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 07-APR-2021, entry version 128. DE RecName: Full=Cytosolic carboxypeptidase 6; DE EC=3.4.17.-; DE AltName: Full=ATP/GTP-binding protein-like 4; GN Name=AGBL4; 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). CC -!- FUNCTION: Metallocarboxypeptidase that mediates deglutamylation of CC target proteins. Catalyzes the deglutamylation of polyglutamate side CC chains generated by post-translational polyglutamylation in proteins CC such as tubulins. Also removes polyglutamates from the carboxy-terminus CC of target proteins such as MYLK. Mediates deglutamylation of CGAS, CC regulating the antiviral activity of CGAS. Acts as a long-chain CC deglutamylase and specifically shortens long polyglutamate chains, CC while it is not able to remove the branching point glutamate, a process CC catalyzed by AGBL5/CCP5. {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 STRING; 9606.ENSP00000360905; -. 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 PRIDE; Q5VU57; -. DR ProteomicsDB; 65385; -. [Q5VU57-1] DR ProteomicsDB; 65386; -. [Q5VU57-2] DR Antibodypedia; 52065; 62 antibodies. DR DNASU; 84871; -. DR Ensembl; ENST00000371839; ENSP00000360905; ENSG00000186094. [Q5VU57-1] DR GeneID; 84871; -. DR KEGG; hsa:84871; -. DR UCSC; uc001cru.3; human. [Q5VU57-1] DR CTD; 84871; -. DR DisGeNET; 84871; -. DR GeneCards; AGBL4; -. DR HGNC; HGNC:25892; AGBL4. DR HPA; ENSG00000186094; Tissue enhanced (brain, pituitary gland). DR MIM; 616476; gene. DR neXtProt; NX_Q5VU57; -. DR OpenTargets; ENSG00000186094; -. DR PharmGKB; PA142672636; -. DR VEuPathDB; HostDB:ENSG00000186094.16; -. DR eggNOG; KOG3641; Eukaryota. DR GeneTree; ENSGT00940000155042; -. DR HOGENOM; CLU_007523_6_1_1; -. DR InParanoid; Q5VU57; -. DR OMA; KWQRIPR; -. DR OrthoDB; 481670at2759; -. DR PhylomeDB; Q5VU57; -. DR TreeFam; TF333009; -. DR PathwayCommons; Q5VU57; -. DR Reactome; R-HSA-8955332; Carboxyterminal post-translational modifications of tubulin. DR BioGRID-ORCS; 84871; 29 hits in 984 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 amniotic fluid and 110 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:0120222; P:regulation of blastocyst development; IEA:Ensembl. DR GO; GO:0098958; P:retrograde axonal transport of mitochondrion; IEA:Ensembl. DR InterPro; IPR040626; Pepdidase_M14_N. DR InterPro; IPR000834; Peptidase_M14. DR Pfam; PF18027; Pepdidase_M14_N; 1. DR Pfam; PF00246; Peptidase_M14; 1. DR SMART; SM00631; Zn_pept; 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 ACT_SITE 280 FT /note="Nucleophile" FT /evidence="ECO:0000250|UniProtKB:P00730" FT METAL 230 FT /note="Zinc" FT /evidence="ECO:0000250|UniProtKB:Q09M02" FT METAL 233 FT /note="Zinc" FT /evidence="ECO:0000250|UniProtKB:Q09M02" FT METAL 328 FT /note="Zinc" 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 //