Q9NYL2 (MLTK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase kinase kinase MLT
EC=2.7.11.25

Alternative name(s):
Human cervical cancer suppressor gene 4 protein
Short name=HCCS-4
Leucine zipper- and sterile alpha motif-containing kinase
MLK-like mitogen-activated protein triple kinase
Mixed lineage kinase-related kinase
Short name=MLK-related kinase
Short name=MRK
Sterile alpha motif- and leucine zipper-containing kinase AZK

Gene names

Name:	MLTK
Synonyms:	ZAK
ORF Names:	HCCS4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	800 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Stress-activated component of a protein kinase signal transduction cascade. Regulates the JNK and p38 pathways. Pro-apoptotic. Role in regulation of S and G2 cell cycle checkpoint by direct phosphorylation of CHEK2. Isoform 1, but not isoform 2, causes cell shrinkage and disruption of actin stress fibers. Isoform 1 may have role in neoplastic cell transformation and cancer development. Isoform 1, but not isoform 2, phosphorylates histone H3 at 'Ser-28'. Ref.1 Ref.2 Ref.4 Ref.15 Ref.16 Ref.17
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.4
Cofactor	Magnesium. Ref.4
Enzyme regulation	Activated by phosphorylation by PKN1 and autophosphorylation on Thr-161 and Ser-165. Ref.2 Ref.14 Ref.16
Subunit structure	Homodimer. Interacts with PKN1 and ZNF33A. Ref.1 Ref.13 Ref.14
Subcellular location	Cytoplasm. Nucleus. Note: Translocates to the nucleus upon ultraviolet B irradiation. Ref.17
Tissue specificity	Ubiquitously expressed. Isoform 2 is the predominant form in all tissues examined, except for liver, in which isoform 1 is more highly expressed. Ref.1 Ref.4
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. Contains 1 protein kinase domain. Contains 1 SAM (sterile alpha motif) domain.
Sequence caution	The sequence BAD92211.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA damage checkpoint Inferred from mutant phenotype Ref.4. Source: UniProtKB activation of JUN kinase activity Inferred from direct assay Ref.4. Source: UniProtKB cell cycle arrest Inferred from mutant phenotype Ref.4. Source: UniProtKB cell death Non-traceable author statement Ref.4. Source: UniProtKB cell differentiation Non-traceable author statement Ref.4. Source: UniProtKB cell proliferation Non-traceable author statement Ref.4. Source: UniProtKB cytoskeleton organization Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from direct assay Ref.1. Source: UniProtKB response to radiation Inferred from direct assay Ref.4. Source: UniProtKB
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from direct assay Ref.4. Source: UniProtKB MAP kinase kinase kinase activity Inferred from direct assay Ref.4. Source: UniProtKB magnesium ion binding Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PKN1	Q16512	2	EBI-687346,EBI-602382
RPS6KA5	O75582	4	EBI-602273,EBI-73869
YWHAZ	P63104	4	EBI-602273,EBI-347088

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 Ref.2 (identifier: Q9NYL2-1)

Also known as: Alpha;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 Ref.2 (identifier: Q9NYL2-2)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     332-455: PSFEIGAWTE...LKPGTGPQDC → LPLAARMSEE...EEDNDMDNSE
     456-800: Missing.

Note: Contains a phosphoserine at position 339. Contains a phosphoserine at position 429. Contains a phosphoserine at position 434. Contains a phosphoserine at position 454.

Isoform 3 Ref.6 (identifier: Q9NYL2-3)

Also known as: HCCS-4;

The sequence of this isoform differs from the canonical sequence as follows:
     285-312: CEIEATLERLKKLERDLSFKEQELKERE → WVAPTAGHSVWLSKTITRLNEEVNQRSE
     313-800: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 800	800	Mitogen-activated protein kinase kinase kinase MLT		PRO_0000086338
Regions
	Domain	16 – 277	262	Protein kinase
	Domain	339 – 410	72	SAM
	Nucleotide binding	22 – 30	9	ATP By similarity UniProtKB P80192
	Region	287 – 308	22	Leucine-zipper
Sites
	Active site	133	1	Proton acceptor By similarity UniProtKB P80192
	Binding site	45	1	ATP Ref.4
Amino acid modifications
	Modified residue	2	1	Phosphoserine
	Modified residue	3	1	Phosphoserine
	Modified residue	155	1	Phosphoserine
	Modified residue	161	1	Phosphothreonine; by autocatalysis Ref.16
	Modified residue	165	1	Phosphoserine; by autocatalysis Ref.16
	Modified residue	264	1	Phosphoserine
	Modified residue	268	1	Phosphoserine
	Modified residue	275	1	Phosphoserine
	Modified residue	302	1	Phosphoserine
	Modified residue	326	1	Phosphoserine
	Modified residue	328	1	Phosphothreonine
	Modified residue	557	1	Phosphoserine
	Modified residue	565	1	Phosphoserine
	Modified residue	568	1	Phosphoserine
	Modified residue	584	1	Phosphoserine
	Modified residue	586	1	Phosphothreonine
	Modified residue	591	1	Phosphoserine
	Modified residue	593	1	Phosphoserine
	Modified residue	599	1	Phosphoserine Ref.19
	Modified residue	628	1	Phosphothreonine Ref.18 Ref.19 Ref.20
	Modified residue	633	1	Phosphoserine Ref.19 Ref.20 Ref.21
	Modified residue	635	1	Phosphoserine
	Modified residue	636	1	Phosphoserine
	Modified residue	637	1	Phosphoserine
	Modified residue	639	1	Phosphothreonine
	Modified residue	648	1	Phosphoserine
	Modified residue	660	1	Phosphoserine
	Modified residue	666	1	Phosphothreonine
	Modified residue	667	1	Phosphoserine
	Modified residue	668	1	Phosphoserine
	Modified residue	687	1	Phosphoserine
	Modified residue	690	1	Phosphoserine
	Modified residue	691	1	Phosphoserine
	Modified residue	718	1	Phosphoserine
	Modified residue	727	1	Phosphoserine Ref.18 Ref.19 Ref.20 Ref.22
	Modified residue	733	1	Phosphoserine Ref.18 Ref.19
	Modified residue	754	1	Phosphoserine
	Modified residue	781	1	Phosphoserine
Natural variations
	Alternative sequence	285 – 312	28	CEIEA…LKERE → WVAPTAGHSVWLSKTITRLN EEVNQRSE in isoform 3. Ref.6		VSP_051741
	Alternative sequence	313 – 800	488	Missing in isoform 3. Ref.6		VSP_051742
	Alternative sequence	332 – 455	124	PSFEI…GPQDC → LPLAARMSEESYFESKTEES NSAEMSCQITATSNGEGHGM NPSLQAMMLMGFGDIFSMNK AGAVMHSGMQINMQAKQNSS KTTSKRRGKKVNMALGFSDF DLSEGDDDDDDDGEEEDNDM DNSE in isoform 2. Ref.2		VSP_051743
	Alternative sequence	456 – 800	345	Missing in isoform 2. Ref.2		VSP_051744
	Natural variant	267	1	T → M. Ref.24 Corresponds to variant rs6758025 [ dbSNP | Ensembl ].		VAR_040806
	Natural variant	281	1	A → T in an ovarian endometrioid sample; somatic mutation. Ref.24		VAR_040807
	Natural variant	281	1	A → V. Ref.24 Corresponds to variant rs34683477 [ dbSNP | Ensembl ].		VAR_040808
	Natural variant	531	1	S → L. Ref.1 Ref.2 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.24 Corresponds to variant rs3769148 [ dbSNP | Ensembl ].		VAR_022827
	Natural variant	580	1	R → W. Ref.24 Corresponds to variant rs7593622 [ dbSNP | Ensembl ].		VAR_040809
	Natural variant	740	1	P → T. Ref.24 Corresponds to variant rs56202258 [ dbSNP | Ensembl ].		VAR_040810
	Natural variant	773	1	Y → H. Ref.24 Corresponds to variant rs35608243 [ dbSNP | Ensembl ].		VAR_040811
	Natural variant	784	1	K → T. Ref.9 Ref.24 Corresponds to variant rs55830025 [ dbSNP | Ensembl ].		VAR_040812
Experimental info
	Mutagenesis	45	1	K → M: Loss of kinase activity. Ref.4
	Mutagenesis	161	1	T → A: Loss of autophosphorylation activity. Ref.16
	Mutagenesis	162	1	T → A: Slight loss of autophosphorylation activity. Ref.16
	Mutagenesis	165	1	S → A: Loss of autophosphorylation activity. Ref.16
	Sequence conflict	346	1	C → W in AAF63490. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Alpha) [UniParc]. Last modified November 30, 2010. Version 3. Checksum: B2814509EC54B07A	FASTA	800	91,155
	10 20 30 40 50 60 MSSLGASFVQ IKFDDLQFFE NCGGGSFGSV YRAKWISQDK EVAVKKLLKI EKEAEILSVL 70 80 90 100 110 120 SHRNIIQFYG VILEPPNYGI VTEYASLGSL YDYINSNRSE EMDMDHIMTW ATDVAKGMHY 130 140 150 160 170 180 LHMEAPVKVI HRDLKSRNVV IAADGVLKIC DFGASRFHNH TTHMSLVGTF PWMAPEVIQS 190 200 210 220 230 240 LPVSETCDTY SYGVVLWEML TREVPFKGLE GLQVAWLVVE KNERLTIPSS CPRSFAELLH 250 260 270 280 290 300 QCWEADAKKR PSFKQIISIL ESMSNDTSLP DKCNSFLHNK AEWRCEIEAT LERLKKLERD 310 320 330 340 350 360 LSFKEQELKE RERRLKMWEQ KLTEQSNTPL LPSFEIGAWT EDDVYCWVQQ LVRKGDSSAE 370 380 390 400 410 420 MSVYASLFKE NNITGKRLLL LEEEDLKDMG IVSKGHIIHF KSAIEKLTHD YINLFHFPPL 430 440 450 460 470 480 IKDSGGEPEE NEEKIVNLEL VFGFHLKPGT GPQDCKWKMY MEMDGDEIAI TYIKDVTFNT 490 500 510 520 530 540 NLPDAEILKM TKPPFVMEKW IVGIAKSQTV ECTVTYESDV RTPKSTKHVH SIQWSRTKPQ 550 560 570 580 590 600 DEVKAVQLAI QTLFTNSDGN PGSRSDSSAD CQWLDTLRMR QIASNTSLQR SQSNPILGSP 610 620 630 640 650 660 FFSHFDGQDS YAAAVRRPQV PIKYQQITPV NQSRSSSPTQ YGLTKNFSSL HLNSRDSGFS 670 680 690 700 710 720 SGNTDTSSER GRYSDRSRNK YGRGSISLNS SPRGRYSGKS QHSTPSRGRY PGKFYRVSQS 730 740 750 760 770 780 ALNPHQSPDF KRSPRDLHQP NTIPGMPLHP ETDSRASEED SKVSEGGWTK VEYRKKPHRP 790 800 SPAKTNKERA RGDHRGWRNF
	Isoform 2 (Beta) [UniParc]. Checksum: E87DB84A4D58B752	FASTA	455	51,582
	10 20 30 40 50 60 MSSLGASFVQ IKFDDLQFFE NCGGGSFGSV YRAKWISQDK EVAVKKLLKI EKEAEILSVL 70 80 90 100 110 120 SHRNIIQFYG VILEPPNYGI VTEYASLGSL YDYINSNRSE EMDMDHIMTW ATDVAKGMHY 130 140 150 160 170 180 LHMEAPVKVI HRDLKSRNVV IAADGVLKIC DFGASRFHNH TTHMSLVGTF PWMAPEVIQS 190 200 210 220 230 240 LPVSETCDTY SYGVVLWEML TREVPFKGLE GLQVAWLVVE KNERLTIPSS CPRSFAELLH 250 260 270 280 290 300 QCWEADAKKR PSFKQIISIL ESMSNDTSLP DKCNSFLHNK AEWRCEIEAT LERLKKLERD 310 320 330 340 350 360 LSFKEQELKE RERRLKMWEQ KLTEQSNTPL LLPLAARMSE ESYFESKTEE SNSAEMSCQI 370 380 390 400 410 420 TATSNGEGHG MNPSLQAMML MGFGDIFSMN KAGAVMHSGM QINMQAKQNS SKTTSKRRGK 430 440 450 KVNMALGFSD FDLSEGDDDD DDDGEEEDND MDNSE
	Isoform 3 (HCCS-4) [UniParc]. Checksum: B655E873246339FB	FASTA	312	35,468
	10 20 30 40 50 60 MSSLGASFVQ IKFDDLQFFE NCGGGSFGSV YRAKWISQDK EVAVKKLLKI EKEAEILSVL 70 80 90 100 110 120 SHRNIIQFYG VILEPPNYGI VTEYASLGSL YDYINSNRSE EMDMDHIMTW ATDVAKGMHY 130 140 150 160 170 180 LHMEAPVKVI HRDLKSRNVV IAADGVLKIC DFGASRFHNH TTHMSLVGTF PWMAPEVIQS 190 200 210 220 230 240 LPVSETCDTY SYGVVLWEML TREVPFKGLE GLQVAWLVVE KNERLTIPSS CPRSFAELLH 250 260 270 280 290 300 QCWEADAKKR PSFKQIISIL ESMSNDTSLP DKCNSFLHNK AEWRWVAPTA GHSVWLSKTI 310 TRLNEEVNQR SE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of ZAK, a mixed lineage kinase-like protein containing a leucine-zipper and a sterile-alpha motif." Liu T.-C., Huang C.-J., Chu Y.-C., Wei C.-C., Chou C.-C., Chou M.-Y., Chou C.-K., Yang J.-J. Biochem. Biophys. Res. Commun. 274:811-816(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, HOMODIMERIZATION, VARIANT LEU-531. Tissue: Placenta.
[2]	"Identification and characterization of a novel MAP kinase kinase kinase, MLTK." Gotoh I., Adachi M., Nishida E. J. Biol. Chem. 276:4276-4286(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, PHOSPHORYLATION, VARIANT LEU-531. Tissue: Fetal brain.
[3]	"Tissue distribution and functional expression of a cDNA encoding a novel mixed lineage kinase." Bloem L.J., Pickard T.R., Acton S., Donoghue M., Beavis R.C., Knierman M.D., Wang X. J. Mol. Cell. Cardiol. 33:1739-1750(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Heart.
[4]	"MRK, a mixed lineage kinase-related molecule that plays a role in gamma-radiation-induced cell cycle arrest." Gross E.A., Callow M.G., Waldbaum L., Thomas S., Ruggieri R. J. Biol. Chem. 277:13873-13882(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-45, VARIANT LEU-531. Tissue: T-cell.
[5]	"Placible mixed-lineage kinase derived from LAK cell." Abe Y., Ueda N. Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Lymphoid tissue.
[6]	"Cloning and characterisation of AZK, a mixed lineage kinase containing a sterile-alpha motif." McNee J.J., Frima N., Diamond T.E., Dower S.K., Guesdon F. Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-531.
[7]	"Identification of a new tumor suppressor in human cancers." Kim J.W. Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[8]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[9]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT THR-784. Tissue: Brain.
[10]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Colon.
[13]	"A novel zinc finger protein, ZZaPK, interacts with ZAK and stimulates the ZAK-expressing cells re-entering the cell cycle." Yang J.-J. Biochem. Biophys. Res. Commun. 301:71-77(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ZNF33A.
[14]	"Regulation of a mitogen-activated protein kinase kinase kinase, MLTK by PKN." Takahashi M., Gotoh Y., Isagawa T., Nishimura T., Goyama E., Kim H.-S., Mukai H., Ono Y. J. Biochem. 133:181-187(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH PKN1.
[15]	"A novel role for mixed-lineage kinase-like mitogen-activated protein triple kinase alpha in neoplastic cell transformation and tumor development." Cho Y.-Y., Bode A.M., Mizuno H., Choi B.Y., Choi H.S., Dong Z. Cancer Res. 64:3855-3864(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[16]	"The stress kinase MRK contributes to regulation of DNA damage checkpoints through a p38gamma-independent pathway." Tosti E., Waldbaum L., Warshaw G., Gross E.A., Ruggieri R. J. Biol. Chem. 279:47652-47660(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DNA DAMAGE CHECKPOINTS, FUNCTION IN PHOSPHORYLATION OF CHEK2, ENZYME REGULATION, PHOSPHORYLATION AT THR-161 AND SER-165, MUTAGENESIS OF THR-161; THR-162 AND SER-165.
[17]	"Phosphorylation of Ser28 in histone H3 mediated by mixed lineage kinase-like mitogen-activated protein triple kinase alpha." Choi H.S., Choi B.Y., Cho Y.-Y., Zhu F., Bode A.M., Dong Z. J. Biol. Chem. 280:13545-13553(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF HISTONE H3, SUBCELLULAR LOCATION.
[18]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-628; SER-727 AND SER-733, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-599; THR-628; SER-633; SER-727 AND SER-733, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[20]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-628; SER-633 AND SER-727, MASS SPECTROMETRY.
[21]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-633, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[22]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[23]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] MET-267; THR-281; VAL-281; LEU-531; TRP-580; THR-740; HIS-773 AND THR-784.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF238255 mRNA. Translation: AAF63490.1. AB049733 mRNA. Translation: BAB16444.1. AB049734 mRNA. Translation: BAB16445.1. AF325454 mRNA. Translation: AAK11615.1. AF480461 mRNA. Translation: AAL85891.1. AF480462 mRNA. Translation: AAL85892.1. AB030034 mRNA. Translation: BAB12040.1. AF251441 mRNA. Translation: AAF65822.1. AF465843 mRNA. Translation: AAO33376.1. AK056310 mRNA. Translation: BAG51674.1. AB208974 mRNA. Translation: BAD92211.1. Different initiation. AC092573 Genomic DNA. Translation: AAX82002.1. AC013461 Genomic DNA. Translation: AAX93067.1. AC019046 Genomic DNA. No translation available. CH471058 Genomic DNA. Translation: EAX11164.1. BC001401 mRNA. Translation: AAH01401.1.
IPI	IPI00029643. IPI00329638. IPI00384771.
RefSeq	NP_057737.2. NM_016653.2. NP_598407.1. NM_133646.2.
UniGene	Hs.444451.
3D structure databases
ProteinModelPortal	Q9NYL2.
SMR	Q9NYL2. Positions 9-325.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NYL2. 4 interactions.
MINT	MINT-1465549.
PTM databases
PhosphoSite	Q9NYL2.
Polymorphism databases
DMDM	68565548.
Proteomic databases
PaxDb	Q9NYL2.
PRIDE	Q9NYL2.
Protocols and materials databases
DNASU	51776.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	51776.
KEGG	hsa:51776.
UCSC	uc002uhx.3. human. uc002uhz.3. human.
Organism-specific databases
CTD	51776.
GeneCards	GC02P173940.
H-InvDB	HIX0030332.
HPA	HPA017205.
MIM	609479. gene.
neXtProt	NX_Q9NYL2.
Phylogenomic databases
eggNOG	COG0515.
HOVERGEN	HBG080445.
KO	K04424.
OMA	LHSGMQI.
Enzyme and pathway databases
Pathway_Interaction_DB	p38gammadeltapathway. Signaling mediated by p38-gamma and p38-delta.
Gene expression databases
ArrayExpress	Q9NYL2.
Bgee	Q9NYL2.
Genevestigator	Q9NYL2.
GermOnline	ENSG00000091436. Homo sapiens.
Family and domain databases
Gene3D	1.10.150.50. 1 hit.
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR001660. SAM. IPR013761. SAM/pointed. IPR021129. SAM_type1. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF00536. SAM_1. 1 hit. [Graphical view]
PRINTS	PR00109. TYRKINASE.
SMART	SM00454. SAM. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF47769. SAM_homology. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS50105. SAM_DOMAIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9NYL2.
ChEMBL	CHEMBL3886.
ChiTaRS	ZAK. human.
GenomeRNAi	51776.
NextBio	55903.
SOURCE	Search...

Entry information

Entry name

MLTK_HUMAN

Accession

Primary (citable) accession number: Q9NYL2
Secondary accession number(s): B3KPG2 , Q53SX1, Q580W8, Q59GY5, Q86YW8, Q9HCC4, Q9HCC5, Q9HDD2, Q9NYE9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 5, 2005
Last sequence update:	November 30, 2010
Last modified:	May 1, 2013
This is version 115 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.