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Protein

Mitogen-activated protein kinase kinase kinase 5

Gene

MAP3K5

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

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1).18 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 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

<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

Activated by various stressors, including oxidative stress, endoplasmic reticulum stress, and calcium overload, as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) and lipopolysaccharide (LPS). Homophilic association of MAP3K5/ASK1 through the C-terminal coiled-coil domains and the heteromeric complex formation of MAP3K5/ASK1 with the reduced form of thioredoxin (TXN), constitutes an inactive form of the kinase (PubMed:17210579, PubMed:9564042). Upon ROS-induced dissociation of TXN from MAP3K5/ASK1, TRAF2 and TRAF6 are reciprocally recruited to MAP3K5/ASK1 and form the active MAP3K5/ASK1 signalosome, in which TRAF2 and TRAF6 appear to facilitate the active configuration of MAP3K5/ASK1 (PubMed:9774977, PubMed:10688666, PubMed:11920685). MAP3K5/ASK1 activity is also regulated through several phosphorylation and dephosphorylation events. Thr-838 is an activating phosphorylation site that is autophosphorylated and phosphorylated by MAP3K6/ASK2 and dephosphorylated by PPP5C (PubMed:11689443). Ser-83 and Ser-1033 are inactivating phosphorylation sites, the former of which is phosphorylated by AKT1 and AKT2 (PubMed:11154276, PubMed:12697749, PubMed:15094778). Phosphorylation of Ser-966 induces association of MAP3K5/ASK1 with the 14-3-3 family proteins, which suppresses MAP3K5/ASK1 activity (PubMed:10411906, PubMed:14688258). Calcium/calmodulin-activated protein phosphatase calcineurin (PPP3CA) has been shown to directly dephosphorylate this site (PubMed:14749717). SOCS1 binds to ASK1 by recognizing phosphorylation of Tyr-718 and induces MAP3K5/ASK1 degradation in endothelial cells (PubMed:16407264). Also dephosphorylated and activated by PGAM5. Contains an N-terminal autoinhibitory domain. Once activated targeted for proteosomal degradation by RC3H2-mediated ubiquitination (PubMed:24448648).15 Publications

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 sitei709ATP1
<p>This subsection of the ‘Function’ 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 sitei803Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ 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 bindingi686 – 694ATPPROSITE-ProRule annotation9

<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 processApoptosis, Host-virus interaction, Immunity, Innate immunity, Stress response
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.7.12.2 2681

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-2559580 Oxidative Stress Induced Senescence

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
Q99683

SIGNOR Signaling Network Open Resource

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SIGNORi
Q99683

<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:
Mitogen-activated protein kinase kinase kinase 5 (EC:2.7.11.25)
Alternative name(s):
Apoptosis signal-regulating kinase 1
Short name:
ASK-1
MAPK/ERK kinase kinase 5
Short name:
MEK kinase 5
Short name:
MEKK 5
<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:MAP3K5
Synonyms:ASK1, MAPKKK5, MEKK5
<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 6

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000197442.9

Human Gene Nomenclature Database

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HGNCi
HGNC:6857 MAP3K5

Online Mendelian Inheritance in Man (OMIM)

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MIMi
602448 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_Q99683

<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, Endoplasmic reticulum

<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>Mutagenesisi709K → M: Loss of kinase activity. Inhibits activation of JNK and apoptosis mediated by TNFRSF6 and DAXX. 2 Publications1
Mutagenesisi709K → R: Loss of kinase activity. Abolishes DAXX-mediated apoptosis. Loss of RC3H2-mediated ubiquitination. 3 Publications1
Mutagenesisi966S → A: Enhanced induction of apoptosis, increased kinase activity, and loss of YWHAG binding. 2 Publications1
Mutagenesisi1033S → A: Enhanced induction of apoptosis and increased kinase activity. 1 Publication1

Organism-specific databases

DisGeNET

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DisGeNETi
4217

Open Targets

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OpenTargetsi
ENSG00000197442

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA30601

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL5285

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
2080

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
MAP3K5

Domain mapping of disease mutations (DMDM)

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DMDMi
6685617

<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_00000862491 – 1374Mitogen-activated protein kinase kinase kinase 5Add BLAST1374

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 residuei83Phosphoserine; by PIM1, PKB/AKT1 and PKB/AKT23 Publications1
Modified residuei718Phosphotyrosine1 Publication1
Modified residuei813Phosphothreonine; by autocatalysis1 Publication1
Modified residuei838Phosphothreonine; by autocatalysis, MELK and MAP3K66 Publications1
Modified residuei842Phosphothreonine; by autocatalysis1 Publication1
Modified residuei958PhosphoserineCombined sources1
Modified residuei966Phosphoserine3 Publications1
Modified residuei1029PhosphoserineCombined sources1
Modified residuei1033PhosphoserineCombined sources2 Publications1

<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 at Thr-838 through autophosphorylation and by MAP3K6/ASK2 which leads to activation. Thr-838 is dephosphorylated by PPP5C. Ser-83 and Ser-1033 are inactivating phosphorylation sites, the former of which is phosphorylated by AKT1 and AKT2. Phosphorylated at Ser-966 which induces association of MAP3K5/ASK1 with the 14-3-3 family proteins and suppresses MAP3K5/ASK1 activity. Calcineurin (CN) dephosphorylates this site. Also dephosphorylated and activated by PGAM5.13 Publications
Ubiquitinated. Tumor necrosis factor (TNF) induces TNFR2-dependent ubiquitination leading to proteasomal degradation.2 Publications

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
Q99683

MaxQB - The MaxQuant DataBase

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MaxQBi
Q99683

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

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PaxDbi
Q99683

PeptideAtlas

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PeptideAtlasi
Q99683

PRoteomics IDEntifications database

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PRIDEi
Q99683

ProteomicsDB human proteome resource

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ProteomicsDBi
78395

PTM databases

CarbonylDB database of protein carbonylation sites

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CarbonylDBi
Q99683

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q99683

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

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PhosphoSitePlusi
Q99683

<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

Abundantly expressed in heart and pancreas.

<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

By TNF. Inhibited by HIV-1 Nef.

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000197442 Expressed in 225 organ(s), highest expression level in primary visual cortex

CleanEx database of gene expression profiles

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CleanExi
HS_MAP3K5

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q99683 HS

Organism-specific databases

Human Protein Atlas

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HPAi
CAB007824
HPA063245
HPA064423

<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

Homodimer when inactive. Binds both upstream activators and downstream substrates in multimolecular complexes. Part of a cytoplasmic complex made of HIPK1, DAB2IP and MAP3K5 in response to TNF (PubMed:15310755, PubMed:15701637, PubMed:17210579, PubMed:17389591). This complex formation promotes MAP3K5-JNK activation and subsequent apoptosis. Interacts with SOCS1 which recognizes phosphorylation of Tyr-718 and induces MAP3K5/ASK1 degradation in endothelial cells. Interacts with the 14-3-3 family proteins such as YWHAB, YWHAE, YWHAQ, YWHAH, YWHAZ and SFN (PubMed:10411906, PubMed:15023544, PubMed:15094778). Interacts with ARRB2, BIRC2, DAB2IP, IGF1R, MAP3K6/ASK2, PGAM5, PIM1, PPP5C, SOCS1, STUB1, TRAF2, TRAF6 and TXN (PubMed:9564042,PubMed:9774977, PubMed:10688666, PubMed:11090355, PubMed:11689443, PubMed:12556535, PubMed:12813029, PubMed:15310755, PubMed:16038411, PubMed:16129676, PubMed:16407264, PubMed:17220297, PubMed:17724081, PubMed:18408005, PubMed:19590015, PubMed:19749799). Interacts with ERN1 in a TRAF2-dependent manner (PubMed:14749717). Interacts with calcineurin subunit PPP3R1 and with PPM1L (PubMed:17456047) (By similarity). Interacts (via N-terminus) with RAF1 and this interaction inhibits the proapoptotic function of MAP3K5 (PubMed:11427728). Interacts with DAB2IP (via N-terminus C2 domain); the interaction occurs in a TNF-alpha-dependent manner (PubMed:15310755). Interacts with DUSP13/DUSP13A; may positively regulate apoptosis (PubMed:20358250). Interacts with DAXX (PubMed:9743501). Interacts with RC3H2 (PubMed:24448648).By similarity28 Publications
(Microbial infection) Interacts with HIV-1 Nef; this interaction inhibits MAP3K5 signaling.1 Publication

<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

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
110381, 99 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
Q99683

Database of interacting proteins

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DIPi
DIP-29516N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
Q99683

Protein interaction database and analysis system

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IntActi
Q99683, 42 interactors

Molecular INTeraction database

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MINTi
Q99683

STRING: functional protein association networks

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STRINGi
9606.ENSP00000351908

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q99683

<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

11374
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
Q99683

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

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SMRi
Q99683

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...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
Q99683

<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>Domaini680 – 938Protein kinasePROSITE-ProRule annotationAdd BLAST259

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and domains’ section denotes the positions of regions of coiled coil within the protein.<p><a href='/help/coiled' target='_top'>More...</a></p>Coiled coili1245 – 1285Sequence analysisAdd BLAST41

<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

Keywords - Domaini

Coiled coil

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG4279 Eukaryota
ENOG410XQGS LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000159155

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000293286

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG006305

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q99683

KEGG Orthology (KO)

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KOi
K04426

Identification of Orthologs from Complete Genome Data

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OMAi
YHYGVRE

Database of Orthologous Groups

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OrthoDBi
EOG091G00SJ

Database for complete collections of gene phylogenies

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PhylomeDBi
Q99683

TreeFam database of animal gene trees

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TreeFami
TF105115

Family and domain databases

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR025136 DUF4071
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR013761 SAM/pointed_sf
IPR008271 Ser/Thr_kinase_AS

Pfam protein domain database

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Pfami
View protein in Pfam
PF13281 DUF4071, 1 hit
PF00069 Pkinase, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00220 S_TKc, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF47769 SSF47769, 1 hit
SSF56112 SSF56112, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 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.

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
Isoform 1 (identifier: Q99683-1) [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
MSTEADEGIT FSVPPFAPSG FCTIPEGGIC RRGGAAAVGE GEEHQLPPPP
60 70 80 90 100
PGSFWNVESA AAPGIGCPAA TSSSSATRGR GSSVGGGSRR TTVAYVINEA
110 120 130 140 150
SQGQLVVAES EALQSLREAC ETVGATLETL HFGKLDFGET TVLDRFYNAD
160 170 180 190 200
IAVVEMSDAF RQPSLFYHLG VRESFSMANN IILYCDTNSD SLQSLKEIIC
210 220 230 240 250
QKNTMCTGNY TFVPYMITPH NKVYCCDSSF MKGLTELMQP NFELLLGPIC
260 270 280 290 300
LPLVDRFIQL LKVAQASSSQ YFRESILNDI RKARNLYTGK ELAAELARIR
310 320 330 340 350
QRVDNIEVLT ADIVINLLLS YRDIQDYDSI VKLVETLEKL PTFDLASHHH
360 370 380 390 400
VKFHYAFALN RRNLPGDRAK ALDIMIPMVQ SEGQVASDMY CLVGRIYKDM
410 420 430 440 450
FLDSNFTDTE SRDHGASWFK KAFESEPTLQ SGINYAVLLL AAGHQFESSF
460 470 480 490 500
ELRKVGVKLS SLLGKKGNLE KLQSYWEVGF FLGASVLAND HMRVIQASEK
510 520 530 540 550
LFKLKTPAWY LKSIVETILI YKHFVKLTTE QPVAKQELVD FWMDFLVEAT
560 570 580 590 600
KTDVTVVRFP VLILEPTKIY QPSYLSINNE VEEKTISIWH VLPDDKKGIH
610 620 630 640 650
EWNFSASSVR GVSISKFEER CCFLYVLHNS DDFQIYFCTE LHCKKFFEMV
660 670 680 690 700
NTITEEKGRS TEEGDCESDL LEYDYEYDEN GDRVVLGKGT YGIVYAGRDL
710 720 730 740 750
SNQVRIAIKE IPERDSRYSQ PLHEEIALHK HLKHKNIVQY LGSFSENGFI
760 770 780 790 800
KIFMEQVPGG SLSALLRSKW GPLKDNEQTI GFYTKQILEG LKYLHDNQIV
810 820 830 840 850
HRDIKGDNVL INTYSGVLKI SDFGTSKRLA GINPCTETFT GTLQYMAPEI
860 870 880 890 900
IDKGPRGYGK AADIWSLGCT IIEMATGKPP FYELGEPQAA MFKVGMFKVH
910 920 930 940 950
PEIPESMSAE AKAFILKCFE PDPDKRACAN DLLVDEFLKV SSKKKKTQPK
960 970 980 990 1000
LSALSAGSNE YLRSISLPVP VLVEDTSSSS EYGSVSPDTE LKVDPFSFKT
1010 1020 1030 1040 1050
RAKSCGERDV KGIRTLFLGI PDENFEDHSA PPSPEEKDSG FFMLRKDSER
1060 1070 1080 1090 1100
RATLHRILTE DQDKIVRNLM ESLAQGAEEP KLKWEHITTL IASLREFVRS
1110 1120 1130 1140 1150
TDRKIIATTL SKLKLELDFD SHGISQVQVV LFGFQDAVNK VLRNHNIKPH
1160 1170 1180 1190 1200
WMFALDSIIR KAVQTAITIL VPELRPHFSL ASESDTADQE DLDVEDDHEE
1210 1220 1230 1240 1250
QPSNQTVRRP QAVIEDAVAT SGVSTLSSTV SHDSQSAHRS LNVQLGRMKI
1260 1270 1280 1290 1300
ETNRLLEELV RKEKELQALL HRAIEEKDQE IKHLKLKSQP IEIPELPVFH
1310 1320 1330 1340 1350
LNSSGTNTED SELTDWLRVN GADEDTISRF LAEDYTLLDV LYYVTRDDLK
1360 1370
CLRLRGGMLC TLWKAIIDFR NKQT
Length:1,374
Mass (Da):154,537
Last modified:May 1, 1997 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i265BDC65968AF985
GO
Isoform 2 (identifier: Q99683-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-753: Missing.

Note: No experimental confirmation available.
Show »
Length:621
Mass (Da):69,839
Checksum:i7EFE3AD82F6AB9FF
GO

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_0406931006G → R1 PublicationCorresponds to variant dbSNP:rs45626535Ensembl.1
Natural variantiVAR_0406941214I → T1 PublicationCorresponds to variant dbSNP:rs56379668Ensembl.1
Natural variantiVAR_0406951250I → V1 PublicationCorresponds to variant dbSNP:rs35551087Ensembl.1
Natural variantiVAR_0406961314T → I1 PublicationCorresponds to variant dbSNP:rs45599539Ensembl.1
Natural variantiVAR_0406971315D → N1 PublicationCorresponds to variant dbSNP:rs41288957Ensembl.1

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_0561821 – 753Missing in isoform 2. 1 PublicationAdd BLAST753

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
U67156 mRNA Translation: AAC50894.1
D84476 mRNA Translation: BAA12684.2
AK294507 mRNA Translation: BAG57723.1
AL024508 Genomic DNA No translation available.
AL121933 Genomic DNA No translation available.
BC054503 mRNA Translation: AAH54503.1
BC088829 mRNA Translation: AAH88829.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS5179.1 [Q99683-1]

NCBI Reference Sequences

More...
RefSeqi
NP_005914.1, NM_005923.3 [Q99683-1]

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.186486

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000359015; ENSP00000351908; ENSG00000197442 [Q99683-1]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
4217

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:4217

UCSC genome browser

More...
UCSCi
uc003qhc.4 human [Q99683-1]

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
U67156 mRNA Translation: AAC50894.1
D84476 mRNA Translation: BAA12684.2
AK294507 mRNA Translation: BAG57723.1
AL024508 Genomic DNA No translation available.
AL121933 Genomic DNA No translation available.
BC054503 mRNA Translation: AAH54503.1
BC088829 mRNA Translation: AAH88829.1
CCDSiCCDS5179.1 [Q99683-1]
RefSeqiNP_005914.1, NM_005923.3 [Q99683-1]
UniGeneiHs.186486

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
2CLQX-ray2.30A/B659-951[»]
3VW6X-ray2.40A/B671-939[»]
4BF2X-ray2.11A/B660-977[»]
4BHNX-ray2.30A/B660-977[»]
4BIBX-ray2.43A/B660-977[»]
4BICX-ray2.62A/B660-977[»]
4BIDX-ray2.80A/B660-977[»]
4BIEX-ray2.36A/B660-977[»]
5ULMX-ray2.10A/B269-658[»]
5UORX-ray2.75A/B670-939[»]
5UOXX-ray2.50A/B670-940[»]
5UP3X-ray2.95A/B670-940[»]
5V19X-ray3.10A/B670-940[»]
5V24X-ray2.50A/B670-940[»]
5VILX-ray2.64A/B/C/D659-951[»]
5VIOX-ray2.84A/B/C/D659-951[»]
6E2MX-ray2.25A/B659-951[»]
6E2NX-ray2.10A/B659-951[»]
6E2OX-ray2.39A/B659-951[»]
6EJLX-ray2.38C/D963-970[»]
ProteinModelPortaliQ99683
SMRiQ99683
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110381, 99 interactors
CORUMiQ99683
DIPiDIP-29516N
ELMiQ99683
IntActiQ99683, 42 interactors
MINTiQ99683
STRINGi9606.ENSP00000351908

Chemistry databases

BindingDBiQ99683
ChEMBLiCHEMBL5285
GuidetoPHARMACOLOGYi2080

PTM databases

CarbonylDBiQ99683
iPTMnetiQ99683
PhosphoSitePlusiQ99683

Polymorphism and mutation databases

BioMutaiMAP3K5
DMDMi6685617

Proteomic databases

EPDiQ99683
MaxQBiQ99683
PaxDbiQ99683
PeptideAtlasiQ99683
PRIDEiQ99683
ProteomicsDBi78395

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
4217
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000359015; ENSP00000351908; ENSG00000197442 [Q99683-1]
GeneIDi4217
KEGGihsa:4217
UCSCiuc003qhc.4 human [Q99683-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
4217
DisGeNETi4217
EuPathDBiHostDB:ENSG00000197442.9

GeneCards: human genes, protein and diseases

More...
GeneCardsi
MAP3K5
HGNCiHGNC:6857 MAP3K5
HPAiCAB007824
HPA063245
HPA064423
MIMi602448 gene
neXtProtiNX_Q99683
OpenTargetsiENSG00000197442
PharmGKBiPA30601

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG4279 Eukaryota
ENOG410XQGS LUCA
GeneTreeiENSGT00940000159155
HOGENOMiHOG000293286
HOVERGENiHBG006305
InParanoidiQ99683
KOiK04426
OMAiYHYGVRE
OrthoDBiEOG091G00SJ
PhylomeDBiQ99683
TreeFamiTF105115

Enzyme and pathway databases

BRENDAi2.7.12.2 2681
ReactomeiR-HSA-2559580 Oxidative Stress Induced Senescence
SignaLinkiQ99683
SIGNORiQ99683

Miscellaneous databases

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

More...
ChiTaRSi
MAP3K5 human
EvolutionaryTraceiQ99683

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
ASK1

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

More...
GenomeRNAii
4217

Protein Ontology

More...
PROi
PR:Q99683

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000197442 Expressed in 225 organ(s), highest expression level in primary visual cortex
CleanExiHS_MAP3K5
GenevisibleiQ99683 HS

Family and domain databases

InterProiView protein in InterPro
IPR025136 DUF4071
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR013761 SAM/pointed_sf
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF13281 DUF4071, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF47769 SSF47769, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 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 nameiM3K5_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: Q99683
Secondary accession number(s): A6NIA0
, B4DGB2, Q5THN3, Q99461
<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: May 30, 2000
Last sequence update: May 1, 1997
Last modified: December 5, 2018
This is version 200 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
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, 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 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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