Q99640 (PMYT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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)

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 CDK1 kinase specifically when CDK1 is complexed to cyclins. Mediates phosphorylation of CDK1 predominantly on 'Thr-14'. Also involved in Golgi fragmentation. May be involved in phosphorylation of CDK1 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.9
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.7 Ref.8
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.8 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14
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: Chimeric cDNA.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Endoplasmic reticulum Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	G1/S transition of mitotic cell cycle Traceable author statement. Source: Reactome G2/M transition of mitotic cell cycle Traceable author statement. Source: Reactome mitosis Traceable author statement. Source: ProtInc negative regulation of phosphatase activity Inferred from direct assay. Source: UniProtKB regulation of cyclin-dependent protein kinase activity Traceable author statement. Source: ProtInc regulation of mitosis Traceable author statement. Source: ProtInc
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane fraction Traceable author statement. Source: ProtInc nucleoplasm Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction Ref.9. 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
CDK1	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

Metal binding

238

1

Magnesium; via carbonyl oxygen By similarity

Metal binding

251

1

Magnesium; via carbonyl oxygen By similarity

Binding site

139

1

ATP By similarity

Amino acid modifications

Modified residue

17

1

Phosphothreonine Ref.13

Modified residue

40

1

Phosphoserine Ref.14

Modified residue

50

1

Phosphoserine Ref.14

Modified residue

94

1

Phosphoserine Ref.11 Ref.13

Modified residue

120

1

Phosphoserine Ref.13 Ref.14

Modified residue

143

1

Phosphoserine Ref.12 Ref.13

Modified residue

160

1

Phosphoserine Ref.13

Modified residue

426

1

Phosphoserine; by PLK1 Ref.10

Modified residue

469

1

Phosphoserine Ref.13 Ref.14

Modified residue

473

1

Phosphoserine Ref.14

Modified residue

495

1

Phosphothreonine; by PLK1 Ref.10 Ref.13

Natural variations

Natural variant

103

1

E → Q. Ref.15
Corresponds to variant rs55834293 [ dbSNP | Ensembl ].

VAR_041034

Natural variant

140

1

R → C. Ref.3 Ref.15
Corresponds to variant rs4149796 [ dbSNP | Ensembl ].

VAR_019928

Natural variant

246

1

R → H. Ref.15
Corresponds to variant rs35192104 [ dbSNP | Ensembl ].

VAR_041035

Natural variant

351

1

E → K. Ref.15
Corresponds to variant rs56382954 [ dbSNP | Ensembl ].

VAR_041036

Natural variant

417

1

P → R. Ref.3
Corresponds to variant rs4149800 [ dbSNP | Ensembl ].

VAR_019929

Natural variant

445

1

V → A. Ref.3
Corresponds to variant rs10546 [ dbSNP | Ensembl ].

VAR_019930

Experimental info

Mutagenesis

238

1

N → A: Loss of kinase activity. Ref.9

Mutagenesis

251

1

D → A: Loss of kinase activity. Ref.8

Mutagenesis

486 – 488

3

RNL → AAA: Loss of CDC2-CCNB1 interaction. Ref.9

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

Secondary structure

1

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499

Helix Strand Turn

Details...

Beta strand

101 – 103

3

Helix

105 – 109

5

Beta strand

110 – 115

6

Beta strand

124 – 130

7

Beta strand

135 – 140

6

Beta strand

142 – 144

3

Helix

149 – 155

7

Turn

161 – 163

3

Beta strand

173 – 178

6

Beta strand

183 – 188

6

Helix

194 – 200

7

Helix

207 – 210

4

Helix

214 – 226

13

Helix

236 – 238

3

Helix

271 – 273

3

Helix

276 – 279

4

Helix

286 – 291

6

Helix

295 – 301

7

Helix

314 – 316

3

Helix

322 – 325

4

Helix

330 – 339

10

Turn

344 – 346

3

Helix

350 – 354

5

Helix

357 – 359

3

Sequences

	Sequence		Length	Mass (Da)
	Q99640 [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]	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].
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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: Cervix adenocarcinoma.
[12]	"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. Tissue: Leukemic T-cell.
[13]	"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. Tissue: Cervix carcinoma.
[14]	"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. Tissue: Cervix carcinoma.
[15]	"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.
CH471112 Genomic DNA. Translation: EAW85439.1.
CH471112 Genomic DNA. Translation: EAW85440.1.
AL713779 mRNA. Translation: CAD28540.1. Sequence problems.

IPI

IPI00384765.

RefSeq

NP_004194.3. NM_004203.4.

UniGene

Hs.77783.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3P1A	X-ray	1.70	A	75-362	[»]

ProteinModelPortal

Q99640.

SMR

Q99640. Positions 76-362.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q99640. 3 interactions.

STRING

Q99640.

PTM databases

PhosphoSite

Q99640.

Polymorphism databases

DMDM

55976573.

Proteomic databases

PRIDE

Q99640.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262300; ENSP00000262300; ENSG00000127564.
ENST00000402679; ENSP00000384251; ENSG00000127564.

GeneID

9088.

KEGG

hsa:9088.

UCSC

uc002csn.1. human.

Organism-specific databases

CTD

9088.

GeneCards

GC16M002995.

H-InvDB

HIX0012747.

HGNC

HGNC:29650. PKMYT1.

MIM

602474. gene.

neXtProt

NX_Q99640.

PharmGKB

PA385.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG18299.

GeneTree

ENSGT00530000063230.

HOVERGEN

HBG053623.

InParanoid

Q99640.

PhylomeDB

Q99640.

Enzyme and pathway databases

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_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR016235. Tyr/Thr_kinase_Cdc2_inhib.
[Graphical view]

KO

K06633.

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

PIRSF

PIRSF000567. TYPK_Myt1. 1 hit.

SUPFAM

SSF56112. Kinase_like. 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

NextBio

34055.

SOURCE

Search...

Entry information

Entry name

PMYT1_HUMAN

Accession

Primary (citable) accession number: Q99640
Secondary accession number(s): D3DUA4 , O14731, Q7LE24, Q8TCM9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 23, 2004
Last sequence update:	May 1, 1997
Last modified:	January 25, 2012
This is version 107 of the entry and version 1 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.