Mitogen-activated protein kinase kinase kinase kinase 1

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P70218 (M4K1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 112. History...

Clusters with 100%, 90%, 50% identity |

Documents (4) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

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 names

Name:	Map4k1
Synonyms:	Hpk1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	827 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MAPK cascade Inferred from electronic annotation. Source: GOC activation of MAPKKK activity Inferred from electronic annotation. Source: GOC peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara response to stress Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	ATP binding Inferred from direct assay Ref.1. Source: UniProtKB MAP kinase kinase kinase kinase activity Inferred from electronic annotation. Source: Compara protein serine/threonine kinase activity Inferred from direct assay Ref.1. Source: UniProtKB small GTPase regulator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 827

827

Mitogen-activated protein kinase kinase kinase kinase 1

PRO_0000086274

Regions

Domain

17 – 274

258

Protein kinase

Domain

501 – 806

306

CNH

Nucleotide binding

23 – 31

ATP By similarity UniProtKB O00506

Sites

Active site

137

Proton acceptor By similarity UniProtKB O00506

Binding site

ATP Ref.1

Amino acid modifications

Modified residue

403

Phosphoserine By similarity

Modified residue

405

Phosphoserine By similarity

Modified residue

419

Phosphoserine By similarity

Modified residue

592

Phosphoserine By similarity

Experimental info

Mutagenesis

K → E: Loss of kinase activity and ability to activate JNK family. Ref.1

Sequence conflict

411

G → V in AAH24832. Ref.2

Sequence conflict

444

C → R in AAH05433. Ref.2

Sequence conflict

444

C → R in AAH24832. Ref.2

Sequence conflict

807

V → I in AAH24832. Ref.2

Secondary structure

827

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P70218 [UniParc].

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

FASTA

827

91,535

        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' referencesShow '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.

IPI

IPI00137361.

RefSeq

NP_032305.2. NM_008279.2.

UniGene

Mm.148278.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1UTI	X-ray	1.50	D	465-480	[»]

ProteinModelPortal

P70218.

SMR

P70218. Positions 9-332.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-42073N.

IntAct

P70218. 1 interaction.

MINT

MINT-1176243.

PTM databases

PhosphoSite

P70218.

Proteomic databases

PaxDb

P70218.

PRIDE

P70218.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000085835; ENSMUSP00000082995; ENSMUSG00000037337.

GeneID

26411.

KEGG

mmu:26411.

UCSC

uc009gam.1. mouse.

Organism-specific databases

CTD

11184.

MGI

MGI:1346882. Map4k1.

Phylogenomic databases

eggNOG

COG0515.

GeneTree

ENSGT00690000101936.

HOGENOM

HOG000230824.

HOVERGEN

HBG036702.

InParanoid

P70218.

K04408.

OMA

KRKGCAL.

OrthoDB

EOG4MPHPH.

Gene expression databases

Bgee

P70218.

Genevestigator

P70218.

GermOnline

ENSMUSG00000037337. Mus musculus.

Family and domain databases

InterPro

IPR001180. Citron.
IPR011009. Kinase-like_dom.
IPR021160. MAPKKKK.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
[Graphical view]

Pfam

PF00780. CNH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]

PIRSF

PIRSF038172. MAPKKKK. 1 hit.

SMART

SM00036. CNH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS50219. CNH. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P70218.

NextBio

304401.

SOURCE

Search...

Entry information

Entry name

M4K1_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 112 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents