Reviewed, UniProtKB/Swiss-Prot Q99640 (PMYT1_HUMAN)

Names and origin

Protein names

Recommended name:
    Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase
    EC=2.7.11.1
Alternative name(s):
    Myt1 kinase

Gene names

Name:	PKMYT1
Synonyms:	MYT1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	499 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Acts as a negative regulator of entry into mitosis (G2 to M transition) by phosphorylation of the cdc2 kinase specifically when cdc2 is complexed to cyclins. Mediates phosphorylation of cdc2 predominantly on 'Thr-14'. Also involved in Golgi fragmentation. May be involved in phosphorylation of cdc2 on 'Tyr-15' to a lesser degree, however tyrosine kinase activity is unclear and may be indirect. May be a downstream target of Notch signaling pathway during eye development. Ref.2 Ref.8
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Negatively regulated by hyperphosphorylation during mitosis. The hyperphosphorylated form does not associate with CCNB1-CDC2 complexes. The PLK1 protein kinase may be required for mitotic phosphorylation. Ref.1
Subunit structure	Interacts with CDC2-CCNB1 complex. Can also interact with PIN1 when phosphorylated by CDC2-CCNB1. Ref.6 Ref.7
Subcellular location	Endoplasmic reticulum membrane; Peripheral membrane protein. Golgi apparatus membrane; Peripheral membrane protein Ref.2.
Domain	The membrane-association motif is essential for the localization to membrane of Golgi stack. According to some authors, it is a transmembrane domain; the existence of a transmembrane region is however unproven.
Post-translational modification	Autophosphorylated. Phosphorylated by CDC2-CCNB1 complexes on undefined serine and threonine residues. The phosphorylation by CDC2-CCNB1 complexes may inhibit the catalytic activity. Ref.7 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WEE1 subfamily. Contains 1 protein kinase domain.
Sequence caution	The sequence CAD28540.1 differs from that shown. Reason: Miscellaneous discrepancy. Chimeric cDNA.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Endoplasmic reticulum Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	mitosis Ref.2 Traceable author statement. Source: ProtInc protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro regulation of cyclin-dependent protein kinase activity Ref.2 Traceable author statement. Source: ProtInc regulation of mitosis Ref.2 Traceable author statement. Source: ProtInc
Cellular component	Golgi apparatus Ref.2 Traceable author statement. Source: ProtInc endoplasmic reticulum Ref.2 Traceable author statement. Source: ProtInc extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane fraction Ref.2 Traceable author statement. Source: ProtInc nucleoplasm Ref.9 Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.8 Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CCNB1	P14635	2	EBI-495308,EBI-495332
CDC2	P06493	2	EBI-495308,EBI-444308

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 499	499	Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase		PRO_0000086573
Regions
	Domain	110 – 359	250	Protein kinase
	Nucleotide binding	116 – 124	9	ATP By similarity
	Region	398 – 499	102	Interaction with PIN1
	Region	437 – 499	63	Interaction with CDC2-CCNB1
	Motif	382 – 398	17	Membrane-association motif
	Compositional bias	5 – 72	68	Pro-rich
Sites
	Active site	233	1	Proton acceptor By similarity
	Binding site	139	1	ATP By similarity
Amino acid modifications
	Modified residue	17	1	Phosphothreonine Ref.12
	Modified residue	40	1	Phosphoserine Ref.13
	Modified residue	50	1	Phosphoserine Ref.13
	Modified residue	94	1	Phosphoserine Ref.10 Ref.12
	Modified residue	120	1	Phosphoserine Ref.12 Ref.13
	Modified residue	143	1	Phosphoserine Ref.11 Ref.12
	Modified residue	160	1	Phosphoserine Ref.12
	Modified residue	426	1	Phosphoserine; by PLK1 Ref.9
	Modified residue	469	1	Phosphoserine Ref.12 Ref.13
	Modified residue	473	1	Phosphoserine Ref.13
	Modified residue	495	1	Phosphothreonine; by PLK1 Ref.9 Ref.12
Natural variations
	Natural variant	103	1	E → Q: dbSNP rs55834293. Ref.14		VAR_041034
	Natural variant	140	1	R → C: dbSNP rs4149796. Ref.14 Ref.3		VAR_019928
	Natural variant	246	1	R → H: dbSNP rs35192104. Ref.14		VAR_041035
	Natural variant	351	1	E → K: dbSNP rs56382954. Ref.14		VAR_041036
	Natural variant	417	1	P → R: dbSNP rs4149800. Ref.3		VAR_019929
	Natural variant	445	1	V → A: dbSNP rs10546. Ref.3		VAR_019930
Experimental info
	Mutagenesis	238	1	N → A: Loss of kinase activity. Ref.8
	Mutagenesis	251	1	D → A: Loss of kinase activity. Ref.7
	Mutagenesis	486 – 488	3	RNL → AAA: Loss of CDC2-CCNB1 interaction. Ref.8
	Sequence conflict	415	1	G → D in AAB71843. Ref.1
	Sequence conflict	427	1	L → F in AAB71843. Ref.1
	Sequence conflict	491	1	L → M in AAB71843. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q99640-1 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 4DF28A5965265567	FASTA	499	54,521
	10 20 30 40 50 60 MLERPPALAM PMPTEGTPPP LSGTPIPVPA YFRHAEPGFS LKRPRGLSRS LPPPPPAKGS 70 80 90 100 110 120 IPISRLFPPR TPGWHQLQPR RVSFRGEASE TLQSPGYDPS RPESFFQQSF QRLSRLGHGS 130 140 150 160 170 180 YGEVFKVRSK EDGRLYAVKR SMSPFRGPKD RARKLAEVGS HEKVGQHPCC VRLEQAWEEG 190 200 210 220 230 240 GILYLQTELC GPSLQQHCEA WGASLPEAQV WGYLRDTLLA LAHLHSQGLV HLDVKPANIF 250 260 270 280 290 300 LGPRGRCKLG DFGLLVELGT AGAGEVQEGD PRYMAPELLQ GSYGTAADVF SLGLTILEVA 310 320 330 340 350 360 CNMELPHGGE GWQQLRQGYL PPEFTAGLSS ELRSVLVMML EPDPKLRATA EALLALPVLR 370 380 390 400 410 420 QPRAWGVLWC MAAEALSRGW ALWQALLALL CWLWHGLAHP ASWLQPLGPP ATPPGSPPCS 430 440 450 460 470 480 LLLDSSLSSN WDDDSLGPSL SPEAVLARTV GSTSTPRSRC TPRDALDLSD INSEPPRGSF 490 PSFEPRNLLS LFEDTLDPT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human Myt1 is a cell cycle-regulated kinase that inhibits Cdc2 but not Cdk2 activity." Booher R.N., Holman P.S., Fattaey A. J. Biol. Chem. 272:22300-22306(1997) [PubMed: 9268380] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME REGULATION.
[2]	"The human Myt1 kinase preferentially phosphorylates Cdc2 on threonine 14 and localizes to the endoplasmic reticulum and Golgi complex." Liu F., Stanton J.J., Wu Z., Piwnica-Worms H. Mol. Cell. Biol. 17:571-583(1997) [PubMed: 9001210] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
[3]	NIEHS SNPs program Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-140; ARG-417 AND ALA-445.
[4]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed: 15616553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 403-499. Tissue: Brain.
[6]	"The essential mitotic peptidyl-prolyl isomerase Pin1 binds and regulates mitosis-specific phosphoproteins." Shen M., Stukenberg P.T., Kirschner M.W., Lu K.P. Genes Dev. 12:706-720(1998) [PubMed: 9499405] [Abstract] Cited for: INTERACTION WITH PIN1.
[7]	"The C-terminal domain of the Cdc2 inhibitory kinase Myt1 interacts with Cdc2 complexes and is required for inhibition of G(2)/M progression." Wells N.J., Watanabe N., Tokusumi T., Jiang W., Verdecia M.A., Hunter T. J. Cell Sci. 112:3361-3371(1999) [PubMed: 10504341] [Abstract] Cited for: PHOSPHORYLATION, COMPONENT OF CDC2-CCNB1 COMPLEX, INTERACTION WITH PIN1, MUTAGENESIS OF ASP-251.
[8]	"Overproduction of human Myt1 kinase induces a G2 cell cycle delay by interfering with the intracellular trafficking of Cdc2-cyclin B1 complexes." Liu F., Rothblum-Oviatt C., Ryan C.E., Piwnica-Worms H. Mol. Cell. Biol. 19:5113-5123(1999) [PubMed: 10373560] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASN-238 AND 486-ARG--LEU-488.
[9]	"Identification of a consensus motif for Plk (Polo-like kinase) phosphorylation reveals Myt1 as a Plk1 substrate." Nakajima H., Toyoshima-Morimoto F., Taniguchi E., Nishida E. J. Biol. Chem. 278:25277-25280(2003) [PubMed: 12738781] [Abstract] Cited for: PHOSPHORYLATION AT SER-426 AND THR-495.
[10]	"Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, MASS SPECTROMETRY.
[12]	"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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-17; SER-94; SER-120; SER-143; SER-160; SER-469 AND THR-495, MASS SPECTROMETRY.
[13]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40; SER-50; SER-120; SER-469 AND SER-473, MASS SPECTROMETRY.
[14]	"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: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-103; CYS-140; HIS-246 AND LYS-351.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF014118 mRNA. Translation: AAB71843.1. U56816 mRNA. Translation: AAC50949.1. AF549406 Genomic DNA. Translation: AAN40703.1. AC004233 Genomic DNA. Translation: AAC04478.1. AC004235 Genomic DNA. Translation: AAC04477.1. AL713779 mRNA. Translation: CAD28540.1. Sequence problems.
IPI	IPI00384765.
RefSeq	NP_004194.3.
UniGene	Hs.77783
3D structure databases
SMR	Q99640. Positions 108-361.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99640. 6 interactions.
STRING	Q99640.
PTM databases
PhosphoSite	Q99640.
Proteomic databases
PRIDE	Q99640.
Genome annotation databases
Ensembl	ENST00000262300; ENSP00000262300; ENSG00000127564; Homo sapiens. [Genome view] ENST00000402679; ENSP00000384251; ENSG00000127564; Homo sapiens. [Genome view]
GeneID	9088.
KEGG	hsa:9088.
UCSC	uc002csn.1. human.
Organism-specific databases
CTD	9088.
GeneCards	GC16M002962.
H-InvDB	HIX0012747.
HGNC	HGNC:29650. PKMYT1.
MIM	602474. gene.
PharmGKB	PA385.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18299.
HOVERGEN	Q99640.
InParanoid	Q99640.
PhylomeDB	Q99640.
Enzyme and pathway databases
BRENDA	2.7.11.1. 247.
Reactome	REACT_152. Cell Cycle, Mitotic.
Gene expression databases
ArrayExpress	Q99640.
Bgee	Q99640.
CleanEx	HS_MYT1. HS_PKMYT1.
Genevestigator	Q99640.
GermOnline	ENSG00000127564. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. IPR016235. Tyr/Thr_prot_kinase_Cdc2_inhib. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PIRSF	PIRSF000567. TYPK_Myt1. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	34055.
SOURCE	Search...

Entry information

Entry name

PMYT1_HUMAN

Accession

Primary (citable) accession number: Q99640
Secondary accession number(s): O14731, Q7LE24, Q8TCM9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 23, 2004
Last sequence update:	May 1, 1997
Last modified:	January 19, 2010
This is version 88 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.