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P41279 (M3K8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
Gene names
Name:MAP3K8
Synonyms:COT, ESTF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length467 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.10 Ref.12 Ref.14 Ref.16 Ref.18 Ref.20 Ref.22 Ref.23

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Subunit structure

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. Ref.11 Ref.13 Ref.14 Ref.15 Ref.16

Subcellular location

Cytoplasm Ref.2 Ref.10.

Tissue specificity

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

Developmental stage

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

Induction

Up-regulated by IL12 in T-lymphocytes. Up-regulated in subcutaneous adipose tissue of obese individuals. Ref.20 Ref.23

Post-translational modification

Autophosphorylated. Isoform 1 undergoes phosphorylation mainly on Ser residues, and isoform 2 on both Ser and Thr residues. Thr-290 is autophosphorylated (Ref.22) and/or transphosphorylated (Ref.15); 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. Ser-400 is autophosphorylated (Ref.22) and/or transphosphorylated by IKBKB (Ref.24); the phosphorylation is required for LPS-stimulated activation of the MAPK/ERK pathway in macrophages. Ref.10 Ref.15 Ref.17 Ref.19 Ref.22 Ref.24

Miscellaneous

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

Sequence similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.

Contains 1 protein kinase domain.

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]
Isoform 1 (identifier: P41279-1)

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.
Isoform 2 (identifier: P41279-2)

Also known as: 52 kDa;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 467467Mitogen-activated protein kinase kinase kinase 8
PRO_0000024350

Regions

Domain138 – 388251Protein kinase
Nucleotide binding144 – 1529ATP By similarity

Sites

Active site2531Proton acceptor By similarity
Binding site1671ATP By similarity

Amino acid modifications

Modified residue621Phosphoserine; by autocatalysis Ref.22
Modified residue801Phosphothreonine Ref.19
Modified residue2901Phosphothreonine Ref.15 Ref.17 Ref.22
Modified residue4001Phosphoserine Ref.19 Ref.22 Ref.24
Modified residue4431Phosphoserine Ref.19

Natural variations

Alternative sequence1 – 2929Missing in isoform 2.
VSP_018843
Natural variant2141S → F.
Corresponds to variant rs3087944 [ dbSNP | Ensembl ].
VAR_051638
Natural variant398 – 41518CQSLD…LLSRK → GHQVIHEGSSTNDPNNSC in oncogenic form.
VAR_006198
Natural variant416 – 46752Missing in oncogenic form.
VAR_006199

Experimental info

Mutagenesis621S → A: Decreased IL1-stimulated activity. Loss of IL1-stimulated phosphorylation of T-290 and MEK phosphorylation activity; when associated with A-400. Ref.22
Mutagenesis1671K → R: Loss of catalytic activity. Ref.22
Mutagenesis2701D → A: Loss of catalytic activity. Ref.22
Mutagenesis2901T → 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. Ref.15 Ref.22
Mutagenesis2901T → D: Impaired MEK phosphorylation and autophosphorylation activities. No effect on KSR2 binding. Ref.15 Ref.22
Mutagenesis2901T → E: Loss of MEK phosphorylation activity and almost abolished autophosphorylation activity. No effect on KSR2 binding. Ref.15 Ref.22
Mutagenesis4001S → A: Slightly decreased IL1-stimulated MEK phosphorylation activity. Loss of IL1-stimulated phosphorylation of T-290 and MEK phosphorylation activity; when associated with A-62. Ref.22
Sequence conflict3991Q → T in BAA03387. Ref.1
Sequence conflict3991Q → T no nucleotide entry Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (58 kDa) [UniParc].

Last modified July 19, 2004. Version 2.
Checksum: 7728969EA3E4E8EC

FASTA46752,925
        10         20         30         40         50         60 
MEYMSTGSDN KEEIDLLIKH LNVSDVIDIM ENLYASEEPA VYEPSLMTMC QDSNQNDERS 

        70         80         90        100        110        120 
KSLLLSGQEV PWLSSVRYGT VEDLLAFANH ISNTAKHFYG QRPQESGILL NMVITPQNGR 

       130        140        150        160        170        180 
YQIDSDVLLI PWKLTYRNIG SDFIPRGAFG KVYLAQDIKT KKRMACKLIP VDQFKPSDVE 

       190        200        210        220        230        240 
IQACFRHENI AELYGAVLWG ETVHLFMEAG EGGSVLEKLE SCGPMREFEI IWVTKHVLKG 

       250        260        270        280        290        300 
LDFLHSKKVI HHDIKPSNIV FMSTKAVLVD FGLSVQMTED VYFPKDLRGT EIYMSPEVIL 

       310        320        330        340        350        360 
CRGHSTKADI YSLGATLIHM QTGTPPWVKR YPRSAYPSYL YIIHKQAPPL EDIADDCSPG 

       370        380        390        400        410        420 
MRELIEASLE RNPNHRPRAA DLLKHEALNP PREDQPRCQS LDSALLERKR LLSRKELELP 

       430        440        450        460 
ENIADSSCTG STEESEMLKR QRSLYIDLGA LAGYFNLVRG PPTLEYG 

« Hide

Isoform 2 (52 kDa) [UniParc].

Checksum: 2121FEF4658882FD
Show »

FASTA43849,620

References

« Hide 'large scale' references
[1]"Structure and transforming potential of the human cot oncogene encoding a putative protein kinase."
Miyoshi J., Higashi T., Mukai H., Ohuchi T., Kakunaga T.
Mol. Cell. Biol. 11:4088-4096(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ONCOGENIC VARIANT.
Tissue: Hepatoma.
[2]"The human cot proto-oncogene encodes two protein serine/threonine kinases with different transforming activities by alternative initiation of translation."
Aoki M., Sugimoto T., Sumida S., Hamada F., Akiyama T., Toyoshima K.
J. Biol. Chem. 268:22723-22732(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION.
[3]"Expression cDNA cloning of a serine kinase transforming gene."
Chan A.M., Chedid M., McGovern E.S., Popescu N.C., Miki T., Aaronson S.A.
Oncogene 8:1329-1333(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Bone.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Tongue.
[5]SeattleSNPs variation discovery resource
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[9]"COT kinase proto-oncogene expression in T cells: implication of the JNK/SAPK signal transduction pathway in COT promoter activation."
Sanchez-Gongora E., Lisbona C., de Gregorio R., Ballester A., Calvo V., Perez-Jurado L., Alemany S.
J. Biol. Chem. 275:31379-31386(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-112.
Tissue: T-cell.
[10]"Identification and characterization of protein products of the cot oncogene with serine kinase activity."
Aoki M., Akiyama T., Miyoshi J., Toyoshima K.
Oncogene 6:1515-1519(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE INITIATION, FUNCTION, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION.
[11]"TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105."
Belich M.P., Salmeron A., Johnston L.H., Ley S.C.
Nature 397:363-368(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NFKB1.
[12]"p27kip protein levels and E2F activity are targets of Cot kinase during G1 phase progression in T cells."
Velasco-Sampayo A., Alemany S.
J. Immunol. 166:6084-6090(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Identification of a novel human kinase supporter of Ras (hKSR-2) that functions as a negative regulator of Cot (Tpl2) signaling."
Channavajhala P.L., Wu L., Cuozzo J.W., Hall J.P., Liu W., Lin L.-L., Zhang Y.
J. Biol. Chem. 278:47089-47097(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KSR2.
[14]"NF-kappaB1/p105 regulates lipopolysaccharide-stimulated MAP kinase signaling by governing the stability and function of the Tpl2 kinase."
Waterfield M.R., Zhang M., Norman L.P., Sun S.C.
Mol. Cell 11:685-694(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NFKB1.
[15]"Phosphorylation of threonine 290 in the activation loop of Tpl2/Cot is necessary but not sufficient for kinase activity."
Luciano B.S., Hsu S., Channavajhala P.L., Lin L.L., Cuozzo J.W.
J. Biol. Chem. 279:52117-52123(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-290, INTERACTION WITH KSR2, MUTAGENESIS OF THR-290.
[16]"ABIN-2 forms a ternary complex with TPL-2 and NF-kappa B1 p105 and is essential for TPL-2 protein stability."
Lang V., Symons A., Watton S.J., Janzen J., Soneji Y., Beinke S., Howell S., Ley S.C.
Mol. Cell. Biol. 24:5235-5248(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NFKB1 AND TNIP2.
[17]"Phosphorylation at Thr-290 regulates Tpl2 binding to NF-kappaB1/p105 and Tpl2 activation and degradation by lipopolysaccharide."
Cho J., Tsichlis P.N.
Proc. Natl. Acad. Sci. U.S.A. 102:2350-2355(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-290.
[18]"TRAF6 and Src kinase activity regulates Cot activation by IL-1."
Rodriguez C., Pozo M., Nieto E., Fernandez M., Alemany S.
Cell. Signal. 18:1376-1385(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[19]"Characterization of phosphorylation sites on Tpl2 using IMAC enrichment and a linear ion trap mass spectrometer."
Black T.M., Andrews C.L., Kilili G., Ivan M., Tsichlis P.N., Vouros P.
J. Proteome Res. 6:2269-2276(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-80; SER-400 AND SER-443.
[20]"Tpl2 kinase regulates T cell interferon-gamma production and host resistance to Toxoplasma gondii."
Watford W.T., Hissong B.D., Durant L.R., Yamane H., Muul L.M., Kanno Y., Tato C.M., Ramos H.L., Berger A.E., Mielke L., Pesu M., Solomon B., Frucht D.M., Paul W.E., Sher A., Jankovic D., Tsichlis P.N., O'Shea J.J.
J. Exp. Med. 205:2803-2812(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[21]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[22]"IRAK1-independent pathways required for the interleukin-1-stimulated activation of the Tpl2 catalytic subunit and its dissociation from ABIN2."
Handoyo H., Stafford M.J., McManus E., Baltzis D., Peggie M., Cohen P.
Biochem. J. 424:109-118(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-62; THR-290 AND SER-400, MUTAGENESIS OF SER-62; LYS-167; ASP-270; THR-290 AND SER-400.
[23]"Tpl2 kinase is upregulated in adipose tissue in obesity and may mediate interleukin-1beta and tumor necrosis factor-{alpha} effects on extracellular signal-regulated kinase activation and lipolysis."
Jager J., Gremeaux T., Gonzalez T., Bonnafous S., Debard C., Laville M., Vidal H., Tran A., Gual P., Le Marchand-Brustel Y., Cormont M., Tanti J.F.
Diabetes 59:61-70(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[24]"IkappaB kinase 2 regulates TPL-2 activation of extracellular signal-regulated kinases 1 and 2 by direct phosphorylation of TPL-2 serine 400."
Roget K., Ben-Addi A., Mambole-Dema A., Gantke T., Yang H.T., Janzen J., Morrice N., Abbott D., Ley S.C.
Mol. Cell. Biol. 32:4684-4690(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-400.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D14497 mRNA. Translation: BAA03387.1.
Z14138 mRNA. Translation: CAA78512.1.
AK290320 mRNA. Translation: BAF83009.1.
AY309013 Genomic DNA. Translation: AAP45053.1.
AL161651 Genomic DNA. Translation: CAI14227.1.
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.
CCDSCCDS7166.1. [P41279-1]
PIRA48713.
RefSeqNP_001231063.1. NM_001244134.1. [P41279-1]
NP_005195.2. NM_005204.3. [P41279-1]
XP_005252421.2. XM_005252364.2. [P41279-1]
XP_005252423.1. XM_005252366.1. [P41279-1]
UniGeneHs.432453.
Hs.731448.

3D structure databases

ProteinModelPortalP41279.
SMRP41279. Positions 88-438.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107719. 20 interactions.
DIPDIP-27534N.
IntActP41279. 11 interactions.
MINTMINT-1140505.
STRING9606.ENSP00000263056.

Chemistry

BindingDBP41279.
ChEMBLCHEMBL4899.
GuidetoPHARMACOLOGY2083.

PTM databases

PhosphoSiteP41279.

Polymorphism databases

DMDM50403742.

Proteomic databases

PaxDbP41279.
PRIDEP41279.

Protocols and materials databases

DNASU1326.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263056; ENSP00000263056; ENSG00000107968. [P41279-1]
ENST00000375321; ENSP00000364470; ENSG00000107968. [P41279-1]
ENST00000542547; ENSP00000443610; ENSG00000107968. [P41279-1]
GeneID1326.
KEGGhsa:1326.
UCSCuc001ivi.2. human. [P41279-1]

Organism-specific databases

CTD1326.
GeneCardsGC10P030722.
HGNCHGNC:6860. MAP3K8.
HPACAB005120.
HPA017962.
MIM191195. gene.
neXtProtNX_P41279.
PharmGKBPA30606.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000285978.
HOVERGENHBG006306.
InParanoidP41279.
KOK04415.
OMAIHLFMEA.
OrthoDBEOG71P29J.
PhylomeDBP41279.
TreeFamTF105117.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkP41279.

Gene expression databases

ArrayExpressP41279.
BgeeP41279.
CleanExHS_MAP3K8.
GenevestigatorP41279.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR017424. MAPKKK8.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFPIRSF038171. MAPKKK8. 1 hit.
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMAP3K8.
GenomeRNAi1326.
NextBio5403.
PROP41279.
SOURCESearch...

Entry information

Entry nameM3K8_HUMAN
AccessionPrimary (citable) accession number: P41279
Secondary accession number(s): A8K2Q5 expand/collapse secondary AC list , D3DRX1, Q14275, Q5T855, Q9HC81
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: July 19, 2004
Last modified: July 9, 2014
This is version 141 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM