CBPC4_HUMAN
ID CBPC4_HUMAN Reviewed; 1112 AA.
AC Q96MI9; A0A1C7CYX3; A1A4X5; A6NJH6; C9JHL5;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 3.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Cytosolic carboxypeptidase 4 {ECO:0000250|UniProtKB:Q09M05};
DE EC=3.4.17.- {ECO:0000250|UniProtKB:Q09M05};
DE EC=3.4.17.24 {ECO:0000250|UniProtKB:Q09M05};
DE AltName: Full=ATP/GTP-binding protein-like 1;
DE AltName: Full=Protein deglutamylase CCP4 {ECO:0000305};
GN Name=AGBL1 {ECO:0000312|HGNC:HGNC:26504};
GN Synonyms=CCP4 {ECO:0000250|UniProtKB:Q09M05};
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 GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 323-792.
RC TISSUE=Prostate;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 348-792.
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 VARIANTS FECD8 SER-1036 AND 1075-LEU--THR-1112 DEL, INTERACTION WITH TCF4,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=24094747; DOI=10.1016/j.ajhg.2013.08.010;
RA Riazuddin S.A., Vasanth S., Katsanis N., Gottsch J.D.;
RT "Mutations in AGBL1 cause dominant late-onset Fuchs corneal dystrophy and
RT alter protein-protein interaction with TCF4.";
RL Am. J. Hum. Genet. 93:758-764(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:Q09M05}.
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:Q09M05};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60005;
CC Evidence={ECO:0000250|UniProtKB:Q09M05};
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:Q09M05};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63793;
CC Evidence={ECO:0000250|UniProtKB:Q09M05};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBUNIT: Interacts with MYLK (By similarity). Interacts with TCF4
CC (PubMed:24094747). {ECO:0000250|UniProtKB:Q09M05,
CC ECO:0000269|PubMed:24094747}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:24094747}.
CC -!- TISSUE SPECIFICITY: Expressed in corneal endothelium.
CC {ECO:0000269|PubMed:24094747}.
CC -!- DISEASE: Corneal dystrophy, Fuchs endothelial, 8 (FECD8) [MIM:615523]:
CC A corneal disease caused by loss of endothelium of the central cornea.
CC It is characterized by focal wart-like guttata that arise from Descemet
CC membrane and develop in the central cornea, epithelial blisters,
CC reduced vision and pain. Descemet membrane is thickened by abnormal
CC collagenous deposition. {ECO:0000269|PubMed:24094747}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI28153.1; Type=Miscellaneous discrepancy; Note=Unlikely isoform. Probable cloning artifact.; Evidence={ECO:0000305};
CC Sequence=BAB71299.1; Type=Miscellaneous discrepancy; Note=Unlikely isoform. Probable cloning artifact.; Evidence={ECO:0000305};
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DR EMBL; AC016180; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC107978; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC025842; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC069197; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022817; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC012229; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC018950; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC078905; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC016987; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF456116; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK056872; BAB71299.1; ALT_SEQ; mRNA.
DR EMBL; BC128152; AAI28153.1; ALT_SEQ; mRNA.
DR CCDS; CCDS58398.2; -.
DR RefSeq; NP_689549.3; NM_152336.3.
DR AlphaFoldDB; Q96MI9; -.
DR SMR; Q96MI9; -.
DR BioGRID; 125828; 6.
DR STRING; 9606.ENSP00000413001; -.
DR MEROPS; M14.030; -.
DR iPTMnet; Q96MI9; -.
DR PhosphoSitePlus; Q96MI9; -.
DR BioMuta; AGBL1; -.
DR DMDM; 158706472; -.
DR MassIVE; Q96MI9; -.
DR PaxDb; Q96MI9; -.
DR PeptideAtlas; Q96MI9; -.
DR PRIDE; Q96MI9; -.
DR Antibodypedia; 78500; 38 antibodies from 15 providers.
DR DNASU; 123624; -.
DR Ensembl; ENST00000441037.7; ENSP00000413001.3; ENSG00000273540.5.
DR GeneID; 123624; -.
DR KEGG; hsa:123624; -.
DR UCSC; uc002blz.2; human.
DR CTD; 123624; -.
DR DisGeNET; 123624; -.
DR GeneCards; AGBL1; -.
DR HGNC; HGNC:26504; AGBL1.
DR HPA; ENSG00000273540; Group enriched (skeletal muscle, tongue).
DR MalaCards; AGBL1; -.
DR MIM; 615496; gene.
DR MIM; 615523; phenotype.
DR neXtProt; NX_Q96MI9; -.
DR OpenTargets; ENSG00000273540; -.
DR Orphanet; 98974; Fuchs endothelial corneal dystrophy.
DR PharmGKB; PA134923894; -.
DR VEuPathDB; HostDB:ENSG00000273540; -.
DR eggNOG; KOG3641; Eukaryota.
DR GeneTree; ENSGT00940000160936; -.
DR InParanoid; Q96MI9; -.
DR OMA; LNRQWCK; -.
DR OrthoDB; 481670at2759; -.
DR PhylomeDB; Q96MI9; -.
DR TreeFam; TF313794; -.
DR PathwayCommons; Q96MI9; -.
DR Reactome; R-HSA-8955332; Carboxyterminal post-translational modifications of tubulin.
DR SignaLink; Q96MI9; -.
DR BioGRID-ORCS; 123624; 8 hits in 1060 CRISPR screens.
DR ChiTaRS; AGBL1; human.
DR GenomeRNAi; 123624; -.
DR Pharos; Q96MI9; Tdark.
DR PRO; PR:Q96MI9; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q96MI9; protein.
DR Bgee; ENSG00000273540; Expressed in biceps brachii and 60 other tissues.
DR ExpressionAtlas; Q96MI9; baseline and differential.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
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:0035609; P:C-terminal 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 CDD; cd06906; M14_Nna1; 1.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR033852; CBPC1/4.
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 SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW Carboxypeptidase; Corneal dystrophy; Cytoplasm; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Zinc.
FT CHAIN 1..1112
FT /note="Cytosolic carboxypeptidase 4"
FT /id="PRO_0000304999"
FT REGION 291..345
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 298..325
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 326..345
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 854
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 804
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q09M02"
FT BINDING 807
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q09M02"
FT BINDING 901
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT VARIANT 463
FT /note="P -> L (in dbSNP:rs8029810)"
FT /id="VAR_048604"
FT VARIANT 481
FT /note="S -> P (in dbSNP:rs11857527)"
FT /id="VAR_048605"
FT VARIANT 1036
FT /note="C -> S (in FECD8; decreased TCF4-binding;
FT dbSNP:rs181958589)"
FT /evidence="ECO:0000269|PubMed:24094747"
FT /id="VAR_070225"
FT VARIANT 1056
FT /note="Q -> R (in dbSNP:rs8028043)"
FT /id="VAR_059195"
FT VARIANT 1075..1112
FT /note="Missing (in FECD8; enriched in the nucleus,
FT decreased TCF4-binding)"
FT /evidence="ECO:0000269|PubMed:24094747"
FT /id="VAR_070226"
FT CONFLICT 492
FT /note="V -> A (in Ref. 2; BAB71299)"
FT /evidence="ECO:0000305"
FT CONFLICT 570
FT /note="S -> G (in Ref. 2; BAB71299)"
FT /evidence="ECO:0000305"
FT CONFLICT 674
FT /note="A -> D (in Ref. 2; BAB71299)"
FT /evidence="ECO:0000305"
FT CONFLICT 704
FT /note="G -> R (in Ref. 3; AAI28153)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1112 AA; 125330 MW; A6116F416E3B65C3 CRC64;
MAEQEASGLQ VLLHTLQSSS DKESILTILK VLGDLLSVGT DRRIHYMISK GGSEALLQTL
VDTARTAPPD YDILLPLFRL LAKVGLRDKK IGRKALELEA LDVTLILARK NLSHGQNLLH
CLWALRVFAS SVSMGAMLGI NGAMELLFKV ITPYTRKRTQ AIRAATEVLA ALLKSKSNGR
RAVNRGYVTS LLGLHQDWHS HDTANAYVQI RRGLLLCLRH IAALRSGREA FLAAQGMEIL
FSTTQNCLDD KSMEPVISVV LQILRQCYPT SPLPLVTASS AYAFPVPGCI TTEPPHDLPE
EDFEDDGDDE VDKDSDTEDG KVEDDDLETD VNKLSSKPGL DRPEEELMQY EVMCLELSYS
FEELQSKLGD DLNSEKTQYA NHHHIPAAAS SKQHCYSKDQ SSCGQEREYA VQTSLLCRVK
TGRSTVHLGS KKNPGVNLYQ NVQSNSLRRD SSESEIPDIQ ASPKADAWDV DAIFCPRMSA
SFSNSTRTRE VVKVIDKLLQ THLKRVPFHD PYLYMAKARR TSSVVDFKMM AFPDVWGHCP
PPTTQPMLER KCGVQRIRIF EDIRRLIQPS DVINKVVFSL DEPWPLQDNA SNCLRFFSKF
ESGNLRKAIQ VREFEYDLLV NADVNSTQHQ QWFYFKVSGM QAAIPYHFNI INCEKPNSQF
NYGMQPTLYS VKEALLGKPT WIRTGHEICY YKNHYRQSTA VAGGASGKCY YTLTFAVTFP
HSEDVCYLAY HYPYTYTALM THLDILEKSV NLKEVYFRQD VLCQTLGGNP CPLVTITAMP
ESNSDEHLEQ FRHRPYQVIT ARVHPGESNA SWVMKGTLEF LVSSDPVARL LRENFIFKII
PMLNPDGVIN GNHRCSLSGE DLNRQWLSPS AHLQPTIYHA KGLLYHLSSI GRSPVVFCDF
HGHSQKKNVF LYGCSIKETL WQAACTVGTS TILEEVNYRT LPKILDKLAP AFTMSSCSFL
VEKSRASTAR VVVWREMGVS RSYTMESSYC GCNQGPYQCT QRLLERTKNE RAHPVDGLQG
LQFGTRELEE MGAMFCLGLL ILELKSASCS HQLLAQAATL LSAEEDALDQ HLQRLKSSNF
LPKHIWFAYH FFAITNFFKM NLLLHVSPVC DT
