC       {ECO:0000250|UniProtKB:Q8CDP0}.
CC   -!- FUNCTION: [Isoform 2]: Metallocarboxypeptidase that mediates tubulin
CC       deglutamylation. {ECO:0000269|PubMed:25103237}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(L-glutamyl)(n+1)-gamma-L-glutamyl-L-glutamyl-[protein] + H2O
CC         = (L-glutamyl)(n)-gamma-L-glutamyl-L-glutamyl-[protein] + L-
CC         glutamate; Xref=Rhea:RHEA:60004, Rhea:RHEA-COMP:15519, Rhea:RHEA-
CC         COMP:15675, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985, ChEBI:CHEBI:143623;
CC         Evidence={ECO:0000250|UniProtKB:Q8CDP0};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60005;
CC         Evidence={ECO:0000250|UniProtKB:Q8CDP0};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:Q8CDP0}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=1;
CC         IsoId=Q8NEM8-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8NEM8-2; Sequence=VSP_024372, VSP_024373;
CC       Name=3;
CC         IsoId=Q8NEM8-3; Sequence=VSP_024370, VSP_024371;
CC       Name=4;
CC         IsoId=Q8NEM8-4; Sequence=VSP_040423;
CC   -!- SIMILARITY: Belongs to the peptidase M14 family.
CC       {ECO:0000305|PubMed:17244817}.
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DR   EMBL; AK023045; BAB14371.1; -; mRNA.
DR   EMBL; AK302827; BAH13813.1; -; mRNA.
DR   EMBL; AC083862; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC083870; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC090497; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC030651; AAH30651.1; -; mRNA.
DR   CCDS; CCDS47718.1; -. [Q8NEM8-4]
DR   RefSeq; NP_848658.3; NM_178563.3. [Q8NEM8-4]
DR   RefSeq; XP_016867625.1; XM_017012136.1.
DR   RefSeq; XP_016867626.1; XM_017012137.1.
DR   AlphaFoldDB; Q8NEM8; -.
DR   SMR; Q8NEM8; -.
DR   BioGRID; 131041; 8.
DR   IntAct; Q8NEM8; 1.
DR   STRING; 9606.ENSP00000388275; -.
DR   MEROPS; M14.026; -.
DR   GlyGen; Q8NEM8; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q8NEM8; -.
DR   PhosphoSitePlus; Q8NEM8; -.
DR   BioMuta; AGBL3; -.
DR   DMDM; 143955274; -.
DR   MassIVE; Q8NEM8; -.
DR   PaxDb; 9606-ENSP00000388275; -.
DR   PeptideAtlas; Q8NEM8; -.
DR   ProteomicsDB; 73184; -. [Q8NEM8-1]
DR   ProteomicsDB; 73185; -. [Q8NEM8-2]
DR   ProteomicsDB; 73186; -. [Q8NEM8-3]
DR   ProteomicsDB; 73187; -. [Q8NEM8-4]
DR   Antibodypedia; 9809; 75 antibodies from 21 providers.
DR   DNASU; 340351; -.
DR   Ensembl; ENST00000275763.10; ENSP00000275763.6; ENSG00000146856.14. [Q8NEM8-2]
DR   Ensembl; ENST00000436302.6; ENSP00000388275.2; ENSG00000146856.14. [Q8NEM8-4]
DR   GeneID; 340351; -.
DR   KEGG; hsa:340351; -.
DR   MANE-Select; ENST00000436302.6; ENSP00000388275.2; NM_178563.4; NP_848658.3. [Q8NEM8-4]
DR   UCSC; uc011kpw.2; human. [Q8NEM8-1]
DR   AGR; HGNC:27981; -.
DR   DisGeNET; 340351; -.
DR   GeneCards; AGBL3; -.
DR   HGNC; HGNC:27981; AGBL3.
DR   HPA; ENSG00000146856; Tissue enhanced (epididymis).
DR   MIM; 617346; gene.
DR   neXtProt; NX_Q8NEM8; -.
DR   OpenTargets; ENSG00000146856; -.
DR   PharmGKB; PA142672635; -.
DR   VEuPathDB; HostDB:ENSG00000146856; -.
DR   eggNOG; KOG1814; Eukaryota.
DR   eggNOG; KOG3641; Eukaryota.
DR   GeneTree; ENSGT00940000160916; -.
DR   HOGENOM; CLU_318835_0_0_1; -.
DR   InParanoid; Q8NEM8; -.
DR   OMA; CGSKLGN; -.
DR   OrthoDB; 168164at2759; -.
DR   PhylomeDB; Q8NEM8; -.
DR   TreeFam; TF313794; -.
DR   PathwayCommons; Q8NEM8; -.
DR   Reactome; R-HSA-8955332; Carboxyterminal post-translational modifications of tubulin.
DR   SignaLink; Q8NEM8; -.
DR   BioGRID-ORCS; 340351; 20 hits in 1149 CRISPR screens.
DR   GenomeRNAi; 340351; -.
DR   Pharos; Q8NEM8; Tbio.
DR   PRO; PR:Q8NEM8; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; Q8NEM8; Protein.
DR   Bgee; ENSG00000146856; Expressed in buccal mucosa cell and 116 other cell types or tissues.
DR   ExpressionAtlas; Q8NEM8; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0004181; F:metallocarboxypeptidase activity; IDA:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0035610; P:protein side chain deglutamylation; IDA:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd06907; M14_AGBL2-3_like; 1.
DR   Gene3D; 2.60.40.3120; -; 1.
DR   Gene3D; 3.40.630.10; Zn peptidases; 1.
DR   InterPro; IPR040626; Pepdidase_M14_N.
DR   InterPro; IPR000834; Peptidase_M14.
DR   PANTHER; PTHR12756; CYTOSOLIC CARBOXYPEPTIDASE; 1.
DR   PANTHER; PTHR12756:SF23; CYTOSOLIC CARBOXYPEPTIDASE 3; 1.
DR   Pfam; PF18027; Pepdidase_M14_N; 1.
DR   Pfam; PF00246; Peptidase_M14; 1.
DR   SUPFAM; SSF53187; Zn-dependent exopeptidases; 1.
DR   PROSITE; PS52035; PEPTIDASE_M14; 1.
DR   Genevisible; Q8NEM8; HS.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Carboxypeptidase; Cytoplasm; Hydrolase;
KW   Metal-binding; Metalloprotease; Protease; Reference proteome; Zinc.
FT   CHAIN           1..1001
FT                   /note="Cytosolic carboxypeptidase 3"
FT                   /id="PRO_0000283751"
FT   DOMAIN          299..570
FT                   /note="Peptidase M14"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   REGION          641..661
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          962..1001
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        534
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   BINDING         364
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   BINDING         367
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   BINDING         460
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   VAR_SEQ         105
FT                   /note="W -> GVSCWSESHQAGAQWCDLGSLQPPPPRFKRFACFSLLSSRDYRRVPP
FT                   RPANFVFLVETGFHHVGQDGLRLLTS (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_024370"
FT   VAR_SEQ         106..1001
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_024371"
FT   VAR_SEQ         614..621
FT                   /note="SSRGSDSS -> RELTFLLR (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_024372"
FT   VAR_SEQ         622..1001
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_024373"
FT   VAR_SEQ         704..784
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_040423"
FT   VARIANT         45
FT                   /note="F -> Y (in dbSNP:rs2348049)"
FT                   /id="VAR_031573"
FT   VARIANT         122
FT                   /note="E -> Q (in dbSNP:rs4236655)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15489334"
FT                   /id="VAR_031574"
FT   VARIANT         360
FT                   /note="T -> I (in dbSNP:rs17804854)"
FT                   /id="VAR_031575"
FT   CONFLICT        210
FT                   /note="F -> S (in Ref. 1; BAH13813)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        396
FT                   /note="V -> A (in Ref. 1; BAH13813)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1001 AA;  116011 MW;  4846AEF2F76336AF CRC64;
     MSEDSEKEDY SDRTISDEDE SDEDMFMKFV SEDLHRCALL TADSFGDPFF PRTTQILLEY
     QLGRWVPRLR EPRDLYGVSS SGPLSPTRWP YHCEVIDEKV QHIDWTPSCP EPVYIPTGLE
     TEPLYPDSKE ATVVYLAEDA YKEPCFVYSR VGGNRTPLKQ PVDYRDNTLM FEARFESGNL
     QKVVKVAEYE YQLTVRPDLF TNKHTQWYYF QVTNMRAGIV YRFTIVNFTK PASLYSRGMR
     PLFYSEKEAK AHHIGWQRIG DQIKYYRNNP GQDGRHYFSL TWTFQFPHNK DTCYFAHCYP
     YTYTNLQEYL SGINNDPVRS KFCKIRVLCH TLARNMVYIL TITTPLKNSD SRKRKAVILT
     ARVHPGETNS SWIMKGFLDY ILGNSSDAQL LRDTFVFKVV PMLNPDGVIV GNYRCSLAGR
     DLNRNYTSLL KESFPSVWYT RNMVHRLMEK REVILYCDLH GHSRKENIFM YGCDGSDRSK
     TLYLQQRIFP LMLSKNCPDK FSFSACKFNV QKSKEGTGRV VMWKMGIRNS FTMEATFCGS
     TLGNKRGTHF STKDLESMGY HFCDSLLDYC DPDRTKYYRC LKELEEMERH ITLEKVFEDS
     DTPVIDITLD VESSSRGSDS SESIDSLTYL LKLTSQKKHL KTKKERNSTI ASHQNARGQE
     VYDRGHLLQR HTQSNSDVKD TRPNEPDDYM VDYFRRQLPN QGLAHCKLRL PGSRHSPASA
     SRVAGTTGTR HHTWLIFVFL VEMGKKIPLK GTDLYGNCFK VTSLQSPMGK QTSTWTEKTR
     IPTEDLHHNL KSKIKECISF QSKKTGINWT DDEKRSYKDK GIVQTQEILQ YLLPIVHSTK
     NMQTTQIKQL FNPRTNFQIQ HQLNPATCRN IKKYSTSWTA PRNHPFVIQG DVMANSSEWV
     QSKPHRSLES LSPLKGPKKN KHSQIWAIKN EDIKPLSSKW ETASSSFGMD ANVLKYKSLQ
     AEETNQQSSK HTALHLTKNK DEQANKNDGQ PTLYLKFQRE S
//