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Protein

Mitogen-activated protein kinase kinase kinase kinase 4

Gene

Map4k4

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

Functioni

Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322 (By similarity).By similarity2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.2 Publications

Cofactori

Mg2+2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei53 – 531ATPPROSITE-ProRule annotation
Active sitei152 – 1521Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi31 – 399ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • creatine kinase activity Source: MGI
  • protein serine/threonine kinase activity Source: UniProtKB
  • receptor signaling protein serine/threonine kinase activity Source: GO_Central

GO - Biological processi

  • intracellular signal transduction Source: UniProtKB
  • negative regulation of apoptotic process Source: MGI
  • protein phosphorylation Source: UniProtKB
  • regulation of JNK cascade Source: UniProtKB
  • response to stress Source: UniProtKB
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 4 (EC:2.7.11.1)
Alternative name(s):
HPK/GCK-like kinase HGK
MAPK/ERK kinase kinase kinase 4
Short name:
MEK kinase kinase 4
Short name:
MEKKK 4
Nck-interacting kinase
Gene namesi
Name:Map4k4
Synonyms:Nik
OrganismiMus musculus (Mouse)Imported
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1349394. Map4k4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 12331232Mitogen-activated protein kinase kinase kinase kinase 4PRO_0000086281Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei5 – 51PhosphoserineBy similarity
Modified residuei323 – 3231PhosphoserineCombined sources
Modified residuei325 – 3251PhosphoserineCombined sources
Modified residuei543 – 5431PhosphoserineCombined sources
Modified residuei619 – 6191PhosphoserineBy similarity
Modified residuei621 – 6211PhosphoserineBy similarity
Modified residuei629 – 6291PhosphoserineCombined sources
Modified residuei646 – 6461PhosphoserineCombined sources
Modified residuei691 – 6911PhosphoserineBy similarity
Modified residuei703 – 7031PhosphoserineBy similarity
Modified residuei706 – 7061PhosphoserineBy similarity
Modified residuei785 – 7851PhosphoserineBy similarity
Modified residuei794 – 7941PhosphoserineCombined sources
Modified residuei795 – 7951PhosphoserineCombined sources
Modified residuei799 – 7991PhosphoserineCombined sources
Modified residuei817 – 8171PhosphoserineBy similarity
Modified residuei822 – 8221PhosphothreonineBy similarity
Modified residuei846 – 8461PhosphoserineBy similarity
Modified residuei849 – 8491PhosphoserineBy similarity
Modified residuei894 – 8941PhosphoserineCombined sources
Modified residuei907 – 9071PhosphoserineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP97820.
MaxQBiP97820.
PaxDbiP97820.
PeptideAtlasiP97820.
PRIDEiP97820.

PTM databases

iPTMnetiP97820.
PhosphoSiteiP97820.

Expressioni

Tissue specificityi

Appears to be ubiquitous, expressed in all tissue types examined. Highest levels observed in heart and brain.1 Publication

Interactioni

Subunit structurei

Interacts with the SH3 domain of the adapter proteins Nck. Interacts (via its CNH regulatory domain) with ATL1 (via the N-terminal region). Interacts with RAP2A (GTP-bound form preferentially) (By similarity).By similarity

Protein-protein interaction databases

BioGridi205065. 1 interaction.
DIPiDIP-40973N.
IntActiP97820. 3 interactions.
MINTiMINT-132612.
STRINGi10090.ENSMUSP00000129796.

Structurei

3D structure databases

ProteinModelPortaliP97820.
SMRiP97820. Positions 10-310.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini25 – 289265Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini920 – 1207288CNHPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni852 – 1206355Mediates interaction with RAP2ABy similarityAdd
BLAST

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0587. Eukaryota.
ENOG410YBF5. LUCA.
HOGENOMiHOG000290708.
HOVERGENiHBG036506.
InParanoidiP97820.
KOiK04407.
PhylomeDBiP97820.

Family and domain databases

InterProiIPR001180. CNH_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00780. CNH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00036. CNH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS50219. CNH. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P97820-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MANDSPAKSL VDIDLSSLRD PAGIFELVEV VGNGTYGQVY KGRHVKTVTA
60 70 80 90 100
AIKVMDVTED EEEEITLEIN MLKKYSHHRN IATYYGAFIK KSPPGHDDQL
110 120 130 140 150
WLVMEFCGAG SITDLVKNTK GNTLKEDWIA YISREILRGL AHLHIHHVIH
160 170 180 190 200
RDIKGQNVLL TENAEVKLVD FGVSAQLDRT VGRRNTFIGT PYWMAPEVIA
210 220 230 240 250
CDENPDATYD YRSDLWSCGI TAIEMAEGGP PLCDMHPMRA LFLIPRNPPP
260 270 280 290 300
RLKSKKWSKK FFSFIEGCLV KNYMQRPSTE QLLKHPFIRD QPNERQVRIQ
310 320 330 340 350
LKDHIDRTRK KRGEKDETEY EYSGSEEEEE EVPEQEGEPS SIVNVPGEST
360 370 380 390 400
LRRDFLRLQQ ENKERSEALR RQQLLQEQQL REQEEYKRQL LAERQKRIEQ
410 420 430 440 450
QKEQRRRLEE QQRREREARR QQEREQRRRE QEEKRRLEEL ERRRKEEEER
460 470 480 490 500
RRAEEEKRRV EREQEYIRRQ LEEEQRHLEI LQQQLLQEQA MLLHDHRRPH
510 520 530 540 550
AQQQPPPPQQ QDRSKPSFHA PEPKPHYDPA DRAREVQWSH LASLKNNVSP
560 570 580 590 600
VSRSHSFSDP SPKFAHHHLR SQDPCPPSRS EGLSQSSDSK SEVPEPTQKA
610 620 630 640 650
WSRSDSDEVP PRVPVRTTSR SPVLSRRDSP LQGGGQQNSQ AGQRNSTSSI
660 670 680 690 700
EPRLLWERVE KLVPRPGSGS SSGSSNSGSQ PGSHPGSQSG SGERFRVRSS
710 720 730 740 750
SKSEGSPSPR QESAAKKPDD KKEVFRSLKP AGEVDLTALA KELRAVEDVR
760 770 780 790 800
PPHKVTDYSS SSEESGTTDE EEEDVEQEGA DDSTSGPEDT RAASSPNLSN
810 820 830 840 850
GETESVKTMI VHDDVESEPA MTPSKEGTLI VRQTQSASST LQKHKSSSSF
860 870 880 890 900
TPFIDPRLLQ ISPSSGTTVT SVVGFSCDGL RPEAIRQDPT RKGSVVNVNP
910 920 930 940 950
TNTRPQSDTP EIRKYKKRFN SEILCAALWG VNLLVGTESG LMLLDRSGQG
960 970 980 990 1000
KVYPLISRRR FQQMDVLEGL NVLVTISGKK DKLRVYYLSW LRNKILHNDP
1010 1020 1030 1040 1050
EVEKKQGWTT VGDLEGCVHY KVVKYERIKF LVIALKSSVE VYAWAPKPYH
1060 1070 1080 1090 1100
KFMAFKSFGE LLHKPLLVDL TVEEGQRLKV IYGSCAGFHA VDVDSGSVYD
1110 1120 1130 1140 1150
IYLPTHIQCS IKPHAIIILP NTDGMELLVC YEDEGVYVNT YGRITKDVVL
1160 1170 1180 1190 1200
QWGEMPTSVA YIRSNQTMGW GEKAIEIRSV ETGHLDGVFM HKRAQRLKFL
1210 1220 1230
CGRNDKVFFS SVRSGGSSQV YFMTLGRTSL LSW
Length:1,233
Mass (Da):140,602
Last modified:May 1, 1997 - v1
Checksum:i869896D414459B19
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88984 mRNA. Translation: AAC53165.1.
PIRiT30989.
RefSeqiNP_001239129.1. NM_001252200.1.
NP_001239130.1. NM_001252201.1.
NP_001239131.1. NM_001252202.1.
NP_032722.2. NM_008696.2.
UniGeneiMm.491139.

Genome annotation databases

GeneIDi26921.
KEGGimmu:26921.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88984 mRNA. Translation: AAC53165.1.
PIRiT30989.
RefSeqiNP_001239129.1. NM_001252200.1.
NP_001239130.1. NM_001252201.1.
NP_001239131.1. NM_001252202.1.
NP_032722.2. NM_008696.2.
UniGeneiMm.491139.

3D structure databases

ProteinModelPortaliP97820.
SMRiP97820. Positions 10-310.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi205065. 1 interaction.
DIPiDIP-40973N.
IntActiP97820. 3 interactions.
MINTiMINT-132612.
STRINGi10090.ENSMUSP00000129796.

PTM databases

iPTMnetiP97820.
PhosphoSiteiP97820.

Proteomic databases

EPDiP97820.
MaxQBiP97820.
PaxDbiP97820.
PeptideAtlasiP97820.
PRIDEiP97820.

Protocols and materials databases

DNASUi26921.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi26921.
KEGGimmu:26921.

Organism-specific databases

CTDi9448.
MGIiMGI:1349394. Map4k4.

Phylogenomic databases

eggNOGiKOG0587. Eukaryota.
ENOG410YBF5. LUCA.
HOGENOMiHOG000290708.
HOVERGENiHBG036506.
InParanoidiP97820.
KOiK04407.
PhylomeDBiP97820.

Miscellaneous databases

ChiTaRSiMap4k4. mouse.
PROiP97820.
SOURCEiSearch...

Family and domain databases

InterProiIPR001180. CNH_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00780. CNH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00036. CNH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS50219. CNH. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain."
    Su Y.-C., Han J., Xu S., Cobb M., Skolnik E.Y.
    EMBO J. 16:1279-1290(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
    Tissue: Brain and Embryo.
  2. "Nck-interacting Ste20 kinase couples Eph receptors to c-Jun N-terminal kinase and integrin activation."
    Becker E., Huynh-Do U., Holland S., Pawson T., Daniel T.O., Skolnik E.Y.
    Mol. Cell. Biol. 20:1537-1545(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH NCK.
  3. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic brain.
  4. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323; SER-325; SER-543; SER-629; SER-646; SER-794; SER-795; SER-799 AND SER-894, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, Spleen and Testis.

Entry informationi

Entry nameiM4K4_MOUSE
AccessioniPrimary (citable) accession number: P97820
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 28, 2003
Last sequence update: May 1, 1997
Last modified: July 6, 2016
This is version 138 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, 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.