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Protein

Cytosolic carboxypeptidase 1

Gene

Agtpbp1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Metallocarboxypeptidase that mediates deglutamylation of target proteins. Catalyzes the deglutamylation of polyglutamate side chains generated by post-translational polyglutamylation in proteins such as tubulins. Also removes gene-encoded polyglutamates from the carboxy-terminus of target proteins such as MYLK. Acts as a long-chain deglutamylase and specifically shortens long polyglutamate chains, while it is not able to remove the branching point glutamate, a process catalyzed by AGBL5/CCP5. Deglutamylation plays a key role in cerebellar Purkinje cell differentiation, accumulation of tubulin polyglutamylation causing neurodegeneration.2 Publications

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi912ZincCurated1
Metal bindingi915ZincCurated1
Active sitei962NucleophileBy similarity1
Metal bindingi1009ZincBy similarity1

GO - Molecular functioni

  • metallocarboxypeptidase activity Source: UniProtKB
  • peptidase activity Source: UniProtKB
  • tubulin binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionCarboxypeptidase, Hydrolase, Metalloprotease, Protease
LigandMetal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Cytosolic carboxypeptidase 1 (EC:3.4.17.-)
Alternative name(s):
ATP/GTP-binding protein 1
Nervous system nuclear protein induced by axotomy protein 1
Gene namesi
Name:Agtpbp1
Synonyms:Ccp1, Nna1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:2159437 Agtpbp1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

Pathology & Biotechi

Involvement in diseasei

Defects in Agtpbp1 are the cause of Purkinje cell degeneration (pcd). Pcd is a spontaneous mutation that causes adult-onset degeneration of cerebellar Purkinje neurons, retinal photoreceptors, olfactory bulb mitral neurons, and selected thalamic neurons, and has defective spermatogenesis. Defects in mitochondrial metabolic functions are also observed. The molecular causes of neurodegeneration are still unclear, but they are probably due to an accumulation of glutamylation, either tubulin hyperglutamylation or another hyperglutamylated target proteins. An increase of intranuclear localization of lysyl oxidase (Lox) propeptide, which interferes with NF-kappa-B Rela signaling and microtubule-associated protein regulation of microtubule stability is also observed, possibly leading to underdevelopment of Purkinje cell dendrites.8 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi912H → A: Abolishes ability to rescue Purkinje cell degeneration in pcd mice when expressed in a transgene. 3 Publications1
Mutagenesisi912H → S: Abolishes deglutamylase activity; when associated with Q-915. 3 Publications1
Mutagenesisi915E → A: Abolishes ability to rescue Purkinje cell degeneration in pcd mice when expressed in a transgene. 3 Publications1
Mutagenesisi915E → Q: Abolishes deglutamylase activity; when associated with S-912. 3 Publications1
Mutagenesisi971 – 972NR → AA: Abolishes ability to rescue Purkinje cell degeneration in pcd mice when expressed in a transgene. 1 Publication2

Keywords - Diseasei

Disease mutation, Neurodegeneration

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003086911 – 1218Cytosolic carboxypeptidase 1Add BLAST1218

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1160PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ641K1
PaxDbiQ641K1
PRIDEiQ641K1

PTM databases

iPTMnetiQ641K1
PhosphoSitePlusiQ641K1

Expressioni

Tissue specificityi

Widely expressed. Highly expressed in the cerebellum and cortex of adult mouse brain. Expressed at similar levels in both the cerebellum and the cortex throughout all developmental stages. Also expressed in sciatic nerve transection, spinal motor neurons undergoing axon regeneration, testis, heart and in developing brain. Expression in cranial motor nuclei is the same as that observed in uninjured primary motor neurons. Expression is prevalent in sensory neurons and hippocampal CA3 neurons in addition to regenerating motor neurons.3 Publications

Developmental stagei

Highly expressed in differentiating neurons. From E16.5, expression is widespread in brain, spinal cord, and peripheral nervous tissue. Within the developing CNS, expression is restricted to regions of brain and spinal cord containing differentiating neurons.1 Publication

Inductioni

By axonal regeneration.2 Publications

Gene expression databases

BgeeiENSMUSG00000021557 Expressed in 288 organ(s), highest expression level in camera-type eye
CleanExiMM_AGTPBP1
ExpressionAtlasiQ641K1 baseline and differential
GenevisibleiQ641K1 MM

Interactioni

Subunit structurei

Interacts with MYLK.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000022040

Structurei

3D structure databases

ProteinModelPortaliQ641K1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase M14 family.Curated

Phylogenomic databases

eggNOGiKOG3641 Eukaryota
COG2866 LUCA
GeneTreeiENSGT00550000074405
HOVERGENiHBG107587
InParanoidiQ641K1
OMAiHIAPAFC
OrthoDBiEOG091G01L5
PhylomeDBiQ641K1
TreeFamiTF313794

Family and domain databases

CDDicd06906 M14_Nna1, 1 hit
Gene3Di1.25.10.10, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR033852 Cytosolic_aminopeptidase_1
IPR000834 Peptidase_M14
PfamiView protein in Pfam
PF00246 Peptidase_M14, 1 hit
SUPFAMiSSF48371 SSF48371, 1 hit

Sequences (5+)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 12 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q641K1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSKLKVVGEK SLTNSSRVVG LLAQLEKINT DSTESDTARY VTSKILHLAQ
60 70 80 90 100
SQEKTRREMT TKGSTGMEVL LSTLENTKDL QTVLNILSIL IELVSSGGGR
110 120 130 140 150
RASFLVAKGG SQILLQLLMN ASKDSPPHEE VMVQTHSILA KIGPKDKKFG
160 170 180 190 200
VKARVNGALT VTLNLVKQHF QNYRLVLPCL QLLRVYSTNS VNSVSLGKNG
210 220 230 240 250
VVELMFKIIG PFSKKNSGLM KVALDTLAAL LKSKTNARRA VDRGYVQVLL
260 270 280 290 300
TIYVDWHRHD NRHRNMLIRK GILQSLKSVT NIKLGRKAFI DANGMKILYN
310 320 330 340 350
TSQECLAVRT LDPLVNTSSL IMRKCFPKNR LPLPTIKSSF HFQLPIIPVT
360 370 380 390 400
GPVAQLYSLP PEVDDVVDES DDNDDIDLEV ENELENEDDL DQSFKNDDIE
410 420 430 440 450
TDINKLRPQQ VPGRTIEELK MYEHLFPELV DDFQDYELIS KEPKPFVFEG
460 470 480 490 500
KARGPIVVPT AGEEVPGNSG SVKKGVVMKE RASPKGEEAK EDPKGHDRTL
510 520 530 540 550
PQQLGGQSRV APSAHSFNND LVKALDRITL QNVPSQVASG LNAGMRKDFG
560 570 580 590 600
LPLTVLSCTK ACPHVAKCGS TLFEGRTVHL GKLCCTGVET EDDEDTESHS
610 620 630 640 650
STEQAPSVEA SDGPTLHDPD LYIEIVKNTK SVPEYSEVAY PDYFGHIPPP
660 670 680 690 700
FKEPILERPY GVQRTKIAQD IERLIHQNDI IDRVVYDLDN PTYTTPEEGD
710 720 730 740 750
TLKFNSKFES GNLRKVIQIR KSEYDLILNS DINSNHYHQW FYFEVSGMRP
760 770 780 790 800
GVAYRFNIIN CEKSNSQFNY GMQPLMYSVQ EALNARPWWI RMGTDICYYK
810 820 830 840 850
NHFSRSSVAA GGQKGKSYYT ITFTVNFPHK DDVCYFAYHY PYTYSTLQMH
860 870 880 890 900
LQKLESAHNP QQIYFRKDVL CETLSGNICP LVTITAMPES NYYEHICQFR
910 920 930 940 950
TRPYIFLSAR VHPGETNASW VMKGTLEYLM SNSPTAQSLR ESYIFKIVPM
960 970 980 990 1000
LNPDGVINGN HRCSLSGEDL NRQWQSPNPE LHPTIYHAKG LLQYLAAVKR
1010 1020 1030 1040 1050
LPLVYCDYHG HSRKKNVFMY GCSIKETVWH THDNSASCDI VEDMGYRTLP
1060 1070 1080 1090 1100
KILSHIAPAF CMSSCSFVVE KSKESTARVV VWREIGVQRS YTMESTLCGC
1110 1120 1130 1140 1150
DQGRYKGLQI GTRELEEMGA KFCVGLLRLK RLTSSLEYNL PSNLLDFEND
1160 1170 1180 1190 1200
LIESSCKVTS PTTYVLDEDE PRFLEEVDYS AESNDELDVE LAENTGDYEP
1210
SAQEEALSDS EVSRTHLI
Length:1,218
Mass (Da):137,197
Last modified:October 23, 2007 - v2
Checksum:i89917C6897AD9DD5
GO
Isoform 2 (identifier: Q641K1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1160-1174: SPTTYVLDEDEPRFL → RTRGSSELQLFPAVL
     1175-1218: Missing.

Note: No experimental confirmation available.
Show »
Length:1,174
Mass (Da):132,220
Checksum:iD1C7D2CFAFB5D0EA
GO
Isoform 3 (identifier: Q641K1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     771-795: GMQPLMYSVQEALNARPWWIRMGTD → EITSHEAQLPQADRRASPTTPSPSP
     796-1218: Missing.

Note: No experimental confirmation available. Apparent retained intron. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:795
Mass (Da):88,657
Checksum:iDE3C127579DC21F3
GO
Isoform 4 (identifier: Q641K1-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     771-789: GMQPLMYSVQEALNARPWW → DGEETCYKMIVVSTICCKD
     790-1218: Missing.

Note: No experimental confirmation available.
Show »
Length:789
Mass (Da):88,120
Checksum:iF765D2CD582ABE31
GO
Isoform 5 (identifier: Q641K1-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     689-1218: Missing.

Note: No experimental confirmation available.
Show »
Length:688
Mass (Da):76,297
Checksum:iB1779CDF33BDDE52
GO

Computationally mapped potential isoform sequencesi

There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F6ZCF0F6ZCF0_MOUSE
Cytosolic carboxypeptidase 1
Agtpbp1
685Annotation score:
Q8C1R2Q8C1R2_MOUSE
Agtpbp1 protein
Agtpbp1
99Annotation score:
E9PXA7E9PXA7_MOUSE
Cytosolic carboxypeptidase 1
Agtpbp1
246Annotation score:
E9Q352E9Q352_MOUSE
Cytosolic carboxypeptidase 1
Agtpbp1
71Annotation score:
E9PX07E9PX07_MOUSE
Cytosolic carboxypeptidase 1
Agtpbp1
332Annotation score:
E9Q3T5E9Q3T5_MOUSE
Cytosolic carboxypeptidase 1
Agtpbp1
103Annotation score:
E9Q878E9Q878_MOUSE
Cytosolic carboxypeptidase 1
Agtpbp1
86Annotation score:
E9Q2R5E9Q2R5_MOUSE
Cytosolic carboxypeptidase 1
Agtpbp1
51Annotation score:
E9PYF9E9PYF9_MOUSE
Cytosolic carboxypeptidase 1
Agtpbp1
42Annotation score:
A0A286YDV2A0A286YDV2_MOUSE
Cytosolic carboxypeptidase 1
Agtpbp1
226Annotation score:
There are more potential isoformsShow all

Sequence cautioni

The sequence AAG37102 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti237A → V in AAG37102 (PubMed:11083920).Curated1
Sequence conflicti274Q → R in AAG37102 (PubMed:11083920).Curated1
Sequence conflicti380V → A in BC060633 (PubMed:15489334).Curated1
Sequence conflicti542 – 548NAGMRKD → ERRNEEG in AAG37102 (PubMed:11083920).Curated7
Sequence conflicti644F → S in AAG37102 (PubMed:11083920).Curated1
Sequence conflicti969D → G in AAG37102 (PubMed:11083920).Curated1
Sequence conflicti1043D → G in AAG37102 (PubMed:11083920).Curated1
Sequence conflicti1121K → Q in AAG37102 (PubMed:11083920).Curated1
Sequence conflicti1126L → I in BAC25412 (PubMed:16141072).Curated1
Sequence conflicti1167D → G in BAB24963 (PubMed:16141072).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti832D → DD in pcd; pcd(5J) mutant. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_038804689 – 1218Missing in isoform 5. 1 PublicationAdd BLAST530
Alternative sequenceiVSP_029045771 – 795GMQPL…RMGTD → EITSHEAQLPQADRRASPTT PSPSP in isoform 3. 1 PublicationAdd BLAST25
Alternative sequenceiVSP_038803771 – 789GMQPL…ARPWW → DGEETCYKMIVVSTICCKD in isoform 4. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_038805790 – 1218Missing in isoform 4. 1 PublicationAdd BLAST429
Alternative sequenceiVSP_029046796 – 1218Missing in isoform 3. 1 PublicationAdd BLAST423
Alternative sequenceiVSP_0290471160 – 1174SPTTY…EPRFL → RTRGSSELQLFPAVL in isoform 2. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_0290481175 – 1218Missing in isoform 2. 1 PublicationAdd BLAST44

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF219141 mRNA Translation: AAG37102.1 Different initiation.
AK007328 mRNA Translation: BAB24963.2
AK013688 mRNA Translation: BAC25412.1
AK132695 mRNA Translation: BAE21306.1
AK170046 mRNA Translation: BAE41530.1
BC082335 mRNA Translation: AAH82335.1
BC060633 mRNA No translation available.
CCDSiCCDS36686.1 [Q641K1-1]
CCDS36687.1 [Q641K1-4]
CCDS70470.1 [Q641K1-2]
RefSeqiNP_001041473.1, NM_001048008.2 [Q641K1-4]
NP_001271147.1, NM_001284218.1 [Q641K1-4]
NP_001271148.1, NM_001284219.1
NP_001271150.1, NM_001284221.1 [Q641K1-2]
NP_075817.2, NM_023328.3 [Q641K1-1]
XP_006517398.1, XM_006517335.2 [Q641K1-1]
XP_006517399.1, XM_006517336.3 [Q641K1-1]
XP_006517400.1, XM_006517337.3 [Q641K1-1]
XP_006517401.1, XM_006517338.3 [Q641K1-1]
XP_011242857.1, XM_011244555.2 [Q641K1-2]
UniGeneiMm.153008

Genome annotation databases

EnsembliENSMUST00000022040; ENSMUSP00000022040; ENSMUSG00000021557 [Q641K1-1]
ENSMUST00000109830; ENSMUSP00000105456; ENSMUSG00000021557 [Q641K1-4]
ENSMUST00000164215; ENSMUSP00000130939; ENSMUSG00000021557 [Q641K1-2]
ENSMUST00000170555; ENSMUSP00000128589; ENSMUSG00000021557 [Q641K1-3]
ENSMUST00000171606; ENSMUSP00000132697; ENSMUSG00000021557 [Q641K1-4]
GeneIDi67269
KEGGimmu:67269
UCSCiuc007qum.1 mouse [Q641K1-1]
uc007quq.2 mouse [Q641K1-4]
uc033gmf.1 mouse [Q641K1-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCBPC1_MOUSE
AccessioniPrimary (citable) accession number: Q641K1
Secondary accession number(s): Q3TDS0
, Q3V147, Q6P9R9, Q8C1K8, Q9D962, Q9EQI4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 23, 2007
Last sequence update: October 23, 2007
Last modified: September 12, 2018
This is version 107 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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