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ZAK

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From Wikipedia, the free encyclopedia

Protein-coding gene in the species Homo sapiens

MAP3K20

Available structures

PDB

Ortholog search:PDBe RCSB

List of PDB id codes
5HES

Identifiers

Aliases

MAP3K20, AZK, MLK7, MLT, MLTK, MRK, mlklak, pk, ZAK, SFMMP, sterile alpha motif and leucine zipper containing kinase AZK, mitogen-activated protein kinase kinase kinase 20, MLTKalpha, MLTKbeta, CNM6

External IDs

OMIM:609479;MGI:2443258;HomoloGene:32331;GeneCards:MAP3K20;OMA:MAP3K20 - orthologs

Gene location (Human)

Chr.	Chromosome 2 (human)^[1]

Band	2q31.1	Start	173,075,435bp^[1]
Band	2q31.1	End	173,268,015bp^[1]

Gene location (Mouse)

Chr.	Chromosome 2 (mouse)^[2]

Band	2\|2 C3	Start	72,115,981bp^[2]
Band	2\|2 C3	End	72,272,954bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

right ventricle

Skeletal muscle tissue of rectus abdominis

biceps brachii

Skeletal muscle tissue of biceps brachii

body of tongue

saphenous vein

tail of epididymis

vena cava

urethra

seminal vesicula

Top expressed in

interventricular septum

temporal muscle

ankle

triceps brachii muscle

digastric muscle

extraocular muscle

sternocleidomastoid muscle

soleus muscle

atrioventricular valve

intercostal muscle

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	transferase activity nucleotide binding protein kinase activity metal ion binding kinase activity protein serine/threonine kinase activity protein binding MAP kinase kinase kinase activity ATP binding magnesium ion binding RNA binding
Cellular component	nucleus cytoplasm cytosol
Biological process	cell differentiation intracellular signal transduction cell cycle checkpoint signaling phosphorylation DNA damage checkpoint signaling response to stress cell death protein phosphorylation cytoskeleton organization positive regulation of apoptotic process cell cycle response to radiation cell population proliferation embryonic digit morphogenesis limb development mitotic cell cycle checkpoint signaling stress-activated MAPK cascade cellular response to gamma radiation
Sources:Amigo /QuickGO

Orthologs

Species

Human

Mouse

Entrez


51776


65964

Ensembl


ENSG00000091436


ENSMUSG00000004085

UniProt


Q9NYL2


Q9ESL4

RefSeq (mRNA)


NM_016653 NM_133646


NM_001164791 NM_023057 NM_178084

RefSeq (protein)


NP_057737 NP_598407


NP_001158263 NP_075544 NP_835185

Location (UCSC)

Chr 2: 173.08 – 173.27 Mb

Chr 2: 72.12 – 72.27 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Sterile alpha motif and leucine zipper containing kinase AZK, also known asZAK, is a humangene.^[5]

This gene is a member of theMAPKKK family ofsignal transduction molecules and encodes a protein with anN-terminal kinase catalytic domain, followed by aleucine zipper motif and asterile-alpha motif (SAM). This magnesium-binding protein formshomodimers and is located in the cytoplasm. The protein mediates gamma radiation signaling leading to cell cycle arrest and activity of this protein plays a role incell cycle checkpoint regulation in cells. The protein also haspro-apoptotic activity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.^[5]^[6]

Interactions

[edit]

ZAK has been shown tointeract withZNF33A.^[7]

References

[edit]

^^a ^b ^cGRCh38: Ensembl release 89: ENSG00000091436 –Ensembl, May 2017
^^a ^b ^cGRCm38: Ensembl release 89: ENSMUSG00000004085 –Ensembl, May 2017
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^^a ^b"Entrez Gene: ZAK sterile alpha motif and leucine zipper containing kinase AZK".
^Liu TC, Huang CJ, Chu YC, Wei CC, Chou CC, Chou MY, et al. (11 August 2000). "Cloning and Expression of ZAK, a Mixed Lineage Kinase-like Protein Containing a Leucine-Zipper and a Sterile-Alpha Motif".Biochemical and Biophysical Research Communications.274 (3):811–816.Bibcode:2000BBRC..274..811L.doi:10.1006/bbrc.2000.3236.PMID 10924358.
^Yang JJ (Jan 2003). "A novel zinc finger protein, ZZaPK, interacts with ZAK and stimulates the ZAK-expressing cells re-entering the cell cycle".Biochemical and Biophysical Research Communications.301 (1):71–77.Bibcode:2003BBRC..301...71Y.doi:10.1016/S0006-291X(02)02980-7.ISSN 0006-291X.PMID 12535642.

Lee JS, Lin YY, Wang TS, Liu JY, Lin WW, Yang JJ (28 February 2018). "Antitumorigenic Effects of ZAKβ, an Alternative Splicing Isoform of ZAK".The Chinese Journal of Physiology.61 (1):25–34.doi:10.4077/CJP.2018.BAG528.PMID 29374956.
Liu TC, Huang CJ, Chu YC, Wei CC, Chou CC, Chou MY, et al. (2000). "Cloning and expression of ZAK, a mixed lineage kinase-like protein containing a leucine-zipper and a sterile-alpha motif".Biochemical and Biophysical Research Communications.274 (3):811–816.Bibcode:2000BBRC..274..811L.doi:10.1006/bbrc.2000.3236.PMID 10924358.
Gotoh I, Adachi M, Nishida E (2001)."Identification and characterization of a novel MAP kinase kinase kinase, MLTK".Journal of Biological Chemistry.276 (6):4276–4286.doi:10.1074/jbc.M008595200.PMID 11042189.
Bloem LJ, Pickard TR, Acton S, Donoghue M, Beavis RC, Knierman MD, et al. (2002). "Tissue distribution and functional expression of a cDNA encoding a novel mixed lineage kinase".Journal of Molecular and Cellular Cardiology.33 (9):1739–1750.doi:10.1006/jmcc.2001.1437.PMID 11549352.
Gross EA, Callow MG, Waldbaum L, Thomas S, Ruggieri R (2002)."MRK, a mixed lineage kinase-related molecule that plays a role in gamma-radiation-induced cell cycle arrest".Journal of Biological Chemistry.277 (16):13873–13882.doi:10.1074/jbc.M111994200.PMID 11836244.
Yang JJ (2002). "Mixed lineage kinase ZAK utilizing MKK7 and not MKK4 to activate the c-Jun N-terminal kinase and playing a role in the cell arrest".Biochemical and Biophysical Research Communications.297 (1):105–110.Bibcode:2002BBRC..297..105Y.doi:10.1016/S0006-291X(02)02123-X.PMID 12220515.
Yang JJ (2003). "A novel zinc finger protein, ZZaPK, interacts with ZAK and stimulates the ZAK-expressing cells re-entering the cell cycle".Biochemical and Biophysical Research Communications.301 (1):71–77.Bibcode:2003BBRC..301...71Y.doi:10.1016/S0006-291X(02)02980-7.PMID 12535642.
Takahashi M, Gotoh Y, Isagawa T, Nishimura T, Goyama E, Kim HS, et al. (2004)."Regulation of a mitogen-activated protein kinase kinase kinase, MLTK by PKN".Journal of Biochemistry.133 (2):181–187.doi:10.1093/jb/mvg022.PMID 12761180.
Cho YY, Bode AM, Mizuno H, Choi BY, Choi HS, Dong Z (2004)."A novel role for mixed-lineage kinase-like mitogen-activated protein triple kinase alpha in neoplastic cell transformation and tumor development".Cancer Research.64 (11):3855–3864.doi:10.1158/0008-5472.CAN-04-0201.PMID 15172994.
Jin J, Smith FD, Stark C, Wells CD, Fawcett JP, Kulkarni S, et al. (2004)."Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization".Current Biology.14 (16):1436–1450.Bibcode:2004CBio...14.1436J.doi:10.1016/j.cub.2004.07.051.PMID 15324660.S2CID 2371325.
Tosti E, Waldbaum L, Warshaw G, Gross EA, Ruggieri R (2005)."The stress kinase MRK contributes to regulation of DNA damage checkpoints through a p38gamma-independent pathway".Journal of Biological Chemistry.279 (46):47652–47660.doi:10.1074/jbc.M409961200.PMID 15342622.
Huang CY, Kuo WW, Chueh PJ, Tseng CT, Chou MY, Yang JJ (2004). "Transforming growth factor-beta induces the expression of ANF and hypertrophic growth in cultured cardiomyoblast cells through ZAK".Biochemical and Biophysical Research Communications.324 (1):424–431.Bibcode:2004BBRC..324..424H.doi:10.1016/j.bbrc.2004.09.067.PMID 15465036.
Huang CY, Chueh PJ, Tseng CT, Liu KY, Tsai HY, Kuo WW, et al. (2004). "ZAK re-programs atrial natriuretic factor expression and induces hypertrophic growth in H9c2 cardiomyoblast cells".Biochemical and Biophysical Research Communications.324 (3):973–980.Bibcode:2004BBRC..324..973H.doi:10.1016/j.bbrc.2004.09.156.PMID 15485649.
Choi HS, Choi BY, Cho YY, Zhu F, Bode AM, Dong Z (2005)."Phosphorylation of Ser28 in histone H3 mediated by mixed lineage kinase-like mitogen-activated protein triple kinase alpha".Journal of Biological Chemistry.280 (14):13545–13553.doi:10.1074/jbc.M410521200.PMID 15684425.
Wang X, Mader MM, Toth JE, Yu X, Jin N, Campbell RM, et al. (2005)."Complete inhibition of anisomycin and UV radiation but not cytokine induced JNK and p38 activation by an aryl-substituted dihydropyrrolopyrazole quinoline and mixed lineage kinase 7 small interfering RNA".Journal of Biological Chemistry.280 (19):19298–19305.doi:10.1074/jbc.M413059200.PMID 15737997.
Benzinger A, Muster N, Koch HB, Yates JR 3rd, Hermeking H (2005)."Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer".Molecular & Cellular Proteomics.4 (6):785–795.doi:10.1074/mcp.M500021-MCP200.PMID 15778465.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network".Nature.437 (7062):1173–1178.Bibcode:2005Natur.437.1173R.doi:10.1038/nature04209.PMID 16189514.S2CID 4427026.

Kinases:Serine/threonine-specific protein kinases (EC 2.7.11-12)

Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20)

Non-specific serine/threonine protein kinases (EC 2.7.11.1)	LATS1 LATS2 MAST1 MAST2 STK38 STK38L CIT ROCK1 SGK SGK2 SGK3 Protein kinase B AKT1 AKT2 AKT3 Ataxia telangiectasia mutated mTOR EIF-2 kinases PKR HRI EIF2AK3 EIF2AK4 Wee1 WEE1
Pyruvate dehydrogenase kinase (EC 2.7.11.2)	PDK1 PDK2 PDK3 PDK4
Dephospho-(reductase kinase) kinase (EC 2.7.11.3)	AMP-activated protein kinase α PRKAA1 PRKAA2 β PRKAB1 PRKAB2 γ PRKAG1 PRKAG2 PRKAG3
3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase (EC 2.7.11.4)	BCKDK BCKDHA BCKDHB
(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)	IDH2 IDH3A IDH3B IDH3G
(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)	STK4
Myosin-heavy-chain kinase (EC 2.7.11.7)	Aurora kinase Aurora A kinase Aurora B kinase Aurora C kinase
Fas-activated serine/threonine kinase (EC 2.7.11.8)	FASTK STK10
Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)	-
IκB kinase (EC 2.7.11.10)	CHUK IKK2 TBK1 IKBKE IKBKG IKBKAP
cAMP-dependent protein kinase (EC 2.7.11.11)	Protein kinase A PRKACG PRKACB PRKACA PRKY
cGMP-dependent protein kinase (EC 2.7.11.12)	Protein kinase G PRKG1
Protein kinase C (EC 2.7.11.13)	Protein kinase C Protein kinase Cζ PKC alpha PRKCB1 PRKCD PRKCE PRKCH PRKCG PRKCI PRKCQ Protein kinase N1 PKN2 PKN3
Rhodopsin kinase (EC 2.7.11.14)	Rhodopsin kinase
Beta adrenergic receptor kinase (EC 2.7.11.15)	Beta adrenergic receptor kinase Beta adrenergic receptor kinase-2
G-protein coupled receptor kinases (EC 2.7.11.16)	GRK4 GRK5 GRK6
Ca2+/calmodulin-dependent (EC 2.7.11.17)	BRSK2 CAMK1 CAMK1A CAMK1B CAMK1D CAMK1G CAMK2 CAMK2A CAMK2B CAMK2D CAMK2G CAMK4 MLCK CASK CHEK1 CHEK2 DAPK1 DAPK2 DAPK3 STK11 MAPKAPK2 MAPKAPK3 MAPKAPK5 MARK1 MARK2 MARK3 MARK4 MELK MKNK1 MKNK2 NUAK1 NUAK2 OBSCN PASK PHKG1 PHKG2 PIM1 PIM2 PKD1 PRKD2 PRKD3 PSKH1 SNF1LK2 KIAA0999 STK40 SNF1LK SNRK SPEG TSSK2 Kalirin TRIB1 TRIB2 TRIB3 TRIO Titin DCLK1
Myosin light-chain kinase (EC 2.7.11.18)	MYLK MYLK2 MYLK3 MYLK4
Phosphorylase kinase (EC 2.7.11.19)	PHKA1 PHKA2 PHKB PHKG1 PHKG2
Elongation factor 2 kinase (EC 2.7.11.20)	EEF2K STK19
Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4
Cyclin-dependent kinase (EC 2.7.11.22)	CDK1 CDK2 CDKL2 CDK3 CDK4 CDK5 CDKL5 CDK6 CDK7 CDK8 CDK9 CDK10 CDK12 CDC2L5 PCTK1 PCTK2 PCTK3 PFTK1 CDC2L1
(RNA-polymerase)-subunit kinase (EC 2.7.11.23)	RPS6KA5 RPS6KA4 P70S6 kinase P70-S6 Kinase 1 RPS6KB2 RPS6KA2 RPS6KA3 RPS6KA1 RPS6KC1
Mitogen-activated protein kinase (EC 2.7.11.24)	Extracellular signal-regulated MAPK1 MAPK3 MAPK4 MAPK6 MAPK7 MAPK12 MAPK15 C-Jun N-terminal MAPK8 MAPK9 MAPK10 P38 mitogen-activated protein MAPK11 MAPK13 MAPK14
MAP3K (EC 2.7.11.25)	MAP kinase kinase kinases MAP3K1 MAP3K2 MAP3K3 MAP3K4 MAP3K5 MAP3K6 MAP3K7 MAP3K8 RAFs ARAF BRAF KSR1 KSR2 MLKs MAP3K12 MAP3K13 MAP3K9 MAP3K10 MAP3K11 MAP3K7 ZAK CDC7 MAP3K14
Tau-protein kinase (EC 2.7.11.26)	TPK1 TTK GSK-3
(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)	-
Tropomyosin kinase (EC 2.7.11.28)	-
Low-density-lipoprotein receptor kinase (EC 2.7.11.29)	-
Receptor protein serine/threonine kinase (EC 2.7.11.30)	Bone morphogenetic protein receptors BMPR1 BMPR1A BMPR1B BMPR2 ACVR1 ACVR1B ACVR1C ACVR2A ACVR2B ACVRL1 Anti-Müllerian hormone receptor

Dual-specificity kinases (EC 2.7.12)

MAP2K	MAP2K1 MAP2K2 MAP2K3 MAP2K4 MAP2K5 MAP2K6 MAP2K7

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1Oxidoreductases (list) EC2Transferases (list) EC3Hydrolases (list) EC4Lyases (list) EC5Isomerases (list) EC6Ligases (list) EC7Translocases (list)

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