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UniProtKB - Q28053 (A4_BOVIN)

Entry version 125 (17 Jun 2020)
Sequence version 1 (01 Nov 1997)
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Protein

Amyloid-beta A4 protein

Gene

APP

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score:

Annotation score:4 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at transcript leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions (By similarity). Can promote transcription activation through binding to APBB1-KAT5 and inhibit Notch signaling through interaction with Numb (By similarity). Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP (By similarity). Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1 (By similarity). By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapes in axons (By similarity). May be involved in copper homeostasis/oxidative stress through copper ion reduction (By similarity). In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu2+-mediated low-density lipoprotein oxidation (By similarity). Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and mitochondrial dysfunction in cultured cortical neurons. Provides Cu2+ ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1 (By similarity).By similarity

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

Complete GO annotation on QuickGO ...

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Amyloid-beta A4 protein
Alternative name(s):
ABPP
Short name:
APP
Alzheimer disease amyloid A4 protein homolog
Amyloid precursor proteinCurated
Amyloid-beta precursor proteinCurated
Cleaved into the following 6 chains:
Soluble APP-beta
Short name:
S-APP-beta
CTF-alpha
Amyloid-beta protein 42
Short name:
Abeta42
Alternative name(s):
Beta-APP42
Amyloid-beta protein 40
Short name:
Abeta40
Alternative name(s):
Beta-APP40
Gamma-secretase C-terminal fragment 59
Alternative name(s):
Gamma-CTF(59)
Gamma-secretase C-terminal fragment 57
Alternative name(s):
Gamma-CTF(57)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:APP
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiBos taurus (Bovine)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9913 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000009136 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Unplaced

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini‹1 – 34ExtracellularSequence analysisAdd BLAST›34
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei35 – 58HelicalSequence analysisAdd BLAST24
Topological domaini59CytoplasmicSequence analysis›1

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywords - Cellular componenti

Amyloid, Cell membrane, Cell projection, Coated pit, Cytoplasm, Cytoplasmic vesicle, Endosome, Membrane, Nucleus, Secreted

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_0000000064‹1 – 6Soluble APP-betaBy similarity›6
ChainiPRO_00000000657 – ›59CTF-alphaBy similarityAdd BLAST›53
ChainiPRO_00000000667 – 48Amyloid-beta protein 42By similarityAdd BLAST42
ChainiPRO_00000000677 – 46Amyloid-beta protein 40By similarityAdd BLAST40
ChainiPRO_000000006847 – ›59Gamma-secretase C-terminal fragment 59By similarityAdd BLAST›13
ChainiPRO_000000006949 – ›59Gamma-secretase C-terminal fragment 57By similarityAdd BLAST›11

Proteomic databases

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		Q28053

PRoteomics IDEntifications database

More...PRIDEi		Q28053

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB family members, the APBA family, MAPK8IP1, SHC1 and NUMB and DAB1 (By similarity). Binding to DAB1 inhibits its serine phosphorylation (By similarity).

Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif.

Also interacts with GPCR-like protein BPP, APPBP1, IB1, KNS2 (via its TPR domains), APPBP2 (via BaSS) and DDB1. In vitro, it binds MAPT via the MT-binding domains (By similarity). Associates with microtubules in the presence of ATP and in a kinesin-dependent manner (By similarity).

Interacts, through a C-terminal domain, with GNAO1.

Interacts with CPEB1, ANKS1B, TNFRSF21 and AGER (By similarity).

Interacts with ITM2B.

Interacts with ITM2C.

Interacts with IDE. Can form homodimers; dimerization is enhanced in the presence of Cu2+ ions. Can form homodimers; this is promoted by heparin binding (By similarity).

Interacts with SORL1 (via N-terminal ectodomain); this interaction retains APP in the trans-Golgi network and reduces processing into soluble APP-alpha and amyloid-beta peptides (By similarity).

Interacts with PLD3 (By similarity).

Interacts with VDAC1 (By similarity).

Interacts with NSG1; could regulate APP processing (By similarity). Amyloid-beta protein 42 interacts with FPR2 (By similarity).

Interacts with LRRK2 (By similarity).

Interacts (via cytoplasmic domain) with KIF5B (By similarity).

By similarity

Protein-protein interaction databases

STRING: functional protein association networks

More...STRINGi		9913.ENSBTAP00000045951

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		Q28053

Database of comparative protein structure models

More...ModBasei		Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the APP family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG3540 Eukaryota
ENOG410ZW2A LUCA

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_014607_2_1_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q28053

Database of Orthologous Groups

More...OrthoDBi		953529at2759

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		4.10.230.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR008155 Amyloid_glyco
IPR013803 Amyloid_glyco_Abeta
IPR037071 Amyloid_glyco_Abeta_sf
IPR028866 APP

The PANTHER Classification System

More...PANTHERi		PTHR23103 PTHR23103, 1 hit
PTHR23103:SF7 PTHR23103:SF7, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF03494 Beta-APP, 1 hit

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00204 BETAAMYLOID

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Fragment.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

Q28053-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
ISEVKMDAEF RHDSGYEVHH QKLVFFAEDV GSNKGAIIGL MVGGVVIATV 

IVITLVMLK
Length:59
Mass (Da):6,414
Last modified:November 1, 1997 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iF43469D488A2E12D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section is used for sequence fragments to indicate that the residue at the extremity of the sequence is not the actual terminal residue in the complete protein sequence.<p><a href='/help/non_ter' target='_top'>More...</a></p>Non-terminal residuei11
Non-terminal residuei591

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
X56124 mRNA Translation: CAA39589.1
X56126 mRNA Translation: CAA39591.1

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X56124 mRNA Translation: CAA39589.1
X56126 mRNA Translation: CAA39591.1

3D structure databases

SMRiQ28053
ModBaseiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000045951

Proteomic databases

PaxDbiQ28053
PRIDEiQ28053

Phylogenomic databases

eggNOGiKOG3540 Eukaryota
ENOG410ZW2A LUCA
HOGENOMiCLU_014607_2_1_1
InParanoidiQ28053
OrthoDBi953529at2759

Family and domain databases

Gene3Di4.10.230.10, 1 hit
InterProiView protein in InterPro
IPR008155 Amyloid_glyco
IPR013803 Amyloid_glyco_Abeta
IPR037071 Amyloid_glyco_Abeta_sf
IPR028866 APP
PANTHERiPTHR23103 PTHR23103, 1 hit
PTHR23103:SF7 PTHR23103:SF7, 1 hit
PfamiView protein in Pfam
PF03494 Beta-APP, 1 hit
PRINTSiPR00204 BETAAMYLOID

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiA4_BOVIN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q28053
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: June 17, 2020
This is version 125 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
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