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Protein

N6-adenosine-methyltransferase catalytic subunit

Gene

METTL3

Organism
Homo sapiens (Human)
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 protein 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

The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N6 position of some RNAs and regulates various processes such as the circadian clock, differentiation of embryonic and haematopoietic stem cells, cortical neurogenesis, response to DNA damage, differentiation of T-cells and primary miRNA processing (PubMed:22575960, PubMed:24284625, PubMed:25719671, PubMed:25799998, PubMed:26321680, PubMed:26593424, PubMed:27627798, PubMed:27373337, PubMed:27281194, PubMed:28297716, PubMed:29506078, PubMed:29348140, PubMed:9409616). In the heterodimer formed with METTL14, METTL3 constitutes the catalytic core (PubMed:27627798, PubMed:27373337, PubMed:27281194). N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability, processing, translation efficiency and editing (PubMed:22575960, PubMed:24284625, PubMed:25719671, PubMed:25799998, PubMed:26321680, PubMed:26593424, PubMed:28297716, PubMed:9409616). M6A acts as a key regulator of mRNA stability: methylation is completed upon the release of mRNA into the nucleoplasm and promotes mRNA destabilization and degradation (PubMed:28637692). In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization, promoting differentiation of ESCs (By similarity). M6A regulates the length of the circadian clock: acts as an early pace-setter in the circadian loop by putting mRNA production on a fast-track for facilitating nuclear processing, thereby providing an early point of control in setting the dynamics of the feedback loop (By similarity). M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (By similarity). Involved in the response to DNA damage: in response to ultraviolet irradiation, METTL3 rapidly catalyzes the formation of m6A on poly(A) transcripts at DNA damage sites, leading to the recruitment of POLK to DNA damage sites (PubMed:28297716). M6A is also required for T-cell homeostasis and differentiation: m6A methylation of transcripts of SOCS family members (SOCS1, SOCS3 and CISH) in naive T-cells promotes mRNA destabilization and degradation, promoting T-cell differentiation (By similarity). M6A also takes place in other RNA molecules, such as primary miRNA (pri-miRNAs) (PubMed:25799998). Mediates m6A methylation of Xist RNA, thereby participating in random X inactivation: m6A methylation of Xist leads to target YTHDC1 reader on Xist and promote transcription repression activity of Xist (PubMed:27602518). M6A also regulates cortical neurogenesis: m6A methylation of transcripts related to transcription factors, neural stem cells, the cell cycle and neuronal differentiation during brain development promotes their destabilization and decay, promoting differentiation of radial glial cells (By similarity). METTL3 mediates methylation of pri-miRNAs, marking them for recognition and processing by DGCR8 (PubMed:25799998). Acts as a positive regulator of mRNA translation independently of the methyltransferase activity: promotes translation by interacting with the translation initiation machinery in the cytoplasm (PubMed:27117702). Its overexpression in a number of cancer cells suggests that it may participate to cancer cell proliferation by promoting mRNA translation (PubMed:27117702).By similarity16 Publications

<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 describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Methyltransferase activity is regulated by miRNAs via a sequence pairing mechanism (By similarity). Methyltransferase activity is inhibited by sumoylation (PubMed:29506078).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ 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 sitei395S-adenosyl-L-methionineCombined sources2 Publications1
Binding sitei438Interaction with METTL14Combined sources1 Publication1
Binding sitei441Interaction with METTL14Combined sources1 Publication1
Binding sitei513S-adenosyl-L-methionineCombined sources2 Publications1

<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 functionMethyltransferase, RNA-binding, Transferase
Biological processBiological rhythms, Differentiation, DNA damage, Spermatogenesis
LigandS-adenosyl-L-methionine

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA

<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:
N6-adenosine-methyltransferase catalytic subunitCurated (EC:2.1.1.3486 Publications)
Alternative name(s):
Methyltransferase-like protein 3Curated
Short name:
hMETTL31 Publication
N6-adenosine-methyltransferase 70 kDa subunit
Short name:
MT-A70
<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:METTL3Imported
Synonyms:MTA70
<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>OrganismiHomo sapiens (Human)
<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 identifieri9606 [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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<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
  • UP000005640 <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 14

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000165819.11

Human Gene Nomenclature Database

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HGNCi
HGNC:17563 METTL3

Online Mendelian Inheritance in Man (OMIM)

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MIMi
612472 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_Q86U44

<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

Keywords - Cellular componenti

Cytoplasm, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi2S → A: Does not affect nuclear localization, interaction with METTL14 or WTAP or catalytic activity; when associated with A-43; A-48 and A-50. 1 Publication1
Mutagenesisi43S → A: Does not affect nuclear localization, interaction with METTL14 or WTAP or catalytic activity; when associated with A-2; A-48 and A-50. 1 Publication1
Mutagenesisi48S → A: Does not affect nuclear localization, interaction with METTL14 or WTAP or catalytic activity; when associated with A-2; A-43 and A-50. 1 Publication1
Mutagenesisi50S → A: Does not affect nuclear localization, interaction with METTL14 or WTAP or catalytic activity; when associated with A-2; A-43 and A-48. 1 Publication1
Mutagenesisi177K → R in 4KR; strongly decreased sumoylation; when associated with 211-R--R-215. 1 Publication1
Mutagenesisi211 – 215KKSRK → GGSGG: Abolishes localization to the nucleus. 1 Publication5
Mutagenesisi211 – 215KKSRK → RRSRR in 3KR; decreased sumoylation. In 4KR; strongly decreased sumoylation; when associated with R-177. 1 Publication5
Mutagenesisi219S → A: Does not affect nuclear localization, interaction with METTL14 or WTAP or catalytic activity; when associated with A-243 and 348-A--A-350. 1 Publication1
Mutagenesisi243S → A: Does not affect nuclear localization, interaction with METTL14 or WTAP or catalytic activity; when associated with A-219 and 348-A--A-350. 1 Publication1
Mutagenesisi294C → A: Abolishes methyltransferase activity. 1 Publication1
Mutagenesisi326C → A: Abolishes methyltransferase activity. 1 Publication1
Mutagenesisi348 – 350TPS → APA: Does not affect nuclear localization, interaction with METTL14 or WTAP or catalytic activity; when associated with A-219 and A-243. 1 Publication3
Mutagenesisi377D → A: Abolishes methyltransferase activity. 1 Publication1
Mutagenesisi395 – 398DPPW → APPA: Loss of function. Abolishes ability to regulate primary miRNA processing. Does not affect ability to promote mRNA translation. Abolishes formation of m6A at DNA damage sites. 4 Publications4
Mutagenesisi395D → A: Abolishes methyltransferase activity. 2 Publications1
Mutagenesisi406Y → A: Strong reduction in methyltransferase activity. 1 Publication1
Mutagenesisi462 – 479QLQRI…WLNHG → AAAAAA: Impaired RNA-binding and methyltransferase activities. 1 PublicationAdd BLAST18
Mutagenesisi475W → A: Decreased methyltransferase activity. 1 Publication1
Mutagenesisi477N → A: Decreased methyltransferase activity. 1 Publication1
Mutagenesisi532E → A: Abolishes methyltransferase activity. 1 Publication1
Mutagenesisi536R → A: Slight reduction in methyltransferase activity. 1 Publication1
Mutagenesisi538H → A: Slight reduction in methyltransferase activity. 1 Publication1
Mutagenesisi539N → A: Abolishes methyltransferase activity. 1 Publication1
Mutagenesisi549N → A: Slight reduction in methyltransferase activity. Strong reduction in methyltransferase activity; when associated with A-550. 2 Publications1
Mutagenesisi550Q → A: Slight reduction in methyltransferase activity. Strong reduction in methyltransferase activity; when associated with A-549. 2 Publications1

Organism-specific databases

DisGeNET

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DisGeNETi
56339

Open Targets

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OpenTargetsi
ENSG00000165819

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA134955499

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
METTL3

Domain mapping of disease mutations (DMDM)

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DMDMi
33301371

<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 methionineiRemovedCombined sources
<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_00002076302 – 580N6-adenosine-methyltransferase catalytic subunitAdd BLAST579

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-acetylserine; alternateCombined sources1
Modified residuei2Phosphoserine; alternate1 Publication1
Modified residuei43PhosphoserineCombined sources1 Publication1
Modified residuei48Phosphoserine1 Publication1
Modified residuei50Phosphoserine1 Publication1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki177Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)1 Publication
Cross-linki211Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)1 Publication
Cross-linki212Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)1 Publication
Cross-linki215Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)1 Publication
Modified residuei219PhosphoserineCombined sources1 Publication1
Modified residuei243PhosphoserineCombined sources1 Publication1
Modified residuei348PhosphothreonineCombined sources1 Publication1
Modified residuei350Phosphoserine1 Publication1

<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

Sumoylation inhibits the N6-adenosine-methyltransferase activity. Sumoylation does not affect subcellular location or interaction with METTL14. Desumoylated by SENP1.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
Q86U44

MaxQB - The MaxQuant DataBase

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MaxQBi
Q86U44

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

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PaxDbi
Q86U44

PeptideAtlas

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PeptideAtlasi
Q86U44

PRoteomics IDEntifications database

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PRIDEi
Q86U44

ProteomicsDB human proteome resource

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ProteomicsDBi
69768
69769 [Q86U44-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q86U44

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

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PhosphoSitePlusi
Q86U44

<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

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Widely expressed at low level. Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes.1 Publication

<p>This subsection of the ‘Expression’ section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Overexpressed in a number of cancer tissues, such as lung adenocarcinoma and colon adenocarcinoma (PubMed:27117702).1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000165819 Expressed in 231 organ(s), highest expression level in endometrium

CleanEx database of gene expression profiles

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CleanExi
HS_METTL3

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q86U44 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q86U44 HS

<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

Heterodimer; heterodimerizes with METTL14 to form an antiparallel heterodimer that constitutes an active methyltransferase (PubMed:27627798, PubMed:27373337, PubMed:27281194). Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM (PubMed:24407421, PubMed:24981863, PubMed:27602518, PubMed:29507755, PubMed:29506078, PubMed:29348140). The MAC subcomplex is composed of METTL3 and METTL14 (PubMed:24407421, PubMed:24981863, PubMed:27602518, PubMed:29507755). The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B) (PubMed:27602518, PubMed:29507755). Interacts with NCBP1/CBP80 (PubMed:27117702). Interacts with EIF4E (PubMed:27117702). Interacts with EIF3B (PubMed:27117702).10 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

WithEntry#Exp.IntActNotes
METTL14Q9HCE520EBI-11105430,EBI-6661081

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
121139, 21 interactors

ComplexPortal: manually curated resource of macromolecular complexes

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ComplexPortali
CPX-1605 WMM N6-adenosine-methyltransferase complex

Database of interacting proteins

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DIPi
DIP-60727N

Protein interaction database and analysis system

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IntActi
Q86U44, 226 interactors

STRING: functional protein association networks

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STRINGi
9606.ENSP00000298717

<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

Secondary structure

1580
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
Q86U44

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

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SMRi
Q86U44

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
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

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>Regioni377 – 378S-adenosyl-L-methionine bindingCombined sources3 Publications2
Regioni396 – 410Gate loop 11 PublicationAdd BLAST15
Regioni450 – 454Interaction with METTL14Combined sources1 Publication5
Regioni462 – 479Interphase loop1 PublicationAdd BLAST18
Regioni464 – 480Interaction with METTL14Combined sources1 PublicationAdd BLAST17
Regioni465 – 478Positively charged region required for RNA-binding1 PublicationAdd BLAST14
Regioni507 – 515Gate loop 21 Publication9
Regioni536 – 539S-adenosyl-L-methionine bindingCombined sources3 Publications4
Regioni549 – 550S-adenosyl-L-methionine bindingCombined sources3 Publications2

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>Motifi210 – 215Nuclear localization signal1 Publication6

<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

Gate loop 1 and gate loop 2 regions are adjacent to the S-adenosyl-L-homocysteine-binding site and display large conformational changes upon ligand-binding. They may play an important role in adenosine recognition. The interface loop contributes to the heterodimer interaction.1 Publication

<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 MT-A70-like family.PROSITE-ProRule annotation

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG2098 Eukaryota
COG4725 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00550000075058

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000012669

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG052521

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q86U44

KEGG Orthology (KO)

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KOi
K05925

Identification of Orthologs from Complete Genome Data

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OMAi
HTKLWAM

Database of Orthologous Groups

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OrthoDBi
EOG091G07WA

Database for complete collections of gene phylogenies

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PhylomeDBi
Q86U44

TreeFam database of animal gene trees

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TreeFami
TF323854

Family and domain databases

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR025848 MT-A70
IPR007757 MT-A70-like
IPR029063 SAM-dependent_MTases

Pfam protein domain database

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Pfami
View protein in Pfam
PF05063 MT-A70, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF53335 SSF53335, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS51143 MT_A70, 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>Sequences (2+)i

<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.

This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q86U44-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSDTWSSIQA HKKQLDSLRE RLQRRRKQDS GHLDLRNPEA ALSPTFRSDS
60 70 80 90 100
PVPTAPTSGG PKPSTASAVP ELATDPELEK KLLHHLSDLA LTLPTDAVSI
110 120 130 140 150
CLAISTPDAP ATQDGVESLL QKFAAQELIE VKRGLLQDDA HPTLVTYADH
160 170 180 190 200
SKLSAMMGAV AEKKGPGEVA GTVTGQKRRA EQDSTTVAAF ASSLVSGLNS
210 220 230 240 250
SASEPAKEPA KKSRKHAASD VDLEIESLLN QQSTKEQQSK KVSQEILELL
260 270 280 290 300
NTTTAKEQSI VEKFRSRGRA QVQEFCDYGT KEECMKASDA DRPCRKLHFR
310 320 330 340 350
RIINKHTDES LGDCSFLNTC FHMDTCKYVH YEIDACMDSE APGSKDHTPS
360 370 380 390 400
QELALTQSVG GDSSADRLFP PQWICCDIRY LDVSILGKFA VVMADPPWDI
410 420 430 440 450
HMELPYGTLT DDEMRRLNIP VLQDDGFLFL WVTGRAMELG RECLNLWGYE
460 470 480 490 500
RVDEIIWVKT NQLQRIIRTG RTGHWLNHGK EHCLVGVKGN PQGFNQGLDC
510 520 530 540 550
DVIVAEVRST SHKPDEIYGM IERLSPGTRK IELFGRPHNV QPNWITLGNQ
560 570 580
LDGIHLLDPD VVARFKQRYP DGIISKPKNL
Length:580
Mass (Da):64,474
Last modified:July 25, 2003 - v2
<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:i63A7F10195A3C6AC
GO
Isoform 2 (identifier: Q86U44-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-284: Missing.
     486-505: GVKGNPQGFNQGLDCDVIVA → SSSGAQFNRWSTKKNHLISY
     506-580: Missing.

Note: No experimental confirmation available.
Show »
Length:221
Mass (Da):25,479
Checksum:iD95A9087F7B99439
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B4DTN4B4DTN4_HUMAN
N6-adenosine-methyltransferase cata...
METTL3
258Annotation score:

Annotation score:1 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>
F5H6D8F5H6D8_HUMAN
N6-adenosine-methyltransferase cata...
METTL3
245Annotation score:

Annotation score:1 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>
B4E349B4E349_HUMAN
N6-adenosine-methyltransferase cata...
METTL3
153Annotation score:

Annotation score:1 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>
H0YFV6H0YFV6_HUMAN
N6-adenosine-methyltransferase cata...
METTL3
336Annotation score:

Annotation score:1 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>
A0A0G2JH39A0A0G2JH39_HUMAN
N6-adenosine-methyltransferase cata...
METTL3
9Annotation score:

Annotation score:1 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 Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti251N → I in AAB71850 (PubMed:9409616).Curated1
Sequence conflicti263 – 264KF → I in AAB71850 (PubMed:9409616).Curated2
Sequence conflicti382D → V in AAB71850 (PubMed:9409616).Curated1
Sequence conflicti568R → K in AAH52244 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_076859406Y → C Found in patients with large intestine cancer; unknown pathological significance; does not affect interaction with METTL14; abolished RNA methyltransferase activity in vitro. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0078641 – 284Missing in isoform 2. 1 PublicationAdd BLAST284
Alternative sequenceiVSP_007865486 – 505GVKGN…DVIVA → SSSGAQFNRWSTKKNHLISY in isoform 2. 1 PublicationAdd BLAST20
Alternative sequenceiVSP_007866506 – 580Missing in isoform 2. 1 PublicationAdd BLAST75

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
AF014837 Genomic DNA Translation: AAB71850.1
AF283991 Genomic DNA Translation: AAG13956.1
AE000658 Genomic DNA No translation available.
BX247964 mRNA Translation: CAD62303.1
BC003031 mRNA Translation: AAH03031.1
BC001650 mRNA Translation: AAH01650.1
BC052244 mRNA Translation: AAH52244.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS32044.1 [Q86U44-1]

NCBI Reference Sequences

More...
RefSeqi
NP_062826.2, NM_019852.4 [Q86U44-1]

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.168799

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000298717; ENSP00000298717; ENSG00000165819 [Q86U44-1]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
56339

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:56339

UCSC genome browser

More...
UCSCi
uc001wbc.4 human [Q86U44-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<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
AF014837 Genomic DNA Translation: AAB71850.1
AF283991 Genomic DNA Translation: AAG13956.1
AE000658 Genomic DNA No translation available.
BX247964 mRNA Translation: CAD62303.1
BC003031 mRNA Translation: AAH03031.1
BC001650 mRNA Translation: AAH01650.1
BC052244 mRNA Translation: AAH52244.1
CCDSiCCDS32044.1 [Q86U44-1]
RefSeqiNP_062826.2, NM_019852.4 [Q86U44-1]
UniGeneiHs.168799

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5IL0X-ray1.88A369-580[»]
5IL1X-ray1.71A369-580[»]
5IL2X-ray1.61A369-580[»]
5K7MX-ray1.65A357-580[»]
5K7UX-ray1.70A357-580[»]
5K7WX-ray1.65A357-580[»]
5L6DX-ray1.85A354-580[»]
5L6EX-ray1.90A354-580[»]
5TEYX-ray1.80A1-580[»]
5YZ9Other-A259-357[»]
ProteinModelPortaliQ86U44
SMRiQ86U44
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121139, 21 interactors
ComplexPortaliCPX-1605 WMM N6-adenosine-methyltransferase complex
DIPiDIP-60727N
IntActiQ86U44, 226 interactors
STRINGi9606.ENSP00000298717

PTM databases

iPTMnetiQ86U44
PhosphoSitePlusiQ86U44

Polymorphism and mutation databases

BioMutaiMETTL3
DMDMi33301371

Proteomic databases

EPDiQ86U44
MaxQBiQ86U44
PaxDbiQ86U44
PeptideAtlasiQ86U44
PRIDEiQ86U44
ProteomicsDBi69768
69769 [Q86U44-2]

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
56339
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000298717; ENSP00000298717; ENSG00000165819 [Q86U44-1]
GeneIDi56339
KEGGihsa:56339
UCSCiuc001wbc.4 human [Q86U44-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
56339
DisGeNETi56339
EuPathDBiHostDB:ENSG00000165819.11

GeneCards: human genes, protein and diseases

More...
GeneCardsi
METTL3
HGNCiHGNC:17563 METTL3
MIMi612472 gene
neXtProtiNX_Q86U44
OpenTargetsiENSG00000165819
PharmGKBiPA134955499

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG2098 Eukaryota
COG4725 LUCA
GeneTreeiENSGT00550000075058
HOGENOMiHOG000012669
HOVERGENiHBG052521
InParanoidiQ86U44
KOiK05925
OMAiHTKLWAM
OrthoDBiEOG091G07WA
PhylomeDBiQ86U44
TreeFamiTF323854

Enzyme and pathway databases

ReactomeiR-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
METTL3 human

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
METTL3

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
56339

Protein Ontology

More...
PROi
PR:Q86U44

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000165819 Expressed in 231 organ(s), highest expression level in endometrium
CleanExiHS_METTL3
ExpressionAtlasiQ86U44 baseline and differential
GenevisibleiQ86U44 HS

Family and domain databases

InterProiView protein in InterPro
IPR025848 MT-A70
IPR007757 MT-A70-like
IPR029063 SAM-dependent_MTases
PfamiView protein in Pfam
PF05063 MT-A70, 1 hit
SUPFAMiSSF53335 SSF53335, 1 hit
PROSITEiView protein in PROSITE
PS51143 MT_A70, 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 nameiMTA70_HUMAN
<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: Q86U44
Secondary accession number(s): O14736, Q86V05, Q9HB32
<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: July 25, 2003
Last sequence update: July 25, 2003
Last modified: December 5, 2018
This is version 140 of the entry and version 2 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
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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