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Q92918 (M4K1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·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
MAPK/ERK kinase kinase kinase 1
Short name=MEK kinase kinase 1
Short name=MEKKK 1
Gene names
Name:MAP4K1
Synonyms:HPK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length833 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. Ref.1

Tissue specificity

Expressed primarily in hematopoietic organs, including bone marrow, spleen and thymus. Also expressed at very low levels in lung, kidney, mammary glands and small intestine. 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.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q92918-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q92918-2)

The sequence of this isoform differs from the canonical sequence as follows:
     800-833: LECSGTISPHCNLLLPGSSNSPASASRVAGITGL → PVVVETRPVDDPTAPSNLYIQE

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 833833Mitogen-activated protein kinase kinase kinase kinase 1
PRO_0000086273

Regions

Domain17 – 274258Protein kinase
Domain495 – 800306CNH
Nucleotide binding23 – 319ATP By similarity UniProtKB O00506

Sites

Active site1371Proton acceptor By similarity UniProtKB O00506
Binding site461ATP By similarity UniProtKB P70218

Amino acid modifications

Modified residue4051Phosphoserine Ref.4
Modified residue4071Phosphoserine Ref.4
Modified residue4131Phosphoserine Ref.4
Modified residue4211Phosphoserine Ref.3 Ref.4
Modified residue5861Phosphoserine Ref.3

Natural variations

Alternative sequence800 – 83334LECSG…GITGL → PVVVETRPVDDPTAPSNLYI QE in isoform 2.
VSP_040340
Natural variant3121P → T. Ref.6
Corresponds to variant rs55924696 [ dbSNP | Ensembl ].
VAR_040739
Natural variant3511P → S. Ref.6
Corresponds to variant rs34591617 [ dbSNP | Ensembl ].
VAR_040740
Natural variant3611P → L. Ref.6
Corresponds to variant rs56060067 [ dbSNP | Ensembl ].
VAR_040741
Natural variant7371S → F in a metastatic melanoma sample; somatic mutation. Ref.6
VAR_040742
Natural variant8111N → S.
Corresponds to variant rs12975825 [ dbSNP | Ensembl ].
VAR_051643

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1997. Version 1.
Checksum: 3C98CF01BE42E151

FASTA83391,296
        10         20         30         40         50         60 
MDVVDPDIFN RDPRDHYDLL QRLGGGTYGE VFKARDKVSG DLVALKMVKM EPDDDVSTLQ 

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

       130        140        150        160        170        180 
VLQGLAYLHS QKKIHRDIKG ANILINDAGE VRLADFGISA QIGATLARRL SFIGTPYWMA 

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

       250        260        270        280        290        300 
GKWSAAFHNF IKVTLTKSPK KRPSATKMLS HQLVSQPGLN RGLILDLLDK LKNPGKGPSI 

       310        320        330        340        350        360 
GDIEDEEPEL PPAIPRRIRS THRSSSLGIP DADCCRRHME FRKLRGMETR PPANTARLQP 

       370        380        390        400        410        420 
PRDLRSSSPR KQLSESSDDD YDDVDIPTPA EDTPPPLPPK PKFRSPSDEG PGSMGDDGQL 

       430        440        450        460        470        480 
SPGVLVRCAS GPPPNSPRPG PPPSTSSPHL TAHSEPSLWN PPSRELDKPP LLPPKKEKMK 

       490        500        510        520        530        540 
RKGCALLVKL FNGCPLRIHS TAAWTHPSTK DQHLLLGAEE GIFILNRNDQ EATLEMLFPS 

       550        560        570        580        590        600 
RTTWVYSINN VLMSLSGKTP HLYSHSILGL LERKETRAGN PIAHISPHRL LARKNMVSTK 

       610        620        630        640        650        660 
IQDTKGCRAC CVAEGASSGG PFLCGALETS VVLLQWYQPM NKFLLVRQVL FPLPTPLSVF 

       670        680        690        700        710        720 
ALLTGPGSEL PAVCIGVSPG RPGKSVLFHT VRFGALSCWL GEMSTEHRGP VQVTQVEEDM 

       730        740        750        760        770        780 
VMVLMDGSVK LVTPEGSPVR GLRTPEIPMT EAVEAVAMVG GQLQAFWKHG VQVWALGSDQ 

       790        800        810        820        830 
LLQELRDPTL TFRLLGSPRL ECSGTISPHC NLLLPGSSNS PASASRVAGI TGL 

« Hide

Isoform 2 [UniParc].

Checksum: A7CBFE3B39D1C66A
Show »

FASTA82190,425

References

« Hide 'large scale' references
[1]"Human HPK1, a novel human hematopoietic progenitor kinase that activates the JNK/SAPK kinase cascade."
Hu M.C.-T., Qiu W.R., Wang X., Meyer C.F., Tan T.-H.
Genes Dev. 10:2251-2264(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH MAP3K1.
Tissue: Fetal liver.
[2]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-421 AND SER-586, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[4]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-405; SER-407; SER-413 AND SER-421, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[5]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-312; SER-351; LEU-361 AND PHE-737.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U66464 mRNA. Translation: AAB97983.1.
AC005933 Genomic DNA. No translation available.
AC008649 Genomic DNA. No translation available.
RefSeqNP_001036065.1. NM_001042600.2.
NP_009112.1. NM_007181.5.
UniGeneHs.95424.

3D structure databases

ProteinModelPortalQ92918.
SMRQ92918. Positions 17-331.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116354. 19 interactions.
DIPDIP-31019N.
IntActQ92918. 16 interactions.
MINTMINT-1176198.
STRING9606.ENSP00000380066.

Chemistry

BindingDBQ92918.
ChEMBLCHEMBL5749.
GuidetoPHARMACOLOGY2085.

PTM databases

PhosphoSiteQ92918.

Polymorphism databases

DMDM29427916.

Proteomic databases

PaxDbQ92918.
PRIDEQ92918.

Protocols and materials databases

DNASU11184.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000396857; ENSP00000380066; ENSG00000104814. [Q92918-2]
ENST00000591517; ENSP00000465039; ENSG00000104814. [Q92918-1]
GeneID11184.
KEGGhsa:11184.
UCSCuc002oix.1. human. [Q92918-1]
uc002oiy.1. human. [Q92918-2]

Organism-specific databases

CTD11184.
GeneCardsGC19M039078.
HGNCHGNC:6863. MAP4K1.
HPACAB007754.
HPA007419.
MIM601983. gene.
neXtProtNX_Q92918.
PharmGKBPA30609.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000230824.
HOVERGENHBG036702.
InParanoidQ92918.
KOK04408.
OMALQWYQPM.
OrthoDBEOG7WX07M.
PhylomeDBQ92918.
TreeFamTF105121.

Enzyme and pathway databases

SignaLinkQ92918.

Gene expression databases

ArrayExpressQ92918.
BgeeQ92918.
CleanExHS_MAP4K1.
GenevestigatorQ92918.

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. 2 hits.
PROSITEPS50219. CNH. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMAP4K1.
GenomeRNAi11184.
NextBio42561.
PMAP-CutDBQ92918.
PROQ92918.
SOURCESearch...

Entry information

Entry nameM4K1_HUMAN
AccessionPrimary (citable) accession number: Q92918
Entry history
Integrated into UniProtKB/Swiss-Prot: March 28, 2003
Last sequence update: February 1, 1997
Last modified: April 16, 2014
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM