AMPN_MOUSE
ID AMPN_MOUSE Reviewed; 966 AA.
AC P97449; Q91YH8; Q99K63;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Aminopeptidase N {ECO:0000305};
DE Short=AP-N;
DE Short=mAPN;
DE EC=3.4.11.2 {ECO:0000269|PubMed:8691132};
DE AltName: Full=Alanyl aminopeptidase;
DE AltName: Full=Aminopeptidase M;
DE Short=AP-M;
DE AltName: Full=Membrane protein p161;
DE AltName: Full=Microsomal aminopeptidase;
DE AltName: CD_antigen=CD13;
GN Name=Anpep; Synonyms=Lap-1, Lap1;
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], PROTEIN SEQUENCE OF 538-564; 886-908; 922-942
RP AND 961-965, SUBCELLULAR LOCATION, GLYCOSYLATION, AND TISSUE SPECIFICITY.
RX PubMed=8805662;
RA Chen H., Kinzer C.A., Paul W.E.;
RT "p161, a murine membrane protein expressed on mast cells and some
RT macrophages, is mouse CD13/aminopeptidase N.";
RL J. Immunol. 157:2593-2600(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II, and FVB/N; TISSUE=Mammary tumor;
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 TISSUE SPECIFICITY.
RX PubMed=8103749; DOI=10.1002/eji.1830230946;
RA Hansen A.S., Noren O., Sjostrom H., Werdelin O.;
RT "A mouse aminopeptidase N is a marker for antigen-presenting cells and
RT appears to be co-expressed with major histocompatibility complex class II
RT molecules.";
RL Eur. J. Immunol. 23:2358-2364(1993).
RN [4]
RP FUNCTION IN ENZYMATIC CLEAVAGE OF ANTIGEN PEPTIDES BOUND TO CLASS II MHC,
RP AND CATALYTIC ACTIVITY.
RX PubMed=8691132; DOI=10.1084/jem.184.1.183;
RA Larsen S.L., Pedersen L.O., Buus S., Stryhn A.;
RT "T cell responses affected by aminopeptidase N (CD13)-mediated trimming of
RT major histocompatibility complex class II-bound peptides.";
RL J. Exp. Med. 184:183-189(1996).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-852, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-106; ASN-128; ASN-606; ASN-784
RP AND ASN-817.
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 [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-106; ASN-114; ASN-332; ASN-606;
RP ASN-784 AND ASN-817.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, 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).
RN [9]
RP FUNCTION, INTERACTION WITH SLC6A19, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP GLU-354; GLU-388; GLU-410 AND TYR-476.
RX PubMed=22677001; DOI=10.1042/bj20120307;
RA Fairweather S.J., Broeer A., O'Mara M.L., Broeer S.;
RT "Intestinal peptidases form functional complexes with the neutral amino
RT acid transporter B(0)AT1.";
RL Biochem. J. 446:135-148(2012).
CC -!- FUNCTION: Broad specificity aminopeptidase which plays a role in the
CC final digestion of peptides generated from hydrolysis of proteins by
CC gastric and pancreatic proteases. Also involved in the processing of
CC various peptides including peptide hormones, such as angiotensin III
CC and IV, neuropeptides, and chemokines (By similarity). May also be
CC involved the cleavage of peptides bound to major histocompatibility
CC complex class II molecules of antigen presenting cells
CC (PubMed:8691132). May have a role in angiogenesis and promote
CC cholesterol crystallization (By similarity). May have a role in amino
CC acid transport by acting as binding partner of amino acid transporter
CC SLC6A19 and regulating its activity (PubMed:22677001).
CC {ECO:0000250|UniProtKB:P15144, ECO:0000269|PubMed:22677001,
CC ECO:0000269|PubMed:8691132}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of an N-terminal amino acid, Xaa-|-Yaa- from a
CC peptide, amide or arylamide. Xaa is preferably Ala, but may be most
CC amino acids including Pro (slow action). When a terminal hydrophobic
CC residue is followed by a prolyl residue, the two may be released as
CC an intact Xaa-Pro dipeptide.; EC=3.4.11.2;
CC Evidence={ECO:0000269|PubMed:8691132};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P15144};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P15144};
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with SLC6A19
CC (PubMed:22677001). {ECO:0000250|UniProtKB:P15144,
CC ECO:0000269|PubMed:22677001}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8805662};
CC Single-pass type II membrane protein {ECO:0000250|UniProtKB:P15144}.
CC Note=Also found as a soluble form. {ECO:0000250|UniProtKB:P15144}.
CC -!- TISSUE SPECIFICITY: Expressed in the intestinal brush border (at
CC protein level) (PubMed:22677001). Highly expressed in intestinal tract
CC and kidney, present in liver, lymph node, spleen, and brain
CC (PubMed:8805662, PubMed:8103749). Found as well in monocytes,
CC macrophages, dendritic cells, veiled cells and B-cells but not on T-
CC cells and thymocytes (PubMed:8103749). {ECO:0000269|PubMed:22677001,
CC ECO:0000269|PubMed:8103749, ECO:0000269|PubMed:8805662}.
CC -!- PTM: N- and O-glycosylated. {ECO:0000269|PubMed:8805662}.
CC -!- PTM: Sulfated. {ECO:0000250|UniProtKB:P15145}.
CC -!- PTM: May undergo proteolysis and give rise to a soluble form.
CC {ECO:0000250|UniProtKB:P15144}.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U77083; AAB19065.1; -; mRNA.
DR EMBL; BC005431; AAH05431.1; -; mRNA.
DR EMBL; BC017011; AAH17011.1; -; mRNA.
DR EMBL; BC040792; AAH40792.1; -; mRNA.
DR CCDS; CCDS21388.1; -.
DR RefSeq; NP_032512.2; NM_008486.2.
DR RefSeq; XP_006540741.1; XM_006540678.3.
DR AlphaFoldDB; P97449; -.
DR SMR; P97449; -.
DR IntAct; P97449; 8.
DR MINT; P97449; -.
DR STRING; 10090.ENSMUSP00000103015; -.
DR BindingDB; P97449; -.
DR ChEMBL; CHEMBL2189140; -.
DR DrugCentral; P97449; -.
DR GuidetoPHARMACOLOGY; 1560; -.
DR MEROPS; M01.001; -.
DR GlyConnect; 2126; 6 N-Linked glycans (3 sites).
DR GlyGen; P97449; 13 sites, 6 N-linked glycans (3 sites).
DR iPTMnet; P97449; -.
DR PhosphoSitePlus; P97449; -.
DR jPOST; P97449; -.
DR MaxQB; P97449; -.
DR PaxDb; P97449; -.
DR PeptideAtlas; P97449; -.
DR PRIDE; P97449; -.
DR ProteomicsDB; 281971; -.
DR Antibodypedia; 3713; 1941 antibodies from 48 providers.
DR DNASU; 16790; -.
DR Ensembl; ENSMUST00000049004; ENSMUSP00000035943; ENSMUSG00000039062.
DR Ensembl; ENSMUST00000107392; ENSMUSP00000103015; ENSMUSG00000039062.
DR GeneID; 16790; -.
DR KEGG; mmu:16790; -.
DR UCSC; uc009hzd.1; mouse.
DR CTD; 290; -.
DR MGI; MGI:5000466; Anpep.
DR VEuPathDB; HostDB:ENSMUSG00000039062; -.
DR eggNOG; KOG1046; Eukaryota.
DR GeneTree; ENSGT00940000154876; -.
DR HOGENOM; CLU_003705_2_2_1; -.
DR InParanoid; P97449; -.
DR OMA; KWFIFNI; -.
DR OrthoDB; 110058at2759; -.
DR PhylomeDB; P97449; -.
DR TreeFam; TF300395; -.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 16790; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Anpep; mouse.
DR PRO; PR:P97449; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P97449; protein.
DR Bgee; ENSMUSG00000039062; Expressed in small intestine Peyer's patch and 180 other tissues.
DR ExpressionAtlas; P97449; baseline and differential.
DR Genevisible; P97449; MM.
DR GO; GO:0031526; C:brush border membrane; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0004177; F:aminopeptidase activity; ISO:MGI.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IBA:GO_Central.
DR GO; GO:0042277; F:peptide binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0035814; P:negative regulation of renal sodium excretion; ISO:MGI.
DR GO; GO:0043171; P:peptide catabolic process; ISO:MGI.
DR GO; GO:0016485; P:protein processing; ISO:MGI.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0008217; P:regulation of blood pressure; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd09601; M1_APN-Q_like; 1.
DR Gene3D; 1.10.390.10; -; 1.
DR Gene3D; 2.60.40.1730; -; 1.
DR InterPro; IPR045357; Aminopeptidase_N-like_N.
DR InterPro; IPR042097; Aminopeptidase_N-like_N_sf.
DR InterPro; IPR024571; ERAP1-like_C_dom.
DR InterPro; IPR034016; M1_APN-typ.
DR InterPro; IPR001930; Peptidase_M1.
DR InterPro; IPR014782; Peptidase_M1_dom.
DR InterPro; IPR027268; Peptidase_M4/M1_CTD_sf.
DR Pfam; PF11838; ERAP1_C; 1.
DR Pfam; PF01433; Peptidase_M1; 1.
DR Pfam; PF17900; Peptidase_M1_N; 1.
DR PRINTS; PR00756; ALADIPTASE.
DR SUPFAM; SSF63737; SSF63737; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Aminopeptidase; Angiogenesis; Cell membrane; Developmental protein;
KW Differentiation; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hydrolase; Membrane; Metal-binding; Metalloprotease; Phosphoprotein;
KW Protease; Reference proteome; Signal-anchor; Sulfation; Transmembrane;
KW Transmembrane helix; Zinc.
FT CHAIN 1..966
FT /note="Aminopeptidase N"
FT /id="PRO_0000095082"
FT TOPO_DOM 1..8
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT TRANSMEM 9..32
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 33..966
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT REGION 33..68
FT /note="Cytosolic Ser/Thr-rich junction"
FT REGION 42..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 69..966
FT /note="Metalloprotease"
FT ACT_SITE 388
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 351..355
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT BINDING 387
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 391
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 410
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT SITE 476
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT MOD_RES 176
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT MOD_RES 418
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT MOD_RES 423
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT MOD_RES 852
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT CARBOHYD 106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:19656770"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 128
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770"
FT CARBOHYD 234
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 332
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 573
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 606
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:19656770"
FT CARBOHYD 624
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 734
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 784
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:19656770"
FT CARBOHYD 817
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:19656770"
FT DISULFID 760..767
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT DISULFID 797..833
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT MUTAGEN 354
FT /note="E->A: Reduces substrate affinity of SLC6A19-mediated
FT amino acid transport."
FT /evidence="ECO:0000269|PubMed:22677001"
FT MUTAGEN 388
FT /note="E->A: No impact on substrate affinity of SLC6A19-
FT mediated amino acid transport."
FT /evidence="ECO:0000269|PubMed:22677001"
FT MUTAGEN 410
FT /note="E->A: Reduces substrate affinity of SLC6A19-mediated
FT amino acid transport."
FT /evidence="ECO:0000269|PubMed:22677001"
FT MUTAGEN 476
FT /note="Y->F: No impact on substrate affinity of SLC6A19-
FT mediated amino acid transport."
FT /evidence="ECO:0000269|PubMed:22677001"
FT CONFLICT 62
FT /note="T -> TATTTATTT (in Ref. 2; AAH17011/AAH40792)"
FT /evidence="ECO:0000305"
FT CONFLICT 84
FT /note="S -> A (in Ref. 1; AAB19065)"
FT /evidence="ECO:0000305"
FT CONFLICT 106
FT /note="N -> S (in Ref. 2; AAH17011/AAH40792)"
FT /evidence="ECO:0000305"
FT CONFLICT 181
FT /note="Q -> E (in Ref. 2; AAH17011/AAH40792)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="D -> G (in Ref. 2; AAH17011/AAH40792)"
FT /evidence="ECO:0000305"
FT CONFLICT 532
FT /note="P -> L (in Ref. 2; AAH17011/AAH40792)"
FT /evidence="ECO:0000305"
FT CONFLICT 557
FT /note="N -> S (in Ref. 2; AAH17011/AAH40792)"
FT /evidence="ECO:0000305"
FT CONFLICT 557
FT /note="Missing (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 689
FT /note="A -> T (in Ref. 2; AAH17011/AAH40792)"
FT /evidence="ECO:0000305"
FT CONFLICT 726
FT /note="T -> M (in Ref. 2; AAH17011/AAH40792)"
FT /evidence="ECO:0000305"
FT CONFLICT 966
FT /note="S -> G (in Ref. 2; AAH17011/AAH40792)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 966 AA; 109651 MW; FD837F7ACE705835 CRC64;
MAKGFYISKT LGILGILLGV AAVCTIIALS VVYAQEKNRN AENSATAPTL PGSTSATTAT
TTPAVDESKP WNQYRLPKTL IPDSYRVILR PYLTPNNQGL YIFQGNSTVR FTCNQTTDVI
IIHSKKLNYT LKGNHRVVLR TLDGTPAPNI DKTELVERTE YLVVHLQGSL VEGRQYEMDS
QFQGELADDL AGFYRSEYME GDVKKVVATT QMQAADARKS FPCFDEPAMK AMFNITLIYP
NNLIALSNML PKESKPYPED PSCTMTEFHS TPKMSTYLLA YIVSEFKNIS SVSANGVQIG
IWARPSAIDE GQGDYALNVT GPILNFFAQH YNTSYPLPKS DQIALPDFNA GAMENWGLVT
YRESSLVFDS QSSSISNKER VVTVIAHELA HQWFGNLVTV AWWNDLWLNE GFASYVEYLG
ADYAEPTWNL KDLMVLNDVY RVMAVDALAS SHPLSSPADE IKTPDQIMEL FDSITYSKGA
SVIRMLSSFL TEDLFKKGLS SYLHTYQYSN TVYLDLWEHL QKAVNQQTAV QPPATVRTIM
DRWILQMGFP VITVNTNTGE ISQKHFLLDS KSNVTRPSEF NYIWIAPIPF LKSGQEDHYW
LDVEKNQSAK FQTSSNEWIL LNINVTGYYL VNYDENNWKK LQNQLQTDLS VIPVINRAQI
IHDSFNLASA KMIPITLALD NTLFLVKEAE YMPWQAALSS LNYFTLMFDR SEVYGPMKRY
LKKQVTPLFF YFQNRTNNWV NRPPTLMEQY NEINAISTAC SSGLKECRDL VVELYSQWMK
NPNNNTIHPN LRSTVYCNAI AFGGEEEWNF AWEQFRNATL VNEADKLRSA LACSKDVWIL
NRYLSYTLNP DYIRKQDTTS TIISIASNVA GHPLVWDFVR SNWKKLFENY GGGSFSFANL
IQGVTRRFSS EFELQQLEQF KADNSATGFG TGTRALEQAL EKTRANIDWV KENKDAVFKW
FTENSS
