NALD2_MOUSE
ID NALD2_MOUSE Reviewed; 740 AA.
AC Q9CZR2; Q80YF8;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=N-acetylated-alpha-linked acidic dipeptidase 2;
DE EC=3.4.17.21;
DE AltName: Full=Glutamate carboxypeptidase III;
DE Short=GCPIII;
DE AltName: Full=N-acetylaspartylglutamate peptidase II;
DE Short=NAAG-peptidase II;
DE AltName: Full=N-acetylated-alpha-linked acidic dipeptidase II;
DE Short=NAALADase II;
GN Name=Naalad2;
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], FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=15086519; DOI=10.1111/j.1471-4159.2004.02361.x;
RA Bzdega T., Crowe S.L., Ramadan E.R., Sciarretta K.H., Olszewski R.T.,
RA Ojeifo O.A., Rafalski V.A., Wroblewska B., Neale J.H.;
RT "The cloning and characterization of a second brain enzyme with NAAG
RT peptidase activity.";
RL J. Neurochem. 89:627-635(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 484-740.
RC STRAIN=C57BL/6J; TISSUE=Embryo;
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 GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-314; ASN-449 AND ASN-603.
RC TISSUE=Myoblast;
RX PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200;
RA Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D.,
RA Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.;
RT "The mouse C2C12 myoblast cell surface N-linked glycoproteome:
RT identification, glycosite occupancy, and membrane orientation.";
RL Mol. Cell. Proteomics 8:2555-2569(2009).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Lung, 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).
CC -!- FUNCTION: Has N-acetylated-alpha-linked-acidic dipeptidase (NAALADase)
CC activity. Also exhibits a dipeptidyl-peptidase IV type activity.
CC Inactivates the peptide neurotransmitter N-acetylaspartylglutamate.
CC {ECO:0000269|PubMed:15086519}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of an unsubstituted, C-terminal glutamyl residue,
CC typically from Ac-Asp-Glu or folylpoly-gamma-glutamates.;
CC EC=3.4.17.21;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 2 Zn(2+) ions per subunit. Required for NAALADase activity.
CC {ECO:0000250};
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q04609};
CC Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q04609}.
CC -!- TISSUE SPECIFICITY: Expressed ovary, testes and lung, but not brain.
CC {ECO:0000269|PubMed:15086519}.
CC -!- DOMAIN: The NAALADase activity is found in the central region, the
CC dipeptidyl peptidase IV type activity in the C-terminal.
CC -!- SIMILARITY: Belongs to the peptidase M28 family. M28B subfamily.
CC {ECO:0000305}.
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DR EMBL; AY243507; AAO89235.1; -; mRNA.
DR EMBL; AK012270; BAB28132.1; -; mRNA.
DR CCDS; CCDS52728.1; -.
DR RefSeq; NP_082555.2; NM_028279.3.
DR AlphaFoldDB; Q9CZR2; -.
DR SMR; Q9CZR2; -.
DR STRING; 10090.ENSMUSP00000128674; -.
DR MEROPS; M28.012; -.
DR GlyConnect; 2524; 1 N-Linked glycan (1 site).
DR GlyGen; Q9CZR2; 7 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q9CZR2; -.
DR PhosphoSitePlus; Q9CZR2; -.
DR SwissPalm; Q9CZR2; -.
DR MaxQB; Q9CZR2; -.
DR PaxDb; Q9CZR2; -.
DR PRIDE; Q9CZR2; -.
DR ProteomicsDB; 286148; -.
DR Antibodypedia; 67811; 51 antibodies from 16 providers.
DR DNASU; 72560; -.
DR Ensembl; ENSMUST00000166825; ENSMUSP00000128674; ENSMUSG00000043943.
DR GeneID; 72560; -.
DR KEGG; mmu:72560; -.
DR UCSC; uc009ogn.1; mouse.
DR CTD; 10003; -.
DR MGI; MGI:1919810; Naalad2.
DR VEuPathDB; HostDB:ENSMUSG00000043943; -.
DR eggNOG; KOG2195; Eukaryota.
DR GeneTree; ENSGT01030000234598; -.
DR HOGENOM; CLU_005688_3_2_1; -.
DR InParanoid; Q9CZR2; -.
DR OrthoDB; 804230at2759; -.
DR PhylomeDB; Q9CZR2; -.
DR TreeFam; TF312981; -.
DR BRENDA; 3.4.17.21; 3474.
DR Reactome; R-MMU-8963693; Aspartate and asparagine metabolism.
DR BioGRID-ORCS; 72560; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Naalad2; mouse.
DR PRO; PR:Q9CZR2; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9CZR2; protein.
DR Bgee; ENSMUSG00000043943; Expressed in cleaving embryo and 178 other tissues.
DR ExpressionAtlas; Q9CZR2; baseline and differential.
DR Genevisible; Q9CZR2; MM.
DR GO; GO:0016021; C:integral component of membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004180; F:carboxypeptidase activity; IDA:MGI.
DR GO; GO:0016805; F:dipeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0050129; F:N-formylglutamate deformylase activity; IDA:MGI.
DR GO; GO:0008233; F:peptidase activity; IDA:MGI.
DR GO; GO:0042135; P:neurotransmitter catabolic process; IDA:MGI.
DR GO; GO:0006508; P:proteolysis; IDA:MGI.
DR Gene3D; 1.20.930.40; -; 1.
DR InterPro; IPR003137; PA_domain.
DR InterPro; IPR007484; Peptidase_M28.
DR InterPro; IPR039373; Peptidase_M28B.
DR InterPro; IPR007365; TFR-like_dimer_dom.
DR InterPro; IPR036757; TFR-like_dimer_dom_sf.
DR PANTHER; PTHR10404; PTHR10404; 1.
DR Pfam; PF02225; PA; 1.
DR Pfam; PF04389; Peptidase_M28; 1.
DR Pfam; PF04253; TFR_dimer; 1.
DR SUPFAM; SSF47672; SSF47672; 1.
PE 1: Evidence at protein level;
KW Carboxypeptidase; Cell membrane; Dipeptidase; Glycoprotein; Hydrolase;
KW Membrane; Metal-binding; Metalloprotease; Multifunctional enzyme; Protease;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW Zinc.
FT CHAIN 1..740
FT /note="N-acetylated-alpha-linked acidic dipeptidase 2"
FT /id="PRO_0000174122"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 8..31
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 32..740
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 264..577
FT /note="NAALADase"
FT ACT_SITE 414
FT /note="Nucleophile; for NAALADase activity"
FT /evidence="ECO:0000250"
FT ACT_SITE 618
FT /note="Charge relay system"
FT /evidence="ECO:0000255"
FT ACT_SITE 656
FT /note="Charge relay system"
FT /evidence="ECO:0000255"
FT ACT_SITE 679
FT /note="Charge relay system"
FT /evidence="ECO:0000255"
FT BINDING 200
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT BINDING 247
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT BINDING 259
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 262
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 367
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT BINDING 377
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT BINDING 377
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 414
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT BINDING 415
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 423
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 426
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 443
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT BINDING 507..508
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT BINDING 524..526
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 542..543
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT BINDING 542
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 543
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT BINDING 689..690
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y3Q0"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT CARBOHYD 314
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770"
FT CARBOHYD 449
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770"
FT CARBOHYD 603
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770"
FT CARBOHYD 628
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q04609"
FT CONFLICT 484..487
FT /note="YESW -> MKAG (in Ref. 2; BAB28132)"
FT /evidence="ECO:0000305"
FT CONFLICT 499
FT /note="C -> L (in Ref. 2; BAB28132)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 740 AA; 82801 MW; B5EDAD7F7900E6C5 CRC64;
MARPRHLRGL GMCITAVLAS FIAGFTVGWF IKPLKETTTS AGYHQSIQQK LLSEMKAENI
RSFLRSFTKL PHLAGTEQNL LLAKKIQTQW KKFGLDSANL VHYDVLLSYP NETNANYVSI
VDEHGVEIFK TSYLEPPPDG YENVTNIIPP YNAFSASGMP EGELVYVNYA RTEDFFKLER
EMNINCTGKI VIARYGKIFR GNKVKNAMLA GAMGIILYSD PADYFAPDVQ PYPKGWNLPG
AAAQRGNVLN LNGAGDPLTP GYPAKEYTFR LPVEEAVGIP NIPVHPIGYN DAERLLRNLG
GAAPPDKSWK GSLNVSYNIG PGFTGSEYSR NIRMHVNNIN KITRIYNVIG TIRGSTEPDR
YVILGGHRDS WVFGGIDPTT GTAVLQEIAR SFGKLVNGGW RPRRTIIFAS WDAEEFGLLG
STEWAEENAK LLQERSIAYI NSDSAIEGNY TLRVDCTPLL NQLVYKVARE ISSPDDGFES
KSLYESWLEK DPSPENKECP RINKLGSGSD FEAYFQRLGI ASGRARYTKN KKTDKYSSYP
VYHTIYETFE LVQNFYDPTF KKQLSVAQLR GALVYELADS VVIPFNIQDY AKALKNYAAS
IFNISKKHDQ QLRNHAVSFD PLFSAVKNFS EAASDFHRRL TQVDLNNPIA VRIMNDQQML
LERAFIDPLG LPGRKFYRHI IFAPSSHNKY AGESFPGIYD AMFDIENKAD PSLAWAEVKK
HISIAAFTIQ AAAGTLTNVL
