CBPC2_HUMAN
ID CBPC2_HUMAN Reviewed; 902 AA.
AC Q5U5Z8; A8MPX2; Q53FV5; Q8IV57; Q9H5C0;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Cytosolic carboxypeptidase 2 {ECO:0000250|UniProtKB:Q8CDK2};
DE EC=3.4.17.- {ECO:0000250|UniProtKB:Q8CDK2};
DE AltName: Full=ATP/GTP-binding protein-like 2;
DE AltName: Full=Protein deglutamylase CCP2 {ECO:0000305};
GN Name=AGBL2 {ECO:0000312|HGNC:HGNC:26296};
GN Synonyms=CCP2 {ECO:0000250|UniProtKB:Q8CDK2};
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] (ISOFORM 2), AND VARIANT ILE-671.
RC TISSUE=Lung;
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 MRNA] (ISOFORM 2), AND VARIANT ILE-671.
RC TISSUE=Lung;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP ILE-671.
RC TISSUE=Lung, and 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 [5]
RP 3D-STRUCTURE MODELING, ACTIVITY REGULATION, AND INTERACTION WITH RARRES1;
RP KIF11 AND MAPRE1.
RX PubMed=21303978; DOI=10.1158/0008-5472.can-10-2294;
RA Sahab Z.J., Hall M.D., Me Sung Y., Dakshanamurthy S., Ji Y., Kumar D.,
RA Byers S.W.;
RT "Tumor suppressor RARRES1 interacts with cytoplasmic carboxypeptidase AGBL2
RT to regulate the alpha-tubulin tyrosination cycle.";
RL Cancer Res. 71:1219-1228(2011).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=23085998; DOI=10.1096/fj.12-209080;
RA Rodriguez de la Vega Otazo M., Lorenzo J., Tort O., Aviles F.X.,
RA Bautista J.M.;
RT "Functional segregation and emerging role of cilia-related cytosolic
RT carboxypeptidases (CCPs).";
RL FASEB J. 27:424-431(2013).
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. {ECO:0000250|UniProtKB:Q8CDK2}.
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:Q8CDK2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60005;
CC Evidence={ECO:0000250|UniProtKB:Q8CDK2};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by RARRES1.
CC {ECO:0000269|PubMed:21303978}.
CC -!- SUBUNIT: Interacts with RARRES1, KIF11 AND MAPRE1.
CC {ECO:0000269|PubMed:21303978}.
CC -!- INTERACTION:
CC Q5U5Z8-3; Q8NHQ1: CEP70; NbExp=3; IntAct=EBI-12226473, EBI-739624;
CC Q5U5Z8-3; P17568: NDUFB7; NbExp=3; IntAct=EBI-12226473, EBI-1246238;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q8CDK2}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome, centriole {ECO:0000269|PubMed:23085998}.
CC Cytoplasm, cytoskeleton, cilium basal body
CC {ECO:0000269|PubMed:23085998}. Note=Colocalizes with gamma-tubulin in
CC the centrioles and with glutamylated tubulin in the basal bodies of
CC ciliated cells. {ECO:0000269|PubMed:23085998}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q5U5Z8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5U5Z8-2; Sequence=VSP_024360;
CC Name=3;
CC IsoId=Q5U5Z8-3; Sequence=VSP_024361;
CC -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}.
CC -!- CAUTION: Was initially shown to catalyze the removal of carboxy-
CC terminus tyrosine from alpha-tubulin (PubMed:21303978). However, later
CC studies did not identified any detyrosinase or deglycylase activities
CC from the carboxy-terminus of tubulin (By similarity).
CC {ECO:0000250|UniProtKB:Q8CDK2, ECO:0000269|PubMed:21303978}.
CC -!- CAUTION: Was originally thought to have detyrosinating activity from C-
CC terminal positions on tubulin. {ECO:0000269|PubMed:21303978}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15707.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD96891.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAD96896.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK027251; BAB15707.1; ALT_SEQ; mRNA.
DR EMBL; AK223171; BAD96891.1; ALT_INIT; mRNA.
DR EMBL; AK223176; BAD96896.1; ALT_INIT; mRNA.
DR EMBL; AC021443; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC028200; AAH28200.1; -; mRNA.
DR EMBL; BC036234; AAH36234.1; -; mRNA.
DR CCDS; CCDS7944.1; -. [Q5U5Z8-1]
DR RefSeq; NP_079059.2; NM_024783.3. [Q5U5Z8-1]
DR AlphaFoldDB; Q5U5Z8; -.
DR SMR; Q5U5Z8; -.
DR BioGRID; 122932; 8.
DR IntAct; Q5U5Z8; 3.
DR STRING; 9606.ENSP00000435582; -.
DR ChEMBL; CHEMBL3886062; -.
DR MEROPS; M14.029; -.
DR iPTMnet; Q5U5Z8; -.
DR PhosphoSitePlus; Q5U5Z8; -.
DR BioMuta; AGBL2; -.
DR DMDM; 206729855; -.
DR EPD; Q5U5Z8; -.
DR jPOST; Q5U5Z8; -.
DR MassIVE; Q5U5Z8; -.
DR PaxDb; Q5U5Z8; -.
DR PeptideAtlas; Q5U5Z8; -.
DR PRIDE; Q5U5Z8; -.
DR Antibodypedia; 1166; 123 antibodies from 22 providers.
DR DNASU; 79841; -.
DR Ensembl; ENST00000525123.6; ENSP00000435582.1; ENSG00000165923.17. [Q5U5Z8-1]
DR Ensembl; ENST00000645431.2; ENSP00000494229.1; ENSG00000285501.2. [Q5U5Z8-1]
DR GeneID; 79841; -.
DR KEGG; hsa:79841; -.
DR MANE-Select; ENST00000525123.6; ENSP00000435582.1; NM_024783.4; NP_079059.2.
DR UCSC; uc001ngg.4; human. [Q5U5Z8-1]
DR CTD; 79841; -.
DR DisGeNET; 79841; -.
DR GeneCards; AGBL2; -.
DR HGNC; HGNC:26296; AGBL2.
DR HPA; ENSG00000165923; Tissue enhanced (fallopian tube, testis).
DR MIM; 617345; gene.
DR neXtProt; NX_Q5U5Z8; -.
DR OpenTargets; ENSG00000165923; -.
DR PharmGKB; PA142672634; -.
DR VEuPathDB; HostDB:ENSG00000165923; -.
DR eggNOG; KOG3641; Eukaryota.
DR GeneTree; ENSGT00940000160201; -.
DR HOGENOM; CLU_007523_5_0_1; -.
DR InParanoid; Q5U5Z8; -.
DR OMA; TDVVLYC; -.
DR PhylomeDB; Q5U5Z8; -.
DR TreeFam; TF313794; -.
DR PathwayCommons; Q5U5Z8; -.
DR Reactome; R-HSA-8955332; Carboxyterminal post-translational modifications of tubulin.
DR SignaLink; Q5U5Z8; -.
DR BioGRID-ORCS; 79841; 8 hits in 1067 CRISPR screens.
DR ChiTaRS; AGBL2; human.
DR GenomeRNAi; 79841; -.
DR Pharos; Q5U5Z8; Tchem.
DR PRO; PR:Q5U5Z8; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q5U5Z8; protein.
DR Bgee; ENSG00000165923; Expressed in right uterine tube and 94 other tissues.
DR ExpressionAtlas; Q5U5Z8; baseline and differential.
DR Genevisible; Q5U5Z8; HS.
DR GO; GO:0005814; C:centriole; IDA:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0035610; P:protein side chain deglutamylation; ISS: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 1: Evidence at protein level;
KW Alternative splicing; Carboxypeptidase; Cell projection; Cytoplasm;
KW Cytoskeleton; Hydrolase; Metal-binding; Metalloprotease; Protease;
KW Reference proteome; Zinc.
FT CHAIN 1..902
FT /note="Cytosolic carboxypeptidase 2"
FT /id="PRO_0000283748"
FT REGION 746..770
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 796..879
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 796..814
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 847..869
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 512
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 462
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q09M02"
FT BINDING 465
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q09M02"
FT BINDING 558
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT VAR_SEQ 1..617
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_024361"
FT VAR_SEQ 1..471
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.2"
FT /id="VSP_024360"
FT VARIANT 90
FT /note="I -> R (in dbSNP:rs12795414)"
FT /id="VAR_046637"
FT VARIANT 333
FT /note="T -> P (in dbSNP:rs35898124)"
FT /id="VAR_046638"
FT VARIANT 349
FT /note="R -> H (in dbSNP:rs7941404)"
FT /id="VAR_031572"
FT VARIANT 368
FT /note="D -> G (in dbSNP:rs1870545)"
FT /id="VAR_046639"
FT VARIANT 671
FT /note="M -> I (in dbSNP:rs12286721)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT /id="VAR_046640"
SQ SEQUENCE 902 AA; 104194 MW; C9C5D8260AFBCF65 CRC64;
MFPALETHLK QTIPDPYEDF MYRHLQYYGY FKAQRGSLPN SATHQHVRKN NPQCLLNGSL
GEKDDLIPDT LQKEKLLWPI SLSSAVHRQI EAINRDFHSC LGWMQWRGLS SLQPPPPRFK
DSPASAFRVA GITDSHMLSL PHLRSRQLLY DELDEVNPRL REPQELFSIL STKRPLQAPR
WPIECEVIKE NIHHIEWAPP QPEYFYQPKG NEKVPEIVGE KKGTVVYQLD SVPIEGSYFT
SSRVGGKRGI VKELAVTLQG PEDNTLLFES RFESGNLQKA VRVDTYEYEL TLRTDLYTNK
HTQWFYFRVQ NTRKDATYRF TIVNLLKPKS LYTVGMKPLL YSQLDANTRN IGWRREGNEI
KYYKNNTDDG QQPFYCLTWT IQFPYDQDTC FFAHFYPYTY TDLQCYLLSV ANNPIQSQFC
KLQTLCRSLA GNTVYLLTIT NPSQTPQEAA AKKAVVLSAR VHPGESNGSW VMKGFLDFIL
SNSPDAQLLR DIFVFKVLPM LNPDGVIVGN YRCSLAGRDL NRHYKTILKE SFPCIWYTRN
MIKRLLEERE VLLYCDFHGH SRKNNIFLYG CNNNNRKYWL HERVFPLMLC KNAPDKFSFH
SCNFKVQKCK EGTGRVVMWR MGILNSYTME STFGGSTLGN KRDTHFTIED LKSLGYHVCD
TLLDFCDPDQ MKFTQCLAEL KELLRQEIHK KFHELGQDVD LEGSWSDISL SDIESSTSGS
DSSLSDGLPV HLANIADELT QKKKMFKKKK KKSLQTRKQR NEQYQKKNLM QKLKLTEDTS
EKAGFASTLQ KQPTFFKNSE NSSFLPMKNE NPRLNETNLN RRDKDTPLDP SMATLILPKN
KGRMQNKKPG FTVSCSPKRT INSSQEPAPG MKPNWPRSRY PATKRGCAAM AAYPSLHIYT
YP
