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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

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.1 Publication

Catalytic activityi

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

Cofactori

Mg2+1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei46 – 461ATP1 PublicationPROSITE-ProRule annotation
Active sitei137 – 1371Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi23 – 319ATPPROSITE-ProRule annotation

GO - Molecular functioni

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

GO - Biological processi

  1. cell proliferation Source: UniProtKB
  2. intracellular signal transduction Source: UniProtKB
  3. peptidyl-serine phosphorylation Source: UniProtKB
  4. protein autophosphorylation Source: UniProtKB
  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)Imported
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:1346882. Map4k1.

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 autocatalysisBy similarity
Modified residuei171 – 1711Phosphoserine; by autocatalysisBy similarity
Modified residuei175 – 1751Phosphothreonine; by autocatalysisBy similarity
Modified residuei354 – 3541Phosphothreonine; by autocatalysisBy similarity
Modified residuei403 – 4031PhosphoserineBy similarity
Modified residuei405 – 4051PhosphoserineBy similarity
Modified residuei419 – 4191PhosphoserineBy similarity
Modified residuei592 – 5921PhosphoserineBy 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

MaxQBiP70218.
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).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 – 4764Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1UTIX-ray1.50D465-480[»]
ProteinModelPortaliP70218.
SMRiP70218. Positions 12-332.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP70218.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini17 – 274258Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini501 – 806306CNHPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118848.
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.
[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 AAH05433.1 differs from that shown. Reason: Intron retention.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti411 – 4111G → V in AAH24832. (PubMed:15489334)Curated
Sequence conflicti444 – 4441C → R in AAH05433. (PubMed:15489334)Curated
Sequence conflicti444 – 4441C → R in AAH24832. (PubMed:15489334)Curated
Sequence conflicti807 – 8071V → I in AAH24832. (PubMed:15489334)Curated

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 .
CCDSi CCDS39865.1.
RefSeqi NP_032305.2. NM_008279.2.
UniGenei Mm.148278.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1UTI X-ray 1.50 D 465-480 [» ]
ProteinModelPortali P70218.
SMRi P70218. Positions 12-332.
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

MaxQBi P70218.
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 ENSGT00760000118848.
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.
[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: November 26, 2014
This is version 125 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