Reviewed, UniProtKB/Swiss-Prot P42679 (MATK_HUMAN)

Names and origin

Protein names

Recommended name:
    Megakaryocyte-associated tyrosine-protein kinase
    EC=2.7.10.2
Alternative name(s):
    Tyrosine-protein kinase CTK
    Protein kinase HYL
    Hematopoietic consensus tyrosine-lacking kinase

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.
Sequence processing	The displayed sequence is not processed.
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.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subcellular location	Cytoplasm.
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.
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
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
Gene Ontology (GO)
Biological process	mesoderm development Ref.2 Traceable author statement. Source: ProtInc positive regulation of cell proliferation Traceable author statement. Source: ProtInc protein amino acid phosphorylation Ref.3 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from direct assay. Source: HPA
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein binding Traceable author statement. Source: ProtInc
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

Modified residue

504

1

Phosphoserine

Natural variations

Natural variant

354

1

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

VAR_041679

Natural variant

496

1

A → T

VAR_041680

Natural variant

503

1

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

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

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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)
	P42679-1 [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.
[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]	"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: Epithelium.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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

EMBLGenBankDDBJ

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

PIR

A49865.
A55625.

RefSeq

NP_647612.1.

UniGene

Hs.631845

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JWO	X-ray	2.50	A	117-213	[»]
1X6G	NMR	-	A	39-108	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P42679.

PTM databases

PhosphoSite

P42679.

Genome annotation databases

Ensembl

ENSG00000007264. Homo sapiens. [Contig view]

GeneID

4145.

KEGG

hsa:4145.

Organism-specific databases

HGNC

HGNC:6906. MATK.

HPA

HPA004847.

MIM

600038. gene.

PharmGKB

PA30649.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

P42679.

Gene expression databases

ArrayExpress

P42679.

CleanEx

HS_MATK.

GermOnline

ENSG00000007264. Homo sapiens.

Family and domain databases

InterPro

IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_bd_CS.
IPR000980. SH2.
IPR001452. SH3.
IPR015773. Tyr_kinase_megakaryocyte-assoc.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
[Graphical view]

Gene3D

G3DSA:3.30.505.10. SH2. 1 hit.

PANTHER

PTHR23256:SF134. MATK. 1 hit.

Pfam

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

PRINTS

PR00401. SH2DOMAIN.
PR00109. TYRKINASE.

ProDom

PD000001. Prot_kinase. 1 hit.
PD000093. SH2. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

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

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 Resources

LinkHub

P42679.

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:	November 25, 2008
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)