CBPC4_MOUSE
ID CBPC4_MOUSE Reviewed; 1122 AA.
AC Q09M05; Q8C768;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 3.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Cytosolic carboxypeptidase 4 {ECO:0000303|PubMed:25103237};
DE EC=3.4.17.- {ECO:0000269|PubMed:21074048};
DE EC=3.4.17.24 {ECO:0000269|PubMed:21074048};
DE AltName: Full=ATP/GTP-binding protein-like 1;
DE AltName: Full=Protein deglutamylase CCP4 {ECO:0000305};
GN Name=Agbl1 {ECO:0000312|MGI:MGI:3646469};
GN Synonyms=Ccp4 {ECO:0000303|PubMed:17244818};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY.
RC STRAIN=C57BLKS/J;
RX PubMed=17244818; DOI=10.1096/fj.06-7329com;
RA Kalinina E., Biswas R., Berezniuk I., Hermoso A., Aviles F.X.,
RA Fricker L.D.;
RT "A novel subfamily of mouse cytosolic carboxypeptidases.";
RL FASEB J. 21:836-850(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP TISSUE SPECIFICITY, INTERACTION WITH MYLK, AND MUTAGENESIS OF HIS-803 AND
RP GLU-806.
RX PubMed=21074048; DOI=10.1016/j.cell.2010.10.014;
RA Rogowski K., van Dijk J., Magiera M.M., Bosc C., Deloulme J.C., Bosson A.,
RA Peris L., Gold N.D., Lacroix B., Grau M.B., Bec N., Larroque C.,
RA Desagher S., Holzer M., Andrieux A., Moutin M.J., Janke C.;
RT "A family of protein-deglutamylating enzymes associated with
RT neurodegeneration.";
RL Cell 143:564-578(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BLKS/J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=25103237; DOI=10.1091/mbc.e14-06-1072;
RA Tort O., Tanco S., Rocha C., Bieche I., Seixas C., Bosc C., Andrieux A.,
RA Moutin M.J., Aviles F.X., Lorenzo J., Janke C.;
RT "The cytosolic carboxypeptidases CCP2 and CCP3 catalyze posttranslational
RT removal of acidic amino acids.";
RL Mol. Biol. Cell 25:3017-3027(2014).
CC -!- FUNCTION: Metallocarboxypeptidase that mediates deglutamylation of
CC tubulin and non-tubulin target proteins (PubMed:21074048). Catalyzes
CC the removal of polyglutamate side chains present on the gamma-carboxyl
CC group of glutamate residues within the C-terminal tail of tubulin
CC protein (PubMed:21074048). Specifically cleaves tubulin long-side-
CC chains, while it is not able to remove the branching point glutamate
CC (PubMed:21074048). Also catalyzes the removal of polyglutamate residues
CC from the carboxy-terminus of non-tubulin proteins such as MYLK
CC (PubMed:21074048). {ECO:0000269|PubMed:21074048}.
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:0000269|PubMed:21074048};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60005;
CC Evidence={ECO:0000305|PubMed:21074048};
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:0000269|PubMed:21074048};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63793;
CC Evidence={ECO:0000305|PubMed:21074048};
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 (PubMed:21074048). Interacts with TCF4 (By
CC similarity). {ECO:0000250|UniProtKB:Q96MI9,
CC ECO:0000269|PubMed:21074048}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q96MI9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q09M05-4; Sequence=Displayed;
CC Name=2;
CC IsoId=Q09M05-2; Sequence=VSP_060162, VSP_060163, VSP_060164;
CC Name=3;
CC IsoId=Q09M05-3; Sequence=VSP_060162, VSP_060165, VSP_060166;
CC -!- TISSUE SPECIFICITY: Widely expressed at low level. Expressed in eye,
CC muscle, pituitary, testis and to a lower extent in brain.
CC {ECO:0000269|PubMed:17244818, ECO:0000269|PubMed:21074048,
CC ECO:0000269|PubMed:25103237}.
CC -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}.
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DR EMBL; DQ867033; ABI51952.1; -; mRNA.
DR EMBL; FN429927; CAZ69802.1; -; mRNA.
DR EMBL; AK052433; BAC34986.1; -; mRNA.
DR EMBL; AC115830; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC165265; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC121812; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC123792; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC121971; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS85321.1; -. [Q09M05-4]
DR RefSeq; NP_001186153.1; NM_001199224.1.
DR AlphaFoldDB; Q09M05; -.
DR SMR; Q09M05; -.
DR STRING; 10090.ENSMUSP00000103066; -.
DR MEROPS; M14.030; -.
DR iPTMnet; Q09M05; -.
DR PhosphoSitePlus; Q09M05; -.
DR PaxDb; Q09M05; -.
DR PRIDE; Q09M05; -.
DR ProteomicsDB; 265562; -. [Q09M05-4]
DR ProteomicsDB; 265563; -. [Q09M05-2]
DR ProteomicsDB; 265564; -. [Q09M05-3]
DR ProteomicsDB; 265565; -. [Q09M05-4]
DR Antibodypedia; 78500; 38 antibodies from 15 providers.
DR DNASU; 244071; -.
DR Ensembl; ENSMUST00000026854; ENSMUSP00000026854; ENSMUSG00000025754. [Q09M05-2]
DR Ensembl; ENSMUST00000107442; ENSMUSP00000103066; ENSMUSG00000025754. [Q09M05-3]
DR GeneID; 244071; -.
DR KEGG; mmu:244071; -.
DR UCSC; uc009hxb.1; mouse. [Q09M05-2]
DR UCSC; uc009hxc.1; mouse. [Q09M05-4]
DR UCSC; uc012fnc.1; mouse. [Q09M05-4]
DR CTD; 123624; -.
DR MGI; MGI:3646469; Agbl1.
DR VEuPathDB; HostDB:ENSMUSG00000025754; -.
DR eggNOG; KOG3641; Eukaryota.
DR GeneTree; ENSGT00940000160936; -.
DR HOGENOM; CLU_007391_1_0_1; -.
DR InParanoid; Q09M05; -.
DR OrthoDB; 481670at2759; -.
DR TreeFam; TF333192; -.
DR BioGRID-ORCS; 244071; 0 hits in 21 CRISPR screens.
DR ChiTaRS; Agbl1; mouse.
DR PRO; PR:Q09M05; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q09M05; protein.
DR Bgee; ENSMUSG00000025754; Expressed in hindlimb stylopod muscle and 40 other tissues.
DR ExpressionAtlas; Q09M05; baseline and differential.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; IDA:UniProtKB.
DR GO; GO:0015631; F:tubulin binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0035609; P:C-terminal protein deglutamylation; IDA:UniProtKB.
DR GO; GO:0035610; P:protein side chain deglutamylation; IDA: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 Alternative splicing; Carboxypeptidase; Cytoplasm; Hydrolase;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Zinc.
FT CHAIN 1..1122
FT /note="Cytosolic carboxypeptidase 4"
FT /id="PRO_0000305000"
FT REGION 287..338
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1099..1122
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 298..324
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 853
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 803
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305"
FT BINDING 806
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305"
FT BINDING 900
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT VAR_SEQ 1..252
FT /note="Missing (in isoform 3 and isoform 2)"
FT /id="VSP_060162"
FT VAR_SEQ 896..903
FT /note="FCDFHGHS -> SHFLLFIL (in isoform 2)"
FT /id="VSP_060163"
FT VAR_SEQ 904..1122
FT /note="Missing (in isoform 2)"
FT /id="VSP_060164"
FT VAR_SEQ 998..1018
FT /note="GLQFGTGELEEMGAMYCLGLL -> VCEVYTARSLCSAADHKNRGK (in
FT isoform 3)"
FT /id="VSP_060165"
FT VAR_SEQ 1019..1122
FT /note="Missing (in isoform 3)"
FT /id="VSP_060166"
FT MUTAGEN 803
FT /note="H->S: Abolishes deglutamylase activity; when
FT associated with Q-806."
FT /evidence="ECO:0000269|PubMed:21074048"
FT MUTAGEN 806
FT /note="E->Q: Abolishes deglutamylase activity; when
FT associated with S-803."
FT /evidence="ECO:0000269|PubMed:21074048"
FT CONFLICT 176..179
FT /note="SKHL -> KSNC (in Ref. 2; CAZ69802)"
FT /evidence="ECO:0000305"
FT CONFLICT 243
FT /note="S -> I (in Ref. 2; CAZ69802)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1122 AA; 126149 MW; F9B818FB39F03B37 CRC64;
MAEQEGSGLQ MLLHTLQNSS DKASTLSILQ VLGDLLSVGT DRRIYYMISK GGSEALLQTL
VDTARSSSPD WDILLPLFRL LAKVGLRDKK FGQKALELEA LDVTLILARK NLSHSQNLLH
CLWVLRVFAS SVTTGAMLGI NGAMELLFKV LSPYTRKHTR TIRAATEVLA ALLKSSKHLR
RAVNRGYVNS LLRLHQDWHS RDVTNTYVTI RHGLLLCLRH IVALRSGREA FLAAQGMETL
FSSAQTCLEN KNMELVISAV IQILRQCYPA SRLPLVTASS AYTFPAPGST SSELPLNLTE
EDFDDDGDEE MDKDSDVEAV KEDDDLETDL SKLSSKPGLD LPEEELAQYD AMCPELSCSF
EELEPKCGDD LNNKDTLHAN HHHIPSVASL RQHCFNREHS SWRQEREDTV HSSILHMVKT
GKSGVPSSSK QRSATNVNQS LQQNGLEIDS SGHDTSDIQA PLEQAAWDME AISCPRITAS
FPNSTKPEES IGAAEKLLHT HAKHIPFHDP HLYIANAMRT RSAVGFKTMA FPDLWGHCPP
PAAQPMLDRK LGVQRIKILE DIRRLLHPSD VINKVVFSLD EPRPLQGSIS NCLMFHSKFE
SGNLRKAIQV REFEYDLLVN ADVNSSQHQQ WFYFKVSGMR AAVPYHFNII NCEKPNSQFN
YGMQPTLYSV KEALLGRPAW IRTGSDICYY KNHYRQNAAT MDGALGKRYY TLTFAVTFPH
NEDACYLAYH YPYTYSTLMT HLEILERSID HREIYFRHDV LCQTLGGNPC PLVTITAFPE
SNSTEHLEQF RCRPYQVITA RVHPGESNAS WVMKGTLEFL VSSDPVAKLL RENFVFKIIP
MLNPDGVING NHRCSLRGED LNRQWLSPQA HLQPTIYHAK GLLHYLSSTG RGPVVFCDFH
GHSQKKNVFL YGCSMKETLW QAGCTVGESA LLEDVSYRTL PKILDKLAPA FTMNSCSFLV
EKSRASTARV VVWREMGVSR SYTMESSYCG CNQGPYQGLQ FGTGELEEMG AMYCLGLLIL
ELKSVNCSHK LLARASSLLN ADVLEHYLQR CSSSSSNSSN RTSEVDDEPY CMEEIDYSAD
SSSDAEQNFT ELDRQIQECA LNKDEEEEEK EEGTGWRRRS VT
