LOCUS       NM_005467               3466 bp    mRNA    linear   PRI 04-APR-2024
DEFINITION  Homo sapiens N-acetylated alpha-linked acidic dipeptidase 2
            (NAALAD2), transcript variant 1, mRNA.
ACCESSION   NM_005467
VERSION     NM_005467.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 3466)
  AUTHORS   Suetsugu,H., Kim,K., Yamamoto,T., Bang,S.Y., Sakamoto,Y.,
            Shin,J.M., Sugano,N., Kim,J.S., Mukai,M., Lee,Y.K., Ohmura,K.,
            Park,D.J., Takahashi,D., Ahn,G.Y., Karino,K., Kwon,Y.C.,
            Miyamura,T., Kim,J., Nakamura,J., Motomura,G., Kuroda,T., Niiro,H.,
            Miyamoto,T., Takeuchi,T., Ikari,K., Amano,K., Tada,Y., Yamaji,K.,
            Shimizu,M., Atsumi,T., Seki,T., Tanaka,Y., Kubo,T., Hisada,R.,
            Yoshioka,T., Yamazaki,M., Kabata,T., Kajino,T., Ohta,Y., Okawa,T.,
            Naito,Y., Kaneuji,A., Yasunaga,Y., Ohzono,K., Tomizuka,K.,
            Koido,M., Matsuda,K., Okada,Y., Suzuki,A., Kim,B.J., Kochi,Y.,
            Lee,H.S., Ikegawa,S., Bae,S.C. and Terao,C.
  TITLE     Novel susceptibility loci for steroid-associated osteonecrosis of
            the femoral head in systemic lupus erythematosus
  JOURNAL   Hum Mol Genet 31 (7), 1082-1095 (2022)
   PUBMED   34850884
  REMARK    GeneRIF: Novel susceptibility loci for steroid-associated
            osteonecrosis of the femoral head in systemic lupus erythematosus.
REFERENCE   2  (bases 1 to 3466)
  AUTHORS   Daniunaite,K., Bakavicius,A., Zukauskaite,K., Rauluseviciute,I.,
            Lazutka,J.R., Ulys,A., Jankevicius,F. and Jarmalaite,S.
  TITLE     Promoter Methylation of PRKCB, ADAMTS12, and NAALAD2 Is Specific to
            Prostate Cancer and Predicts Biochemical Disease Recurrence
  JOURNAL   Int J Mol Sci 22 (11), 6091 (2021)
   PUBMED   34198725
  REMARK    GeneRIF: Promoter Methylation of PRKCB, ADAMTS12, and NAALAD2 Is
            Specific to Prostate Cancer and Predicts Biochemical Disease
            Recurrence.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 3466)
  AUTHORS   Haenig,C., Atias,N., Taylor,A.K., Mazza,A., Schaefer,M.H., Russ,J.,
            Riechers,S.P., Jain,S., Coughlin,M., Fontaine,J.F., Freibaum,B.D.,
            Brusendorf,L., Zenkner,M., Porras,P., Stroedicke,M., Schnoegl,S.,
            Arnsburg,K., Boeddrich,A., Pigazzini,L., Heutink,P., Taylor,J.P.,
            Kirstein,J., Andrade-Navarro,M.A., Sharan,R. and Wanker,E.E.
  TITLE     Interactome Mapping Provides a Network of Neurodegenerative Disease
            Proteins and Uncovers Widespread Protein Aggregation in Affected
            Brains
  JOURNAL   Cell Rep 32 (7), 108050 (2020)
   PUBMED   32814053
REFERENCE   4  (bases 1 to 3466)
  AUTHORS   Vorlova,B., Knedlik,T., Tykvart,J. and Konvalinka,J.
  TITLE     GCPII and its close homolog GCPIII: from a neuropeptidase to a
            cancer marker and beyond
  JOURNAL   Front Biosci (Landmark Ed) 24 (4), 648-687 (2019)
   PUBMED   30844704
  REMARK    GeneRIF: GCPII has been recognized as a neuropeptidase in the
            central nervous system, as a folate hydrolase participating in
            absorption of folates in the jejunum and, most importantly, as a
            prostate-specific membrane antigen that is highly expressed in
            prostate adenocarcinoma; GCPIII has not been associated with any
            specific physiolological functions [review]
            Review article
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 3466)
  AUTHORS   Navratil,M., Tykvart,J., Schimer,J., Pachl,P., Navratil,V.,
            Rokob,T.A., Hlouchova,K., Rulisek,L. and Konvalinka,J.
  TITLE     Comparison of human glutamate carboxypeptidases II and III reveals
            their divergent substrate specificities
  JOURNAL   FEBS J 283 (13), 2528-2545 (2016)
   PUBMED   27208881
REFERENCE   6  (bases 1 to 3466)
  AUTHORS   Hlouchova,K., Barinka,C., Konvalinka,J. and Lubkowski,J.
  TITLE     Structural insight into the evolutionary and pharmacologic homology
            of glutamate carboxypeptidases II and III
  JOURNAL   FEBS J 276 (16), 4448-4462 (2009)
   PUBMED   19678840
REFERENCE   7  (bases 1 to 3466)
  AUTHORS   Hlouchova,K., Barinka,C., Klusak,V., Sacha,P., Mlcochova,P.,
            Majer,P., Rulisek,L. and Konvalinka,J.
  TITLE     Biochemical characterization of human glutamate carboxypeptidase
            III
  JOURNAL   J Neurochem 101 (3), 682-696 (2007)
   PUBMED   17241121
REFERENCE   8  (bases 1 to 3466)
  AUTHORS   Lambert,L.A. and Mitchell,S.L.
  TITLE     Molecular evolution of the transferrin receptor/glutamate
            carboxypeptidase II family
  JOURNAL   J Mol Evol 64 (1), 113-128 (2007)
   PUBMED   17160644
REFERENCE   9  (bases 1 to 3466)
  AUTHORS   Semple,C.A., Devon,R.S., Le Hellard,S. and Porteous,D.J.
  TITLE     Identification of genes from a schizophrenia-linked translocation
            breakpoint region
  JOURNAL   Genomics 73 (1), 123-126 (2001)
   PUBMED   11352574
REFERENCE   10 (bases 1 to 3466)
  AUTHORS   Pangalos,M.N., Neefs,J.M., Somers,M., Verhasselt,P., Bekkers,M.,
            van der Helm,L., Fraiponts,E., Ashton,D. and Gordon,R.D.
  TITLE     Isolation and expression of novel human glutamate carboxypeptidases
            with N-acetylated alpha-linked acidic dipeptidase and dipeptidyl
            peptidase IV activity
  JOURNAL   J Biol Chem 274 (13), 8470-8483 (1999)
   PUBMED   10085079
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from CN355388.1, AK075390.1,
            AJ012370.1 and AP000648.5.
            
            On Nov 22, 2018 this sequence version replaced NM_005467.3.
            
            Summary: This gene is a member of the N-acetylated alpha-linked
            acidic dipeptidase (NAALADase) gene family. The representative
            member of this family is the gene encoding human prostate-specific
            membrane antigen (PSM), which is a marker of prostatic carcinomas
            and is the first to be shown to possess NAALADase activity.
            NAALADase cleaves N-acetyl-L-aspartate-L-glutamate (NAAG), which is
            a neuropeptide expressed both in the central nervous systems and in
            the periphery and is thought to function as a neurotransmitter. The
            product of this gene is a type II integral membrane protein.
            Transient transfection of this gene confers both NAALADase and
            dipetidyl peptidase IV activities to mammalian cells. This gene is
            highly expressed in ovary and testis as well as within discrete
            brain areas. Two transcript variants encoding different isoforms
            have been found for this gene. [provided by RefSeq, Jul 2014].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AK075390.1, AJ012370.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968968, SAMEA2142680
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000534061.6/ ENSP00000432481.1
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-12                CN355388.1         15-26
            13-2476             AK075390.1         1-2464
            2477-3142           AJ012370.1         2428-3093
            3143-3181           AK075390.1         3133-3171
            3182-3183           AJ012370.1         3133-3134
            3184-3466           AP000648.5         98735-99017
FEATURES             Location/Qualifiers
     source          1..3466
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11q14.3"
     gene            1..3466
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /note="N-acetylated alpha-linked acidic dipeptidase 2"
                     /db_xref="GeneID:10003"
                     /db_xref="HGNC:HGNC:14526"
                     /db_xref="MIM:611636"
     exon            1..178
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     CDS             97..2319
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /EC_number="3.4.17.21"
                     /note="isoform 1 is encoded by transcript variant 1;
                     N-acetylated alpha-linked acidic dipeptidase II; NAALADase
                     II; glutamate carboxypeptidase III; NAALADASE2"
                     /codon_start=1
                     /product="N-acetylated-alpha-linked acidic dipeptidase 2
                     isoform 1"
                     /protein_id="NP_005458.1"
                     /db_xref="CCDS:CCDS8288.1"
                     /db_xref="GeneID:10003"
                     /db_xref="HGNC:HGNC:14526"
                     /db_xref="MIM:611636"
                     /translation="MAESRGRLYLWMCLAAALASFLMGFMVGWFIKPLKETTTSVRYH
                     QSIRWKLVSEMKAENIKSFLRSFTKLPHLAGTEQNFLLAKKIQTQWKKFGLDSAKLVH
                     YDVLLSYPNETNANYISIVDEHETEIFKTSYLEPPPDGYENVTNIVPPYNAFSAQGMP
                     EGDLVYVNYARTEDFFKLEREMGINCTGKIVIARYGKIFRGNKVKNAMLAGAIGIILY
                     SDPADYFAPEVQPYPKGWNLPGTAAQRGNVLNLNGAGDPLTPGYPAKEYTFRLDVEEG
                     VGIPRIPVHPIGYNDAEILLRYLGGIAPPDKSWKGALNVSYSIGPGFTGSDSFRKVRM
                     HVYNINKITRIYNVVGTIRGSVEPDRYVILGGHRDSWVFGAIDPTSGVAVLQEIARSF
                     GKLMSKGWRPRRTIIFASWDAEEFGLLGSTEWAEENVKILQERSIAYINSDSSIEGNY
                     TLRVDCTPLLYQLVYKLTKEIPSPDDGFESKSLYESWLEKDPSPENKNLPRINKLGSG
                     SDFEAYFQRLGIASGRARYTKNKKTDKYSSYPVYHTIYETFELVEKFYDPTFKKQLSV
                     AQLRGALVYELVDSKIIPFNIQDYAEALKNYAASIYNLSKKHDQQLTDHGVSFDSLFS
                     AVKNFSEAASDFHKRLIQVDLNNPIAVRMMNDQLMLLERAFIDPLGLPGKLFYRHIIF
                     APSSHNKYAGESFPGIYDAIFDIENKANSRLAWKEVKKHISIAAFTIQAAAGTLKEVL
                     "
     exon            179..290
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     exon            291..477
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     exon            478..579
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     exon            580..705
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     exon            706..892
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     exon            893..986
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     exon            987..1085
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     exon            1086..1171
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     exon            1172..1291
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     exon            1292..1374
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     exon            1375..1438
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     exon            1439..1506
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     exon            1507..1598
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     exon            1599..1689
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     exon            1690..1954
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     exon            1955..2036
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     exon            2037..2129
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     exon            2130..3466
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3160..3165
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /note="hexamer: AATAAA"
     regulatory      3179..3184
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /note="hexamer: AACAAG"
     polyA_site      3183
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /note="major polyA site"
     polyA_site      3196
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
     regulatory      3440..3445
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
                     /note="hexamer: AATAAA"
     polyA_site      3466
                     /gene="NAALAD2"
                     /gene_synonym="GCP3; GCPIII; GPCIII"
ORIGIN      
        1 agagctcaca gcctcctgcc agcgcgctct ctgtttctct gcagccccga agctcgcgaa
       61 tgtagcaggc gccccaagct cggtcctcaa gaagccatgg cggaatccag gggccgtctg
      121 tacctttgga tgtgcttggc tgctgcgctg gcatctttcc tgatgggatt tatggtgggc
      181 tggtttatta agcctctcaa agaaacgacc acttctgtgc gctatcatca aagtatacgg
      241 tggaaactgg tatccgaaat gaaagctgaa aacatcaaat catttcttcg ttcttttaca
      301 aagcttcctc atctggcagg aacagaacaa aatttcttgc ttgccaagaa aatccaaacc
      361 cagtggaaga aatttggact agattcagcc aagttggttc attatgatgt cctcttatct
      421 taccccaatg agacaaatgc caactatata tcgattgtgg atgaacatga aactgagatt
      481 ttcaaaacat cataccttga accaccacca gatggctatg agaatgttac aaatattgtg
      541 ccaccatata atgctttctc agcccaaggc atgccagagg gagatcttgt atatgtgaac
      601 tatgctcgca ctgaagactt tttcaaacta gaaagagaga tgggcatcaa ctgtactggg
      661 aagattgtta ttgcaagata tggaaaaatc ttcagaggaa ataaagttaa aaatgccatg
      721 ttagcaggag ccataggaat catcttgtac tcagatccag ctgactactt tgctcctgag
      781 gtacagccat atcccaaagg atggaatctt cctggaactg cagcccagag aggaaatgtg
      841 ttaaatttga atggtgctgg tgacccactc actccaggct atccagcaaa agaatacact
      901 ttcagacttg atgttgaaga aggagtggga atcccccgaa tacctgtaca tcccattgga
      961 tataatgatg cagaaatatt attacgctac ttgggaggaa ttgctccacc agataagagt
     1021 tggaagggag cccttaatgt gagttatagt atcggacctg gctttacagg gagtgattct
     1081 ttcaggaagg ttagaatgca tgtttataac atcaataaaa ttacaaggat ttacaatgta
     1141 gttggaacta tcagaggatc tgtggaacct gacaggtatg ttattctggg aggtcaccgg
     1201 gactcctggg tatttggagc tattgaccca accagtgggg ttgctgtttt gcaagaaatt
     1261 gcccggagtt ttggaaaact gatgagtaaa ggctggagac ctagaagaac tatcattttt
     1321 gccagctggg atgcagaaga atttggactt ctgggttcca cagaatgggc tgaggagaat
     1381 gtcaaaatac tccaggagag aagcattgct tatatcaact cggattcatc tatagaaggc
     1441 aattatactc tcagagttga ctgtactccc cttctttacc aattagtgta taaactgaca
     1501 aaagagatcc ccagccctga tgatgggttt gagagtaaat cactgtatga aagctggttg
     1561 gaaaaagacc cttcacctga aaataaaaat ttgcctagaa tcaataagct gggatctgga
     1621 agtgactttg aagcttattt tcagagactt ggaattgctt caggcagagc ccgttacact
     1681 aagaataaga aaacagataa gtacagcagc tacccagtgt accacacaat ttatgagaca
     1741 tttgaattgg tagagaaatt ttatgacccc acatttaaaa aacaactttc tgtggctcaa
     1801 ttacgaggag cactggtata tgagcttgtg gattctaaaa tcattccttt taatattcaa
     1861 gactatgcag aagctttgaa aaactatgca gcaagtatct ataatctatc taagaaacat
     1921 gatcaacaat tgacagacca tggagtatca tttgactcct tattttctgc tgtgaaaaac
     1981 ttctcagagg ctgcttcaga ttttcataaa cgacttatac aagttgatct taacaatccc
     2041 attgcagtga gaatgatgaa tgaccaactg atgctcctgg aaagagcatt catcgatcct
     2101 cttggtttac caggaaagct gttctatagg cacatcatat ttgctccaag tagccacaac
     2161 aaatatgctg gagaatcatt tcctggaatc tatgatgcta tctttgatat tgaaaataaa
     2221 gccaactctc gtttggcctg gaaagaagta aagaaacata tttctattgc agcttttaca
     2281 attcaagcag cagcaggaac tctgaaagaa gtattataga aggtctcaag tggctagcca
     2341 ttaaaggtgt tgctaaaagt ctgaggataa aattcacctt tctgataact tatgaagcca
     2401 gggtgttcta aactcttttc atgtcatgtt ttgattatag gctttggtct tttcatctgc
     2461 aaagcctttt ttttttgctc tttaaaagtt aataattata ttagcaaagt gttaatctaa
     2521 tgaagtaaaa aactcctgtg tggcagaaag taaaagaaaa ttccctaaat tatagcaagg
     2581 aacatgaatt ctcagacatt gtgagtgtgg gaatgtaaaa tggtaaaatc acttttgaaa
     2641 acagtttggc agtttcctat aaagttaaac atacactttt actttaggac tccagaattc
     2701 cacttctagt tatttattca agagaaggaa aaacaatgat cacagcaata cttgtatgca
     2761 tgttcattgc aacttaaaag cgtaaaaacc ccaaatgtcc atccacagac gaatgtataa
     2821 actgtggtat ccattacaca atagactact tactactcag caataaaaat gaagtaactt
     2881 tcaataaatg caatattatt ggcagacatt gttgaaggaa aaaagccaga caaacaacta
     2941 cataaaatat gtttctattt agatgaagtg gcaaactaat ctgtagtgtt aaaaattaga
     3001 ttagtgattg cctgggccaa gtggcaggtt ggggaggatg gctgcaaaga agtatgagga
     3061 aactttctcc aatagatgag aattttccgt atcttgatct gagtggcaaa ttgtaaactt
     3121 aaaatatata taaaatttat tgtatgaaaa ttaagcctca ataaacgtga ttataaaaaa
     3181 caagtctgca aggaaaccag aatcatatac cttctcttgt gaaatcacca tgaagtgtga
     3241 atggtcagga aaaagccagt aatattcata catttaataa tttcagctct actgaataaa
     3301 catataagtc tgatgggtga tgaaaatagc tactacaatc ttcatattct aactcctata
     3361 aagactgtat atcagaatct gcaaactttt atgcagatcc cagtgactca attacatgtt
     3421 caactatgat taaagcttca ataaacttgg ttgttcatct acttca
//
