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UniProtKB - P41279 (M3K8_HUMAN)

Entry version 185 (13 Feb 2019)
Sequence version 2 (19 Jul 2004)
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Protein

Mitogen-activated protein kinase kinase kinase 8

Gene

MAP3K8

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

Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.7 Publications

Miscellaneous

Can be converted to an oncogenic protein by proviral activation, leading to a C-terminally truncated protein with transforming activity.

Caution

A paper describing a role for this protein in IRAK1-independent activation of the MAPK/ERK pathway in response to IL1 has been retracted, because some of the experimental data could not be reproduced.2 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

Mg2+

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 sitei167ATPPROSITE-ProRule annotation1
<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 sitei253Proton 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 bindingi144 – 152ATPPROSITE-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

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

<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 processCell cycle, Immunity
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-389357 CD28 dependent PI3K/Akt signaling
R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation

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

More...SignaLinki		P41279

SIGNOR Signaling Network Open Resource

More...SIGNORi		P41279

<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 8 (EC:2.7.11.25)
Alternative name(s):
Cancer Osaka thyroid oncogene
Proto-oncogene c-Cot
Serine/threonine-protein kinase cot
Tumor progression locus 2
Short name:
TPL-2
<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:MAP3K8
Synonyms:COT, ESTF
<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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<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 10

Organism-specific databases

Eukaryotic Pathogen Database Resources

More...EuPathDBi		HostDB:ENSG00000107968.9

Human Gene Nomenclature Database

More...HGNCi		HGNC:6860 MAP3K8

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		191195 gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P41279

<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 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>Mutagenesisi290T → A: Loss of MEK phosphorylation activity and almost abolished autophosphorylation activity. Loss of IL1-stimulated MEK phosphorylation activity but not of IL1-stimulated autophosphorylation activity. No effect on KSR2 binding. 1 Publication1
Mutagenesisi290T → D: Impaired MEK phosphorylation and autophosphorylation activities. No effect on KSR2 binding. 1 Publication1
Mutagenesisi290T → E: Loss of MEK phosphorylation activity and almost abolished autophosphorylation activity. No effect on KSR2 binding. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNET

More...DisGeNETi		1326

MalaCards human disease database

More...MalaCardsi		MAP3K8

Open Targets

More...OpenTargetsi		ENSG00000107968

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA30606

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL4899

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		2083

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		MAP3K8

Domain mapping of disease mutations (DMDM)

More...DMDMi		50403742

<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_00000243501 – 467Mitogen-activated protein kinase kinase kinase 8Add BLAST467

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 residuei80Phosphothreonine1 Publication1
Modified residuei141PhosphoserineCombined sources1
Modified residuei290Phosphothreonine2 Publications1
Modified residuei400Phosphoserine2 Publications1
Modified residuei443Phosphoserine1 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

Autophosphorylated (PubMed:8226782, PubMed:1833717). Isoform 1 undergoes phosphorylation mainly on Ser residues, and isoform 2 on both Ser and Thr residues (PubMed:8226782). Phosphorylated on Thr-290; the phosphorylation is necessary but not sufficient for full kinase activity in vitro and for the dissociation of isoform 1 from NFKB1, leading to its degradation (PubMed:15466476, PubMed:15699325). Phosphorylated on Ser-400 by IKBKB; the phosphorylation is required for LPS-stimulated activation of the MAPK/ERK pathway in macrophages (PubMed:17472361, PubMed:22988300).6 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P41279

MaxQB - The MaxQuant DataBase

More...MaxQBi		P41279

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

More...PaxDbi		P41279

PeptideAtlas

More...PeptideAtlasi		P41279

PRoteomics IDEntifications database

More...PRIDEi		P41279

ProteomicsDB human proteome resource

More...ProteomicsDBi		55458
55459 [P41279-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P41279

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

More...PhosphoSitePlusi		P41279

<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

Expressed in several normal tissues and human tumor-derived cell lines.

<p>This subsection of the ‘Expression’ section provides information on the expression of the gene product at various stages of a cell, tissue or organism development. By default, the information is derived from experiments at the mRNA level, unless specified ‘at the protein level’.<p><a href='/help/developmental_stage' target='_top'>More...</a></p>Developmental stagei

Isoform 1 is activated specifically during the S and G2/M phases of the cell cycle.

<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

Up-regulated by IL12 in T-lymphocytes. Up-regulated in subcutaneous adipose tissue of obese individuals.2 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000107968 Expressed in 192 organ(s), highest expression level in omental fat pad

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P41279 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P41279 HS

Organism-specific databases

Human Protein Atlas

More...HPAi		CAB005120
HPA017962

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

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

Forms a ternary complex with NFKB1/p105 and TNIP2. Interacts with NFKB1; the interaction increases the stability of MAP3K8 but inhibits its MEK phosphorylation activity, whereas loss of interaction following LPS stimulation leads to its degradation. Interacts with CD40 and TRAF6; the interaction is required for ERK activation. Interacts with KSR2; the interaction inhibits ERK and NF-kappa-B activation.5 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

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...BioGridi		107719, 21 interactors

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		P41279

Database of interacting proteins

More...DIPi		DIP-27534N

Protein interaction database and analysis system

More...IntActi		P41279, 14 interactors

Molecular INTeraction database

More...MINTi		P41279

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000263056

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P41279

<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

1467
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

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
4Y83X-ray2.89A/B/C66-395[»]
4Y85X-ray2.33A/B/C66-395[»]
5IU2X-ray2.70A/B66-395[»]

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

More...ProteinModelPortali		P41279

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

More...SMRi		P41279

Database of comparative protein structure models

More...ModBasei		Search...

MobiDB: a database of protein disorder and mobility annotations

More...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

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>Domaini138 – 388Protein kinasePROSITE-ProRule annotationAdd BLAST251

<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 protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG0201 Eukaryota
ENOG410XP9G LUCA

Ensembl GeneTree

More...GeneTreei		ENSGT00940000158806

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		HOG000285978

The HOVERGEN Database of Homologous Vertebrate Genes

More...HOVERGENi		HBG006306

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P41279

KEGG Orthology (KO)

More...KOi		K04415

Identification of Orthologs from Complete Genome Data

More...OMAi		EGGSVME

Database of Orthologous Groups

More...OrthoDBi		681235at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		P41279

TreeFam database of animal gene trees

More...TreeFami		TF105117

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR017424 MAPKKK8
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS

Pfam protein domain database

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

PIRSF; a whole-protein classification database

More...PIRSFi		PIRSF038171 MAPKKK8, 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		SSF56112 SSF56112, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
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 initiation. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P41279-1) [UniParc]FASTAAdd to basket
Also known as: 58 kDa

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
MEYMSTGSDN KEEIDLLIKH LNVSDVIDIM ENLYASEEPA VYEPSLMTMC 
        60         70         80         90        100
QDSNQNDERS KSLLLSGQEV PWLSSVRYGT VEDLLAFANH ISNTAKHFYG 
       110        120        130        140        150
QRPQESGILL NMVITPQNGR YQIDSDVLLI PWKLTYRNIG SDFIPRGAFG 
       160        170        180        190        200
KVYLAQDIKT KKRMACKLIP VDQFKPSDVE IQACFRHENI AELYGAVLWG 
       210        220        230        240        250
ETVHLFMEAG EGGSVLEKLE SCGPMREFEI IWVTKHVLKG LDFLHSKKVI 
       260        270        280        290        300
HHDIKPSNIV FMSTKAVLVD FGLSVQMTED VYFPKDLRGT EIYMSPEVIL 
       310        320        330        340        350
CRGHSTKADI YSLGATLIHM QTGTPPWVKR YPRSAYPSYL YIIHKQAPPL 
       360        370        380        390        400
EDIADDCSPG MRELIEASLE RNPNHRPRAA DLLKHEALNP PREDQPRCQS 
       410        420        430        440        450
LDSALLERKR LLSRKELELP ENIADSSCTG STEESEMLKR QRSLYIDLGA 
       460 
LAGYFNLVRG PPTLEYG
Length:467
Mass (Da):52,925
Last modified:July 19, 2004 - 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:i7728969EA3E4E8EC
GO
Isoform 2 (identifier: P41279-2) [UniParc]FASTAAdd to basket
Also known as: 52 kDa

The sequence of this isoform differs from the canonical sequence as follows:
     1-29: Missing.

Show »
Length:438
Mass (Da):49,620
Checksum:i2121FEF4658882FD
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 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5T857Q5T857_HUMAN
Mitogen-activated protein kinase ki...
MAP3K8
255Annotation 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>
Q5T853Q5T853_HUMAN
Mitogen-activated protein kinase ki...
MAP3K8
223Annotation 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>
Q5T854Q5T854_HUMAN
Mitogen-activated protein kinase ki...
MAP3K8
132Annotation 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 conflicti399Q → T in BAA03387 (PubMed:2072910).Curated1
Sequence conflicti399Q → T no nucleotide entry (PubMed:8226782).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_051638214S → F. Corresponds to variant dbSNP:rs3087944Ensembl.1
Natural variantiVAR_006198398 – 415CQSLD…LLSRK → GHQVIHEGSSTNDPNNSC in oncogenic form. Add BLAST18
Natural variantiVAR_006199416 – 467Missing in oncogenic form. Add BLAST52

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.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0188431 – 29Missing in isoform 2. 1 PublicationAdd BLAST29

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
D14497 mRNA Translation: BAA03387.1
Z14138 mRNA Translation: CAA78512.1
AK290320 mRNA Translation: BAF83009.1
AY309013 Genomic DNA Translation: AAP45053.1
AL161651 Genomic DNA No translation available.
CH471072 Genomic DNA Translation: EAW86004.1
CH471072 Genomic DNA Translation: EAW86005.1
CH471072 Genomic DNA Translation: EAW86006.1
CH471072 Genomic DNA Translation: EAW86007.1
BC104833 mRNA Translation: AAI04834.1
BC113566 mRNA Translation: AAI13567.1
AF133211 Genomic DNA Translation: AAG13454.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS7166.1 [P41279-1]

Protein sequence database of the Protein Information Resource

More...PIRi		A48713

NCBI Reference Sequences

More...RefSeqi		NP_001231063.1, NM_001244134.1 [P41279-1]
NP_001307890.1, NM_001320961.1 [P41279-1]
NP_005195.2, NM_005204.3 [P41279-1]
XP_016871196.1, XM_017015707.1
XP_016871197.1, XM_017015708.1 [P41279-1]
XP_016871198.1, XM_017015709.1 [P41279-1]
XP_016871199.1, XM_017015710.1 [P41279-1]

UniGene gene-oriented nucleotide sequence clusters

More...UniGenei		Hs.432453
Hs.663033
Hs.731448

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000263056; ENSP00000263056; ENSG00000107968 [P41279-1]
ENST00000375321; ENSP00000364470; ENSG00000107968 [P41279-1]
ENST00000542547; ENSP00000443610; ENSG00000107968 [P41279-1]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		1326

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:1326

UCSC genome browser

More...UCSCi		uc001ivi.3 human [P41279-1]

Keywords - Coding sequence diversityi

Alternative initiation, 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

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D14497 mRNA Translation: BAA03387.1
Z14138 mRNA Translation: CAA78512.1
AK290320 mRNA Translation: BAF83009.1
AY309013 Genomic DNA Translation: AAP45053.1
AL161651 Genomic DNA No translation available.
CH471072 Genomic DNA Translation: EAW86004.1
CH471072 Genomic DNA Translation: EAW86005.1
CH471072 Genomic DNA Translation: EAW86006.1
CH471072 Genomic DNA Translation: EAW86007.1
BC104833 mRNA Translation: AAI04834.1
BC113566 mRNA Translation: AAI13567.1
AF133211 Genomic DNA Translation: AAG13454.1
CCDSiCCDS7166.1 [P41279-1]
PIRiA48713
RefSeqiNP_001231063.1, NM_001244134.1 [P41279-1]
NP_001307890.1, NM_001320961.1 [P41279-1]
NP_005195.2, NM_005204.3 [P41279-1]
XP_016871196.1, XM_017015707.1
XP_016871197.1, XM_017015708.1 [P41279-1]
XP_016871198.1, XM_017015709.1 [P41279-1]
XP_016871199.1, XM_017015710.1 [P41279-1]
UniGeneiHs.432453
Hs.663033
Hs.731448

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4Y83X-ray2.89A/B/C66-395[»]
4Y85X-ray2.33A/B/C66-395[»]
5IU2X-ray2.70A/B66-395[»]
ProteinModelPortaliP41279
SMRiP41279
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107719, 21 interactors
CORUMiP41279
DIPiDIP-27534N
IntActiP41279, 14 interactors
MINTiP41279
STRINGi9606.ENSP00000263056

Chemistry databases

BindingDBiP41279
ChEMBLiCHEMBL4899
GuidetoPHARMACOLOGYi2083

PTM databases

iPTMnetiP41279
PhosphoSitePlusiP41279

Polymorphism and mutation databases

BioMutaiMAP3K8
DMDMi50403742

Proteomic databases

jPOSTiP41279
MaxQBiP41279
PaxDbiP41279
PeptideAtlasiP41279
PRIDEiP41279
ProteomicsDBi55458
55459 [P41279-2]

Protocols and materials databases

The DNASU plasmid repository

More...DNASUi		1326
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263056; ENSP00000263056; ENSG00000107968 [P41279-1]
ENST00000375321; ENSP00000364470; ENSG00000107968 [P41279-1]
ENST00000542547; ENSP00000443610; ENSG00000107968 [P41279-1]
GeneIDi1326
KEGGihsa:1326
UCSCiuc001ivi.3 human [P41279-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		1326
DisGeNETi1326
EuPathDBiHostDB:ENSG00000107968.9

GeneCards: human genes, protein and diseases

More...GeneCardsi		MAP3K8
HGNCiHGNC:6860 MAP3K8
HPAiCAB005120
HPA017962
MalaCardsiMAP3K8
MIMi191195 gene
neXtProtiNX_P41279
OpenTargetsiENSG00000107968
PharmGKBiPA30606

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG0201 Eukaryota
ENOG410XP9G LUCA
GeneTreeiENSGT00940000158806
HOGENOMiHOG000285978
HOVERGENiHBG006306
InParanoidiP41279
KOiK04415
OMAiEGGSVME
OrthoDBi681235at2759
PhylomeDBiP41279
TreeFamiTF105117

Enzyme and pathway databases

ReactomeiR-HSA-389357 CD28 dependent PI3K/Akt signaling
R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation
SignaLinkiP41279
SIGNORiP41279

Miscellaneous databases

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

More...ChiTaRSi		MAP3K8 human

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		MAP3K8

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

More...GenomeRNAii		1326

Protein Ontology

More...PROi		PR:P41279

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000107968 Expressed in 192 organ(s), highest expression level in omental fat pad
ExpressionAtlasiP41279 baseline and differential
GenevisibleiP41279 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR017424 MAPKKK8
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PIRSFiPIRSF038171 MAPKKK8, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
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 nameiM3K8_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: P41279
Secondary accession number(s): A8K2Q5
, D3DRX1, Q14275, Q5T855, Q9HC81
<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: February 1, 1995
Last sequence update: July 19, 2004
Last modified: February 13, 2019
This is version 185 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, Reference proteome

Documents

  1. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  7. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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