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Protein

Mitogen-activated protein kinase kinase kinase kinase 1

Gene

Map4k1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

  • ATP binding Source: UniProtKB
  • MAP kinase kinase kinase kinase activity Source: MGI
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1346882 Map4k1

Subcellular locationi

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

Show more details

Protein-protein interaction databases

BioGridi2049645 interactors.
DIPiDIP-42073N
IntActiP70218 8 interactors.
MINTiP70218
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

Phylogenomic databases

eggNOGiKOG0576 Eukaryota
ENOG410XP9G LUCA
GeneTreeiENSGT00900000140794
HOGENOMiHOG000230824
HOVERGENiHBG036702
InParanoidiP70218
KOiK04408
OMAiLQWYQPM
OrthoDBiEOG091G022R
PhylomeDBiP70218
TreeFamiTF105121

Family and domain databases

InterProiView protein in InterPro
IPR001180 CNH_dom
IPR011009 Kinase-like_dom_sf
IPR021160 MAPKKKK
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
PfamiView protein in Pfam
PF00780 CNH, 1 hit
PF00069 Pkinase, 1 hit
PIRSFiPIRSF038172 MAPKKKK, 1 hit
SMARTiView protein in SMART
SM00036 CNH, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50219 CNH, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiM4K1_MOUSE
AccessioniPrimary (citable) accession number: P70218
Secondary accession number(s): Q8R3R0, Q99K62
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 28, 2003
Last sequence update: February 1, 1997
Last modified: March 28, 2018
This is version 158 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome