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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)DescriptionActionsGraphical viewLength
Binding sitei53ATPPROSITE-ProRule annotation1
Active sitei152Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi31 – 39ATPPROSITE-ProRule annotation9

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1349394. Map4k4.

Subcellular locationi

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000862812 – 1233Mitogen-activated protein kinase kinase kinase kinase 4Add BLAST1232

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei5PhosphoserineBy similarity1
Modified residuei323PhosphoserineCombined sources1
Modified residuei325PhosphoserineCombined sources1
Modified residuei543PhosphoserineCombined sources1
Modified residuei619PhosphoserineBy similarity1
Modified residuei621PhosphoserineBy similarity1
Modified residuei629PhosphoserineCombined sources1
Modified residuei646PhosphoserineCombined sources1
Modified residuei691PhosphoserineBy similarity1
Modified residuei703PhosphoserineBy similarity1
Modified residuei706PhosphoserineBy similarity1
Modified residuei785PhosphoserineBy similarity1
Modified residuei794PhosphoserineCombined sources1
Modified residuei795PhosphoserineCombined sources1
Modified residuei799PhosphoserineCombined sources1
Modified residuei817PhosphoserineBy similarity1
Modified residuei822PhosphothreonineBy similarity1
Modified residuei846PhosphoserineBy similarity1
Modified residuei849PhosphoserineBy similarity1
Modified residuei894PhosphoserineCombined sources1
Modified residuei907PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP97820.
MaxQBiP97820.
PaxDbiP97820.
PeptideAtlasiP97820.
PRIDEiP97820.

PTM databases

iPTMnetiP97820.
PhosphoSitePlusiP97820.

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 interactor.
CORUMiP97820.
DIPiDIP-40973N.
IntActiP97820. 3 interactors.
MINTiMINT-132612.
STRINGi10090.ENSMUSP00000129796.

Structurei

3D structure databases

ProteinModelPortaliP97820.
SMRiP97820.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 289Protein kinasePROSITE-ProRule annotationAdd BLAST265
Domaini920 – 1207CNHPROSITE-ProRule annotationAdd BLAST288

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni852 – 1206Mediates interaction with RAP2ABy similarityAdd BLAST355

Sequence similaritiesi

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR001180. CNH_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF00780. CNH. 1 hit.
PF00069. Pkinase. 1 hit.
SMARTiView protein in SMART
SM00036. CNH. 1 hit.
SM00220. S_TKc. 1 hit.
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiView protein in PROSITE
PS50219. CNH. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.

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.

Similar proteinsi

Entry informationi

Entry nameiM4K4_MOUSE
AccessioniPrimary (citable) accession number: P97820
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 28, 2003
Last sequence update: May 1, 1997
Last modified: September 27, 2017
This is version 144 of the entry and version 1 of the sequence. See 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