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P70218 (M4K1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Map4k1
Synonyms:Hpk1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length827 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1

Catalytic activity

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

Cofactor

Magnesium. Ref.1

Subunit structure

Interacts with MAP3K1.

Tissue specificity

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. Ref.1

Sequence similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

Contains 1 CNH domain.

Contains 1 protein kinase domain.

Sequence caution

The sequence AAH05433.1 differs from that shown. Reason: Intron retention.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MAP3K11Q165843EBI-2906801,EBI-49961From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 827827Mitogen-activated protein kinase kinase kinase kinase 1
PRO_0000086274

Regions

Domain17 – 274258Protein kinase
Domain501 – 806306CNH
Nucleotide binding23 – 319ATP By similarity UniProtKB O00506

Sites

Active site1371Proton acceptor By similarity UniProtKB O00506
Binding site461ATP Ref.1

Amino acid modifications

Modified residue4031Phosphoserine By similarity
Modified residue4051Phosphoserine By similarity
Modified residue4191Phosphoserine By similarity
Modified residue5921Phosphoserine By similarity

Experimental info

Mutagenesis461K → E: Loss of kinase activity and ability to activate JNK family. Ref.1
Sequence conflict4111G → V in AAH24832. Ref.2
Sequence conflict4441C → R in AAH05433. Ref.2
Sequence conflict4441C → R in AAH24832. Ref.2
Sequence conflict8071V → I in AAH24832. Ref.2

Secondary structure

... 827
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P70218 [UniParc].

Last modified February 1, 1997. Version 1.
Checksum: 82341BE9D13036BA

FASTA82791,535
        10         20         30         40         50         60 
MALVDPDIFN KDPREHYDLL QRLGGGTYGE VFKARDKVSK DLVALKMVKM EPDDDVATLQ 

        70         80         90        100        110        120 
KEILMLKTCR HANIVAYHGS YLWLQKLWIC MEFCGAGSLQ DIYQVTGSLS ELQISYVCRE 

       130        140        150        160        170        180 
VLQGLAYLHS EKKIHRDIKG ANILINDCGE VKLADFGISA QIGATLARRL SFIGTPYWMA 

       190        200        210        220        230        240 
PEVAAVALKG GYNELCDIWS LGITAIELAE LQPPLFDVHP LRVLFLMTKS GYQPPRLKEK 

       250        260        270        280        290        300 
SRWSSSFHNF VKVTLTKNSK KRPSATKMLS HQLVSQPGLN RGLILDLLDK MKNPGKGLPV 

       310        320        330        340        350        360 
DIEDEEPEPP PAIPRRIRST YRASSLGIPD ADCCRRQMEF QRPRCVDCRP QAETVRLYPP 

       370        380        390        400        410        420 
AHFGSTSPRS QLSDSDDDYD DVDIPAPSEN IPPPLPPKPK FRSPSDDGSG GIRDDGQLSP 

       430        440        450        460        470        480 
GVLVRCASGP PPRTPRPGPP PATCSPHLTA RSDPSLWNPA APEPGQPPLV PPRKEKMRGK 

       490        500        510        520        530        540 
MENEKRREKY PLLVKLFNGC PLQIHSTAAW THPSTKDQNL LLGAEEGIFI LNRNDQEATL 

       550        560        570        580        590        600 
EMIFPGRTTW LYCINNLLMS LSGKTPYLYS HSILGLLERK DGRTGSPIAH ISPHRLLARK 

       610        620        630        640        650        660 
NMVSSKIQDT KGCRACCVAE SASSGGPFLC GALETSVVLL QWYQPMNKFL LVRQVLFPLP 

       670        680        690        700        710        720 
TPLPVFTLLT TPGSELPAVC IGVSPGQAAK SVLFHTVRFG ALSCWLDDSS TEHKGPVQVI 

       730        740        750        760        770        780 
QVKEDMVMVL MDGSLKLVTP EGAPAPGLRT PEIPMTEAVE AVAMVEDRLE AFWKHGVQVW 

       790        800        810        820 
APGLKQPLQE LRDPTLTFRL LCSPRPVVVE TRPTDDPTAP SNLYIQE 

« Hide

References

« Hide 'large scale' references
[1]"HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway."
Kiefer F., Tibbles L.A., Anafi M., Janssen A., Zanke B.W., Lassam N., Pawson T., Woodgett J.R., Iscove N.N.
EMBO J. 15:7013-7025(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-46.
Tissue: Pre-B cell.
[2]"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].
Tissue: Mammary gland.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y09010 mRNA. Translation: CAA70213.1.
BC005433 mRNA. Translation: AAH05433.1. Sequence problems.
BC024832 mRNA. Translation: AAH24832.1.
RefSeqNP_032305.2. NM_008279.2.
UniGeneMm.148278.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1UTIX-ray1.50D465-480[»]
ProteinModelPortalP70218.
SMRP70218. Positions 12-332.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204964. 4 interactions.
DIPDIP-42073N.
IntActP70218. 4 interactions.
MINTMINT-1176243.

PTM databases

PhosphoSiteP70218.

Proteomic databases

PaxDbP70218.
PRIDEP70218.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000085835; ENSMUSP00000082995; ENSMUSG00000037337.
GeneID26411.
KEGGmmu:26411.
UCSCuc009gam.1. mouse.

Organism-specific databases

CTD11184.
MGIMGI:1346882. Map4k1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00690000101936.
HOGENOMHOG000230824.
HOVERGENHBG036702.
InParanoidP70218.
KOK04408.
OMALQWYQPM.
OrthoDBEOG7WX07M.
PhylomeDBP70218.
TreeFamTF105121.

Gene expression databases

BgeeP70218.
GenevestigatorP70218.

Family and domain databases

InterProIPR001180. Citron.
IPR011009. Kinase-like_dom.
IPR021160. MAPKKKK.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
[Graphical view]
PfamPF00780. CNH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFPIRSF038172. MAPKKKK. 1 hit.
SMARTSM00036. CNH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50219. CNH. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP70218.
NextBio304401.
PROP70218.
SOURCESearch...

Entry information

Entry nameM4K1_MOUSE
AccessionPrimary (citable) accession number: P70218
Secondary accession number(s): Q8R3R0, Q99K62
Entry history
Integrated into UniProtKB/Swiss-Prot: March 28, 2003
Last sequence update: February 1, 1997
Last modified: April 16, 2014
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot