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Reviewed, UniProtKB/Swiss-Prot Q13233 (M3K1_HUMAN)

Last modified November 25, 2008. Version 86. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Mitogen-activated protein kinase kinase kinase 1
    EC=2.7.11.25
Alternative name(s):
    MAPK/ERK kinase kinase 1
      Short name=MEK kinase 1
      Short name=MEKK 1
Gene names
Name: MAP3K1
Synonyms: MAPKKK1, MEKK, MEKK1
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1514 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Component of a protein kinase signal transduction cascade. Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4. Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathway.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Enzyme regulation

Activated by autophosphorylation on Thr-1402 and Thr-1414 following oligomerization.

Subunit structure

Binds both upstream activators and downstream substrates in multimolecular complexes through its N-terminus. Oligomerizes after binding MAP4K2 or TRAF2. Interacts with AXIN1.

Post-translational modification

Autophosphorylated By similarity.

Sequence similarities

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

Contains 1 protein kinase domain.

Contains 1 RING-type zinc finger.

Contains 1 SWIM-type zinc finger.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 15141514Mitogen-activated protein kinase kinase kinase 1
PRO_0000086240

Regions

Domain1245 – 1510266Protein kinase
Zinc finger338 – 36629SWIM-type
Zinc finger443 – 49250RING-type
Nucleotide binding1251 – 12599ATP By similarity
Compositional bias2 – 54Poly-Ala
Compositional bias25 – 295Poly-Gly
Compositional bias36 – 416Poly-Ala
Compositional bias422 – 43110Poly-Ser
Compositional bias842 – 8476Poly-Ser
Compositional bias944 – 9518Poly-Thr
Compositional bias1184 – 11896Poly-Glu
Compositional bias1218 – 12214Poly-Ile

Sites

Active site13711Proton acceptor By similarity
Binding site12741ATP By similarity

Amino acid modifications

Modified residue2921Phosphoserine
Modified residue2971Phosphoserine
Modified residue3001Phosphoserine
Modified residue5071Phosphoserine
Modified residue5111Phosphoserine
Modified residue6571Phosphothreonine
Modified residue6651Phosphothreonine
Modified residue10201Phosphoserine
Modified residue14021Phosphothreonine; by autocatalysis By similarity
Modified residue14141Phosphothreonine; by autocatalysis By similarity

Natural variations

Natural variant921S → N
VAR_040680
Natural variant4431C → S
VAR_040681

Experimental info

Sequence conflict201T → P in AAC97073. Ref.2
Sequence conflict371P → R in AAC97073. Ref.2
Sequence conflict1201G → R in AAC97073. Ref.2
Sequence conflict3511R → H in AAC97073. Ref.2
Sequence conflict8461S → V in AAC97073. Ref.2
Sequence conflict8601I → Y in AAC97073. Ref.2
Sequence conflict879 – 8802DG → QR in AAC97073. Ref.2
Sequence conflict9351S → R in AAC97073. Ref.2
Sequence conflict10991C → L in AAC97073. Ref.2
Sequence conflict1106 – 11094AVIP → CCYT in AAC97073. Ref.2
Sequence conflict12021D → V in AAC97073. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q13233-1 [UniParc].

Last modified June 12, 2007. Version 3.
Checksum: A5B436E94785243D

FASTA1,514164,923
        10         20         30         40         50         60 
MAAAAGNRAS SSGFPGARAT SPEAGGGGGA LKASSAPAAA AGLLREAGSG GRERADWRRR 

        70         80         90        100        110        120 
QLRKVRSVEL DQLPEQPLFL AASPPASSTS PSPEPADAAG SGTGFQPVAV PPPHGAASRG 

       130        140        150        160        170        180 
GAHLTESVAA PDSGASSPAA AEPGEKRAPA AEPSPAAAPA GREMENKETL KGLHKMDDRP 

       190        200        210        220        230        240 
EERMIREKLK ATCMPAWKHE WLERRNRRGP VVVKPIPVKG DGSEMNHLAA ESPGEVQASA 

       250        260        270        280        290        300 
ASPASKGRRS PSPGNSPSGR TVKSESPGVR RKRVSPVPFQ SGRITPPRRA PSPDGFSPYS 

       310        320        330        340        350        360 
PEETNRRVNK VMRARLYLLQ QIGPNSFLIG GDSPDNKYRV FIGPQNCSCA RGTFCIHLLF 

       370        380        390        400        410        420 
VMLRVFQLEP SDPMLWRKTL KNFEVESLFQ KYHSRRSSRI KAPSRNTIQK FVSRMSNSHT 

       430        440        450        460        470        480 
LSSSSTSTSS SENSIKDEEE QMCPICLLGM LDEESLTVCE DGCRNKLHHH CMSIWAEECR 

       490        500        510        520        530        540 
RNREPLICPL CRSKWRSHDF YSHELSSPVD SPSSLRAAQQ QTVQQQPLAG SRRNQESNFN 

       550        560        570        580        590        600 
LTHYGTQQIP PAYKDLAEPW IQVFGMELVG CLFSRNWNVR EMALRRLSHD VSGALLLANG 

       610        620        630        640        650        660 
ESTGNSGGSS GSSPSGGATS GSSQTSISGD VVEACCSVLS MVCADPVYKV YVAALKTLRA 

       670        680        690        700        710        720 
MLVYTPCHSL AERIKLQRLL QPVVDTILVK CADANSRTSQ LSISTLLELC KGQAGELAVG 

       730        740        750        760        770        780 
REILKAGSIG IGGVDYVLNC ILGNQTESNN WQELLGRLCL IDRLLLEFPA EFYPHIVSTD 

       790        800        810        820        830        840 
VSQAEPVEIR YKKLLSLLTF ALQSIDNSHS MVGKLSRRIY LSSARMVTTV PHVFSKLLEM 

       850        860        870        880        890        900 
LSVSSSSTHF TRMRRRLMAI ADEVEIAEAI QLGVEDTLDG QQHNSFCRHL FPTTIWKPQR 

       910        920        930        940        950        960 
TVPLECTVHL EKTGKGLCAT KLSASSEDIS ERLASISVGP SSSTTTTTTT TEQPKPMVQT 

       970        980        990       1000       1010       1020 
KGRPHSQCLN SSPLSHHSQL MFPALSTPSS STPSVPAGTA TDVSKHRLQG FIPCRIPSAS 

      1030       1040       1050       1060       1070       1080 
PQTQRKFSLQ FHRNCPENKD SDKLSPVFTQ SRPLPSSNIH RPKPSRPTPG NTSKQGDPSK 

      1090       1100       1110       1120       1130       1140 
NSMTLDLNSS SKCDDSFGCS SNSSNAVIPS DETVFTPVEE KCRLDVNTEL NSSIEDLLEA 

      1150       1160       1170       1180       1190       1200 
SMPSSDTTVT FKSEVAVLSP EKAENDDTYK DDVNHNQKCK EKMEAEEEEA LAIAMAMSAS 

      1210       1220       1230       1240       1250       1260 
QDALPIVPQL QVENGEDIII IQQDTPETLP GHTKAKQPYR EDTEWLKGQQ IGLGAFSSCY 

      1270       1280       1290       1300       1310       1320 
QAQDVGTGTL MAVKQVTYVR NTSSEQEEVV EALREEIRMM SHLNHPNIIR MLGATCEKSN 

      1330       1340       1350       1360       1370       1380 
YNLFIEWMAG GSVAHLLSKY GAFKESVVIN YTEQLLRGLS YLHENQIIHR DVKGANLLID 

      1390       1400       1410       1420       1430       1440 
STGQRLRIAD FGAAARLASK GTGAGEFQGQ LLGTIAFMAP EVLRGQQYGR SCDVWSVGCA 

      1450       1460       1470       1480       1490       1500 
IIEMACAKPP WNAEKHSNHL ALIFKIASAT TAPSIPSHLS PGLRDVALRC LELQPQDRPP 

      1510 
SRELLKHPVF RTTW 

« Hide

References

« Hide 'large scale' references
[1]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed: 15372022] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]"JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino-terminal extension."
Xia Y., Wu Z., Su B., Murray B., Karin M.
Genes Dev. 12:3369-3381(1998) [PubMed: 9808624] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 20-1514, FUNCTION, INTERACTION WITH MAP2K4.
[3]"Mapping of the MEK kinase gene (Mekk) to mouse chromosome 13 and human chromosome 5."
Vinik B.S., Kay E.S., Fiedorek F.T. Jr.
Mamm. Genome 6:782-783(1995) [PubMed: 8597633] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1240-1276.
Tissue: Leukocyte.
[4]"The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase activation by Axin and dishevelled through distinct mechanisms."
Wong C.K., Luo W., Deng Y., Zou H., Ye Z., Lin S.-C.
J. Biol. Chem. 279:39366-39373(2004) [PubMed: 15262978] [Abstract]
Cited for: INTERACTION WITH AXIN1.
[5]"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column."
Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.
Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-657 AND THR-665, MASS SPECTROMETRY.
[6]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-292, MASS SPECTROMETRY.
[7]"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: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-292; SER-297; SER-300; SER-507; SER-511 AND SER-1020, MASS SPECTROMETRY.
[8]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed: 17344846] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASN-92 AND SER-443.
+Additional computationally mapped references.

Cross-references

Sequence databases

AC008937 Genomic DNA. No translation available.
AF042838 mRNA. Translation: AAC97073.1.
U29671 Genomic DNA. Translation: AAB05828.1.
PIRG01887.
RefSeqNP_005912.1.
UniGeneHs.657756

3D structure databases

HSSPHSSP built from PDB template 1KV1 based on UniProtKB Q16539.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:27520N.
IntActQ13233.

PTM databases

PhosphoSiteQ13233.

2-D gel databases

SWISS-2DPAGEQ13233.

Genome annotation databases

EnsemblENSG00000095015. Homo sapiens. [Contig view]
GeneID4214.
KEGGhsa:4214.

Organism-specific databases

H-InvDBHIX0024789.
HGNCHGNC:6848. MAP3K1.
HPACAB004500.
MIM600982. gene.
PharmGKBPA30592.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMQ13233.
HOVERGENQ13233.

Enzyme and pathway databases

ReactomeREACT_6900. Signaling in Immune System.

Gene expression databases

ArrayExpressQ13233.
CleanExHS_MAP3K1.
GermOnlineENSG00000095015. Homo sapiens.

Family and domain databases

InterProIPR015749. MAPKKK1.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_bd_CS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR007527. Znf_SWIM.
[Graphical view]
Gene3DG3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.
PANTHERPTHR22986:SF65. MAPKKK1. 1 hit.
PfamPF00069. Pkinase. 1 hit.
PF04434. SWIM. 1 hit.
[Graphical view]
ProDomPD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00184. RING. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00518. ZF_RING_1. False negative.
PS50089. ZF_RING_2. 1 hit.
PS50966. ZF_SWIM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio16613.
SOURCESearch...

Entry information

Entry nameM3K1_HUMAN
AccessionPrimary (citable) accession number: Q13233
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: June 12, 2007
Last modified: November 25, 2008
This is version 86 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents