CBPC6_HUMAN
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 03-AUG-2022, entry version 133.
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};
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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; 31.
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 PRIDE; Q5VU57; -.
DR ProteomicsDB; 65385; -. [Q5VU57-1]
DR ProteomicsDB; 65386; -. [Q5VU57-2]
DR Antibodypedia; 52065; 65 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 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; 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; 36 hits in 1068 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 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 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
