ANPEP

Protein identityUniProt · HPA

UniProt accession

P15144

Gene

ANPEP

Ensembl

ENSG00000166825

Chromosome

15

Canonical length

967 aa

Protein class

CD markers, Enzymes, Metabolic proteins, Plasma proteins, Predicted membrane proteins

Subcellular location

Plasma membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

Aminopeptidase N is located in the small-intestinal and renal microvillar membrane, and also in other plasma membranes. In the small intestine aminopeptidase N plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Its function in proximal tubular epithelial cells and other cell types is less clear. The large extracellular carboxyterminal domain contains a pentapeptide consensus sequence characteristic of members of the zinc-binding metalloproteinase superfamily. Sequence comparisons with known enzymes of this class showed that CD13 and aminopeptidase N are identical. The latter enzyme was thought to be involved in the metabolism of regulatory peptides by diverse cell types, including small intestinal and renal tubular epithelial cells, macrophages, granulocytes, and synaptic membranes from the CNS. This membrane-bound zinc metalloprotease is known to serve as a receptor for the HCoV-229E alphacoronavirus as well as other non-human coronaviruses. This gene has also been shown to promote angiogenesis, tumor growth, and metastasis and defects in this gene are associated with various types of leukemia and lymphoma. [provided by RefSeq, Apr 2020]

Canonical amino-acid sequenceUniProt

967 residues, UniProt reviewed canonical sequence.

>P15144|ANPEP
     1  MAKGFYISKS LGILGILLGV AAVCTIIALS VVYSQEKNKN ANSSPVASTT PSASATTNPA
    61  SATTLDQSKA WNRYRLPNTL KPDSYRVTLR PYLTPNDRGL YVFKGSSTVR FTCKEATDVI
   121  IIHSKKLNYT LSQGHRVVLR GVGGSQPPDI DKTELVEPTE YLVVHLKGSL VKDSQYEMDS
   181  EFEGELADDL AGFYRSEYME GNVRKVVATT QMQAADARKS FPCFDEPAMK AEFNITLIHP
   241  KDLTALSNML PKGPSTPLPE DPNWNVTEFH TTPKMSTYLL AFIVSEFDYV EKQASNGVLI
   301  RIWARPSAIA AGHGDYALNV TGPILNFFAG HYDTPYPLPK SDQIGLPDFN AGAMENWGLV
   361  TYRENSLLFD PLSSSSSNKE RVVTVIAHEL AHQWFGNLVT IEWWNDLWLN EGFASYVEYL
   421  GADYAEPTWN LKDLMVLNDV YRVMAVDALA SSHPLSTPAS EINTPAQISE LFDAISYSKG
   481  ASVLRMLSSF LSEDVFKQGL ASYLHTFAYQ NTIYLNLWDH LQEAVNNRSI QLPTTVRDIM
   541  NRWTLQMGFP VITVDTSTGT LSQEHFLLDP DSNVTRPSEF NYVWIVPITS IRDGRQQQDY
   601  WLIDVRAQND LFSTSGNEWV LLNLNVTGYY RVNYDEENWR KIQTQLQRDH SAIPVINRAQ
   661  IINDAFNLAS AHKVPVTLAL NNTLFLIEER QYMPWEAALS SLSYFKLMFD RSEVYGPMKN
   721  YLKKQVTPLF IHFRNNTNNW REIPENLMDQ YSEVNAISTA CSNGVPECEE MVSGLFKQWM
   781  ENPNNNPIHP NLRSTVYCNA IAQGGEEEWD FAWEQFRNAT LVNEADKLRA ALACSKELWI
   841  LNRYLSYTLN PDLIRKQDAT STIISITNNV IGQGLVWDFV QSNWKKLFND YGGGSFSFSN
   901  LIQAVTRRFS TEYELQQLEQ FKKDNEETGF GSGTRALEQA LEKTKANIKW VKENKEVVLQ
   961  WFTENSK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ANPEP can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.22

Highest tissue expression

2,245 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ANPEP.

Disease | AutoantibodyPubMed

Conditions in which antibodies against ANPEP are reported. Each links to that disease's full target list.

• Cytomegalovirus Infections 5

ReferencesPubMed · IEDB

Publications for ANPEP from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.64

gnomAD pLI

0

gnomAD missense Z

1.43

DepMap mean gene effect

0.06

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• angiogenesis
• angiotensin maturation
• cell differentiation
• peptide catabolic process

Molecular functions

• alanyl aminopeptidase activity
• aminopeptidase activity
• metalloaminopeptidase activity
• metallopeptidase activity
• signaling receptor activity
• virus receptor activity
• zinc ion binding

Cellular components

• endoplasmic reticulum-Golgi intermediate compartment
• external side of plasma membrane
• extracellular exosome
• extracellular space
• lysosomal membrane
• plasma membrane
• secretory granule membrane

Protein domainsUniProt · Pfam · InterPro

• Peptidase M1, alanine aminopeptidase/leukotriene A4 hydrolase
• Peptidase M1, membrane alanine aminopeptidase
• ERAP1-like C-terminal domain
• Peptidase M4/M1, CTD superfamily
• Aminopeptidase N-type
• Aminopeptidase N-like , N-terminal domain superfamliy
• Aminopeptidase N-like , N-terminal domain
• Peptidase M1 family aminopeptidases
• Peptidase family M1 domain
• ERAP1-like C-terminal domain
• Peptidase M1 N-terminal domain

KeywordsUniProt

• Aminopeptidase
• Angiogenesis
• Cell membrane
• Developmental protein
• Differentiation
• Disulfide bond
• Glycoprotein
• Host cell receptor for virus entry
• Host-virus interaction
• Hydrolase
• Membrane
• Metal-binding
• Metalloprotease
• Protease
• Receptor
• Signal-anchor
• Sulfation
• Transmembrane
• Transmembrane helix
• Zinc

InteractionsUniProt · HPA

Protein binding partners of ANPEP in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SLC6A19