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Protein

Mitogen-activated protein kinase kinase kinase 1

Gene

Map3k1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Enzyme regulationi

Activated by autophosphorylation on Thr-1381 and Thr-1393 following oligomerization.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei1253 – 12531ATPPROSITE-ProRule annotation
Active sitei1350 – 13501Proton acceptor

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri328 – 35629SWIM-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri433 – 48250RING-typePROSITE-ProRule annotationAdd
BLAST
Nucleotide bindingi1230 – 12389ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • JUN kinase binding Source: RGD
  • JUN kinase kinase kinase activity Source: RGD
  • MAP kinase kinase kinase activity Source: RGD
  • mitogen-activated protein kinase binding Source: RGD
  • mitogen-activated protein kinase kinase binding Source: RGD
  • sphingolipid binding Source: RGD
  • ubiquitin-protein transferase activity Source: RGD
  • zinc ion binding Source: InterPro

GO - Biological processi

  • activation of JNKK activity Source: RGD
  • activation of MAPKK activity Source: RGD
  • MAPK cascade Source: RGD
  • negative regulation of actin filament bundle assembly Source: RGD
  • peptidyl-serine phosphorylation Source: RGD
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of JUN kinase activity Source: RGD
  • positive regulation of MAP kinase activity Source: RGD
  • positive regulation of transcription from RNA polymerase II promoter Source: RGD
  • positive regulation of viral transcription Source: RGD
  • protein autophosphorylation Source: RGD
  • protein oligomerization Source: RGD
  • protein phosphorylation Source: RGD
  • protein polyubiquitination Source: RGD
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: RGD
  • response to osmotic stress Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.12.2. 5301.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Map3k1
Synonyms:Mekk, Mekk1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620966. Map3k1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: RGD
  • membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi1350 – 13501D → N: Loss of kinase activity and of autophosphorylation activity. 1 Publication
Mutagenesisi1369 – 13691D → A: Inactivation. 1 Publication
Mutagenesisi1381 – 13811T → A: Loss of kinase activity and activation by autophosphorylation; when associated with T-1393. 1 Publication
Mutagenesisi1393 – 13931T → A: Loss of kinase activity and activation by autophosphorylation; when associated with T-1381. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 14931492Mitogen-activated protein kinase kinase kinase 1PRO_0000086242Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei21 – 211PhosphoserineBy similarity
Modified residuei137 – 1371PhosphoserineBy similarity
Modified residuei265 – 2651PhosphoserineBy similarity
Modified residuei275 – 2751PhosphothreonineBy similarity
Modified residuei282 – 2821PhosphoserineBy similarity
Modified residuei287 – 2871PhosphoserineBy similarity
Modified residuei290 – 2901PhosphoserineBy similarity
Modified residuei497 – 4971PhosphoserineBy similarity
Modified residuei521 – 5211PhosphoserineBy similarity
Modified residuei910 – 9101PhosphoserineBy similarity
Modified residuei999 – 9991PhosphoserineBy similarity
Modified residuei1024 – 10241PhosphoserineBy similarity
Modified residuei1381 – 13811Phosphothreonine; by autocatalysis1 Publication
Modified residuei1393 – 13931Phosphothreonine; by autocatalysis1 Publication

Post-translational modificationi

Autophosphorylated.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ62925.
PRIDEiQ62925.

PTM databases

iPTMnetiQ62925.
PhosphoSiteiQ62925.

Expressioni

Tissue specificityi

Most highly expressed in spleen, kidney and lung.

Interactioni

Subunit structurei

Binds both upstream activators and downstream substrates in multimolecular complexes through its N-terminus. Oligomerizes after binding MAP4K2 or TRAF2. Interacts (via the kinase catalytic domain) with STK38 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
TRAF2Q129332EBI-636664,EBI-355744From a different organism.
UBE2NP6108844EBI-636664,EBI-1052908From a different organism.

GO - Molecular functioni

  • JUN kinase binding Source: RGD
  • mitogen-activated protein kinase binding Source: RGD
  • mitogen-activated protein kinase kinase binding Source: RGD

Protein-protein interaction databases

IntActiQ62925. 85 interactions.
MINTiMINT-143953.
STRINGi10116.ENSRNOP00000017968.

Structurei

3D structure databases

ProteinModelPortaliQ62925.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1224 – 1489266Protein kinasePROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi25 – 295Poly-Gly
Compositional biasi74 – 14976Pro-richAdd
BLAST
Compositional biasi233 – 29159Pro-richAdd
BLAST
Compositional biasi412 – 42110Poly-Ser
Compositional biasi1163 – 11686Poly-Glu

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation
Contains 1 SWIM-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri328 – 35629SWIM-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri433 – 48250RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4279. Eukaryota.
ENOG410XQGS. LUCA.
HOGENOMiHOG000113437.
HOVERGENiHBG006302.
InParanoidiQ62925.
KOiK04416.
PhylomeDBiQ62925.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR016024. ARM-type_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR007527. Znf_SWIM.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50089. ZF_RING_2. 1 hit.
PS50966. ZF_SWIM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q62925-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAAAGDRAS SSGFPGAAAA SPEAGGGGGA LQGSGAPAAG AGLLRETGSA
60 70 80 90 100
GRERADWRRQ QLRKVRSVEL DQLPEQPLFL TASPPCPSTS PSPEPADAAA
110 120 130 140 150
GASGFQPAAG PPPPGAASRC GSHSAELAAA RDSGARSPAG AEPPSAAAPS
160 170 180 190 200
GREMENKETL KGLHKMDDRP EERMIREKLK ATCMPAWKHE WLERRNRRGP
210 220 230 240 250
VVVKPIPIKG DGSEMSNLAA ELQGEGQAGS AAPAPKGRRS PSPGSSPSGR
260 270 280 290 300
SGKPESPGVR RKRVSPVPFQ SGRITPPRRA PSPDGFSPYS PEETSRRVNK
310 320 330 340 350
VMRARLYLLQ QIGPNSFLIG GDSPDNKYRV FIGPQNCSCG RGTFCIHLLF
360 370 380 390 400
VMLRVFQLEP SDPMLWRKTL KNFEVESLFQ KYHSRRSSRI KAPSRNTIQK
410 420 430 440 450
FVSRMSNCHT LSSSSTSTSS SENSIKDEEE QMCPICLLGM LDEESLTVCE
460 470 480 490 500
DGCRNKLHHH CMSIWAEECR RNREPLICPL CRSKWRSHDF YSHELSSPVD
510 520 530 540 550
SPTSLRGVQQ PSSPQQPVAG SQRRNQESNF NLTHYGTQQI PPAYKDLAEP
560 570 580 590 600
WIQAFGMELV GCLFSRNWNV REMALRRLSH DVSGALLLAN GESTGTSGGG
610 620 630 640 650
SGGSLSAGAA SGSSQPSISG DVVEAFCSVL SIVCADPVYK VYVAALKTLR
660 670 680 690 700
AMLVYTPCHS LAERIKLQRL LRPVVDTILV KCADANSRTS QLSISTLLEL
710 720 730 740 750
CKGQAGELAV GREILKAGSI GVGGVDYVLS CILGNQAESN NWQELLGRLC
760 770 780 790 800
LIDRLLLEIS AEFYPHIVST DVSQAEPVEI RYKKLLSLLA FALQSIDNSH
810 820 830 840 850
SMVGKLSRRI YLSSARMVTT VPPLFSKLVT MLSASGSSHF ARMRRRLMAI
860 870 880 890 900
ADEVEIAEVI QLGSEDTLDG QQDSSQALAP PRYPESSSLE HTAHVEKTGK
910 920 930 940 950
GLKATRLSAS SEDISDRLAG VSVGLPSSAT TEQPKPTVQT KGRPHSQCLN
960 970 980 990 1000
SSPLSPPQLM FPAISAPCSS APSVPAGSVT DASKHRPRAF VPCKIPSASP
1010 1020 1030 1040 1050
QTQRKFSLQF QRTCSENRDS EKLSPVFTQS RPPPSSNIHR AKASRPVPGS
1060 1070 1080 1090 1100
TSKLGDASKN SMTLDLNSAS QCDDSFGSGS NSGSAVIPSE ETAFTPAEDK
1110 1120 1130 1140 1150
CRLDVNPELN SSIEDLLEAS MPSSDTTVTF KSEVAVLSPE KAESDDTYKD
1160 1170 1180 1190 1200
DVNHNQKCKE KMEAEEEEAL AIAMAMSASQ DALPIVPQLQ VENGEDIIII
1210 1220 1230 1240 1250
QQDTPETLPG HTKANEPYRE DTEWLKGQQI GLGAFSSCYQ AQDVGTGTLM
1260 1270 1280 1290 1300
AVKQVTYVRN TSSEQEEVVE ALREEIRMMS HLNHPNIIRM LGATCEKSNY
1310 1320 1330 1340 1350
NLFIEWMAGA SVAHLLSKYG AFKESVVINY TEQLLRGLSY LHENQIIHRD
1360 1370 1380 1390 1400
VKGANLLIDS TGQRLRIADF GAAARLASKG TGAGEFQGQL LGTIAFMAPE
1410 1420 1430 1440 1450
VLRGQQYGRS CDVWSVGCAI IEMACAKPPW NAEKHSNHLA LIFKIASATT
1460 1470 1480 1490
APSIPSHLSP GLRDVALRCL ELQPQDRPPS RELLKHPVFR TTW
Length:1,493
Mass (Da):161,315
Last modified:November 1, 1996 - v1
Checksum:i8C5F29F866898524
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U48596 mRNA. Translation: AAC52596.1.
PIRiT10757.
RefSeqiNP_446339.1. NM_053887.1.
UniGeneiRn.11081.

Genome annotation databases

GeneIDi116667.
KEGGirno:116667.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U48596 mRNA. Translation: AAC52596.1.
PIRiT10757.
RefSeqiNP_446339.1. NM_053887.1.
UniGeneiRn.11081.

3D structure databases

ProteinModelPortaliQ62925.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ62925. 85 interactions.
MINTiMINT-143953.
STRINGi10116.ENSRNOP00000017968.

PTM databases

iPTMnetiQ62925.
PhosphoSiteiQ62925.

Proteomic databases

PaxDbiQ62925.
PRIDEiQ62925.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi116667.
KEGGirno:116667.

Organism-specific databases

CTDi4214.
RGDi620966. Map3k1.

Phylogenomic databases

eggNOGiKOG4279. Eukaryota.
ENOG410XQGS. LUCA.
HOGENOMiHOG000113437.
HOVERGENiHBG006302.
InParanoidiQ62925.
KOiK04416.
PhylomeDBiQ62925.

Enzyme and pathway databases

BRENDAi2.7.12.2. 5301.

Miscellaneous databases

PROiQ62925.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR016024. ARM-type_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR007527. Znf_SWIM.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50089. ZF_RING_2. 1 hit.
PS50966. ZF_SWIM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiM3K1_RAT
AccessioniPrimary (citable) accession number: Q62925
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: July 6, 2016
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.