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Protein

Mitogen-activated protein kinase kinase kinase MLT

Gene

Zak

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Stress-activated component of a protein kinase signal transduction cascade. Regulates the JNK and p38 pathways (PubMed:11042189). Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14 (By similarity). Pro-apoptotic. Role in regulation of S and G2 cell cycle checkpoint by direct phosphorylation of CHEK2 (By similarity). Involved in limb development (PubMed:26755636).By similarity2 Publications

Catalytic activityi

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

Cofactori

Mg2+1 Publication

Enzyme regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei45ATPPROSITE-ProRule annotationBy similarity1
Active sitei133Proton acceptorPROSITE-ProRule annotationBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi22 – 30ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • MAP kinase kinase kinase activity Source: MGI
  • poly(A) RNA binding Source: MGI
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • activation of JUN kinase activity Source: MGI
  • cell cycle arrest Source: MGI
  • cell cycle checkpoint Source: UniProtKB
  • cytoskeleton organization Source: MGI
  • DNA damage checkpoint Source: MGI
  • embryonic digit morphogenesis Source: UniProtKB
  • intracellular signal transduction Source: UniProtKB
  • limb development Source: UniProtKB
  • positive regulation of apoptotic process Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • response to radiation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Zak
Synonyms:Mltk
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:2443258. Zak.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

  • Note: Appears to shuttle between nucleus and cytoplasm.1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Knockout results in fully penetrant lethality at E9.5 duse to severe cardiac edema and growth retardation. Embryos show polydactyly of the feet.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi45K → M: Loss of kinase activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863391 – 802Mitogen-activated protein kinase kinase kinase MLTAdd BLAST802

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei161Phosphothreonine; by autocatalysisBy similarity1
Modified residuei165Phosphoserine; by autocatalysisBy similarity1
Modified residuei567PhosphoserineBy similarity1
Modified residuei593PhosphoserineBy similarity1
Modified residuei599PhosphoserineBy similarity1
Modified residuei628PhosphothreonineBy similarity1
Modified residuei634PhosphoserineCombined sources1
Modified residuei638PhosphoserineCombined sources1
Modified residuei649PhosphoserineCombined sources1
Modified residuei650PhosphoserineCombined sources1
Modified residuei685PhosphoserineBy similarity1
Modified residuei727PhosphoserineBy similarity1
Modified residuei733PhosphoserineBy similarity1
Isoform 21 Publication (identifier: Q9ESL4-2)
Modified residuei434PhosphoserineCombined sources1
Modified residuei453PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9ESL4.
PeptideAtlasiQ9ESL4.
PRIDEiQ9ESL4.

PTM databases

iPTMnetiQ9ESL4.
PhosphoSitePlusiQ9ESL4.

Expressioni

Developmental stagei

Mainly expressed in heart and developing limbs.1 Publication

Gene expression databases

BgeeiENSMUSG00000004085.
CleanExiMM_B230120H23RIK.
ExpressionAtlasiQ9ESL4. baseline and differential.
GenevisibleiQ9ESL4. MM.

Interactioni

Subunit structurei

Homodimer (PubMed:11042189). Interacts with PKN1 and ZNF33A. Component of a signaling complex containing at least AKAP13, PKN1, MAPK14, ZAK and MAP2K3. Within this complex, AKAP13 interacts directly with PKN1, which in turn recruits MAPK14, MAP2K3 and ZAK.By similarity1 Publication

Protein-protein interaction databases

IntActiQ9ESL4. 1 interactor.
MINTiMINT-4129310.
STRINGi10090.ENSMUSP00000088334.

Structurei

3D structure databases

ProteinModelPortaliQ9ESL4.
SMRiQ9ESL4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 277Protein kinasePROSITE-ProRule annotationAdd BLAST262
Domaini339 – 410SAMPROSITE-ProRule annotationAdd BLAST72

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni287 – 308Leucine-zipperAdd BLAST22

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SAM (sterile alpha motif) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0192. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000231813.
HOVERGENiHBG080445.
InParanoidiQ9ESL4.
KOiK04424.
OMAiGHSGMQV.
OrthoDBiEOG091G037E.
PhylomeDBiQ9ESL4.
TreeFamiTF106505.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR032938. MLTK.
IPR000719. Prot_kinase_dom.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR23257:SF424. PTHR23257:SF424. 1 hit.
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00220. S_TKc. 1 hit.
SM00454. SAM. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 11 Publication (identifier: Q9ESL4-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MSSLGASFVQ IKFDDLQFFE NCGGGSFGSV YRAKWISQDK EVAVKKLLKI
60 70 80 90 100
EKEAEILSVL SHRNIIQFYG VILEPPNYGI VTEYASLGSL YDYINSNRSE
110 120 130 140 150
EMDMEHIMTW ATDVAKGMHY LHMEAPVKVI HRDLKSRNVV IAADGVLKIC
160 170 180 190 200
DFGASRFHNH TTHMSLVGTF PWMAPEVIQS LPVSETCDTY SYGVVLWEML
210 220 230 240 250
TREVPFKGLE GLQVAWLVVE KNERLTIPSS CPRSFAELLH QCWEADAKKR
260 270 280 290 300
PSFKQIISIL ESMSNDTNLP DQCNSFLHNK AEWRCEIEAT LERLKKLERD
310 320 330 340 350
LSFKEQELKE RERRLKMWEQ KLTEQSNTPL LPSFEIGAWT EDDVYFWVQQ
360 370 380 390 400
LVRKGESSVE MSGYASLFKE NNITGKRLLL LEEEDLKDMG IVSKGHIIHF
410 420 430 440 450
KSAIEKLTHD YLNLFHFPPL IKDSGGEPEE NEEKIVNLEL VFGFHLKPGT
460 470 480 490 500
GPQDCKWKMY MEMDGDEVAI TYIKDVTFNT SLPDAEILKM TKPPFVMEKW
510 520 530 540 550
IVGIAEDQTV ECTVTYENDV RTPKLTKHVH SIQWDRTKPQ DEVKAVQLAI
560 570 580 590 600
QTLFSSSEGN PGSRSDSSAD CQWLDTLRMR QIASHTSLQR SQSNPILGSP
610 620 630 640 650
FFPYFANQDS YAAAVRRTQT PVKYQQITPS INPSRSSSPT QYGLSRNFSS
660 670 680 690 700
LNLSSRDSGF SSLNDSSSER GRYSDRSRNK YYRGSVSLNS SPKGRYGGKS
710 720 730 740 750
QHSTPSRERY SGKFYRLPQS ALNTHQSPDF KRSPNDHDRR VPRTIPGMPL
760 770 780 790 800
HPETASKAGE EESRVSEGGW TKVEYRKKTH RQLSAKTSKE RTRGNYRGRR

NF
Length:802
Mass (Da):91,720
Last modified:March 1, 2001 - v1
Checksum:iD431DF8F312A43CC
GO
Isoform 21 Publication (identifier: Q9ESL4-2) [UniParc]FASTAAdd to basket
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.

Show »
Length:454
Mass (Da):51,366
Checksum:i35C2FC0D729D9395
GO
Isoform 3Curated (identifier: Q9ESL4-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     285-289: CEIEA → WVAPA
     290-802: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:289
Mass (Da):32,842
Checksum:i440E5651076A04A4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti171P → Q in BAC32371 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_051747285 – 289CEIEA → WVAPA in isoform 3. 1 Publication5
Alternative sequenceiVSP_051748290 – 802Missing in isoform 3. 1 PublicationAdd BLAST513
Alternative sequenceiVSP_051745332 – 454PSFEI…TGPQD → LPLSARMSEESYFESKTEES NSAEMSCQITAASNGEGHGM NPGLQAMMLMGFGDVFSMNK AGAVLHSGMQINMQAKQNSS KTTCKRRGKKVNMALGFSDF DLSEGDDDDHDGDDAENDVD NSE in isoform 2. 1 PublicationAdd BLAST123
Alternative sequenceiVSP_051746455 – 802Missing in isoform 2. 1 PublicationAdd BLAST348

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS38143.1. [Q9ESL4-1]
CCDS50605.1. [Q9ESL4-2]
RefSeqiNP_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_006499997.2. [Q9ESL4-1]
UniGeneiMm.304143.
Mm.314618.

Genome annotation databases

EnsembliENSMUST00000090824; ENSMUSP00000088334; ENSMUSG00000004085. [Q9ESL4-1]
ENSMUST00000135469; ENSMUSP00000118983; ENSMUSG00000004085. [Q9ESL4-2]
GeneIDi65964.
KEGGimmu:65964.
UCSCiuc008kbs.2. mouse. [Q9ESL4-3]
uc008kbv.2. mouse. [Q9ESL4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS38143.1. [Q9ESL4-1]
CCDS50605.1. [Q9ESL4-2]
RefSeqiNP_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_006499997.2. [Q9ESL4-1]
UniGeneiMm.304143.
Mm.314618.

3D structure databases

ProteinModelPortaliQ9ESL4.
SMRiQ9ESL4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9ESL4. 1 interactor.
MINTiMINT-4129310.
STRINGi10090.ENSMUSP00000088334.

PTM databases

iPTMnetiQ9ESL4.
PhosphoSitePlusiQ9ESL4.

Proteomic databases

PaxDbiQ9ESL4.
PeptideAtlasiQ9ESL4.
PRIDEiQ9ESL4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000090824; ENSMUSP00000088334; ENSMUSG00000004085. [Q9ESL4-1]
ENSMUST00000135469; ENSMUSP00000118983; ENSMUSG00000004085. [Q9ESL4-2]
GeneIDi65964.
KEGGimmu:65964.
UCSCiuc008kbs.2. mouse. [Q9ESL4-3]
uc008kbv.2. mouse. [Q9ESL4-1]

Organism-specific databases

CTDi51776.
MGIiMGI:2443258. Zak.

Phylogenomic databases

eggNOGiKOG0192. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000231813.
HOVERGENiHBG080445.
InParanoidiQ9ESL4.
KOiK04424.
OMAiGHSGMQV.
OrthoDBiEOG091G037E.
PhylomeDBiQ9ESL4.
TreeFamiTF106505.

Miscellaneous databases

PROiQ9ESL4.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000004085.
CleanExiMM_B230120H23RIK.
ExpressionAtlasiQ9ESL4. baseline and differential.
GenevisibleiQ9ESL4. MM.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR032938. MLTK.
IPR000719. Prot_kinase_dom.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR23257:SF424. PTHR23257:SF424. 1 hit.
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00220. S_TKc. 1 hit.
SM00454. SAM. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMLTK_MOUSE
AccessioniPrimary (citable) accession number: Q9ESL4
Secondary accession number(s): Q3V1X8, Q8BR73, Q9ESL3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: March 1, 2001
Last modified: November 2, 2016
This is version 141 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.