NTAN1_HUMAN
ID NTAN1_HUMAN Reviewed; 310 AA.
AC Q96AB6; Q7Z4Z0;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Protein N-terminal asparagine amidohydrolase;
DE EC=3.5.1.121 {ECO:0000269|PubMed:21375249};
DE AltName: Full=Protein NH2-terminal asparagine amidohydrolase;
DE Short=PNAA;
DE AltName: Full=Protein NH2-terminal asparagine deamidase;
DE Short=PNAD;
DE Short=Protein N-terminal Asn amidase;
DE Short=Protein N-terminal asparagine amidase;
DE Short=Protein NTN-amidase;
GN Name=NTAN1;
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 [MRNA].
RA Jiang C.L., Yu L., Fan Y.X., Tu Q., Jiang J.X., Zhao S.Y.;
RT "Cloning and expression of a novel human cDNA homology to murine N-terminal
RT asparagine amidohydrolase (Ntan1) mRNA.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, REMOVAL OF INITIATOR METHIONINE, AND MUTAGENESIS OF PRO-2 AND
RP CYS-75.
RX PubMed=21375249; DOI=10.1021/bi101832w;
RA Cantor J.R., Stone E.M., Georgiou G.;
RT "Expression and biochemical characterization of the human enzyme N-terminal
RT asparagine amidohydrolase.";
RL Biochemistry 50:3025-3033(2011).
CC -!- FUNCTION: N-terminal asparagine deamidase that mediates deamidation of
CC N-terminal asparagine residues to aspartate. Required for the
CC ubiquitin-dependent turnover of intracellular proteins that initiate
CC with Met-Asn. These proteins are acetylated on the retained initiator
CC methionine and can subsequently be modified by the removal of N-acetyl
CC methionine by acylaminoacid hydrolase (AAH). Conversion of the
CC resulting N-terminal asparagine to aspartate by NTAN1/PNAD renders the
CC protein susceptible to arginylation, polyubiquitination and degradation
CC as specified by the N-end rule. This enzyme does not act on substrates
CC with internal or C-terminal asparagines and does not act on glutamine
CC residues in any position, nor on acetylated N-terminal peptidyl Asn.
CC {ECO:0000269|PubMed:21375249}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + H2O + N-terminal L-asparaginyl-[protein] = N-terminal
CC L-aspartyl-[protein] + NH4(+); Xref=Rhea:RHEA:50676, Rhea:RHEA-
CC COMP:12669, Rhea:RHEA-COMP:12776, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:50348,
CC ChEBI:CHEBI:64720; EC=3.5.1.121;
CC Evidence={ECO:0000269|PubMed:21375249};
CC -!- ACTIVITY REGULATION: Inhibited by micromolar concentrations of copper
CC and zinc ions. {ECO:0000269|PubMed:21375249}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 6.0-7.5. {ECO:0000269|PubMed:21375249};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q28955}.
CC -!- INTERACTION:
CC Q96AB6; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12401218, EBI-16439278;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q28955}.
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DR EMBL; AF092440; AAP97215.1; -; mRNA.
DR EMBL; BC017336; AAH17336.1; -; mRNA.
DR CCDS; CCDS10558.1; -.
DR RefSeq; NP_001257695.1; NM_001270766.1.
DR RefSeq; NP_001257696.1; NM_001270767.1.
DR RefSeq; NP_775745.1; NM_173474.3.
DR PDB; 6A0E; X-ray; 1.95 A; A/B=1-310.
DR PDB; 6A0F; X-ray; 2.38 A; A/B=1-310.
DR PDB; 6A0H; X-ray; 3.19 A; A/B=1-310.
DR PDB; 6A0I; X-ray; 2.00 A; A/B=1-310.
DR PDBsum; 6A0E; -.
DR PDBsum; 6A0F; -.
DR PDBsum; 6A0H; -.
DR PDBsum; 6A0I; -.
DR AlphaFoldDB; Q96AB6; -.
DR SMR; Q96AB6; -.
DR BioGRID; 125835; 10.
DR IntAct; Q96AB6; 2.
DR STRING; 9606.ENSP00000287706; -.
DR iPTMnet; Q96AB6; -.
DR PhosphoSitePlus; Q96AB6; -.
DR BioMuta; NTAN1; -.
DR DMDM; 37082118; -.
DR EPD; Q96AB6; -.
DR jPOST; Q96AB6; -.
DR MassIVE; Q96AB6; -.
DR MaxQB; Q96AB6; -.
DR PaxDb; Q96AB6; -.
DR PeptideAtlas; Q96AB6; -.
DR PRIDE; Q96AB6; -.
DR ProteomicsDB; 75948; -.
DR Antibodypedia; 24973; 98 antibodies from 20 providers.
DR DNASU; 123803; -.
DR Ensembl; ENST00000287706.8; ENSP00000287706.3; ENSG00000157045.9.
DR Ensembl; ENST00000620176.4; ENSP00000484380.1; ENSG00000275779.4.
DR GeneID; 123803; -.
DR KEGG; hsa:123803; -.
DR MANE-Select; ENST00000287706.8; ENSP00000287706.3; NM_173474.4; NP_775745.1.
DR UCSC; uc002ddd.5; human.
DR CTD; 123803; -.
DR DisGeNET; 123803; -.
DR GeneCards; NTAN1; -.
DR HGNC; HGNC:29909; NTAN1.
DR HPA; ENSG00000157045; Low tissue specificity.
DR MIM; 615367; gene.
DR neXtProt; NX_Q96AB6; -.
DR OpenTargets; ENSG00000157045; -.
DR PharmGKB; PA134863573; -.
DR VEuPathDB; HostDB:ENSG00000157045; -.
DR eggNOG; ENOG502QSQW; Eukaryota.
DR GeneTree; ENSGT00390000016730; -.
DR HOGENOM; CLU_077981_1_0_1; -.
DR InParanoid; Q96AB6; -.
DR OMA; YVQQREM; -.
DR OrthoDB; 804210at2759; -.
DR PhylomeDB; Q96AB6; -.
DR TreeFam; TF325597; -.
DR BioCyc; MetaCyc:ENSG00000157045-MON; -.
DR BRENDA; 3.5.1.121; 2681.
DR PathwayCommons; Q96AB6; -.
DR SignaLink; Q96AB6; -.
DR BioGRID-ORCS; 123803; 10 hits in 1078 CRISPR screens.
DR ChiTaRS; NTAN1; human.
DR GenomeRNAi; 123803; -.
DR Pharos; Q96AB6; Tbio.
DR PRO; PR:Q96AB6; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q96AB6; protein.
DR Bgee; ENSG00000157045; Expressed in subcutaneous adipose tissue and 98 other tissues.
DR ExpressionAtlas; Q96AB6; baseline and differential.
DR Genevisible; Q96AB6; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0008418; F:protein-N-terminal asparagine amidohydrolase activity; IDA:UniProtKB.
DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR InterPro; IPR026750; NTAN1.
DR PANTHER; PTHR12498; PTHR12498; 1.
DR Pfam; PF14736; N_Asn_amidohyd; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Hydrolase; Reference proteome.
FT CHAIN 1..310
FT /note="Protein N-terminal asparagine amidohydrolase"
FT /id="PRO_0000057971"
FT SITE 75
FT /note="Essential for catalytic activity"
FT VARIANT 283
FT /note="H -> N (in dbSNP:rs1136001)"
FT /id="VAR_051244"
FT VARIANT 287
FT /note="S -> P (in dbSNP:rs1135999)"
FT /id="VAR_051245"
FT MUTAGEN 2
FT /note="P->G: 3-fold reduction in catalytic activity."
FT /evidence="ECO:0000269|PubMed:21375249"
FT MUTAGEN 75
FT /note="C->A,S,T: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:21375249"
FT CONFLICT 6
FT /note="E -> D (in Ref. 1; AAP97215)"
FT /evidence="ECO:0000305"
FT CONFLICT 14
FT /note="Q -> R (in Ref. 1; AAP97215)"
FT /evidence="ECO:0000305"
FT STRAND 3..5
FT /evidence="ECO:0007829|PDB:6A0E"
FT HELIX 16..22
FT /evidence="ECO:0007829|PDB:6A0E"
FT HELIX 24..35
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 53..57
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 76..82
FT /evidence="ECO:0007829|PDB:6A0E"
FT TURN 83..85
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 88..93
FT /evidence="ECO:0007829|PDB:6A0E"
FT HELIX 98..110
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 121..127
FT /evidence="ECO:0007829|PDB:6A0E"
FT HELIX 135..148
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 154..161
FT /evidence="ECO:0007829|PDB:6A0E"
FT HELIX 162..165
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 166..169
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 172..176
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 180..183
FT /evidence="ECO:0007829|PDB:6A0E"
FT TURN 184..186
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 189..195
FT /evidence="ECO:0007829|PDB:6A0E"
FT HELIX 201..209
FT /evidence="ECO:0007829|PDB:6A0E"
FT TURN 220..223
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 224..227
FT /evidence="ECO:0007829|PDB:6A0E"
FT HELIX 238..242
FT /evidence="ECO:0007829|PDB:6A0E"
FT HELIX 246..253
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:6A0I"
FT HELIX 257..259
FT /evidence="ECO:0007829|PDB:6A0E"
FT HELIX 264..277
FT /evidence="ECO:0007829|PDB:6A0E"
FT TURN 282..284
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 285..287
FT /evidence="ECO:0007829|PDB:6A0I"
FT STRAND 292..296
FT /evidence="ECO:0007829|PDB:6A0E"
FT STRAND 302..305
FT /evidence="ECO:0007829|PDB:6A0E"
SQ SEQUENCE 310 AA; 34677 MW; C7FE8C550883DFC3 CRC64;
MPLLVEGRRV RLPQSAGDLV RAHPPLEERA RLLRGQSVQQ VGPQGLLYVQ QRELAVTSPK
DGSISILGSD DATTCHIVVL RHTGNGATCL THCDGTDTKA EVPLIMNSIK SFSDHAQCGR
LEVHLVGGFS DDRQLSQKLT HQLLSEFDRQ EDDIHLVTLC VTELNDREEN ENHFPVIYGI
AVNIKTAEIY RASFQDRGPE EQLRAARTLA GGPMISIYDA ETEQLRIGPY SWTPFPHVDF
WLHQDDKQIL ENLSTSPLAE PPHFVEHIRS TLMFLKKHPS PAHTLFSGNK ALLYKKNEDG
LWEKISSPGS
