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Protein

NEDD4 family-interacting protein 1

Gene

Ndfip1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score:

Annotation score:5 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

Activates HECT domain-containing E3 ubiquitin-protein ligases, including NEDD4 and ITCH, and consequently modulates the stability of their targets. As a result, controls many cellular processes. Prevents chronic T-helper cell-mediated inflammation by activating ITCH and thus controlling JUNB degradation. Promotes pancreatic beta cell death through degradation of JUNB and inhibition of the unfolded protein response, leading to reduction of insulin secretion. Restricts the production of proinflammatory cytokines in effector Th17 T-cells by promoting ITCH-mediated ubiquitination degradation of RORC. Together with NDFIP2, limits the cytokine signaling and expansion of effector Th2 T-cells by promoting degradation of JAK1, probably by ITCH- and NEDD4L-mediated ubiquitination. Regulates peripheral T-cell tolerance to self and foreign antigens, forcing the exit of naive CD4+ T-cells from the cell cycle before they become effector T-cells. Negatively regulates RLR-mediated antiviral response by promoting SMURF1-mediated ubiquitination and subsequent degradation of MAVS. Negatively regulates KCNH2 potassium channel activity by decreasing its cell-surface expression and interfering with channel maturation through recruitment of NEDD4L to the Golgi apparatus where it mediates KCNH2 degradation. In cortical neurons, mediates the ubiquitination of the divalent metal transporter SLC11A2/DMT1 by NEDD4L, leading to its down-regulation and protection of the cells from cobalt and iron toxicity. Important for normal development of dendrites and dendritic spines in cortex. Enhances the ubiquitination of BRAT1 mediated by: NEDD4, NEDD4L and ITCH and is required for the nuclear localization of ubiquitinated BRAT1. Enhances the ITCH-mediated ubiquitination of MAP3K7 by recruiting E2 ubiquitin-conjugating enzyme UBE2L3 to ITCH. Modulates EGFR signaling through multiple pathways. In particular, may regulate the ratio of AKT1-to-MAPK8 signaling in response to EGF, acting on AKT1 probably through PTEN destabilization and on MAPK8 through ITCH-dependent MAP2K4 inactivation. As a result, may control cell growth rate. Inhibits cell proliferation by promoting PTEN nuclear localization and changing its signaling specificity.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 - Molecular functioni

  • WW domain binding Source: GO_Central

GO - Biological processi

<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_and_taxonomy_section">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:
NEDD4 family-interacting protein 1
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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:Ndfip1
Synonyms:N4wbp5
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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>OrganismiRattus norvegicus (Rat)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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 identifieri10116 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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
  • UP000002494 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">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: Chromosome 18

Organism-specific databases

Rat genome database

More...
RGDi
1310053 Ndfip1

<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; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'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 domaini2 – 116CytoplasmicSequence analysisAdd BLAST115
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'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>Transmembranei117 – 137HelicalSequence analysisAdd BLAST21
Topological domaini138 – 143ExtracellularSequence analysis6
Transmembranei144 – 164HelicalSequence analysisAdd BLAST21
Topological domaini165 – 172CytoplasmicSequence analysis8
Transmembranei173 – 193HelicalSequence analysisAdd BLAST21
Topological domaini194 – 221ExtracellularSequence analysisAdd BLAST28

<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

Cell junction, Cell projection, Endosome, Golgi apparatus, Membrane, Secreted, Synapse, Synaptosome

<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 <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemovedBy similarity
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000762712 – 221NEDD4 family-interacting protein 1Add BLAST220

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei2N-acetylalanineBy similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Ubiquitinated by NEDD4; mono-, di- and polyubiquitinated forms are detected. Ubiquitination regulates its degradation (By similarity).By similarity
Undergoes transient tyrosine phosphorylation following EGF stimulation, most probably by catalyzed by SRC. Phosphorylation SRC is enhanced in the presence of NDFIP2 which may act as a scaffold to recruit SRC to NDFIP1 (By similarity).By similarity

Keywords - PTMi

Acetylation, Ubl conjugation

Proteomic databases

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

More...
PaxDbi
Q5U2S1

PRoteomics IDEntifications database

More...
PRIDEi
Q5U2S1

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
Q5U2S1

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
Q5U2S1

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSRNOG00000013562 Expressed in 10 organ(s), highest expression level in brain

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
Q5U2S1 RN

<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_section">'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_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Forms heterodimers with NDFIP2. Interacts with several E3 ubiquitin-protein ligases, including ITCH, NEDD4, NEDD4L and WWP2. The interaction with NEDD4, NEDD4L and ITCH leads to relocalization of these proteins to exosomes and eventually to exosomal secretion. Interacts with SR1402. Interacts with SLC11A2/DMT1. Interacts with PTEN. May interact with phosphorylated EGFR. Interacts with BRAT1. Interacts with KCNH2. Interacts with MAVS. Part of a complex containing ITCH, NDFIP1 and MAP3K7. Interacts (via N-terminus) with UBE2L3; the interaction mediates recruitment of UBE2L3 to ITCH.By similarity

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
253573, 2 interactors

STRING: functional protein association networks

More...
STRINGi
10116.ENSRNOP00000018499

<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

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni2 – 41Interaction with UBE2L3By similarityAdd BLAST40
Regioni42 – 76Interaction with ITCHBy similarityAdd BLAST35

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi39 – 42PPxY motif 14
Motifi64 – 67PPxY motif 24
Motifi74 – 76PPxY motif 33

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The PPxY motifs are required for E3 ubiquitin-protein ligase binding and activation and for ubiquitination.By similarity

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG4812 Eukaryota
ENOG4111M6U LUCA

Ensembl GeneTree

More...
GeneTreei
ENSGT00390000012721

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000038752

The HOVERGEN Database of Homologous Vertebrate Genes

More...
HOVERGENi
HBG057103

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
Q5U2S1

Identification of Orthologs from Complete Genome Data

More...
OMAi
IPMQMQV

Database of Orthologous Groups

More...
OrthoDBi
EOG091G0IMV

Database for complete collections of gene phylogenies

More...
PhylomeDBi
Q5U2S1

TreeFam database of animal gene trees

More...
TreeFami
TF324911

Family and domain databases

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR019325 NEDD4/Bsd2

The PANTHER Classification System

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PANTHERi
PTHR13396 PTHR13396, 1 hit

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF10176 DUF2370, 1 hit

<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_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<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_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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.

Q5U2S1-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MALALAALAA VEPACGTGYQ QLQNEEEPGE REQTAGDAPP PYSSISAESA
60 70 80 90 100
AYFDYKDESG FPKPPSYNVA TTLPSYDEAE RTKAEATIPL VPGRDEDFVG
110 120 130 140 150
RDDFDDADQL RIGNDGIFML TFFMAFLFNW IGFFLSFCLT TSAAGRYGAI
160 170 180 190 200
SGFGLSLIKW ILIVRFSTYF PGYFDGQYWL WWVFLVLGFL LFLRGFINYA
210 220
KVRKMPETFS NLPRTRVLFI Y
Length:221
Mass (Da):24,913
Last modified:December 7, 2004 - 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:i96CA5183C1C17F0B
GO

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
BC085887 mRNA Translation: AAH85887.1

NCBI Reference Sequences

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RefSeqi
NP_001013077.1, NM_001013059.1
XP_006254695.1, XM_006254633.3

UniGene gene-oriented nucleotide sequence clusters

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UniGenei
Rn.59254

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENSRNOT00000018499; ENSRNOP00000018499; ENSRNOG00000013562

Database of genes from NCBI RefSeq genomes

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GeneIDi
291609

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
rno:291609

UCSC genome browser

More...
UCSCi
RGD:1310053 rat

<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
BC085887 mRNA Translation: AAH85887.1
RefSeqiNP_001013077.1, NM_001013059.1
XP_006254695.1, XM_006254633.3
UniGeneiRn.59254

3D structure databases

Database of comparative protein structure models

More...
ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

Protein-protein interaction databases

BioGridi253573, 2 interactors
STRINGi10116.ENSRNOP00000018499

PTM databases

iPTMnetiQ5U2S1
PhosphoSitePlusiQ5U2S1

Proteomic databases

PaxDbiQ5U2S1
PRIDEiQ5U2S1

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000018499; ENSRNOP00000018499; ENSRNOG00000013562
GeneIDi291609
KEGGirno:291609
UCSCiRGD:1310053 rat

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
80762
RGDi1310053 Ndfip1

Phylogenomic databases

eggNOGiKOG4812 Eukaryota
ENOG4111M6U LUCA
GeneTreeiENSGT00390000012721
HOGENOMiHOG000038752
HOVERGENiHBG057103
InParanoidiQ5U2S1
OMAiIPMQMQV
OrthoDBiEOG091G0IMV
PhylomeDBiQ5U2S1
TreeFamiTF324911

Miscellaneous databases

Protein Ontology

More...
PROi
PR:Q5U2S1

Gene expression databases

BgeeiENSRNOG00000013562 Expressed in 10 organ(s), highest expression level in brain
GenevisibleiQ5U2S1 RN

Family and domain databases

InterProiView protein in InterPro
IPR019325 NEDD4/Bsd2
PANTHERiPTHR13396 PTHR13396, 1 hit
PfamiView protein in Pfam
PF10176 DUF2370, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
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 nameiNFIP1_RAT
<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: Q5U2S1
<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_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: December 7, 2004
Last modified: November 7, 2018
This is version 87 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

Complete proteome, Reference proteome
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