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UniProtKB - Q8IVH8 (M4K3_HUMAN)

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Protein

Mitogen-activated protein kinase kinase kinase kinase 3

Gene

MAP4K3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.1 Publication

Catalytic activityi

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

Cofactori

Mg2+1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei45ATPPROSITE-ProRule annotation1
Binding sitei48ATPPROSITE-ProRule annotation1 Publication1
Active sitei136Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi22 – 30ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • MAP kinase kinase kinase kinase activity Source: GO_Central
  • protein kinase activity Source: ProtInc
  • protein serine/threonine kinase activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • intracellular signal transduction Source: UniProtKB
  • JNK cascade Source: ProtInc
  • protein phosphorylation Source: UniProtKB
  • regulation of apoptotic process Source: GO_Central
  • regulation of mitotic cell cycle Source: GO_Central
  • response to tumor necrosis factor Source: UniProtKB
  • response to UV Source: UniProtKB
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

SignaLinkiQ8IVH8
SIGNORiQ8IVH8

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase kinase kinase kinase 3 (EC:2.7.11.1)
Alternative name(s):
Germinal center kinase-related protein kinase
Short name:
GLK
MAPK/ERK kinase kinase kinase 3
Short name:
MEK kinase kinase 3
Short name:
MEKKK 3
Gene namesi
Name:MAP4K3
Synonyms:RAB8IPL1
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000011566.14
HGNCiHGNC:6865 MAP4K3
MIMi604921 gene
neXtProtiNX_Q8IVH8

Subcellular locationi

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi48K → E: Loss of kinase activity and ability to activate JNK family. 1 Publication1

Organism-specific databases

DisGeNETi8491
OpenTargetsiENSG00000011566
PharmGKBiPA30611

Chemistry databases

ChEMBLiCHEMBL5432
GuidetoPHARMACOLOGYi2087

Polymorphism and mutation databases

BioMutaiMAP4K3
DMDMi29427817

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862771 – 894Mitogen-activated protein kinase kinase kinase kinase 3Add BLAST894

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei329PhosphoserineBy similarity1
Modified residuei398PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ8IVH8
MaxQBiQ8IVH8
PaxDbiQ8IVH8
PeptideAtlasiQ8IVH8
PRIDEiQ8IVH8
ProteomicsDBi70709
70710 [Q8IVH8-2]
70711 [Q8IVH8-3]

PTM databases

iPTMnetiQ8IVH8
PhosphoSitePlusiQ8IVH8

Expressioni

Tissue specificityi

Ubiquitously expressed in all tissues examined, with high levels in heart, brain, placenta, skeletal muscle, kidney and pancreas and lower levels in lung and liver.1 Publication

Gene expression databases

BgeeiENSG00000011566
CleanExiHS_MAP4K3
ExpressionAtlasiQ8IVH8 baseline and differential
GenevisibleiQ8IVH8 HS

Organism-specific databases

HPAiHPA030380

Interactioni

Subunit structurei

Interacts with SH3GL2. Interaction appears to regulate MAP4K3-mediated JNK activation (By similarity).By similarity

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi114063, 11 interactors
DIPiDIP-48924N
IntActiQ8IVH8, 11 interactors
STRINGi9606.ENSP00000263881

Chemistry databases

BindingDBiQ8IVH8

Structurei

Secondary structure

1894
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi13 – 15Combined sources3
Beta strandi16 – 24Combined sources9
Beta strandi26 – 35Combined sources10
Turni36 – 38Combined sources3
Beta strandi41 – 48Combined sources8
Helixi56 – 66Combined sources11
Beta strandi76 – 81Combined sources6
Beta strandi83 – 90Combined sources8
Helixi98 – 104Combined sources7
Helixi110 – 129Combined sources20
Beta strandi141 – 144Combined sources4
Beta strandi150 – 152Combined sources3
Helixi156 – 163Combined sources8
Helixi175 – 177Combined sources3
Helixi180 – 186Combined sources7
Helixi195 – 209Combined sources15
Turni213 – 216Combined sources4
Helixi219 – 227Combined sources9
Turni239 – 241Combined sources3
Helixi244 – 253Combined sources10
Turni258 – 260Combined sources3
Helixi264 – 268Combined sources5
Helixi271 – 274Combined sources4
Helixi280 – 289Combined sources10
Helixi307 – 309Combined sources3

3D structure databases

ProteinModelPortaliQ8IVH8
SMRiQ8IVH8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 273Protein kinasePROSITE-ProRule annotationAdd BLAST258
Domaini556 – 867CNHPROSITE-ProRule annotationAdd BLAST312

Sequence similaritiesi

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.Curated

Phylogenomic databases

eggNOGiKOG0576 Eukaryota
ENOG410XP9G LUCA
GeneTreeiENSGT00920000148966
HOGENOMiHOG000230824
HOVERGENiHBG036702
InParanoidiQ8IVH8
KOiK04406
OMAiQETHSTE
OrthoDBiEOG091G022R
PhylomeDBiQ8IVH8
TreeFamiTF105121

Family and domain databases

InterProiView protein in InterPro
IPR001180 CNH_dom
IPR011009 Kinase-like_dom_sf
IPR021160 MAPKKKK
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
PfamiView protein in Pfam
PF00780 CNH, 1 hit
PF00069 Pkinase, 1 hit
PIRSFiPIRSF038172 MAPKKKK, 1 hit
SMARTiView protein in SMART
SM00036 CNH, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50219 CNH, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit

Sequences (3)i

Sequence statusi: Complete.

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

Isoform 11 PublicationCurated (identifier: Q8IVH8-1) [UniParc]FASTAAdd to basket

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
MNPGFDLSRR NPQEDFELIQ RIGSGTYGDV YKARNVNTGE LAAIKVIKLE 
        60         70         80         90        100
PGEDFAVVQQ EIIMMKDCKH PNIVAYFGSY LRRDKLWICM EFCGGGSLQD 
       110        120        130        140        150
IYHVTGPLSE LQIAYVSRET LQGLYYLHSK GKMHRDIKGA NILLTDNGHV 
       160        170        180        190        200
KLADFGVSAQ ITATIAKRKS FIGTPYWMAP EVAAVERKGG YNQLCDLWAV 
       210        220        230        240        250
GITAIELAEL QPPMFDLHPM RALFLMTKSN FQPPKLKDKM KWSNSFHHFV 
       260        270        280        290        300
KMALTKNPKK RPTAEKLLQH PFVTQHLTRS LAIELLDKVN NPDHSTYHDF 
       310        320        330        340        350
DDDDPEPLVA VPHRIHSTSR NVREEKTRSE ITFGQVKFDP PLRKETEPHH 
       360        370        380        390        400
ELPDSDGFLD SSEEIYYTAR SNLDLQLEYG QGHQGGYFLG ANKSLLKSVE 
       410        420        430        440        450
EELHQRGHVA HLEDDEGDDD ESKHSTLKAK IPPPLPPKPK SIFIPQEMHS 
       460        470        480        490        500
TEDENQGTIK RCPMSGSPAK PSQVPPRPPP PRLPPHKPVA LGNGMSSFQL 
       510        520        530        540        550
NGERDGSLCQ QQNEHRGTNL SRKEKKDVPK PISNGLPPTP KVHMGACFSK 
       560        570        580        590        600
VFNGCPLKIH CASSWINPDT RDQYLIFGAE EGIYTLNLNE LHETSMEQLF 
       610        620        630        640        650
PRRCTWLYVM NNCLLSISGK ASQLYSHNLP GLFDYARQMQ KLPVAIPAHK 
       660        670        680        690        700
LPDRILPRKF SVSAKIPETK WCQKCCVVRN PYTGHKYLCG ALQTSIVLLE 
       710        720        730        740        750
WVEPMQKFML IKHIDFPIPC PLRMFEMLVV PEQEYPLVCV GVSRGRDFNQ 
       760        770        780        790        800
VVRFETVNPN STSSWFTESD TPQTNVTHVT QLERDTILVC LDCCIKIVNL 
       810        820        830        840        850
QGRLKSSRKL SSELTFDFQI ESIVCLQDSV LAFWKHGMQG RSFRSNEVTQ 
       860        870        880        890 
EISDSTRIFR LLGSDRVVVL ESRPTDNPTA NSNLYILAGH ENSY
Note: No experimental confirmation available.
Length:894
Mass (Da):101,316
Last modified:March 1, 2003 - v1
Checksum:i6EB77BBB34E5B733
GO
Isoform 21 PublicationCurated (identifier: Q8IVH8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: MNPGFDLSRRNP → MA

Show »
Length:884
Mass (Da):100,133
Checksum:i14839222F5360166
GO
Isoform 31 PublicationCurated (identifier: Q8IVH8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     352-372: Missing.

Note: No experimental confirmation available.
Show »
Length:873
Mass (Da):98,954
Checksum:i0C7D648387CFFE0C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti392N → D in AAC15472 (PubMed:9275185).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040743200V → L1 PublicationCorresponds to variant dbSNP:rs35957290Ensembl.1
Natural variantiVAR_040744424H → Q1 PublicationCorresponds to variant dbSNP:rs56317466Ensembl.1
Natural variantiVAR_040745669T → S in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0070521 – 12MNPGF…SRRNP → MA in isoform 2. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_007053352 – 372Missing in isoform 3. 1 PublicationAdd BLAST21

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF000145 mRNA Translation: AAC15472.1
AF445413
, AF445385, AF445386, AF445387, AF445388, AF445390, AF445391, AF445392, AF445393, AF445394, AF445395, AF445396, AF445397, AF445398, AF445399, AF445400, AF445401, AF445402, AF445403, AF445404, AF445405, AF445406, AF445407, AF445408, AF445409, AF445410, AF445411, AF445412 Genomic DNA Translation: AAN75849.1
AF445413
, AF445385, AF445386, AF445387, AF445388, AF445390, AF445391, AF445392, AF445393, AF445394, AF445395, AF445397, AF445398, AF445399, AF445400, AF445401, AF445402, AF445403, AF445404, AF445405, AF445406, AF445407, AF445408, AF445409, AF445410, AF445411, AF445412 Genomic DNA Translation: AAN75850.1
CH471053 Genomic DNA Translation: EAX00346.1
BC071579 mRNA Translation: AAH71579.1
AC007684 Genomic DNA Translation: AAF19240.1
CCDSiCCDS1803.1 [Q8IVH8-1]
CCDS58707.1 [Q8IVH8-3]
RefSeqiNP_001257354.1, NM_001270425.1 [Q8IVH8-3]
NP_003609.2, NM_003618.3 [Q8IVH8-1]
UniGeneiHs.655750

Genome annotation databases

EnsembliENST00000263881; ENSP00000263881; ENSG00000011566 [Q8IVH8-1]
ENST00000341681; ENSP00000345434; ENSG00000011566 [Q8IVH8-3]
GeneIDi8491
KEGGihsa:8491
UCSCiuc002rro.4 human [Q8IVH8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiM4K3_HUMAN
AccessioniPrimary (citable) accession number: Q8IVH8
Secondary accession number(s): Q6IQ39
, Q8IVH7, Q9UDM5, Q9Y6R5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 28, 2003
Last sequence update: March 1, 2003
Last modified: June 20, 2018
This is version 149 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

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