MAP4K3 mitogen-activated protein kinase kinase kinase kinase 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MAP4K3provided by HGNC
Official Full Name: mitogen-activated protein kinase kinase kinase kinase 3provided by HGNC
Primary source: HGNC:HGNC:6865
See related: Ensembl:ENSG00000011566 MIM:604921; AllianceGenome:HGNC:6865
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GLK; MEKKK3; MEKKK 3; MAPKKKK3; RAB8IPL1
Summary: This gene encodes a member of the mitogen-activated protein kinase kinase kinase kinase family. The encoded protein activates key effectors in cell signalling, among them c-Jun. Alternatively spliced transcripts encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]
Expression: Ubiquitous expression in thyroid (RPKM 14.7), testis (RPKM 13.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2p22.1

Exon count:: 35

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (39249266..39437285, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (39258084..39446168, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (39476407..39664426, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Genomic sequencing and functional analyses identify MAP4K3/GLK germline and somatic variants associated with systemic lupus erythematosus.
Title: Genomic sequencing and functional analyses identify MAP4K3/GLK germline and somatic variants associated with systemic lupus erythematosus.
MiR-338-3p inhibits growth of glioblastoma through targeting MAP4K3.
Title: MiR-338-3p inhibits growth of glioblastoma through targeting MAP4K3.
The GLK-induced AhR-ROR-gammat (and AhR-phosphorylated ROR-gammat) complex is a therapeutic target for the GLK(high)IL-17A(high) subpopulation of human patients with SLE.
Title: AhR-ROR-γt complex is a therapeutic target for MAP4K3/GLK(high)IL-17A(high) subpopulation of systemic lupus erythematosus.
These findings show the critical role of the GLK-IQGAP cascade in cell migration and tumor metastasis
Title: MAP4K3/GLK Promotes Lung Cancer Metastasis by Phosphorylating and Activating IQGAP1.
MiR-206 contributed to euthyrox resistance in PTC cells through blockage p38 and JNK signaling pathway by targeting MAP4K3.
Title: Over-expression of miR-206 decreases the Euthyrox-resistance by targeting MAP4K3 in papillary thyroid carcinoma.
MAP4K3 is identified as an amino acid-dependent regulator of autophagy through its phosphorylation of transcription factor EB (TFEB), a transcriptional activator of autophagy.
Title: MAP4K3 mediates amino acid-dependent regulation of autophagy via phosphorylation of TFEB.
hepatocellular carcinoma recurrence may involve germinal center kinase-like kinase
Title: Prediction of early hepatocellular carcinoma recurrence using germinal center kinase-like kinase.
Data indicate that GLK/MAP4K3 is a prognostic biomarker for non-small cell lung cancer (NSCLC) recurrence.
Title: GLK/MAP4K3 overexpression associates with recurrence risk for non-small cell lung cancer.
Authors report that miR-199a-5p and let-7c cooperatively and efficiently inhibit HCC cell migration and invasion by targeting the metastasis promoter MAP4K3 and MAP4K3-mediated drug sensitization.
Title: MiR-199a-5p and let-7c cooperatively inhibit migration and invasion by targeting MAP4K3 in hepatocellular carcinoma.
This report details the first structure of GLK; comparison of its activation loop sequence and P-loop structure to that of Map4k4 suggests ideas for designing inhibitors that can distinguish between these family members to achieve selective pharmacological inhibitors.
Title: Germinal-center kinase-like kinase co-crystal structure reveals a swapped activation loop and C-terminal extension.

Submit: New GeneRIF Correction See all GeneRIFs (19)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G09793 (e-PCR)
- UniSTS:2097

1386 (e-PCR)
- UniSTS:15194

D2S1852 (e-PCR)
- UniSTS:81001

SHGC-54631 (e-PCR)
- UniSTS:24541

MAP4K3_361 (e-PCR)
- UniSTS:277472

G63164 (e-PCR)
- UniSTS:140281

SHGC-64118 (e-PCR)
- UniSTS:82431

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 3-phosphoinositide-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables AMP-activated protein kinase activity	IEA Inferred from Electronic Annotation more info
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables MAP kinase kinase kinase kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables Rho-dependent protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables eukaryotic translation initiation factor 2alpha kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS121 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AT120 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXS139 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS14 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS36 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S10 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S28 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S57 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T11 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T3 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T45 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T6 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H4S1 kinase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	TAS Traceable Author Statement more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables ribosomal protein S6 kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in JNK cascade	TAS Traceable Author Statement more info	PubMed
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in response to UV	IDA Inferred from Direct Assay more info	PubMed
involved_in response to tumor necrosis factor	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: mitogen-activated protein kinase kinase kinase kinase 3

Names: MAPK/ERK kinase kinase kinase 3; MEK kinase kinase 3; germinal center kinase-like kinase; germinal center kinase-related protein kinase

NP_001257354.1

EC 2.7.11.1

NP_001397682.1

EC 2.7.11.1

NP_003609.2

EC 2.7.11.1

XP_024308951.1

EC 2.7.11.1

XP_047302047.1

EC 2.7.11.1

XP_047302048.1

EC 2.7.11.1

XP_054200218.1

EC 2.7.11.1

XP_054200219.1

EC 2.7.11.1

XP_054200220.1

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_028007.1 RefSeqGene

Range

4794..192813

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001270425.2 → NP_001257354.1 mitogen-activated protein kinase kinase kinase kinase 3 isoform 2

See identical proteins and their annotated locations for NP_001257354.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the coding region, but maintains the reading frame, compared to variant 1. The encoded protein (isoform 2) is shorter than isoform 1.

Source sequence(s)

AC007684, AC079615, AK021553, AK314487, DA409370

Consensus CDS

CCDS58707.1

UniProtKB/TrEMBL

A8K602

Related

ENSP00000345434.5, ENST00000341681.9

Conserved Domains (3) summary

smart00036
Location:540 → 853

CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2

smart00220
Location:16 → 273

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd06613
Location:15 → 273

STKc_MAP4K3_like; Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases
NM_001410753.1 → NP_001397682.1 mitogen-activated protein kinase kinase kinase kinase 3 isoform 3

Status: REVIEWED

Source sequence(s)

AC007684, AC079615

Consensus CDS

CCDS92741.1

UniProtKB/TrEMBL

F5H5A3

Related

ENSP00000416958.1, ENST00000437545.5
NM_003618.4 → NP_003609.2 mitogen-activated protein kinase kinase kinase kinase 3 isoform 1

See identical proteins and their annotated locations for NP_003609.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer protein (isoform 1).

Source sequence(s)

AC007684, AC079615, AK021553, AK291467, DA409370

Consensus CDS

CCDS1803.1

UniProtKB/Swiss-Prot

Q6IQ39, Q8IVH7, Q8IVH8, Q9UDM5, Q9Y6R5

UniProtKB/TrEMBL

A8K602

Related

ENSP00000263881.3, ENST00000263881.8

Conserved Domains (3) summary

smart00036
Location:561 → 874

CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2

smart00220
Location:16 → 273

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd06613
Location:15 → 273

STKc_MAP4K3_like; Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

39249266..39437285 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047446092.1 → XP_047302048.1 mitogen-activated protein kinase kinase kinase kinase 3 isoform X2
XM_024453183.2 → XP_024308951.1 mitogen-activated protein kinase kinase kinase kinase 3 isoform X3

UniProtKB/TrEMBL

B4DSS3

Conserved Domains (1) summary

smart00036
Location:114 → 427

CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
XM_047446091.1 → XP_047302047.1 mitogen-activated protein kinase kinase kinase kinase 3 isoform X1

Alternate T2T-CHM13v2.0

Genomic

NC_060926.1 Alternate T2T-CHM13v2.0

Range

39258084..39446168 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054344244.1 → XP_054200219.1 mitogen-activated protein kinase kinase kinase kinase 3 isoform X2
XM_054344245.1 → XP_054200220.1 mitogen-activated protein kinase kinase kinase kinase 3 isoform X3

UniProtKB/TrEMBL

B4DSS3
XM_054344243.1 → XP_054200218.1 mitogen-activated protein kinase kinase kinase kinase 3 isoform X1