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P70218

- M4K1_MOUSE

UniProt

P70218 - M4K1_MOUSE

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Protein

Mitogen-activated protein kinase kinase kinase kinase 1

Gene
Map4k1, Hpk1
Organism
Mus musculus (Mouse)
Status
Reviewed - 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.

Catalytic activityi

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

Cofactori

Magnesium.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei46 – 461ATP1 Publication
Active sitei137 – 1371Proton acceptor By similarityBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi23 – 319ATP By similarityBy similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. MAP kinase kinase kinase kinase activity Source: RefGenome
  3. protein binding Source: IntAct
  4. protein serine/threonine kinase activity Source: UniProtKB
  5. small GTPase regulator activity Source: InterPro

GO - Biological processi

  1. activation of MAPKKK activity Source: GOC
  2. intracellular signal transduction Source: UniProtKB
  3. MAPK cascade Source: GOC
  4. peptidyl-serine phosphorylation Source: Ensembl
  5. protein phosphorylation Source: UniProtKB
  6. 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)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:1346882. Map4k1.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: RefGenome
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi46 – 461K → E: Loss of kinase activity and ability to activate JNK family. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 827827Mitogen-activated protein kinase kinase kinase kinase 1PRO_0000086274Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei165 – 1651Phosphothreonine; by autocatalysis By similarity
Modified residuei171 – 1711Phosphoserine; by autocatalysis By similarity
Modified residuei175 – 1751Phosphothreonine; by autocatalysis By similarity
Modified residuei354 – 3541Phosphothreonine; by autocatalysis By similarity
Modified residuei403 – 4031Phosphoserine By similarity
Modified residuei405 – 4051Phosphoserine By similarity
Modified residuei419 – 4191Phosphoserine By similarity
Modified residuei592 – 5921Phosphoserine By similarity

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

PaxDbiP70218.
PRIDEiP70218.

PTM databases

PhosphoSiteiP70218.

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

BgeeiP70218.
GenevestigatoriP70218.

Interactioni

Subunit structurei

Interacts with MAP3K1. Interacts with FBXW8 By similarity.

Binary interactionsi

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

Protein-protein interaction databases

BioGridi204964. 4 interactions.
DIPiDIP-42073N.
IntActiP70218. 4 interactions.
MINTiMINT-1176243.

Structurei

Secondary structure

1
827
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi473 – 4764

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1UTIX-ray1.50D465-480[»]
ProteinModelPortaliP70218.
SMRiP70218. Positions 9-332.

Miscellaneous databases

EvolutionaryTraceiP70218.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini17 – 274258Protein kinaseAdd
BLAST
Domaini501 – 806306CNHAdd
BLAST

Sequence similaritiesi

Contains 1 CNH domain.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00690000101936.
HOGENOMiHOG000230824.
HOVERGENiHBG036702.
InParanoidiP70218.
KOiK04408.
OMAiLQWYQPM.
OrthoDBiEOG7WX07M.
PhylomeDBiP70218.
TreeFamiTF105121.

Family and domain databases

InterProiIPR001180. 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]
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

MALVDPDIFN KDPREHYDLL QRLGGGTYGE VFKARDKVSK DLVALKMVKM    50
EPDDDVATLQ KEILMLKTCR HANIVAYHGS YLWLQKLWIC MEFCGAGSLQ 100
DIYQVTGSLS ELQISYVCRE VLQGLAYLHS EKKIHRDIKG ANILINDCGE 150
VKLADFGISA QIGATLARRL SFIGTPYWMA PEVAAVALKG GYNELCDIWS 200
LGITAIELAE LQPPLFDVHP LRVLFLMTKS GYQPPRLKEK SRWSSSFHNF 250
VKVTLTKNSK KRPSATKMLS HQLVSQPGLN RGLILDLLDK MKNPGKGLPV 300
DIEDEEPEPP PAIPRRIRST YRASSLGIPD ADCCRRQMEF QRPRCVDCRP 350
QAETVRLYPP AHFGSTSPRS QLSDSDDDYD DVDIPAPSEN IPPPLPPKPK 400
FRSPSDDGSG GIRDDGQLSP GVLVRCASGP PPRTPRPGPP PATCSPHLTA 450
RSDPSLWNPA APEPGQPPLV PPRKEKMRGK MENEKRREKY PLLVKLFNGC 500
PLQIHSTAAW THPSTKDQNL LLGAEEGIFI LNRNDQEATL EMIFPGRTTW 550
LYCINNLLMS LSGKTPYLYS HSILGLLERK DGRTGSPIAH ISPHRLLARK 600
NMVSSKIQDT KGCRACCVAE SASSGGPFLC GALETSVVLL QWYQPMNKFL 650
LVRQVLFPLP TPLPVFTLLT TPGSELPAVC IGVSPGQAAK SVLFHTVRFG 700
ALSCWLDDSS TEHKGPVQVI QVKEDMVMVL MDGSLKLVTP EGAPAPGLRT 750
PEIPMTEAVE AVAMVEDRLE AFWKHGVQVW APGLKQPLQE LRDPTLTFRL 800
LCSPRPVVVE TRPTDDPTAP SNLYIQE 827
Length:827
Mass (Da):91,535
Last modified:February 1, 1997 - v1
Checksum:i82341BE9D13036BA
GO

Sequence cautioni

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti411 – 4111G → V in AAH24832. 1 Publication
Sequence conflicti444 – 4441C → R in AAH05433. 1 Publication
Sequence conflicti444 – 4441C → R in AAH24832. 1 Publication
Sequence conflicti807 – 8071V → I in AAH24832. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
Y09010 mRNA. Translation: CAA70213.1 .
BC005433 mRNA. Translation: AAH05433.1 . Sequence problems.
BC024832 mRNA. Translation: AAH24832.1 .
CCDSi CCDS39865.1.
RefSeqi NP_032305.2. NM_008279.2.
UniGenei Mm.148278.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1UTI X-ray 1.50 D 465-480 [» ]
ProteinModelPortali P70218.
SMRi P70218. Positions 9-332.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 204964. 4 interactions.
DIPi DIP-42073N.
IntActi P70218. 4 interactions.
MINTi MINT-1176243.

PTM databases

PhosphoSitei P70218.

Proteomic databases

PaxDbi P70218.
PRIDEi P70218.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000085835 ; ENSMUSP00000082995 ; ENSMUSG00000037337 .
GeneIDi 26411.
KEGGi mmu:26411.
UCSCi uc009gam.1. mouse.

Organism-specific databases

CTDi 11184.
MGIi MGI:1346882. Map4k1.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00690000101936.
HOGENOMi HOG000230824.
HOVERGENi HBG036702.
InParanoidi P70218.
KOi K04408.
OMAi LQWYQPM.
OrthoDBi EOG7WX07M.
PhylomeDBi P70218.
TreeFami TF105121.

Miscellaneous databases

EvolutionaryTracei P70218.
NextBioi 304401.
PROi P70218.
SOURCEi Search...

Gene expression databases

Bgeei P70218.
Genevestigatori P70218.

Family and domain databases

InterProi IPR001180. 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 ]
Pfami PF00780. CNH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view ]
PIRSFi PIRSF038172. MAPKKKK. 1 hit.
SMARTi SM00036. CNH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS50219. CNH. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

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: September 3, 2014
This is version 122 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

External Data

Dasty 3

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