CBPC1_MOUSE
ID CBPC1_MOUSE Reviewed; 1218 AA.
AC Q641K1; Q3TDS0; Q3V147; Q6P9R9; Q8C1K8; Q9D962; Q9EQI4;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Cytosolic carboxypeptidase 1 {ECO:0000303|PubMed:21074048};
DE EC=3.4.17.- {ECO:0000269|PubMed:21074048, ECO:0000269|PubMed:22170066, ECO:0000269|PubMed:25103237, ECO:0000269|PubMed:29593216, ECO:0000269|PubMed:30420557};
DE EC=3.4.17.24 {ECO:0000269|PubMed:21074048, ECO:0000269|PubMed:22170066};
DE AltName: Full=ATP/GTP-binding protein 1;
DE AltName: Full=Nervous system nuclear protein induced by axotomy protein 1 {ECO:0000303|PubMed:11083920};
DE AltName: Full=Protein deglutamylase CCP1 {ECO:0000305};
GN Name=Agtpbp1 {ECO:0000312|MGI:MGI:2159437};
GN Synonyms=Ccp1 {ECO:0000303|PubMed:22170066},
GN Nna1 {ECO:0000303|PubMed:11083920};
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 1), SUBCELLULAR LOCATION, INDUCTION BY
RP AXON REGENERATION, AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J;
RX PubMed=11083920; DOI=10.1006/mcne.2000.0900;
RA Harris A., Morgan J.I., Pecot M., Soumare A., Osborne A., Soares H.D.;
RT "Regenerating motor neurons express Nna1, a novel ATP/GTP-binding protein
RT related to zinc carboxypeptidases.";
RL Mol. Cell. Neurosci. 16:578-596(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 1115-1218 (ISOFORM 1).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Hippocampus, Pancreas, and Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 INVOLVEMENT IN PCD, INDUCTION BY AXONAL REGENERATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=11884758; DOI=10.1126/science.1068912;
RA Fernandez-Gonzalez A., La Spada A.R., Treadaway J., Higdon J.C.,
RA Harris B.S., Sidman R.L., Morgan J.I., Zuo J.;
RT "Purkinje cell degeneration (pcd) phenotypes caused by mutations in the
RT axotomy-induced gene, Nna1.";
RL Science 295:1904-1906(2002).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Pancreas, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP VARIANT PCD ASP-832 INS.
RX PubMed=16465590; DOI=10.1007/s00335-005-0096-x;
RA Chakrabarti L., Neal J.T., Miles M., Martinez R.A., Smith A.C.,
RA Sopher B.L., La Spada A.R.;
RT "The Purkinje cell degeneration 5J mutation is a single amino acid
RT insertion that destabilizes Nna1 protein.";
RL Mamm. Genome 17:103-110(2006).
RN [7]
RP INVOLVEMENT IN PCD.
RX PubMed=16942761; DOI=10.1016/j.brainres.2006.07.065;
RA Wang T., Morgan J.I.;
RT "The Purkinje cell degeneration (pcd) mouse: an unexpected molecular link
RT between neuronal degeneration and regeneration.";
RL Brain Res. 1140:26-40(2007).
RN [8]
RP INVOLVEMENT IN PCD, AND MUTAGENESIS OF 971-ASN-ARG-972.
RX PubMed=16952463; DOI=10.1016/j.mcn.2006.07.009;
RA Wang T., Parris J., Li L., Morgan J.I.;
RT "The carboxypeptidase-like substrate-binding site in Nna1 is essential for
RT the rescue of the Purkinje cell degeneration (pcd) phenotype.";
RL Mol. Cell. Neurosci. 33:200-213(2006).
RN [9]
RP INVOLVEMENT IN PCD, AND MUTAGENESIS OF HIS-912 AND GLU-915.
RX PubMed=18602413; DOI=10.1016/j.visres.2008.05.026;
RA Chakrabarti L., Eng J., Martinez R.A., Jackson S., Huang J., Possin D.E.,
RA Sopher B.L., La Spada A.R.;
RT "The zinc-binding domain of Nna1 is required to prevent retinal
RT photoreceptor loss and cerebellar ataxia in Purkinje cell degeneration
RT (pcd) mice.";
RL Vision Res. 48:1999-2005(2008).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, INVOLVEMENT IN PCD,
RP INTERACTION WITH MYLK, AND MUTAGENESIS OF HIS-912 AND GLU-915.
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 [11]
RP INVOLVEMENT IN PCD, SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-912 AND
RP GLU-915.
RX PubMed=20620870; DOI=10.1016/j.neuron.2010.05.024;
RA Chakrabarti L., Zahra R., Jackson S.M., Kazemi-Esfarjani P., Sopher B.L.,
RA Mason A.G., Toneff T., Ryu S., Shaffer S., Kansy J.W., Eng J., Merrihew G.,
RA MacCoss M.J., Murphy A., Goodlett D.R., Hook V., Bennett C.L.,
RA Pallanck L.J., La Spada A.R.;
RT "Mitochondrial dysfunction in NnaD mutant flies and Purkinje cell
RT degeneration mice reveals a role for Nna proteins in neuronal
RT bioenergetics.";
RL Neuron 66:835-847(2010).
RN [12]
RP INVOLVEMENT IN PCD.
RX PubMed=20920790; DOI=10.1016/j.neuron.2010.08.013;
RA Li J., Gu X., Ma Y., Calicchio M.L., Kong D., Teng Y.D., Yu L., Crain A.M.,
RA Vartanian T.K., Pasqualini R., Arap W., Libermann T.A., Snyder E.Y.,
RA Sidman R.L.;
RT "Nna1 mediates Purkinje cell dendritic development via lysyl oxidase
RT propeptide and NF-kappaB signaling.";
RL Neuron 68:45-60(2010).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=22170066; DOI=10.1074/jbc.m111.309138;
RA Berezniuk I., Vu H.T., Lyons P.J., Sironi J.J., Xiao H., Burd B., Setou M.,
RA Angeletti R.H., Ikegami K., Fricker L.D.;
RT "Cytosolic carboxypeptidase 1 is involved in processing alpha- and beta-
RT tubulin.";
RL J. Biol. Chem. 287:6503-6517(2012).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, AND 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).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, INVOLVEMENT IN PCD, AND MUTAGENESIS OF
RP TYR-686; THR-843; ARG-910 AND HIS-982.
RX PubMed=30420557; DOI=10.15252/embj.2018100540;
RG Undiagnosed Diseases Network;
RA Shashi V., Magiera M.M., Klein D., Zaki M., Schoch K.,
RA Rudnik-Schoeneborn S., Norman A., Lopes Abath Neto O., Dusl M., Yuan X.,
RA Bartesaghi L., De Marco P., Alfares A.A., Marom R., Arold S.T.,
RA Guzman-Vega F.J., Pena L.D., Smith E.C., Steinlin M., Babiker M.O.,
RA Mohassel P., Foley A.R., Donkervoort S., Kaur R., Ghosh P.S., Stanley V.,
RA Musaev D., Nava C., Mignot C., Keren B., Scala M., Tassano E., Picco P.,
RA Doneda P., Fiorillo C., Issa M.Y., Alassiri A., Alahmad A., Gerard A.,
RA Liu P., Yang Y., Ertl-Wagner B., Kranz P.G., Wentzensen I.M., Stucka R.,
RA Stong N., Allen A.S., Goldstein D.B., Schoser B., Roesler K.M.,
RA Alfadhel M., Capra V., Chrast R., Strom T.M., Kamsteeg E.J.,
RA Boennemann C.G., Gleeson J.G., Martini R., Janke C., Senderek J.;
RT "Loss of tubulin deglutamylase CCP1 causes infantile-onset
RT neurodegeneration.";
RL EMBO J. 37:0-0(2018).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
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 (PubMed:21074048,
CC PubMed:22170066, PubMed:25103237, PubMed:30420557, PubMed:29593216).
CC Catalyzes the removal of polyglutamate side chains present on the
CC gamma-carboxyl group of glutamate residues within the C-terminal tail
CC of alpha- and beta-tubulin (PubMed:22170066, PubMed:25103237,
CC PubMed:30420557). Specifically cleaves tubulin long-side-chains, while
CC 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 alpha-tubulin as well as non-tubulin
CC proteins such as MYLK (PubMed:21074048, PubMed:22170066). Involved in
CC KLF4 deglutamylation which promotes KLF4 proteasome-mediated
CC degradation, thereby negatively regulating cell pluripotency
CC maintenance and embryogenesis (PubMed:29593216).
CC {ECO:0000269|PubMed:21074048, ECO:0000269|PubMed:22170066,
CC ECO:0000269|PubMed:25103237, ECO:0000269|PubMed:29593216,
CC ECO:0000269|PubMed:30420557}.
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, ECO:0000269|PubMed:22170066,
CC ECO:0000269|PubMed:25103237, ECO:0000269|PubMed:29593216,
CC ECO:0000269|PubMed:30420557};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60005;
CC Evidence={ECO:0000305|PubMed:21074048, ECO:0000305|PubMed:22170066,
CC ECO:0000305|PubMed:25103237, ECO:0000305|PubMed:29593216,
CC ECO:0000305|PubMed:30420557};
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, ECO:0000269|PubMed:22170066};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63793;
CC Evidence={ECO:0000305|PubMed:21074048, ECO:0000305|PubMed:22170066};
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. {ECO:0000269|PubMed:21074048}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9UPW5}.
CC Cytoplasm, cytosol {ECO:0000269|PubMed:11083920}. Nucleus
CC {ECO:0000269|PubMed:11083920}. Mitochondrion
CC {ECO:0000269|PubMed:20620870}. Note=Localizes in both the cytoplasm and
CC nuclei of interphase and dividing cells.
CC {ECO:0000250|UniProtKB:Q9UPW5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q641K1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q641K1-2; Sequence=VSP_029047, VSP_029048;
CC Name=3;
CC IsoId=Q641K1-3; Sequence=VSP_029045, VSP_029046;
CC Name=4;
CC IsoId=Q641K1-4; Sequence=VSP_038803, VSP_038805;
CC Name=5;
CC IsoId=Q641K1-5; Sequence=VSP_038804;
CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in the
CC cerebellum and cortex of adult mouse brain. Expressed at similar levels
CC in both the cerebellum and the cortex throughout all developmental
CC stages. Also expressed in sciatic nerve transection, spinal motor
CC neurons undergoing axon regeneration, testis, heart, eye, lung,
CC pancreas, intestine, stomach, pituitary, spleen, adrenal, kidney and in
CC developing brain. Expression in cranial motor nuclei is the same as
CC that observed in uninjured primary motor neurons. Expression is
CC prevalent in sensory neurons and hippocampal CA3 neurons in addition to
CC regenerating motor neurons. {ECO:0000269|PubMed:11884758,
CC ECO:0000269|PubMed:21074048, ECO:0000269|PubMed:25103237}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in differentiating neurons. From
CC 16.5 dpc, expression is widespread in brain, spinal cord, and
CC peripheral nervous tissue. Within the developing CNS, expression is
CC restricted to regions of brain and spinal cord containing
CC differentiating neurons. {ECO:0000269|PubMed:11083920}.
CC -!- INDUCTION: By axonal regeneration. {ECO:0000269|PubMed:11083920,
CC ECO:0000269|PubMed:11884758}.
CC -!- DISEASE: Note=Defects in Agtpbp1 are the cause of Purkinje cell
CC degeneration (pcd). Pcd is a spontaneous mutation that results in
CC adult-onset degeneration of cerebellar Purkinje neurons, retinal
CC photoreceptors, olfactory bulb mitral neurons and selected thalamic
CC neurons, and causes defective spermatogenesis. Pcd mice also manifest
CC cerebellar atrophy and a peripheral nerve degeneration resulting in
CC pure motor or motor-predominant neuropathy. Motoric femoral quadriceps
CC nerves are characterized by reduced total calibers, a loss of
CC myelinated axons, perturbed axon morphology, and macrophage activation.
CC The amount of motor neurons in the ventral horns of lumbar spinal cords
CC is reduced. These anomalies are accompanied by dysregulated tubulin
CC polyglutamylation (PubMed:30420557). Defects in mitochondrial metabolic
CC functions are also observed. The molecular causes of neurodegeneration
CC are probably due to an accumulation of glutamylation, either tubulin
CC hyperglutamylation or another hyperglutamylated target proteins. An
CC increase of intranuclear localization of lysyl oxidase (Lox)
CC propeptide, which interferes with NF-kappa-B Rela signaling and
CC microtubule-associated protein regulation of microtubule stability is
CC also observed, possibly leading to underdevelopment of Purkinje cell
CC dendrites. {ECO:0000269|PubMed:11884758, ECO:0000269|PubMed:16465590,
CC ECO:0000269|PubMed:16942761, ECO:0000269|PubMed:16952463,
CC ECO:0000269|PubMed:18602413, ECO:0000269|PubMed:20620870,
CC ECO:0000269|PubMed:20920790, ECO:0000269|PubMed:21074048,
CC ECO:0000269|PubMed:30420557}.
CC -!- DISRUPTION PHENOTYPE: Knockout pcd mice show hyperglutamylation of
CC alpha- and beta-tubulins in the brain (PubMed:22170066). Knockout mice
CC promote somatic cell reprogramming and higher litter size at birth
CC (PubMed:29593216). {ECO:0000269|PubMed:22170066,
CC ECO:0000269|PubMed:29593216}.
CC -!- MISCELLANEOUS: [Isoform 3]: Apparent retained intron. May be produced
CC at very low levels due to a premature stop codon in the mRNA, leading
CC to nonsense-mediated mRNA decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG37102.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF219141; AAG37102.1; ALT_INIT; mRNA.
DR EMBL; AK007328; BAB24963.2; -; mRNA.
DR EMBL; AK013688; BAC25412.1; -; mRNA.
DR EMBL; AK132695; BAE21306.1; -; mRNA.
DR EMBL; AK170046; BAE41530.1; -; mRNA.
DR EMBL; BC082335; AAH82335.1; -; mRNA.
DR EMBL; BC060633; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS36686.1; -. [Q641K1-1]
DR CCDS; CCDS36687.1; -. [Q641K1-4]
DR CCDS; CCDS70470.1; -. [Q641K1-2]
DR RefSeq; NP_001041473.1; NM_001048008.2. [Q641K1-4]
DR RefSeq; NP_001271147.1; NM_001284218.1. [Q641K1-4]
DR RefSeq; NP_001271148.1; NM_001284219.1.
DR RefSeq; NP_001271150.1; NM_001284221.1. [Q641K1-2]
DR RefSeq; NP_075817.2; NM_023328.3. [Q641K1-1]
DR RefSeq; XP_006517398.1; XM_006517335.2.
DR RefSeq; XP_006517399.1; XM_006517336.3. [Q641K1-1]
DR RefSeq; XP_006517400.1; XM_006517337.3. [Q641K1-1]
DR RefSeq; XP_006517401.1; XM_006517338.3. [Q641K1-1]
DR RefSeq; XP_011242857.1; XM_011244555.2.
DR AlphaFoldDB; Q641K1; -.
DR SMR; Q641K1; -.
DR BioGRID; 212061; 3.
DR STRING; 10090.ENSMUSP00000022040; -.
DR MEROPS; M14.028; -.
DR iPTMnet; Q641K1; -.
DR PhosphoSitePlus; Q641K1; -.
DR EPD; Q641K1; -.
DR MaxQB; Q641K1; -.
DR PaxDb; Q641K1; -.
DR PRIDE; Q641K1; -.
DR ProteomicsDB; 281226; -. [Q641K1-1]
DR ProteomicsDB; 281227; -. [Q641K1-2]
DR ProteomicsDB; 281228; -. [Q641K1-3]
DR ProteomicsDB; 281229; -. [Q641K1-4]
DR ProteomicsDB; 281230; -. [Q641K1-5]
DR Antibodypedia; 27717; 347 antibodies from 31 providers.
DR DNASU; 67269; -.
DR Ensembl; ENSMUST00000022040; ENSMUSP00000022040; ENSMUSG00000021557. [Q641K1-1]
DR Ensembl; ENSMUST00000109830; ENSMUSP00000105456; ENSMUSG00000021557. [Q641K1-4]
DR Ensembl; ENSMUST00000164215; ENSMUSP00000130939; ENSMUSG00000021557. [Q641K1-2]
DR Ensembl; ENSMUST00000170555; ENSMUSP00000128589; ENSMUSG00000021557. [Q641K1-3]
DR Ensembl; ENSMUST00000171606; ENSMUSP00000132697; ENSMUSG00000021557. [Q641K1-4]
DR GeneID; 67269; -.
DR KEGG; mmu:67269; -.
DR UCSC; uc007qum.1; mouse. [Q641K1-1]
DR UCSC; uc007quq.2; mouse. [Q641K1-4]
DR UCSC; uc033gmf.1; mouse. [Q641K1-2]
DR CTD; 23287; -.
DR MGI; MGI:2159437; Agtpbp1.
DR VEuPathDB; HostDB:ENSMUSG00000021557; -.
DR eggNOG; KOG3641; Eukaryota.
DR GeneTree; ENSGT00940000157707; -.
DR HOGENOM; CLU_007391_0_0_1; -.
DR InParanoid; Q641K1; -.
DR OMA; HVATCGN; -.
DR OrthoDB; 481670at2759; -.
DR PhylomeDB; Q641K1; -.
DR TreeFam; TF313794; -.
DR BRENDA; 3.4.17.24; 3474.
DR BioGRID-ORCS; 67269; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Agtpbp1; mouse.
DR PRO; PR:Q641K1; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q641K1; protein.
DR Bgee; ENSMUSG00000021557; Expressed in spermatid and 259 other tissues.
DR ExpressionAtlas; Q641K1; baseline and differential.
DR Genevisible; Q641K1; MM.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; IDA:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; TAS:UniProtKB.
DR GO; GO:0015631; F:tubulin binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007628; P:adult walking behavior; IMP:MGI.
DR GO; GO:0098957; P:anterograde axonal transport of mitochondrion; IGI:MGI.
DR GO; GO:0098930; P:axonal transport; IGI:MGI.
DR GO; GO:0035609; P:C-terminal protein deglutamylation; IDA:UniProtKB.
DR GO; GO:0021954; P:central nervous system neuron development; IGI:MGI.
DR GO; GO:0021702; P:cerebellar Purkinje cell differentiation; IMP:UniProtKB.
DR GO; GO:0021680; P:cerebellar Purkinje cell layer development; IMP:MGI.
DR GO; GO:0021549; P:cerebellum development; IMP:MGI.
DR GO; GO:0001754; P:eye photoreceptor cell differentiation; IMP:UniProtKB.
DR GO; GO:0007005; P:mitochondrion organization; IMP:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0050905; P:neuromuscular process; IMP:UniProtKB.
DR GO; GO:0042133; P:neurotransmitter metabolic process; IMP:MGI.
DR GO; GO:0021772; P:olfactory bulb development; IMP:UniProtKB.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IMP:MGI.
DR GO; GO:0035608; P:protein deglutamylation; IMP:MGI.
DR GO; GO:0035610; P:protein side chain deglutamylation; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0060041; P:retina development in camera-type eye; IMP:MGI.
DR GO; GO:0098958; P:retrograde axonal transport of mitochondrion; IGI:MGI.
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; Disease variant;
KW Hydrolase; Metal-binding; Metalloprotease; Mitochondrion;
KW Neurodegeneration; Nucleus; Phosphoprotein; Protease; Reference proteome;
KW Zinc.
FT CHAIN 1..1218
FT /note="Cytosolic carboxypeptidase 1"
FT /id="PRO_0000308691"
FT REGION 476..512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 590..617
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1193..1218
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 478..498
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 962
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 912
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305"
FT BINDING 915
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305"
FT BINDING 1009
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT MOD_RES 1160
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPW5"
FT VAR_SEQ 689..1218
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_038804"
FT VAR_SEQ 771..795
FT /note="GMQPLMYSVQEALNARPWWIRMGTD -> EITSHEAQLPQADRRASPTTPSP
FT SP (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029045"
FT VAR_SEQ 771..789
FT /note="GMQPLMYSVQEALNARPWW -> DGEETCYKMIVVSTICCKD (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_038803"
FT VAR_SEQ 790..1218
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_038805"
FT VAR_SEQ 796..1218
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029046"
FT VAR_SEQ 1160..1174
FT /note="SPTTYVLDEDEPRFL -> RTRGSSELQLFPAVL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029047"
FT VAR_SEQ 1175..1218
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029048"
FT VARIANT 832
FT /note="D -> DD (in pcd; pcd(5J) mutant)"
FT /evidence="ECO:0000269|PubMed:16465590"
FT MUTAGEN 686
FT /note="Y->D: Decreased tubulin deglutamylation."
FT /evidence="ECO:0000269|PubMed:30420557"
FT MUTAGEN 843
FT /note="T->M: Decreased tubulin deglutamylation."
FT /evidence="ECO:0000269|PubMed:30420557"
FT MUTAGEN 910
FT /note="R->W: Decreased tubulin deglutamylation."
FT /evidence="ECO:0000269|PubMed:30420557"
FT MUTAGEN 912
FT /note="H->A: Abolishes ability to rescue Purkinje cell
FT degeneration in pcd mice when expressed in a transgene."
FT /evidence="ECO:0000269|PubMed:18602413,
FT ECO:0000269|PubMed:20620870, ECO:0000269|PubMed:21074048"
FT MUTAGEN 912
FT /note="H->S: Abolishes deglutamylase activity; when
FT associated with Q-915."
FT /evidence="ECO:0000269|PubMed:18602413,
FT ECO:0000269|PubMed:20620870, ECO:0000269|PubMed:21074048"
FT MUTAGEN 915
FT /note="E->A: Abolishes ability to rescue Purkinje cell
FT degeneration in pcd mice when expressed in a transgene."
FT /evidence="ECO:0000269|PubMed:18602413,
FT ECO:0000269|PubMed:20620870, ECO:0000269|PubMed:21074048"
FT MUTAGEN 915
FT /note="E->Q: Abolishes deglutamylase activity; when
FT associated with S-912."
FT /evidence="ECO:0000269|PubMed:18602413,
FT ECO:0000269|PubMed:20620870, ECO:0000269|PubMed:21074048"
FT MUTAGEN 971..972
FT /note="NR->AA: Abolishes ability to rescue Purkinje cell
FT degeneration in pcd mice when expressed in a transgene."
FT /evidence="ECO:0000269|PubMed:16952463"
FT MUTAGEN 982
FT /note="H->L: Decreased tubulin deglutamylation."
FT /evidence="ECO:0000269|PubMed:30420557"
FT CONFLICT 237
FT /note="A -> V (in Ref. 1; AAG37102)"
FT /evidence="ECO:0000305"
FT CONFLICT 274
FT /note="Q -> R (in Ref. 1; AAG37102)"
FT /evidence="ECO:0000305"
FT CONFLICT 380
FT /note="V -> A (in Ref. 3; BC060633)"
FT /evidence="ECO:0000305"
FT CONFLICT 542..548
FT /note="NAGMRKD -> ERRNEEG (in Ref. 1; AAG37102)"
FT /evidence="ECO:0000305"
FT CONFLICT 644
FT /note="F -> S (in Ref. 1; AAG37102)"
FT /evidence="ECO:0000305"
FT CONFLICT 969
FT /note="D -> G (in Ref. 1; AAG37102)"
FT /evidence="ECO:0000305"
FT CONFLICT 1043
FT /note="D -> G (in Ref. 1; AAG37102)"
FT /evidence="ECO:0000305"
FT CONFLICT 1121
FT /note="K -> Q (in Ref. 1; AAG37102)"
FT /evidence="ECO:0000305"
FT CONFLICT 1126
FT /note="L -> I (in Ref. 2; BAC25412)"
FT /evidence="ECO:0000305"
FT CONFLICT 1167
FT /note="D -> G (in Ref. 2; BAB24963)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1218 AA; 137197 MW; 89917C6897AD9DD5 CRC64;
MSKLKVVGEK SLTNSSRVVG LLAQLEKINT DSTESDTARY VTSKILHLAQ SQEKTRREMT
TKGSTGMEVL LSTLENTKDL QTVLNILSIL IELVSSGGGR RASFLVAKGG SQILLQLLMN
ASKDSPPHEE VMVQTHSILA KIGPKDKKFG VKARVNGALT VTLNLVKQHF QNYRLVLPCL
QLLRVYSTNS VNSVSLGKNG VVELMFKIIG PFSKKNSGLM KVALDTLAAL LKSKTNARRA
VDRGYVQVLL TIYVDWHRHD NRHRNMLIRK GILQSLKSVT NIKLGRKAFI DANGMKILYN
TSQECLAVRT LDPLVNTSSL IMRKCFPKNR LPLPTIKSSF HFQLPIIPVT GPVAQLYSLP
PEVDDVVDES DDNDDIDLEV ENELENEDDL DQSFKNDDIE TDINKLRPQQ VPGRTIEELK
MYEHLFPELV DDFQDYELIS KEPKPFVFEG KARGPIVVPT AGEEVPGNSG SVKKGVVMKE
RASPKGEEAK EDPKGHDRTL PQQLGGQSRV APSAHSFNND LVKALDRITL QNVPSQVASG
LNAGMRKDFG LPLTVLSCTK ACPHVAKCGS TLFEGRTVHL GKLCCTGVET EDDEDTESHS
STEQAPSVEA SDGPTLHDPD LYIEIVKNTK SVPEYSEVAY PDYFGHIPPP FKEPILERPY
GVQRTKIAQD IERLIHQNDI IDRVVYDLDN PTYTTPEEGD TLKFNSKFES GNLRKVIQIR
KSEYDLILNS DINSNHYHQW FYFEVSGMRP GVAYRFNIIN CEKSNSQFNY GMQPLMYSVQ
EALNARPWWI RMGTDICYYK NHFSRSSVAA GGQKGKSYYT ITFTVNFPHK DDVCYFAYHY
PYTYSTLQMH LQKLESAHNP QQIYFRKDVL CETLSGNICP LVTITAMPES NYYEHICQFR
TRPYIFLSAR VHPGETNASW VMKGTLEYLM SNSPTAQSLR ESYIFKIVPM LNPDGVINGN
HRCSLSGEDL NRQWQSPNPE LHPTIYHAKG LLQYLAAVKR LPLVYCDYHG HSRKKNVFMY
GCSIKETVWH THDNSASCDI VEDMGYRTLP KILSHIAPAF CMSSCSFVVE KSKESTARVV
VWREIGVQRS YTMESTLCGC DQGRYKGLQI GTRELEEMGA KFCVGLLRLK RLTSSLEYNL
PSNLLDFEND LIESSCKVTS PTTYVLDEDE PRFLEEVDYS AESNDELDVE LAENTGDYEP
SAQEEALSDS EVSRTHLI
