Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Mitogen-activated protein kinase kinase kinase kinase 1

Gene

Map4k1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine/threonine-protein kinase, which may play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation. Able to autophosphorylate.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Mg2+1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei46ATPPROSITE-ProRule annotation1 Publication1
Active sitei137Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi23 – 31ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • cell proliferation Source: UniProtKB
  • intracellular signal transduction Source: UniProtKB
  • peptidyl-serine phosphorylation Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • response to stress Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase kinase kinase kinase 1 (EC:2.7.11.1)
Alternative name(s):
Hematopoietic progenitor kinase
Short name:
HPK
MAPK/ERK kinase kinase kinase 1
Short name:
MEK kinase kinase 1
Short name:
MEKKK 1
Gene namesi
Name:Map4k1
Synonyms:Hpk1
OrganismiMus musculus (Mouse)Imported
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1346882. Map4k1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi46K → E: Loss of kinase activity and ability to activate JNK family. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862741 – 827Mitogen-activated protein kinase kinase kinase kinase 1Add BLAST827

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei165Phosphothreonine; by autocatalysisBy similarity1
Modified residuei171Phosphoserine; by autocatalysisBy similarity1
Modified residuei175Phosphothreonine; by autocatalysisBy similarity1
Modified residuei354Phosphothreonine; by autocatalysisBy similarity1
Modified residuei373PhosphoserineCombined sources1
Modified residuei375PhosphoserineCombined sources1
Modified residuei403PhosphoserineBy similarity1
Modified residuei405PhosphoserineBy similarity1
Modified residuei419PhosphoserineCombined sources1
Modified residuei592PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylates: phosphorylation promotes ubiquitination by the Cul7-RING(FBXW8) ubiquitin-protein ligase complex, leading to its degradation by the proteasome.By similarity
Ubiquitinated by the Cul7-RING(FBXW8) ubiquitin-protein ligase complex following autophosphorylation, leading to its degradation by the proteasome.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP70218.
MaxQBiP70218.
PaxDbiP70218.
PeptideAtlasiP70218.
PRIDEiP70218.

PTM databases

iPTMnetiP70218.
PhosphoSitePlusiP70218.

Expressioni

Tissue specificityi

Ubiquitously expressed in all tissues examined at embryonic stage E16.5 with high levels in lung, heart and fetal liver. In the neonate, expression is restricted to the tissues which undergo lineage decisions, lung, thymus, liver, kidney and brain. In the adult, expression is limited to hemopoietic organs, thymus, bone marrow, and spleen and to the testis.1 Publication

Gene expression databases

BgeeiENSMUSG00000037337.
ExpressionAtlasiP70218. baseline and differential.
GenevisibleiP70218. MM.

Interactioni

Subunit structurei

Interacts with MAP3K1. Interacts with FBXW8 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
MAP3K11Q165843EBI-2906801,EBI-49961From a different organism.

Protein-protein interaction databases

BioGridi204964. 4 interactors.
DIPiDIP-42073N.
IntActiP70218. 4 interactors.
MINTiMINT-1176243.
STRINGi10090.ENSMUSP00000082995.

Structurei

Secondary structure

1827
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi473 – 476Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1UTIX-ray1.50D465-480[»]
ProteinModelPortaliP70218.
SMRiP70218.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP70218.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini17 – 274Protein kinasePROSITE-ProRule annotationAdd BLAST258
Domaini501 – 806CNHPROSITE-ProRule annotationAdd BLAST306

Sequence similaritiesi

Contains 1 CNH domain.PROSITE-ProRule annotationCurated
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0576. Eukaryota.
ENOG410XP9G. LUCA.
GeneTreeiENSGT00810000125351.
HOGENOMiHOG000230824.
HOVERGENiHBG036702.
InParanoidiP70218.
KOiK04408.
OMAiEMSTEHR.
OrthoDBiEOG091G022R.
PhylomeDBiP70218.
TreeFamiTF105121.

Family and domain databases

InterProiIPR001180. CNH_dom.
IPR011009. Kinase-like_dom.
IPR021160. MAPKKKK.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00780. CNH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF038172. MAPKKKK. 1 hit.
SMARTiSM00036. CNH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50219. CNH. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P70218-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALVDPDIFN KDPREHYDLL QRLGGGTYGE VFKARDKVSK DLVALKMVKM
60 70 80 90 100
EPDDDVATLQ KEILMLKTCR HANIVAYHGS YLWLQKLWIC MEFCGAGSLQ
110 120 130 140 150
DIYQVTGSLS ELQISYVCRE VLQGLAYLHS EKKIHRDIKG ANILINDCGE
160 170 180 190 200
VKLADFGISA QIGATLARRL SFIGTPYWMA PEVAAVALKG GYNELCDIWS
210 220 230 240 250
LGITAIELAE LQPPLFDVHP LRVLFLMTKS GYQPPRLKEK SRWSSSFHNF
260 270 280 290 300
VKVTLTKNSK KRPSATKMLS HQLVSQPGLN RGLILDLLDK MKNPGKGLPV
310 320 330 340 350
DIEDEEPEPP PAIPRRIRST YRASSLGIPD ADCCRRQMEF QRPRCVDCRP
360 370 380 390 400
QAETVRLYPP AHFGSTSPRS QLSDSDDDYD DVDIPAPSEN IPPPLPPKPK
410 420 430 440 450
FRSPSDDGSG GIRDDGQLSP GVLVRCASGP PPRTPRPGPP PATCSPHLTA
460 470 480 490 500
RSDPSLWNPA APEPGQPPLV PPRKEKMRGK MENEKRREKY PLLVKLFNGC
510 520 530 540 550
PLQIHSTAAW THPSTKDQNL LLGAEEGIFI LNRNDQEATL EMIFPGRTTW
560 570 580 590 600
LYCINNLLMS LSGKTPYLYS HSILGLLERK DGRTGSPIAH ISPHRLLARK
610 620 630 640 650
NMVSSKIQDT KGCRACCVAE SASSGGPFLC GALETSVVLL QWYQPMNKFL
660 670 680 690 700
LVRQVLFPLP TPLPVFTLLT TPGSELPAVC IGVSPGQAAK SVLFHTVRFG
710 720 730 740 750
ALSCWLDDSS TEHKGPVQVI QVKEDMVMVL MDGSLKLVTP EGAPAPGLRT
760 770 780 790 800
PEIPMTEAVE AVAMVEDRLE AFWKHGVQVW APGLKQPLQE LRDPTLTFRL
810 820
LCSPRPVVVE TRPTDDPTAP SNLYIQE
Length:827
Mass (Da):91,535
Last modified:February 1, 1997 - v1
Checksum:i82341BE9D13036BA
GO

Sequence cautioni

The sequence AAH05433 differs from that shown. Intron retention.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti411G → V in AAH24832 (PubMed:15489334).Curated1
Sequence conflicti444C → R in AAH05433 (PubMed:15489334).Curated1
Sequence conflicti444C → R in AAH24832 (PubMed:15489334).Curated1
Sequence conflicti807V → I in AAH24832 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y09010 mRNA. Translation: CAA70213.1.
BC005433 mRNA. Translation: AAH05433.1. Sequence problems.
BC024832 mRNA. Translation: AAH24832.1.
CCDSiCCDS39865.1.
RefSeqiNP_032305.2. NM_008279.2.
UniGeneiMm.148278.

Genome annotation databases

EnsembliENSMUST00000085835; ENSMUSP00000082995; ENSMUSG00000037337.
GeneIDi26411.
KEGGimmu:26411.
UCSCiuc009gam.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y09010 mRNA. Translation: CAA70213.1.
BC005433 mRNA. Translation: AAH05433.1. Sequence problems.
BC024832 mRNA. Translation: AAH24832.1.
CCDSiCCDS39865.1.
RefSeqiNP_032305.2. NM_008279.2.
UniGeneiMm.148278.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1UTIX-ray1.50D465-480[»]
ProteinModelPortaliP70218.
SMRiP70218.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204964. 4 interactors.
DIPiDIP-42073N.
IntActiP70218. 4 interactors.
MINTiMINT-1176243.
STRINGi10090.ENSMUSP00000082995.

PTM databases

iPTMnetiP70218.
PhosphoSitePlusiP70218.

Proteomic databases

EPDiP70218.
MaxQBiP70218.
PaxDbiP70218.
PeptideAtlasiP70218.
PRIDEiP70218.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000085835; ENSMUSP00000082995; ENSMUSG00000037337.
GeneIDi26411.
KEGGimmu:26411.
UCSCiuc009gam.1. mouse.

Organism-specific databases

CTDi11184.
MGIiMGI:1346882. Map4k1.

Phylogenomic databases

eggNOGiKOG0576. Eukaryota.
ENOG410XP9G. LUCA.
GeneTreeiENSGT00810000125351.
HOGENOMiHOG000230824.
HOVERGENiHBG036702.
InParanoidiP70218.
KOiK04408.
OMAiEMSTEHR.
OrthoDBiEOG091G022R.
PhylomeDBiP70218.
TreeFamiTF105121.

Miscellaneous databases

EvolutionaryTraceiP70218.
PROiP70218.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000037337.
ExpressionAtlasiP70218. baseline and differential.
GenevisibleiP70218. MM.

Family and domain databases

InterProiIPR001180. CNH_dom.
IPR011009. Kinase-like_dom.
IPR021160. MAPKKKK.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00780. CNH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF038172. MAPKKKK. 1 hit.
SMARTiSM00036. CNH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50219. CNH. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiM4K1_MOUSE
AccessioniPrimary (citable) accession number: P70218
Secondary accession number(s): Q8R3R0, Q99K62
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 28, 2003
Last sequence update: February 1, 1997
Last modified: November 2, 2016
This is version 146 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. 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.