NADL2_HUMAN
ID NADL2_HUMAN Reviewed; 795 AA.
AC Q58DX5; Q658X9; Q6H9J8; Q6H9J9; Q6PG38;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Inactive N-acetylated-alpha-linked acidic dipeptidase-like protein 2;
DE Short=NAALADase L2;
GN Name=NAALADL2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], NUCLEOTIDE SEQUENCE [MRNA] OF 1-291
RP (ISOFORM 2), IDENTIFICATION (ISOFORM 1), AND VARIANTS SER-68; MET-128;
RP SER-385; ARG-622 AND SER-677.
RX PubMed=15168106; DOI=10.1007/s00439-004-1134-6;
RA Tonkin E.T., Smith M., Eichhorn P., Jones S., Imamwerdi B., Lindsay S.,
RA Jackson M., Wang T.-J., Ireland M., Burn J., Krantz I.D., Carr P.,
RA Strachan T.;
RT "A giant novel gene undergoing extensive alternative splicing is severed by
RT a Cornelia de Lange-associated translocation breakpoint at 3q26.3.";
RL Hum. Genet. 115:139-148(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS SER-68 AND
RP MET-128.
RC TISSUE=Kidney;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 277-795, AND VARIANTS SER-385;
RP ARG-622 AND SER-677.
RC TISSUE=Stomach;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-92, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: May be catalytically inactive.
CC -!- INTERACTION:
CC Q58DX5; O00155: GPR25; NbExp=3; IntAct=EBI-10178964, EBI-10178951;
CC Q58DX5; Q14416: GRM2; NbExp=3; IntAct=EBI-10178964, EBI-10232876;
CC Q58DX5; Q9Y287: ITM2B; NbExp=3; IntAct=EBI-10178964, EBI-2866431;
CC Q58DX5; Q86VI4: LAPTM4B; NbExp=3; IntAct=EBI-10178964, EBI-3267258;
CC Q58DX5; Q99726: SLC30A3; NbExp=3; IntAct=EBI-10178964, EBI-10294651;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type II
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q58DX5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q58DX5-2; Sequence=VSP_030676, VSP_030677, VSP_030678;
CC -!- TISSUE SPECIFICITY: Expressed at higher level in kidney and placenta.
CC In embryo, it is mainly confined to duodenal and stomach endoderm,
CC mesonephros, metanephros and pancreas.
CC -!- MISCELLANEOUS: The gene maps to 3q26.31, a region associated with
CC Cornelia de Lange syndrome. However, PubMed:15168106 failed to identify
CC specific mutations in a panel of DNA samples from patients with
CC Cornelia de Lange syndrome.
CC -!- SIMILARITY: Belongs to the peptidase M28 family. M28B subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: Although related to the peptidase M28 family, it lacks the
CC conserved zinc-binding and active sites and therefore has probably lost
CC hydrolase activity. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAE54974.2; Type=Miscellaneous discrepancy; Note=Contaminating sequence at the C-terminus.; Evidence={ECO:0000305};
CC Sequence=CAH56310.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AJ607395; CAE54973.1; -; Genomic_DNA.
DR EMBL; AJ607396; CAE54974.2; ALT_SEQ; mRNA.
DR EMBL; BC057243; AAH57243.1; -; mRNA.
DR EMBL; AL832931; CAH56310.1; ALT_FRAME; mRNA.
DR EMBL; BN000432; CAE75743.1; -; mRNA.
DR CCDS; CCDS46960.1; -. [Q58DX5-1]
DR RefSeq; NP_996898.2; NM_207015.2. [Q58DX5-1]
DR AlphaFoldDB; Q58DX5; -.
DR SMR; Q58DX5; -.
DR BioGRID; 129052; 18.
DR IntAct; Q58DX5; 14.
DR MINT; Q58DX5; -.
DR STRING; 9606.ENSP00000404705; -.
DR MEROPS; M28.975; -.
DR GlyConnect; 1397; 3 N-Linked glycans (2 sites).
DR GlyGen; Q58DX5; 4 sites, 3 N-linked glycans (2 sites).
DR iPTMnet; Q58DX5; -.
DR PhosphoSitePlus; Q58DX5; -.
DR SwissPalm; Q58DX5; -.
DR BioMuta; NAALADL2; -.
DR DMDM; 296439292; -.
DR jPOST; Q58DX5; -.
DR MassIVE; Q58DX5; -.
DR MaxQB; Q58DX5; -.
DR PaxDb; Q58DX5; -.
DR PeptideAtlas; Q58DX5; -.
DR PRIDE; Q58DX5; -.
DR ProteomicsDB; 62609; -. [Q58DX5-1]
DR ProteomicsDB; 62610; -. [Q58DX5-2]
DR Antibodypedia; 9309; 115 antibodies from 20 providers.
DR DNASU; 254827; -.
DR Ensembl; ENST00000454872.6; ENSP00000404705.1; ENSG00000177694.16. [Q58DX5-1]
DR GeneID; 254827; -.
DR KEGG; hsa:254827; -.
DR MANE-Select; ENST00000454872.6; ENSP00000404705.1; NM_207015.3; NP_996898.2.
DR UCSC; uc003fit.4; human. [Q58DX5-1]
DR CTD; 254827; -.
DR DisGeNET; 254827; -.
DR GeneCards; NAALADL2; -.
DR HGNC; HGNC:23219; NAALADL2.
DR HPA; ENSG00000177694; Low tissue specificity.
DR MIM; 608806; gene.
DR neXtProt; NX_Q58DX5; -.
DR OpenTargets; ENSG00000177694; -.
DR PharmGKB; PA142671295; -.
DR VEuPathDB; HostDB:ENSG00000177694; -.
DR eggNOG; KOG2195; Eukaryota.
DR GeneTree; ENSGT01030000234598; -.
DR InParanoid; Q58DX5; -.
DR OMA; KIKTHWT; -.
DR OrthoDB; 804230at2759; -.
DR PhylomeDB; Q58DX5; -.
DR TreeFam; TF312981; -.
DR PathwayCommons; Q58DX5; -.
DR SignaLink; Q58DX5; -.
DR BioGRID-ORCS; 254827; 6 hits in 1061 CRISPR screens.
DR ChiTaRS; NAALADL2; human.
DR GenomeRNAi; 254827; -.
DR Pharos; Q58DX5; Tbio.
DR PRO; PR:Q58DX5; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q58DX5; protein.
DR Bgee; ENSG00000177694; Expressed in calcaneal tendon and 120 other tissues.
DR ExpressionAtlas; Q58DX5; baseline and differential.
DR Genevisible; Q58DX5; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR Gene3D; 1.20.930.40; -; 1.
DR InterPro; IPR007484; Peptidase_M28.
DR InterPro; IPR039373; Peptidase_M28B.
DR InterPro; IPR036757; TFR-like_dimer_dom_sf.
DR PANTHER; PTHR10404; PTHR10404; 1.
DR Pfam; PF04389; Peptidase_M28; 1.
DR SUPFAM; SSF47672; SSF47672; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Glycoprotein; Membrane; Phosphoprotein;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..795
FT /note="Inactive N-acetylated-alpha-linked acidic
FT dipeptidase-like protein 2"
FT /id="PRO_0000315721"
FT TOPO_DOM 1..121
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 143..795
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..17
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 92
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 295
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 373
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 534
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 759
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..17
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15168106,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_030676"
FT VAR_SEQ 314..337
FT /note="LSSLEKAGFGGVLLYIDPCDLPKT -> VGPVNVIQWFGQYFALFCWNYMLL
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15168106,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_030677"
FT VAR_SEQ 338..795
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15168106,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_030678"
FT VARIANT 68
FT /note="G -> S (in dbSNP:rs9823911)"
FT /evidence="ECO:0000269|PubMed:15168106,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_038288"
FT VARIANT 128
FT /note="I -> M (in dbSNP:rs9836841)"
FT /evidence="ECO:0000269|PubMed:15168106,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_038289"
FT VARIANT 194
FT /note="M -> T (in dbSNP:rs4371530)"
FT /id="VAR_038290"
FT VARIANT 385
FT /note="P -> S (in dbSNP:rs6802937)"
FT /evidence="ECO:0000269|PubMed:15168106,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_038291"
FT VARIANT 622
FT /note="P -> R (in dbSNP:rs9866564)"
FT /evidence="ECO:0000269|PubMed:15168106,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_038292"
FT VARIANT 677
FT /note="L -> S (in dbSNP:rs9826737)"
FT /evidence="ECO:0000269|PubMed:15168106,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_038293"
SQ SEQUENCE 795 AA; 88682 MW; 7636F2627F4B6DAB CRC64;
MGENEASLPN TSLQGKKMAY QKVHADQRAP GHSQYLDNDD LQATALDLEW DMEKELEESG
FDQFQLDGAE NQNLGHSETI DLNLDSIQPA TSPKGRFQRL QEESDYITHY TRSAPKSNRC
NFCHVLKILC TATILFIFGI LIGYYVHTNC PSDAPSSGTV DPQLYQEILK TIQAEDIKKS
FRNLVQLYKN EDDMEISKKI KTQWTSLGLE DVQFVNYSVL LDLPGPSPST VTLSSSGQCF
HPNGQPCSEE ARKDSSQDLL YSYAAYSAKG TLKAEVIDVS YGMADDLKRI RKIKNVTNQI
ALLKLGKLPL LYKLSSLEKA GFGGVLLYID PCDLPKTVNP SHDTFMVSLN PGGDPSTPGY
PSVDESFRQS RSNLTSLLVQ PISAPLVAKL ISSPKARTKN EACSSLELPN NEIRVVSMQV
QTVTKLKTVT NVVGFVMGLT SPDRYIIVGS HHHTAHSYNG QEWASSTAII TAFIRALMSK
VKRGWRPDRT IVFCSWGGTA FGNIGSYEWG EDFKKVLQKN VVAYISLHSP IRGNSSLYPV
ASPSLQQLVV EKNNFNCTRR AQCPETNISS IQIQGDADYF INHLGVPIVQ FAYEDIKTLE
GPSFLSEARF STRATKIEEM DPSFNLHETI TKLSGEVILQ IANEPVLPFN ALDIALEVQN
NLKGDQPNTH QLLAMALRLR ESAELFQSDE MRPANDPKER APIRIRMLND ILQDMEKSFL
VKQAPPGFYR NILYHLDEKT SRFSILIEAW EHCKPLASNE TLQEALSEVL NSINSAQVYF
KAGLDVFKSV LDGKN
