MAP3K6 (mitogen-activated protein kinase kinase kinase 6)

Gene

• Entrez ID: 9064
• Gene name: Mitogen-activated protein kinase kinase kinase 6
• Gene symbol: MAP3K6
• Synonyms (NCBI Gene): ASK2, MAPKKK6, MEKK6
• Chromosome: 1
• Chromosome location: 1p36.11
• Summary: This gene encodes a serine/threonine protein kinase that forms a component of protein kinase-mediated signal transduction cascades. The encoded kinase participates in the regulation of vascular endothelial growth factor (VEGF) expression. Alternative spli

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs34008139	G>-,GG	Likely-pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant, genic downstream transcript variant
rs768616209	G>-	Likely-pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant, genic downstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT049479	hsa-miR-92a-3p	CLASH	23622248
MIRT736712	hsa-miR-4492	RNA-seq, qRT-PCR, Flow cytometry	32620026
MIRT2036729	hsa-miR-1273g	CLIP-seq
MIRT2036730	hsa-miR-4768-5p	CLIP-seq
MIRT2390578	hsa-miR-4691-5p	CLIP-seq
MIRT2390579	hsa-miR-516a-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	IEA
GO:0000166	Function	Nucleotide binding	IEA
GO:0000287	Function	Magnesium ion binding	IDA	9875215
GO:0004672	Function	Protein kinase activity	IEA
GO:0004674	Function	Protein serine/threonine kinase activity	IEA
GO:0004709	Function	MAP kinase kinase kinase activity	IBA
GO:0004709	Function	MAP kinase kinase kinase activity	IDA	9875215
GO:0004709	Function	MAP kinase kinase kinase activity	IEA
GO:0004709	Function	MAP kinase kinase kinase activity	TAS	9875215
GO:0005515	Function	Protein binding	IPI	19935702, 28514442, 32707033, 33961781, 36931259
GO:0005524	Function	ATP binding	IDA	9875215
GO:0005524	Function	ATP binding	IEA
GO:0006468	Process	Protein phosphorylation	IDA	9875215
GO:0007165	Process	Signal transduction	TAS	9875215
GO:0007254	Process	JNK cascade	IBA
GO:0016301	Function	Kinase activity	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0038066	Process	P38MAPK cascade	IBA
GO:0046872	Function	Metal ion binding	IEA
GO:0106310	Function	Protein serine kinase activity	IEA

Other IDs

• MIM: 604468
• HGNC: 6858
• e!Ensembl: ENSG00000142733

Protein

• UniProt ID: O95382
• Protein name: Mitogen-activated protein kinase kinase kinase 6 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 2)
• Protein function: Component of a protein kinase signal transduction cascade. Activates the JNK, but not ERK or p38 kinase pathways.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13281	DUF4071	129 → 507	Domain of unknown function (DUF4071)	Family
  PF19039	ASK_PH	521 → 620	ASK kinase PH domain	Domain
  PF00069	Pkinase	649 → 906	Protein kinase domain	Domain

• Sequence:

  MAGPCPRSGAERAGSCWQDPLAVALSRGRQLAAPPGRGCARSRPLSVVYVLTREPQPGLE
  PREGTEAEPLPLRCLREACAQVPRPRPPPQLRSLPFGTLELGDTAALDAFYNADVVVLEV
  SSSLVQPSLFYHLGVRESFSMTNNVLLCSQADLPDLQALREDVFQKNSDCVGSYTLIPYV
  VTATGRVLCGDAGLLRGLADGLVQAGVGTEALLTPLVGRLARLLEATPTDSCGYFRETIR
  RDIRQARERFSGPQLRQELARLQRRLDSVELLSPDIIMNLLLSYRDVQDYSAIIELVETL
  QALPTCDVAEQHNVCFHYTFALNRRNRPGDRAKALSVLLPLVQLEGSVAPDLYCMCGRIY
  KDMFFSSGFQDAGHREQAYHWYRKAFDVEPSLHSGINAAVLLIAAGQHFEDSKELRLIGM
  KLGCLLARKGCVEKMQYYWDVGFYLGAQILANDPTQVVLAAEQLYKLNAPIWYLVSVMET
  FLLYQHFRPTPEPPGGPPRRAHFWLHFLLQSCQPFKTACAQGDQCLVLVLEMNKVLLPAK
  LEVRGTDPVSTVTLSLLEPETQDIPSSWTFPVASICGVSASKRDERCCFLYALPPAQDVQ
  LCFPSVGHCQWFCGLIQAWVTNPDSTAPAEEAEGAGEMLEFDYEYTETGERLVLGKGTYG
  VVYAGRDRHTRVRIAIKEIPERDSRFSQPLHEEIALHRRLRHKNIVRYLGSASQGGYLKI
  FMEEVPGGSLSSLLRSVWGPLKDNESTISFYTRQILQGLGYLHDNHIVHRDIKGDNVLIN
  TFSGLLKISDFGTSKRLAGITPCTETFTGTLQYMAPEIIDQGPRGYGKAADIWSLGCTVI
  EMATGRPPFHELGSPQAAMFQVGMYKVHPPMPSSLSAEAQAFLLRTFEPDPRLRASAQTL
  LGDPFLQPGKRSRSPSSPRHAPRPSDAPSASPTPSANSTTQSQTFPCPQAPSQHPPSPPK
  RCLSYGGTSQLRVPEEPAAEEPASPEESSGLSLLHQESKRRAMLAAVLEQELPALAENLH
  QEQKQEQGARLGRNHVEELLRCLGAHIHTPNRRQLAQELRALQGRLRAQGLGPALLHRPL
  FAFPDAVKQILRKRQIRPHWMFVLDSLLSRAVRAALGVLGPEVEKEAVSPRSEELSNEGD
  SQQSPGQQSPLPVEPEQGPAPLMVQLSLLRAETDRLREILAGKEREYQALVQRALQRLNE
  EARTYVLAPEPPTALSTDQGLVQWLQELNVDSGTIQMLLNHSFTLHTLLTYATRDDLIYT
  RIRGGMVCRIWRAILAQRAGSTPVTSGP

• Sequence length: 1288

Pathways

KEGG:

MAPK signaling pathway

Associated diseases

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Acute myeloid leukemia	Uncertain significance	rs371702909	RCV005931039
Cervical cancer	Likely benign	rs55841735	RCV005906069
Cholangiocarcinoma	Likely benign	rs55841735	RCV005906077
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Likely benign	rs55841735	RCV005906079
Clear cell carcinoma of kidney	Likely benign	rs55841735	RCV005906070
Familial cancer of breast	Likely benign	rs55841735	RCV005906065
Hepatocellular carcinoma	Likely benign	rs55841735	RCV005906067
Lung cancer	Likely benign	rs55841735	RCV005906078
Lymphoma	Likely benign	rs55841735	RCV005906073
Malignant tumor of urinary bladder	Likely benign	rs55841735	RCV005906066
MAP3K6-related disorder	Benign; Likely benign; Uncertain significance	rs552271487, rs141787524, rs145528948, rs77153547, rs1138294, rs750378178, rs373729597, rs111568119, rs75893867, rs202156425, rs373777368, rs150334965, rs140079878, rs537500636, rs41291098, rs55869163, rs114560243, rs145815944, rs17162549, rs55990440, rs41291096, rs35659744, rs11247641, rs76570472, rs182712391, rs55972073, rs55841735, rs370344078, rs373458406	RCV003973802 RCV003919068 RCV003919069 RCV003921922 RCV003974733 RCV003964558 RCV003911916 RCV003916948 RCV003899498 RCV003969861 RCV003917095 RCV003919537 RCV003941560 RCV003914311 RCV003956978 RCV003956833 RCV003964310 RCV003971836 RCV003976603 RCV003976720 RCV003972314 RCV003972721 RCV003926030 RCV003978411 RCV003926232 RCV003910600 RCV003940698 RCV003977951 RCV003977952
Melanoma	Likely benign	rs55841735	RCV005906076
Nonpapillary renal cell carcinoma	Likely benign	rs55841735	RCV005906068
Ovarian serous cystadenocarcinoma	Likely benign	rs55841735	RCV005906074
Sarcoma	Likely benign	rs55841735	RCV005906072
Squamous cell carcinoma of the head and neck	Uncertain significance	rs371702909	RCV005931038
Thyroid cancer, nonmedullary, 1	Likely benign	rs55841735	RCV005906075
Uveal melanoma	Likely benign	rs55841735	RCV005906071

Associations from Text Mining
Disease Name	Relationship Type	References
Breast Neoplasms	Associate	33517263
Neoplasms	Associate	21097718, 25340522
Neoplasms	Inhibit	25340522
Prostatic Intraepithelial Neoplasia	Associate	32740981
Stomach Neoplasms	Associate	21097718, 25340522, 29330337