P42679 (MATK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Megakaryocyte-associated tyrosine-protein kinase
EC=2.7.10.2

Alternative name(s):
CSK homologous kinase
Short name=CHK
Hematopoietic consensus tyrosine-lacking kinase
Protein kinase HYL
Tyrosine-protein kinase CTK

Gene names

Name:	MATK
Synonyms:	CTK, HYL

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	507 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Could play a significant role in the signal transduction of hematopoietic cells. May regulate tyrosine kinase activity of SRC-family members in brain by specifically phosphorylating their C-terminal regulatory tyrosine residue which acts as a negative regulatory site. It may play an inhibitory role in the control of T-cell proliferation. Ref.7
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with KIT. Ref.8
Subcellular location	Cytoplasm. Membrane. Note: In platelets, 90% of MATK localizes to the membrane fraction, and translocates to the cytoskeleton upon thrombin stimulation. Ref.7
Tissue specificity	Expressed in various myeloid cell lines, detected in brain and lung.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. CSK subfamily. Contains 1 protein kinase domain. Contains 1 SH2 domain. Contains 1 SH3 domain.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell proliferation Traceable author statement. Source: ProtInc mesoderm development Traceable author statement. Source: ProtInc positive regulation of cell proliferation Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 507

507

Megakaryocyte-associated tyrosine-protein kinase

PRO_0000088073

Regions

Domain

58 – 110

53

SH3

Domain

122 – 211

90

SH2

Domain

235 – 482

248

Protein kinase

Nucleotide binding

241 – 249

9

ATP By similarity

Sites

Active site

352

1

Proton acceptor By similarity

Binding site

262

1

ATP By similarity

Amino acid modifications

Modified residue

501

1

Phosphoserine Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15

Modified residue

504

1

Phosphoserine Ref.11

Natural variations

Natural variant

354

1

A → T in an ovarian mucinous carcinoma sample; somatic mutation. Ref.17

VAR_041679

Natural variant

496

1

A → T. Ref.17
Corresponds to variant rs35351680 [ dbSNP | Ensembl ].

VAR_041680

Natural variant

503

1

R → Q in a colorectal adenocarcinoma sample; somatic mutation. Ref.17

VAR_041681

Experimental info

Sequence conflict

107 – 108

2

ER → DG in AAA16703. Ref.1

Sequence conflict

400

1

Missing in AAA16703. Ref.1

Sequence conflict

466 – 507

42

ARRPP…RSQEP → PAGHPSANWPRSWPGSYAVQ VPQPPSQGRTPTVHLAPKPG ALTPPGGPWPQRTERVESAA WGH in AAA16703. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

507

Helix Strand Turn

Details...

Beta strand

52 – 57

6

Beta strand

59 – 61

3

Beta strand

74 – 79

6

Beta strand

83 – 91

9

Turn

92 – 94

3

Beta strand

97 – 101

5

Helix

102 – 104

3

Beta strand

105 – 107

3

Beta strand

123 – 126

4

Helix

129 – 135

7

Beta strand

144 – 148

5

Beta strand

150 – 152

3

Beta strand

156 – 162

7

Beta strand

165 – 180

16

Beta strand

183 – 187

5

Helix

189 – 198

10

Beta strand

203 – 205

3

Sequences

	Sequence		Length	Mass (Da)
	P42679 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 85721C6E024575EF	FASTA	507	56,469
	10 20 30 40 50 60 MAGRGSLVSW RAFHGCDSAE ELPRVSPRFL RAWHPPPVSA RMPTRRWAPG TQCITKCEHT 70 80 90 100 110 120 RPKPGELAFR KGDVVTILEA CENKSWYRVK HHTSGQEGLL AAGALREREA LSADPKLSLM 130 140 150 160 170 180 PWFHGKISGQ EAVQQLQPPE DGLFLVRESA RHPGDYVLCV SFGRDVIHYR VLHRDGHLTI 190 200 210 220 230 240 DEAVFFCNLM DMVEHYSKDK GAICTKLVRP KRKHGTKSAE EELARAGWLL NLQHLTLGAQ 250 260 270 280 290 300 IGEGEFGAVL QGEYLGQKVA VKNIKCDVTA QAFLDETAVM TKMQHENLVR LLGVILHQGL 310 320 330 340 350 360 YIVMEHVSKG NLVNFLRTRG RALVNTAQLL QFSLHVAEGM EYLESKKLVH RDLAARNILV 370 380 390 400 410 420 SEDLVAKVSD FGLAKAERKG LDSSRLPVKW TAPEALKHGK FTSKSDVWSF GVLLWEVFSY 430 440 450 460 470 480 GRAPYPKMSL KEVSEAVEKG YRMEPPEGCP GPVHVLMSSC WEAEPARRPP FRKLAEKLAR 490 500 ELRSAGAPAS VSGQDADGST SPRSQEP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a novel non-receptor tyrosine kinase, HYL (hematopoietic consensus tyrosine-lacking kinase)." Sakano S., Iwama A., Inazawa J., Ariyama T., Ohno M., Suda T. Oncogene 9:1155-1161(1994) [PubMed: 8134117] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Identification and characterization of a novel tyrosine kinase from megakaryocytes." Bennett B.D., Cowley S., Jiang S., London R., Deng B., Grabarek J., Groopman J.E., Goeddel D.V., Avraham H. J. Biol. Chem. 269:1068-1074(1994) [PubMed: 8288563] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Megakaryocyte.
[3]	"Structural and functional studies of the intracellular tyrosine kinase MATK gene and its translated product." Avraham S., Jiang S., Ota S., Fu Y., Deng B., Dowler L.L., White R.A., Avraham H. J. Biol. Chem. 270:1833-1842(1995) [PubMed: 7530249] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye.
[6]	"Characterization of mouse non-receptor tyrosine kinase gene, HYL." Hamaguchi I., Iwama A., Yamaguchi N., Sakano S., Matsuda Y., Suda T. Oncogene 9:3371-3374(1994) [PubMed: 7936664] [Abstract] Cited for: CHARACTERIZATION.
[7]	"Translocation of the Csk homologous kinase (Chk/Hyl) controls activity of CD36-anchored Lyn tyrosine kinase in thrombin-stimulated platelets." Hirao A., Hamaguchi I., Suda T., Yamaguchi N. EMBO J. 16:2342-2351(1997) [PubMed: 9171348] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION. Tissue: Platelet.
[8]	"Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes." Price D.J., Rivnay B., Fu Y., Jiang S., Avraham S., Avraham H. J. Biol. Chem. 272:5915-5920(1997) [PubMed: 9038210] [Abstract] Cited for: INTERACTION WITH KIT.
[9]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-501, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor." Roskoski R. Jr. Biochem. Biophys. Res. Commun. 337:1-13(2005) [PubMed: 16129412] [Abstract] Cited for: REVIEW ON ROLE IN KIT SIGNALING.
[11]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-501 AND SER-504, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[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 SER-501, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[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-501, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-501, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[15]	"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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-501, MASS SPECTROMETRY.
[16]	"Solution structures of the SH3 domain of human megakaryocyte-associated tyrosine-protein kinase." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 39-108.
[17]	"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] THR-354; THR-496 AND GLN-503.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L18974 mRNA. Translation: AAA16703.1.
X77278 mRNA. Translation: CAA54493.1.
S75164 , S75145, S75147, S75166, S75168, S75151, S75153, S75155, S75156, S75158, S75159, S75162 Genomic DNA. Translation: AAC60645.1.
AC005777 Genomic DNA. Translation: AAC62843.1.
BC000114 mRNA. Translation: AAH00114.1.
BC003109 mRNA. Translation: AAH03109.1.

IPI

IPI00000868.

PIR

A49865.
A55625.

RefSeq

NP_002369.2. NM_002378.3.
NP_647611.1. NM_139354.2.
NP_647612.1. NM_139355.2.

UniGene

Hs.631845.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JWO	X-ray	2.50	A	117-213	[»]
1X6G	NMR	-	A	41-108	[»]

ProteinModelPortal

P42679.

SMR

P42679. Positions 39-486.

ModBase

Search...

Protein-protein interaction databases

IntAct

P42679. 1 interaction.

MINT

MINT-1496198.

STRING

P42679.

PTM databases

PhosphoSite

P42679.

Polymorphism databases

DMDM

1169123.

Proteomic databases

PRIDE

P42679.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000310132; ENSP00000308734; ENSG00000007264.

GeneID

4145.

KEGG

hsa:4145.

UCSC

uc002lyt.1. human.

Organism-specific databases

CTD

4145.

GeneCards

GC19M003777.

HGNC

HGNC:6906. MATK.

HPA

HPA004847.

MIM

600038. gene.

neXtProt

NX_P42679.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08992.

HOVERGEN

HBG008761.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

Pathway_Interaction_DB

trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).

Gene expression databases

ArrayExpress

P42679.

Bgee

P42679.

CleanEx

HS_MATK.

Genevestigator

P42679.

GermOnline

ENSG00000007264. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]

Gene3D

G3DSA:3.30.505.10. SH2. 1 hit.

KO

K08888.

Pfam

PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.
PR00109. TYRKINASE.

SMART

SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.
SSF50044. SH3. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

16280.

SOURCE

Search...

Entry information

Entry name

MATK_HUMAN

Accession

Primary (citable) accession number: P42679

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	January 25, 2012
This is version 131 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.