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   24-JAN-2024, entry version 140.
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   GlyGen; Q96MI9; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q96MI9; -.
DR   PhosphoSitePlus; Q96MI9; -.
DR   BioMuta; AGBL1; -.
DR   DMDM; 158706472; -.
DR   MassIVE; Q96MI9; -.
DR   PaxDb; 9606-ENSP00000413001; -.
DR   PeptideAtlas; Q96MI9; -.
DR   Antibodypedia; 78500; 48 antibodies from 17 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   AGR; HGNC:26504; -.
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; SNQHHQW; -.
DR   OrthoDB; 168164at2759; -.
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 1135 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 61 other cell types or 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; 2.60.40.3120; -; 1.
DR   Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 1.
DR   Gene3D; 3.40.630.10; Zn peptidases; 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   PANTHER; PTHR12756; CYTOSOLIC CARBOXYPEPTIDASE; 1.
DR   PANTHER; PTHR12756:SF5; CYTOSOLIC CARBOXYPEPTIDASE 4; 1.
DR   Pfam; PF18027; Pepdidase_M14_N; 1.
DR   Pfam; PF00246; Peptidase_M14; 1.
DR   SUPFAM; SSF48371; ARM repeat; 1.
DR   SUPFAM; SSF53187; Zn-dependent exopeptidases; 1.
DR   PROSITE; PS52035; PEPTIDASE_M14; 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   DOMAIN          732..1022
FT                   /note="Peptidase M14"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
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        986
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   BINDING         804
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   BINDING         807
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   BINDING         901
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
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
//