ID CBPC6_HUMAN Reviewed; 503 AA. AC Q5VU57; B3KT26; B4DG37; DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 3. DT 13-SEP-2023, entry version 138. DE RecName: Full=Cytosolic carboxypeptidase 6 {ECO:0000250|UniProtKB:Q09LZ8}; DE EC=3.4.17.24 {ECO:0000250|UniProtKB:Q09LZ8}; DE AltName: Full=ATP/GTP-binding protein-like 4; DE AltName: Full=Protein deglutamylase CCP6 {ECO:0000305}; GN Name=AGBL4 {ECO:0000312|HGNC:HGNC:25892}; Synonyms=CCP6; 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 1 AND 2). RC TISSUE=Amygdala, and Brain; 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=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [3] 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). RN [4] RP FUNCTION. RX PubMed=29593216; DOI=10.1038/s41467-018-03008-2; RA Ye B., Liu B., Hao L., Zhu X., Yang L., Wang S., Xia P., Du Y., Meng S., RA Huang G., Qin X., Wang Y., Yan X., Li C., Hao J., Zhu P., He L., Tian Y., RA Fan Z.; RT "Klf4 glutamylation is required for cell reprogramming and early embryonic RT development in mice."; RL Nat. Commun. 9:1261-1261(2018). CC -!- FUNCTION: Metallocarboxypeptidase that mediates protein deglutamylation CC of 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. Mediates the deglutamylation of CC nucleotidyltransferase CGAS, leading to CGAS antiviral defense response CC activation (By similarity). Involved in KLF4 deglutamylation which CC promotes KLF4 proteasome-mediated degradation, thereby negatively CC regulating cell pluripotency maintenance and embryogenesis CC (PubMed:29593216). {ECO:0000250|UniProtKB:Q09LZ8, CC ECO:0000269|PubMed:29593216}. 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:Q09LZ8}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60005; CC Evidence={ECO:0000250|UniProtKB:Q09LZ8}; CC -!- CATALYTIC ACTIVITY: CC Reaction=C-terminal L-alpha-aminoacyl-L-glutamyl-L-glutamyl-[tubulin] + CC H2O = C-terminal L-alpha-aminoacyl-L-glutamyl-[tubulin] + L- CC glutamate; Xref=Rhea:RHEA:63792, Rhea:RHEA-COMP:16435, Rhea:RHEA- CC COMP:16436, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985, ChEBI:CHEBI:149555, CC ChEBI:CHEBI:149556; EC=3.4.17.24; CC Evidence={ECO:0000250|UniProtKB:Q09LZ8}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63793; CC Evidence={ECO:0000250|UniProtKB:Q09LZ8}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:P00730}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P00730}; CC -!- SUBUNIT: Interacts with MYLK. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:Q09LZ8}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome, centriole {ECO:0000269|PubMed:23085998}. CC Golgi apparatus {ECO:0000269|PubMed:23085998}. Cytoplasm, cytoskeleton, CC cilium basal body {ECO:0000269|PubMed:23085998}. Note=Colocalizes with CC gamma-tubulin in the centrioles at interphase and dividing cells and CC with glutamylated tubulin in basal bodies of ciliated cells. CC {ECO:0000269|PubMed:23085998}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q5VU57-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5VU57-2; Sequence=VSP_040435, VSP_040436; CC -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAG52938.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAG57648.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK094826; BAG52938.1; ALT_FRAME; mRNA. DR EMBL; AK294394; BAG57648.1; ALT_FRAME; mRNA. DR EMBL; AC099788; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL355809; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL390023; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL391844; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL590432; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL591602; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL645507; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL645730; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS44137.1; -. [Q5VU57-1] DR RefSeq; NP_001310502.1; NM_001323573.1. [Q5VU57-2] DR RefSeq; NP_116174.3; NM_032785.3. [Q5VU57-1] DR AlphaFoldDB; Q5VU57; -. DR SMR; Q5VU57; -. DR BioGRID; 124316; 68. DR STRING; 9606.ENSP00000360905; -. DR ChEMBL; CHEMBL4523328; -. DR MEROPS; M14.027; -. DR iPTMnet; Q5VU57; -. DR PhosphoSitePlus; Q5VU57; -. DR BioMuta; AGBL4; -. DR DMDM; 317373463; -. DR EPD; Q5VU57; -. DR MassIVE; Q5VU57; -. DR PaxDb; Q5VU57; -. DR PeptideAtlas; Q5VU57; -. DR ProteomicsDB; 65385; -. [Q5VU57-1] DR ProteomicsDB; 65386; -. [Q5VU57-2] DR Antibodypedia; 52065; 72 antibodies from 19 providers. DR DNASU; 84871; -. DR Ensembl; ENST00000371839.6; ENSP00000360905.1; ENSG00000186094.18. [Q5VU57-1] DR GeneID; 84871; -. DR KEGG; hsa:84871; -. DR MANE-Select; ENST00000371839.6; ENSP00000360905.1; NM_032785.4; NP_116174.3. DR UCSC; uc001cru.3; human. [Q5VU57-1] DR AGR; HGNC:25892; -. DR CTD; 84871; -. DR DisGeNET; 84871; -. DR GeneCards; AGBL4; -. DR HGNC; HGNC:25892; AGBL4. DR HPA; ENSG00000186094; Tissue enhanced (brain, retina). DR MIM; 616476; gene. DR neXtProt; NX_Q5VU57; -. DR OpenTargets; ENSG00000186094; -. DR PharmGKB; PA142672636; -. DR VEuPathDB; HostDB:ENSG00000186094; -. DR eggNOG; KOG3641; Eukaryota. DR GeneTree; ENSGT00940000155042; -. DR HOGENOM; CLU_007523_6_1_1; -. DR InParanoid; Q5VU57; -. DR OMA; CHAPISY; -. DR OrthoDB; 168164at2759; -. DR PhylomeDB; Q5VU57; -. DR TreeFam; TF333009; -. DR PathwayCommons; Q5VU57; -. DR Reactome; R-HSA-8955332; Carboxyterminal post-translational modifications of tubulin. DR BioGRID-ORCS; 84871; 37 hits in 1146 CRISPR screens. DR ChiTaRS; AGBL4; human. DR GenomeRNAi; 84871; -. DR Pharos; Q5VU57; Tbio. DR PRO; PR:Q5VU57; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q5VU57; Protein. DR Bgee; ENSG00000186094; Expressed in buccal mucosa cell and 101 other tissues. DR ExpressionAtlas; Q5VU57; baseline and differential. DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC. 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:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0004181; F:metallocarboxypeptidase activity; ISS:UniProtKB. DR GO; GO:0015631; F:tubulin binding; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0098957; P:anterograde axonal transport of mitochondrion; IEA:Ensembl. DR GO; GO:0035609; P:C-terminal protein deglutamylation; ISS:UniProtKB. DR GO; GO:0021954; P:central nervous system neuron development; IEA:Ensembl. DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IEA:Ensembl. DR GO; GO:0035608; P:protein deglutamylation; ISS:UniProtKB. DR GO; GO:0035610; P:protein side chain deglutamylation; ISS:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:0120222; P:regulation of blastocyst development; IEA:Ensembl. DR GO; GO:0098958; P:retrograde axonal transport of mitochondrion; IEA:Ensembl. DR CDD; cd06908; M14_AGBL4_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:SF9; CYTOSOLIC CARBOXYPEPTIDASE 6; 1. DR Pfam; PF18027; Pepdidase_M14_N; 1. DR Pfam; PF00246; Peptidase_M14; 1. DR SMART; SM00631; Zn_pept; 1. DR SUPFAM; SSF53187; Zn-dependent exopeptidases; 1. PE 2: Evidence at transcript level; KW Alternative splicing; Carboxypeptidase; Cell projection; Cytoplasm; KW Cytoskeleton; Golgi apparatus; Hydrolase; Metal-binding; Metalloprotease; KW Protease; Reference proteome; Zinc. FT CHAIN 1..503 FT /note="Cytosolic carboxypeptidase 6" FT /id="PRO_0000284835" FT REGION 459..503 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 280 FT /note="Nucleophile" FT /evidence="ECO:0000250|UniProtKB:P00730" FT BINDING 230 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q09M02" FT BINDING 233 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q09M02" FT BINDING 328 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P00730" FT VAR_SEQ 94 FT /note="Q -> QVREIVDTFRVVL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_040435" FT VAR_SEQ 455..463 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_040436" FT VARIANT 443 FT /note="V -> M (in dbSNP:rs60977321)" FT /id="VAR_061078" FT CONFLICT 237 FT /note="S -> L (in Ref. 1; BAG57648)" FT /evidence="ECO:0000305" FT CONFLICT 490 FT /note="K -> R (in Ref. 1; BAG57648)" FT /evidence="ECO:0000305" SQ SEQUENCE 503 AA; 58230 MW; 4D1AD20229664D90 CRC64; MAEGSQSAPE AGNDMGNDDA IGGNVSKYIV LPTGYCGQPK KGHLIFDACF ESGNLGRVDQ VSEFEYDLFI RPDTCNPRFR VWFNFTVENV KESQRVIFNI VNFSKTKSLY RDGMAPMVKS TSRPKWQRLP PKNVYYYRCP DHRKNYVMSF AFCFDREEDI YQFAYCYPYT YTRFQHYLDS LQKRNMDYFF REQLGQSVQQ RKLDLLTITS PDNLREGAEQ KVVFITGRVH PGETPSSFVC QGIIDFLVSQ HPIACVLREY LVFKIAPMLN PDGVYLGNYR CSLMGFDLNR HWLDPSPWVH PTLHGVKQLI VQMYNDPKTS LEFYIDIHAH STMMNGFMYG NIFEDEERFQ RQAIFPKLLC QNAEDFSYSS TSFNRDAVKA GTGRRFLGGL LDHTSYCYTL EVSFYSYIIS GTTAAVPYTE EAYMKLGRNV ARTFLDYYRL NPVVEKVAIP MPRLRNKEIE VQRRKEKSPP YKHPLLRGPA SNYPNSKGDK KSSVNHKDPS TPF //