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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

GO - Biological processi

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
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 Expressed in 227 organ(s), highest expression level in kidney
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

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

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

Phylogenomic databases

eggNOGiKOG0576 Eukaryota
ENOG410XP9G LUCA
GeneTreeiENSGT00930000150827
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

This entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H5A3F5H5A3_HUMAN
Mitogen-activated protein kinase ki...
MAP4K3
810Annotation score:
F8WAZ1F8WAZ1_HUMAN
Mitogen-activated protein kinase ki...
MAP4K3
131Annotation score:
V9GY95V9GY95_HUMAN
Mitogen-activated protein kinase ki...
MAP4K3
92Annotation score:
H7C1A4H7C1A4_HUMAN
Mitogen-activated protein kinase ki...
MAP4K3
143Annotation score:
F8WBC3F8WBC3_HUMAN
Mitogen-activated protein kinase ki...
MAP4K3
44Annotation score:

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

Cross-referencesi

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5J5TX-ray2.85A13-380[»]
ProteinModelPortaliQ8IVH8
SMRiQ8IVH8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry databases

BindingDBiQ8IVH8
ChEMBLiCHEMBL5432
GuidetoPHARMACOLOGYi2087

PTM databases

iPTMnetiQ8IVH8
PhosphoSitePlusiQ8IVH8

Polymorphism and mutation databases

BioMutaiMAP4K3
DMDMi29427817

Proteomic databases

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

Protocols and materials databases

DNASUi8491
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi8491
DisGeNETi8491
EuPathDBiHostDB:ENSG00000011566.14
GeneCardsiMAP4K3
H-InvDBiHIX0001996
HGNCiHGNC:6865 MAP4K3
HPAiHPA030380
MIMi604921 gene
neXtProtiNX_Q8IVH8
OpenTargetsiENSG00000011566
PharmGKBiPA30611
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0576 Eukaryota
ENOG410XP9G LUCA
GeneTreeiENSGT00930000150827
HOGENOMiHOG000230824
HOVERGENiHBG036702
InParanoidiQ8IVH8
KOiK04406
OMAiQETHSTE
OrthoDBiEOG091G022R
PhylomeDBiQ8IVH8
TreeFamiTF105121

Enzyme and pathway databases

SignaLinkiQ8IVH8
SIGNORiQ8IVH8

Miscellaneous databases

ChiTaRSiMAP4K3 human
GenomeRNAii8491
PROiPR:Q8IVH8
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000011566 Expressed in 227 organ(s), highest expression level in kidney
CleanExiHS_MAP4K3
ExpressionAtlasiQ8IVH8 baseline and differential
GenevisibleiQ8IVH8 HS

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
ProtoNetiSearch...

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: November 7, 2018
This is version 151 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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