MAP4K4 - mitogen-activated protein kinase kinase kinase kinase 4 Gene

Also Known as HGK; NIK; MEKKK4; FLH21957; HEL-S-31

Species: Homo sapiens

Gene Type: protein coding
Gene ID: 9448

About MAP4K4

Cytogenetic location: 2q11.2 Genomic coordinates (GRCh38): 2:101,697,707-101,894,690 (from NCBI)

This gene has 18 transcripts (splice variants), 281 orthologues and 35 paralogues. Ubiquitous expression in brain (RPKM 42.7), fat (RPKM 25.1) and 23 other tissues.

Summary

The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase has been shown to specifically activate MAPK8/JNK. The activation of MAPK8 by this kinase is found to be inhibited by the dominant-negative mutants of MAP3K7/TAK1, MAP2K4/MKK4, and MAP2K7/MKK7, which suggests that this kinase may function through the MAP3K7-MAP2K4-MAP2K7 kinase cascade, and mediate the TNF-alpha signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

MAP4K4 Products (55)

mRNA Protein Name
NM_145686.4 NP_663719.2 mitogen-activated protein kinase kinase kinase kinase 4 isoform 2
NM_001384483.1 NP_001371412.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 11
NM_001384494.1 NP_001371423.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 22
NM_001384507.1 NP_001371436.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 28
NM_001384496.1 NP_001371425.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 24
NM_001384555.1 NP_001371484.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 42
NM_001384478.1 NP_001371407.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 8
NM_001384559.1 NP_001371488.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 46
NM_001384488.1 NP_001371417.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 16
NR_169282.1
NM_001384560.1 NP_001371489.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 47
NM_001384490.1 NP_001371419.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 18
NM_001384556.1 NP_001371485.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 43
NM_001384493.1 NP_001371422.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 21
NM_001384491.1 NP_001371420.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 19
NM_001384476.1 NP_001371405.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 6
NM_001384550.1 NP_001371479.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 37
NM_001384572.1 NP_001371501.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 53
NM_001384485.1 NP_001371414.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 13
NM_001384553.1 NP_001371482.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 40
NM_001384558.1 NP_001371487.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 45
NR_169280.1
NM_001384487.1 NP_001371416.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 15
NM_001384482.1 NP_001371411.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 10
NM_001384579.1 NP_001371508.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 54
NM_001395002.1 NP_001381931.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 55
NR_169279.1
NM_001384548.1 NP_001371477.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 35
NM_001384554.1 NP_001371483.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 41
NM_001384484.1 NP_001371413.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 12
NM_001384486.1 NP_001371415.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 14
NM_001384509.1 NP_001371438.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 30
NM_001384520.1 NP_001371449.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 31
NM_001384477.1 NP_001371406.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 7
NM_001384561.1 NP_001371490.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 48
NM_001384564.1 NP_001371493.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 51
NM_001384495.1 NP_001371424.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 23
NM_001384506.1 NP_001371435.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 27
NM_001384508.1 NP_001371437.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 29
NM_001384552.1 NP_001371481.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 39
NM_001384497.1 NP_001371426.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 25
NM_001242559.2 NP_001229488.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 4
NM_001384492.1 NP_001371421.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 20
NM_001384549.1 NP_001371478.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 36
NM_001242560.2 NP_001229489.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 5
NM_001384543.1 NP_001371472.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 32
NM_001384567.1 NP_001371496.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 52
NM_004834.5 NP_004825.3 mitogen-activated protein kinase kinase kinase kinase 4 isoform 1
NM_001384562.1 NP_001371491.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 49
NM_001384563.1 NP_001371492.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 50
NR_169281.1
NM_001384481.1 NP_001371410.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 9
NM_001384551.1 NP_001371480.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 38
NM_145687.4 NP_663720.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 3
NM_001384557.1 NP_001371486.1 mitogen-activated protein kinase kinase kinase kinase 4 isoform 44

Gene Ontology

  • Molecular Function
  • Biological Process
  • Cellular Component
Molecular Function GO Annotation Evidence References Source
enables ATP binding IDA
IDA: Inferred from direct assay
9890973 GOA
enables MAP kinase kinase kinase kinase activity IDA
IDA: Inferred from direct assay
26437443 GOA
enables creatine kinase activity IDA
IDA: Inferred from direct assay
23207904 GOA
enables microtubule binding IDA
IDA: Inferred from direct assay
25490267 GOA
enables protein binding IPI
IPI: Inferred from physical interaction
12387898 GOA
enables protein serine/threonine kinase activity IDA
IDA: Inferred from direct assay
9890973 GOA
Biological Process GO Annotation Evidence References Source
involved in intracellular signal transduction IDA
IDA: Inferred from direct assay
9890973 GOA
NOT involved in microvillus assembly IMP
IMP: Inferred from mutant phenotype
22797597 GOA
involved in negative regulation of apoptotic process IMP
IMP: Inferred from mutant phenotype
21196414 GOA
involved in positive regulation of cell migration IMP
IMP: Inferred from mutant phenotype
24163766 GOA
involved in positive regulation of hippo signaling IDA
IDA: Inferred from direct assay
26437443 GOA
involved in protein phosphorylation IDA
IDA: Inferred from direct assay
9890973 GOA
involved in regulation of JNK cascade IDA
IDA: Inferred from direct assay
14966141 GOA
Cellular Component GO Annotation Evidence References Source
is active in cytoplasm IDA
IDA: Inferred from direct assay
26437443 GOA
located in cytoplasm IDA
IDA: Inferred from direct assay
14966141 GOA
located in focal adhesion IDA
IDA: Inferred from direct assay
25490267 GOA
EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

MAP4K4 Protein Structure

Pkinase

Pkinase: Protein kinase domain (25 - 289)

CNH

CNH: CNH domain (931 - 1209)

  • 0
  • 200
  • 400
  • 600
  • 800
  • 1000
  • 1239 a.a.
Protein Preferred Names Protein Names

mitogen-activated protein kinase kinase kinase kinase 4

  • HPK/GCK-like kinase HGK

  • MAPK/ERK kinase kinase kinase 4

  • MEK kinase kinase 4

  • Ste20 group protein kinase HGK

  • epididymis secretory protein Li 31

  • hepatocyte progenitor kinase-like/germinal center kinase-like kinase

  • nck-interacting kinase

MAP4K4 Protein-protein interaction Information

Type
Protein Name Protein ID Interactor Interactor Species Interactor ID Detection Method References
Intra
MAP4K4 O95819 GBP3 Homo sapiens Q9H0R5
Anti Tag CoIP
12387898
Cross: Cross-species interaction Intra: Intraspecies interaction

MAP4K4 Antibodies

Cat. No. Product Name Application Reactivity
HY-P81378 MAP4K4/NIK Antibody (YA1123) IHC-P Human
HY-P81378A MAP4K4/NIK Antibody (YA1123)(PBS only) IHC-P Human
HY-P85200 MAP4K4/NIK Antibody (YA4892) WB, FC, ELISA Human, Mouse
HY-P85200A MAP4K4/NIK Antibody (YA4892)(PBS only) WB, FC, ELISA Human, Mouse

Related Diseases

Diseases Alias
Hyperpigmentation With Or Without Hypopigmentation, Familial Progressive

  • FPHH

  • Melanosis Universalis Hereditaria

  • Muh

  • Familial Progressive Hyperpigmentation With Or Without Hypopigmentation

  • Hyperpigmentation, Familial Progressive, 2, Formerly

  • Fph2, Formerly

  • Hyperpigmentation With Or Without Hypopigmentation

  • Familial Progressive Hyper- And Hypopigmentation

  • Hyperpigmentation, Familial Progressive
Arteriovenous Malformations Of The Brain

  • Cerebral Arteriovenous Malformation

  • Intracranial Arteriovenous Malformation

  • Intracranial Hemorrhage In Brain Cerebrovascular Malformations, Susceptibility To

  • Intracranial Arteriovenous Malformations

  • Bavm

  • Cerebral Arteriovenous Malformations

  • Intracranial Hemorrhage In Brain Cerebrovascular Malformations

  • Arteriovenous Malformation Of The Brain, Somatic

  • Intracranial Avm

  • Arteriovenous Malformations Cerebral
Diseases Alias
Waldenstroem'S Macroglobulinemia

Waldenstroem'S Macroglobulinemia

Waldenstroem'S Macroglobulinemia

Macroglobulinemia Of Waldenstrom

Lymphoplasmacytic Lymphoma With Igm Gammopathy

Lymphoplasmacytic Lymphoma

Waldenstroem'S Macroglobulinemia

Waldenstroem'S Macroglobulinemia

Macroglobulinemia Of Waldenstrom

Lymphoplasmacytic Lymphoma With Igm Gammopathy

Lymphoplasmacytic Lymphoma

Related Agents

  • Clinical Phase
  • Pre-clinical Phase

Clinical Phase

Bioactive Molecules (1)
Cat. No. Product Name Effect
Purity Phase
HY-160623 Rentosertib 99.96% Phase 2

Pre-clinical Phase

Bioactive Molecules (21)
Cat. No. Product Name
Effect
Purity
Rare Diseases
HY-100343 GNE-495 Inhibitor 99.49% Unkown
HY-19562 PF-06260933 Inhibitor 99.39% Unkown
HY-111754 DMX-5804 Inhibitor 99.64% Unkown
HY-168972 Famlasertib Inhibitor 99.94% Unkown
HY-125012 MAP4K4-IN-3 Inhibitor 99.77% Unkown
HY-156715 MASTL-IN-1 Inhibitor 99.54% Unkown
HY-132290 TGFβRI-IN-3 Inhibitor 98.21% Unkown
HY-W003471 Pyrrolo[2,1-f][1,2,4]triazin-4-amine Inhibitor / Unkown
HY-U00428A GNE 220 hydrochloride Inhibitor 98.22% Unkown
HY-137340 WH-10417-099 Degrader 98.14% Unkown
HY-156523 TNIK&MAP4K4-IN-1 99.73% Unkown
HY-19562A PF-06260933 hydrochloride Inhibitor 99.42% Unkown
HY-U00428 GNE 220 Inhibitor / Unkown
HY-123965 PF-06745013 Inhibitor / Unkown
HY-162922 MAP4K4-IN-6 Inhibitor / Unkown
HY-RS08080 MAP4K4 Human Pre-designed siRNA Set A Pre-designed Set / Unkown
HY-RS08081 Map4k4 Mouse Pre-designed siRNA Set A Pre-designed Set / Unkown
HY-RS08082 Map4k4 Rat Pre-designed siRNA Set A Pre-designed Set / Unkown
HY-W207224 F1386-0303 Inhibitor / Unkown
HY-W402208 MAP4K4-IN-7 Inhibitor / Unkown
HY-178775 PI4K-IN-3 Inhibitor / Unkown

Orthologs Information

Species Symbol Source ID
Felis catus MAP4K4 VGNC VGNC:81118
Mus musculus MAP4K4 MGD MGI:1349394
Bos taurus MAP4K4 VGNC VGNC:31207
Rattus norvegicus MAP4K4 RGD RGD:1305322
Canis familiaris MAP4K4 VGNC VGNC:42984
Macaca mulatta MAP4K4 VGNC VGNC:81467
Others MAP4K4 NCBI