CBPC3_HUMAN
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 03-AUG-2022, entry version 135.
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. [Q8NEM8-4]
DR RefSeq; XP_016867626.1; XM_017012137.1. [Q8NEM8-4]
DR AlphaFoldDB; Q8NEM8; -.
DR SMR; Q8NEM8; -.
DR BioGRID; 131041; 8.
DR IntAct; Q8NEM8; 1.
DR STRING; 9606.ENSP00000388275; -.
DR MEROPS; M14.026; -.
DR iPTMnet; Q8NEM8; -.
DR PhosphoSitePlus; Q8NEM8; -.
DR BioMuta; AGBL3; -.
DR DMDM; 143955274; -.
DR PaxDb; Q8NEM8; -.
DR PeptideAtlas; Q8NEM8; -.
DR PRIDE; Q8NEM8; -.
DR ProteomicsDB; 73184; -. [Q8NEM8-1]
DR ProteomicsDB; 73185; -. [Q8NEM8-2]
DR ProteomicsDB; 73186; -. [Q8NEM8-3]
DR ProteomicsDB; 73187; -. [Q8NEM8-4]
DR Antibodypedia; 9809; 65 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 CTD; 340351; -.
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; NCDNTLM; -.
DR OrthoDB; 481670at2759; -.
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; 19 hits in 1070 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 114 other tissues.
DR ExpressionAtlas; Q8NEM8; baseline and differential.
DR Genevisible; Q8NEM8; HS.
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 InterPro; IPR040626; Pepdidase_M14_N.
DR InterPro; IPR000834; Peptidase_M14.
DR Pfam; PF18027; Pepdidase_M14_N; 1.
DR Pfam; PF00246; Peptidase_M14; 1.
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 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 414
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 364
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q09M02"
FT BINDING 367
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q09M02"
FT BINDING 460
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P00730"
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
