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Entry version 105 (16 Oct 2019)
Sequence version 1 (16 May 2006)
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Protein

Interleukin-1 receptor-associated kinase 4

Gene

IRAK4

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

Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections (By similarity).By similarity

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei214ATPPROSITE-ProRule annotation1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei312Proton acceptorPROSITE-ProRule annotation1
Binding sitei330ATPPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi193 – 201ATPPROSITE-ProRule annotation9
Nucleotide bindingi314 – 317ATPPROSITE-ProRule annotation4

<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

GO - Biological processi

<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>Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processImmunity, Innate immunity
LigandATP-binding, Magnesium, Nucleotide-binding

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-BTA-1257604 PIP3 activates AKT signaling
R-BTA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-BTA-9020702 Interleukin-1 signaling
R-BTA-975110 TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
R-BTA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-BTA-975155 MyD88 dependent cascade initiated on endosome

<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:
Interleukin-1 receptor-associated kinase 4 (EC:2.7.11.1)
Short name:
IRAK-4
<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:IRAK4
<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>OrganismiBos taurus (Bovine)
<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 identifieri9913 [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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
<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
  • UP000009136 <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 5

Organism-specific databases

Vertebrate Gene Nomenclature Database

More...
VGNCi
VGNC:30268 IRAK4

<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

Keywords - Cellular componenti

Cytoplasm

<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.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00002601581 – 461Interleukin-1 receptor-associated kinase 4Add BLAST461

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 residuei1N-acetylmethionineBy similarity1
Modified residuei34N6-acetyllysineBy similarity1
Modified residuei343PhosphothreonineBy similarity1
Modified residuei346PhosphothreonineBy similarity1
Modified residuei347PhosphoserineBy 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

Phosphorylated.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

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

More...
PaxDbi
Q1RMT8

PRoteomics IDEntifications database

More...
PRIDEi
Q1RMT8

<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
ENSBTAG00000021105 Expressed in 10 organ(s), highest expression level in spleen

<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

Associates with MYD88 and IRAK2 to form a ternary complex called the Myddosome. Once phosphorylated, IRAK4 dissociates from the receptor complex and then associates with the TNF receptor-associated factor 6 (TRAF6), IRAK1, and PELI1; this intermediate complex is required for subsequent NF-kappa-B activation. Direct binding of SMAD6 to PELI1 prevents complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression.

Interacts with IL1RL1 (By similarity).

By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRING: functional protein association networks

More...
STRINGi
9913.ENSBTAP00000028115

<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
Q1RMT8

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

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini20 – 104DeathAdd BLAST85
Domaini187 – 455Protein kinasePROSITE-ProRule annotationAdd BLAST269

<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

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG1187 Eukaryota
COG0515 LUCA

Ensembl GeneTree

More...
GeneTreei
ENSGT00940000158792

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000116550

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
Q1RMT8

KEGG Orthology (KO)

More...
KOi
K04733

Identification of Orthologs from Complete Genome Data

More...
OMAi
TTMMTER

Database of Orthologous Groups

More...
OrthoDBi
684563at2759

TreeFam database of animal gene trees

More...
TreeFami
TF351380

Family and domain databases

Conserved Domains Database

More...
CDDi
cd08793 Death_IRAK4, 1 hit

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR011029 DEATH-like_dom_sf
IPR017428 IRAK4
IPR037970 IRAK4_Death
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00069 Pkinase, 1 hit

PIRSF; a whole-protein classification database

More...
PIRSFi
PIRSF038189 IRAK4, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM00220 S_TKc, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF47986 SSF47986, 1 hit
SSF56112 SSF56112, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 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>. 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_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.

Q1RMT8-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MNKPITASTY VRCLSLGLIR KLSDFIDPQE GWKKLAVAIK KPSGDDRYNQ
60 70 80 90 100
FHIRRFEALL QIGKSPTCEL LFDWGTTNCT VGDLVDILVQ NEFFAPASLL
110 120 130 140 150
LPDAVPKNVN TLPSKVTVVA VQQKPKPLCG KDRTSVISDE NPEQNYVLPD
160 170 180 190 200
SSSPENTSLE FSDTRFHSFS FFELKDVTNN FDERPISVGG NKMGEGGFGV
210 220 230 240 250
VYKGYVNNRT VAVKKLAAMV DISTEELKQQ FDQEIKVMAK CQHENLVELL
260 270 280 290 300
GFSSDGDDLC LVYVYMPNGS LLDRLSCLDG TPPLSWNMRC KIAQGAANGL
310 320 330 340 350
SYLHENHHIH RDIKSANILL DEDFTAKISD FGLARASEKF AQTVMTSRIV
360 370 380 390 400
GTTAYMAPEA LRGEITPKSD IYSFGVVLLE IITGLPAVDE HREPQLLLDI
410 420 430 440 450
KEEIEDEEKT IEDYVDRKMN DIDSTSIETM YSVASQCLHE KKNKRPDIKK
460
VQQLLEEMTG S
Length:461
Mass (Da):51,575
Last modified:May 16, 2006 - 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:iEF9DE6D50AD2D9CC
GO

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
BC114720 mRNA Translation: AAI14721.1

NCBI Reference Sequences

More...
RefSeqi
NP_001069466.1, NM_001075998.1
XP_005206483.1, XM_005206426.3

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENSBTAT00000028115; ENSBTAP00000028115; ENSBTAG00000021105

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
533692

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
bta:533692

<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
BC114720 mRNA Translation: AAI14721.1
RefSeqiNP_001069466.1, NM_001075998.1
XP_005206483.1, XM_005206426.3

3D structure databases

SMRiQ1RMT8
ModBaseiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000028115

Proteomic databases

PaxDbiQ1RMT8
PRIDEiQ1RMT8

Genome annotation databases

EnsembliENSBTAT00000028115; ENSBTAP00000028115; ENSBTAG00000021105
GeneIDi533692
KEGGibta:533692

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
51135
VGNCiVGNC:30268 IRAK4

Phylogenomic databases

eggNOGiKOG1187 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00940000158792
HOGENOMiHOG000116550
InParanoidiQ1RMT8
KOiK04733
OMAiTTMMTER
OrthoDBi684563at2759
TreeFamiTF351380

Enzyme and pathway databases

ReactomeiR-BTA-1257604 PIP3 activates AKT signaling
R-BTA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-BTA-9020702 Interleukin-1 signaling
R-BTA-975110 TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
R-BTA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-BTA-975155 MyD88 dependent cascade initiated on endosome

Gene expression databases

BgeeiENSBTAG00000021105 Expressed in 10 organ(s), highest expression level in spleen

Family and domain databases

CDDicd08793 Death_IRAK4, 1 hit
InterProiView protein in InterPro
IPR011029 DEATH-like_dom_sf
IPR017428 IRAK4
IPR037970 IRAK4_Death
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PIRSFiPIRSF038189 IRAK4, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit

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 nameiIRAK4_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: Q1RMT8
<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: November 28, 2006
Last sequence update: May 16, 2006
Last modified: October 16, 2019
This is version 105 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
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