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FLASH GENE

Symbol

MAP4K1

contributors: mct/npt - updated : 27-05-2019

HGNC name	mitogen-activated protein kinase kinase kinase kinase 1
HGNC id	6863

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	19q13.2      Physical location : 39.078.280 - 39.108.643
Synonym name	hematopoietic progenitor kinase 1
	MEK kinase kinase 1
	MAPK/ERK kinase kinase kinase 1
Synonym symbol(s)	HPK1
EC.number	2.7.11.1

DNA

TYPE	functioning gene
STRUCTURE	30.36 kb     31 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

Map	cen - D19S425 - D19S208 - D19S224 - SCN1B - D19S228 - D19S421 - D19S223 - MAP4K1 - D19S211 - D19S219 - D19S412 - D19S606 - D19S907 - KLK1 - RPS9 - D19S571 - D19S927 - D19S418 - qter
Authors	Gene Map (98)

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001042600 31 - 2681 NP_001036065 - 821 - - NM_007181 32 - 2779 NP_009112 91.3 833 - -

EXPRESSION

Type

expressed in	(based on citations)
organ(s)

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Connective bone

cell lineage	predominantly, in hematopoietic cells
cell lines
fluid/secretion

at STAGE

physiological period

fetal

Text

liver

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an N-terminal kinase domain, HPK1-N, comprising the kinase domain, confering progenitor cell survival independent of the growth factor IL3 (Arnold 2007)
	a C-terminal citron homology (CNH) domain, HPK1-C, suppresses NF-kappaB and sensitizes toward activation-induced cell death by a yet undefined cell death pathway (Brenner 2007)

HOMOLOGY

interspecies

homolog to murine Map4k1

Homologene

FAMILY	protein kinase superfamily
	STE Ser/Thr protein kinase family
	STE20 subfamily

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus

basic FUNCTION	activation of JUN kinase in the MEKK/JNK/SAPK signaling pathway
	protein phosphorylation (serine/threonine kinase) activity
	stress response
	essential for NF-kappaB activation in T cells (Brenner 2007)
	kinase specific for CARD11 and MAP4K1-mediated phosphorylation of CARD11 as an additional regulatory mechanism tuning the NF-KB response upon TCR stimulation (Brenner 2009)
	regulator of TCR-mediated NF-KB activation and that NF-KB activation via MAP4K1 is dependent on CARD11 (Brenner 2009)
	may function as a novel tumor suppressor and its loss plays a critical role in pancreatic cancer (Wang 2009)
	regulates stress responses, proliferation, and apoptosis in hematopoietic cells (Wang 2009)
	regulates stress responses, proliferation, and apoptosis in hematopoietic cells

CELLULAR PROCESS

protein, post translation

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacts with CARD11 in a TCR stimulation-dependent manner and phosphorylates the linker region of CARD11 (Brenner 2009)
	CUL7/FBXW8 ubiquitin ligase-mediated MAP4K1 degradation revealed a direct link and novel role of CUL7/FBXW8 ubiquitin ligase in the MAPK pathway, which plays a critical role in cell proliferation and differentiation
	PDIA6 interacted with MAP4K1 and inhibited its phosphorylation, ultimately inhibiting the JNK/JUN signaling pathway

cell & other

REGULATION

activated by

phosphorylation

ASSOCIATED DISORDERS

ANIMAL & CELL MODELS