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Q9ESL4 (MLTK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitogen-activated protein kinase kinase kinase MLT

EC=2.7.11.25
Alternative name(s):
Leucine zipper- and sterile alpha motif kinase ZAK
MLK-like mitogen-activated protein triple kinase
Mixed lineage kinase-related kinase
Short name=MLK-related kinase
Short name=MRK
Sterile alpha motif- and leucine zipper-containing kinase AZK
Gene names
Name:Zak
Synonyms:Mltk
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length802 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Stress-activated component of a protein kinase signal transduction cascade. Regulates the JNK and p38 pathways. Pro-apoptotic. Role in regulation of S and G2 cell cycle checkpoint by direct phosphorylation of CHEK2. Isoform 1, but not isoform 2, phosphorylates histone H3 at 'Ser-28'. Ref.1 UniProtKB Q9NYL2

Catalytic activity

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

Cofactor

Magnesium. Ref.1

Enzyme regulation

Activated by phosphorylation by PKN1 and autophosphorylation on Thr-161 and Ser-165 By similarity. UniProtKB Q9NYL2

Subunit structure

Homodimer. Interacts with PKN1 and ZNF33A By similarity. Ref.1

Subcellular location

Cytoplasm. Nucleus. Note: Appears to shuttle between nucleus and cytoplasm. Ref.1

Sequence similarities

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

Contains 1 protein kinase domain.

Contains 1 SAM (sterile alpha motif) domain.

Ontologies

Keywords
   Biological processCell cycle
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage checkpoint

Inferred from electronic annotation. Source: Ensembl

activation of JUN kinase activity

Inferred from electronic annotation. Source: Ensembl

activation of MAPKK activity

Inferred from direct assay Ref.1. Source: GOC

cell cycle arrest

Inferred from electronic annotation. Source: Ensembl

cell cycle checkpoint

Inferred from sequence or structural similarity. Source: UniProtKB

cytoskeleton organization

Inferred from direct assay Ref.1. Source: MGI

intracellular signal transduction

Inferred from direct assay Ref.1. Source: UniProtKB

positive regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.1. Source: UniProtKB

response to radiation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay Ref.1. Source: UniProtKB

nucleus

Inferred from direct assay Ref.1. Source: MGI

   Molecular_functionATP binding

Inferred from direct assay Ref.1. Source: UniProtKB

MAP kinase kinase kinase activity

Inferred from direct assay Ref.1. Source: MGI

magnesium ion binding

Inferred from direct assay Ref.1. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.1. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.1 (identifier: Q9ESL4-1)

Also known as: Alpha;

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 Ref.1 (identifier: Q9ESL4-2)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     332-454: PSFEIGAWTE...HLKPGTGPQD → LPLSARMSEE...DAENDVDNSE
     455-802: Missing.
Note: Contains a phosphoserine at position 434 (By similarity). Contains a phosphoserine at position 453 (By similarity).
Isoform 3 (identifier: Q9ESL4-3)

The sequence of this isoform differs from the canonical sequence as follows:
     285-289: CEIEA → WVAPA
     290-802: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 802802Mitogen-activated protein kinase kinase kinase MLT
PRO_0000086339

Regions

Domain16 – 277262Protein kinase
Domain339 – 41072SAM
Nucleotide binding22 – 309ATP By similarity UniProtKB P80192
Region287 – 30822Leucine-zipper

Sites

Active site1331Proton acceptor By similarity UniProtKB P80192
Binding site451ATP By similarity UniProtKB Q9NYL2

Amino acid modifications

Modified residue21Phosphoserine By similarity
Modified residue31Phosphoserine By similarity
Modified residue1551Phosphoserine By similarity
Modified residue1611Phosphothreonine; by autocatalysis By similarity UniProtKB Q9NYL2
Modified residue1651Phosphoserine; by autocatalysis By similarity UniProtKB Q9NYL2
Modified residue2641Phosphoserine By similarity
Modified residue2751Phosphoserine By similarity
Modified residue3021Phosphoserine By similarity
Modified residue3261Phosphoserine By similarity
Modified residue3281Phosphothreonine By similarity
Modified residue5571Phosphoserine By similarity
Modified residue5651Phosphoserine By similarity
Modified residue5681Phosphoserine By similarity
Modified residue5841Phosphoserine By similarity
Modified residue5861Phosphothreonine By similarity
Modified residue5911Phosphoserine By similarity
Modified residue5931Phosphoserine By similarity
Modified residue5991Phosphoserine By similarity
Modified residue6281Phosphothreonine By similarity
Modified residue6341Phosphoserine By similarity
Modified residue6361Phosphoserine By similarity
Modified residue6371Phosphoserine By similarity
Modified residue6381Phosphoserine By similarity
Modified residue6401Phosphothreonine By similarity
Modified residue6491Phosphoserine By similarity
Modified residue6611Phosphoserine By similarity
Modified residue6671Phosphoserine By similarity
Modified residue6681Phosphoserine By similarity
Modified residue6871Phosphoserine By similarity
Modified residue6901Phosphoserine By similarity
Modified residue6911Phosphoserine By similarity
Modified residue7271Phosphoserine By similarity
Modified residue7331Phosphoserine By similarity
Modified residue7561Phosphoserine By similarity

Natural variations

Alternative sequence285 – 2895CEIEA → WVAPA in isoform 3.
VSP_051747
Alternative sequence290 – 802513Missing in isoform 3.
VSP_051748
Alternative sequence332 – 454123PSFEI…TGPQD → LPLSARMSEESYFESKTEES NSAEMSCQITAASNGEGHGM NPGLQAMMLMGFGDVFSMNK AGAVLHSGMQINMQAKQNSS KTTCKRRGKKVNMALGFSDF DLSEGDDDDHDGDDAENDVD NSE in isoform 2. Ref.1
VSP_051745
Alternative sequence455 – 802348Missing in isoform 2. Ref.1
VSP_051746

Experimental info

Mutagenesis451K → M: Loss of kinase activity. Ref.1
Sequence conflict1711P → Q in BAC32371. Ref.2

Sequences

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

Last modified March 1, 2001. Version 1.
Checksum: D431DF8F312A43CC

FASTA80291,720
        10         20         30         40         50         60 
MSSLGASFVQ IKFDDLQFFE NCGGGSFGSV YRAKWISQDK EVAVKKLLKI EKEAEILSVL 

        70         80         90        100        110        120 
SHRNIIQFYG VILEPPNYGI VTEYASLGSL YDYINSNRSE EMDMEHIMTW ATDVAKGMHY 

       130        140        150        160        170        180 
LHMEAPVKVI HRDLKSRNVV IAADGVLKIC DFGASRFHNH TTHMSLVGTF PWMAPEVIQS 

       190        200        210        220        230        240 
LPVSETCDTY SYGVVLWEML TREVPFKGLE GLQVAWLVVE KNERLTIPSS CPRSFAELLH 

       250        260        270        280        290        300 
QCWEADAKKR PSFKQIISIL ESMSNDTNLP DQCNSFLHNK AEWRCEIEAT LERLKKLERD 

       310        320        330        340        350        360 
LSFKEQELKE RERRLKMWEQ KLTEQSNTPL LPSFEIGAWT EDDVYFWVQQ LVRKGESSVE 

       370        380        390        400        410        420 
MSGYASLFKE NNITGKRLLL LEEEDLKDMG IVSKGHIIHF KSAIEKLTHD YLNLFHFPPL 

       430        440        450        460        470        480 
IKDSGGEPEE NEEKIVNLEL VFGFHLKPGT GPQDCKWKMY MEMDGDEVAI TYIKDVTFNT 

       490        500        510        520        530        540 
SLPDAEILKM TKPPFVMEKW IVGIAEDQTV ECTVTYENDV RTPKLTKHVH SIQWDRTKPQ 

       550        560        570        580        590        600 
DEVKAVQLAI QTLFSSSEGN PGSRSDSSAD CQWLDTLRMR QIASHTSLQR SQSNPILGSP 

       610        620        630        640        650        660 
FFPYFANQDS YAAAVRRTQT PVKYQQITPS INPSRSSSPT QYGLSRNFSS LNLSSRDSGF 

       670        680        690        700        710        720 
SSLNDSSSER GRYSDRSRNK YYRGSVSLNS SPKGRYGGKS QHSTPSRERY SGKFYRLPQS 

       730        740        750        760        770        780 
ALNTHQSPDF KRSPNDHDRR VPRTIPGMPL HPETASKAGE EESRVSEGGW TKVEYRKKTH 

       790        800 
RQLSAKTSKE RTRGNYRGRR NF 

« Hide

Isoform 2 (Beta) [UniParc].

Checksum: 35C2FC0D729D9395
Show »

FASTA45451,366
Isoform 3 [UniParc].

Checksum: 440E5651076A04A4
Show »

FASTA28932,842

References

« Hide 'large scale' references
[1]"Identification and characterization of a novel MAP kinase kinase kinase, MLTK."
Gotoh I., Adachi M., Nishida E.
J. Biol. Chem. 276:4276-4286(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, HOMODIMERIZATION, MUTAGENESIS OF LYS-45.
Tissue: Heart.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
Strain: C57BL/6J.
Tissue: Head.
[3]"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] (ISOFORM 1).
Strain: FVB/N.
Tissue: Mammary gland.
[4]Lubec G., Kang S.U.
Submitted (APR-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 225-233, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: C57BL/6.
Tissue: Brain.
[5]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB049731 mRNA. Translation: BAB16442.1.
AB049732 mRNA. Translation: BAB16443.1.
AK045444 mRNA. Translation: BAC32371.1.
AK132186 mRNA. Translation: BAE21021.1.
BC023718 mRNA. Translation: AAH23718.1.
CCDSCCDS38143.1. [Q9ESL4-1]
CCDS50605.1. [Q9ESL4-2]
RefSeqNP_001158263.1. NM_001164791.1. [Q9ESL4-2]
NP_075544.1. NM_023057.5. [Q9ESL4-1]
NP_835185.2. NM_178084.4. [Q9ESL4-3]
XP_006500060.1. XM_006499997.1. [Q9ESL4-1]
UniGeneMm.304143.
Mm.314618.

3D structure databases

ProteinModelPortalQ9ESL4.
SMRQ9ESL4. Positions 9-325.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9ESL4. 1 interaction.
MINTMINT-4129310.
STRING10090.ENSMUSP00000088334.

PTM databases

PhosphoSiteQ9ESL4.

Proteomic databases

MaxQBQ9ESL4.
PaxDbQ9ESL4.
PRIDEQ9ESL4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000090824; ENSMUSP00000088334; ENSMUSG00000004085. [Q9ESL4-1]
ENSMUST00000135469; ENSMUSP00000118983; ENSMUSG00000004085. [Q9ESL4-2]
GeneID65964.
KEGGmmu:65964.
UCSCuc008kbs.2. mouse. [Q9ESL4-3]
uc008kbv.2. mouse. [Q9ESL4-1]

Organism-specific databases

CTD51776.
MGIMGI:2443258. Zak.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117425.
HOGENOMHOG000231813.
HOVERGENHBG080445.
InParanoidQ9ESL4.
KOK04424.
OMAHRDSHET.
OrthoDBEOG7D85VN.
PhylomeDBQ9ESL4.
TreeFamTF106505.

Gene expression databases

ArrayExpressQ9ESL4.
BgeeQ9ESL4.
CleanExMM_B230120H23RIK.
GenevestigatorQ9ESL4.

Family and domain databases

Gene3D1.10.150.50. 1 hit.
InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR021129. SAM_type1.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF07714. Pkinase_Tyr. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
SMARTSM00454. SAM. 1 hit.
[Graphical view]
SUPFAMSSF47769. SSF47769. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio320398.
PROQ9ESL4.
SOURCESearch...

Entry information

Entry nameMLTK_MOUSE
AccessionPrimary (citable) accession number: Q9ESL4
Secondary accession number(s): Q3V1X8, Q8BR73, Q9ESL3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 120 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

MGD cross-references

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