Reviewed, UniProtKB/Swiss-Prot P51813 (BMX_HUMAN)

Names and origin

Protein names

Recommended name:
    Cytoplasmic tyrosine-protein kinase BMX
    EC=2.7.10.2
Alternative name(s):
    Bone marrow tyrosine kinase gene in chromosome X protein
    Epithelial and endothelial tyrosine kinase
      Short name=ETK
    NTK38

Gene names

Name:

BMX

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

General annotation (Comments)

Function	Activity is required for interleukin 6 (IL-6) induced differentiation. May play a role in the growth and differentiation of hematopoietic cells. May be involved in signal transduction in endocardial and arterial endothelial cells. Ref.2
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subunit structure	Interacts with RUFY1 and RUFY2. Ref.8
Subcellular location	Cytoplasm Probable.
Tissue specificity	Preferentially expressed in epithelial and endothelial cells.
Induction	Activated by IL-6 through phosphatidylinositol 3-kinase (PI3-kinase) pathway. It is likely that activation occurs through binding of phosphoinositides to the PH domain. Ref.2
Domain	SH2 domain mediates interaction with RUFY1.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily. Contains 1 Btk-type zinc finger. Contains 1 PH domain. Contains 1 protein kinase domain. Contains 1 SH2 domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Domain	SH2 domain Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	intracellular signaling cascade Inferred from electronic annotation. Source: InterPro mesoderm development Ref.2 Traceable author statement. Source: ProtInc protein amino acid phosphorylation Ref.1 Traceable author statement. Source: ProtInc
Cellular component	centrosome Inferred from direct assay. Source: HPA cytosol Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction. Source: IntAct signal transducer activity Ref.2 Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CRK	P46108	1	EBI-696657,EBI-886
PIM1	P11309	2	EBI-696657,EBI-696621
TP53	P04637	1	EBI-696657,EBI-366083

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 675

675

Cytoplasmic tyrosine-protein kinase BMX

PRO_0000088063

Regions

Domain

4 – 111

108

PH

Domain

296 – 392

97

SH2

Domain

417 – 675

259

Protein kinase

Zinc finger

113 – 149

37

Btk-type

Nucleotide binding

423 – 431

9

ATP By similarity

Compositional bias

251 – 255

5

Poly-Ser

Compositional bias

282 – 285

4

Poly-Ser

Compositional bias

286 – 289

4

Poly-Glu

Sites

Active site

536

1

Proton acceptor By similarity

Metal binding

121

1

Zinc By similarity

Metal binding

132

1

Zinc By similarity

Metal binding

133

1

Zinc By similarity

Metal binding

143

1

Zinc By similarity

Binding site

445

1

ATP By similarity

Amino acid modifications

Modified residue

216

1

Phosphotyrosine; by autocatalysis Ref.6

Modified residue

224

1

Phosphotyrosine; by autocatalysis Ref.6

Modified residue

566

1

Phosphotyrosine; by autocatalysis By similarity

Natural variations

Natural variant

284

1

S → L: dbSNP rs35353387. Ref.10

VAR_041674

Natural variant

670

1

R → W in a lung large cell carcinoma sample; somatic mutation. Ref.10

VAR_041675

Experimental info

Sequence conflict

207

1

P → G AA sequence Ref.6

Sequence conflict

597

1

A → S in AAA17744. Ref.7

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

675

Helix Strand Turn

Details...

Beta strand

129 – 133

5

Beta strand

136 – 139

4

Beta strand

294 – 297

4

Helix

303 – 312

10

Beta strand

318 – 323

6

Beta strand

330 – 334

5

Beta strand

347 – 350

4

Beta strand

359 – 362

4

Helix

370 – 379

10

Beta strand

383 – 385

3

Sequences

	Sequence		Length	Mass (Da)
	P51813-1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: CB22382A3BD02599	FASTA	675	78,011
	10 20 30 40 50 60 MDTKSILEEL LLKRSQQKKK MSPNNYKERL FVLTKTNLSY YEYDKMKRGS RKGSIEIKKI 70 80 90 100 110 120 RCVEKVNLEE QTPVERQYPF QIVYKDGLLY VYASNEESRS QWLKALQKEI RGNPHLLVKY 130 140 150 160 170 180 HSGFFVDGKF LCCQQSCKAA PGCTLWEAYA NLHTAVNEEK HRVPTFPDRV LKIPRAVPVL 190 200 210 220 230 240 KMDAPSSSTT LAQYDNESKK NYGSQPPSSS TSLAQYDSNS KKIYGSQPNF NMQYIPREDF 250 260 270 280 290 300 PDWWQVRKLK SSSSSEDVAS SNQKERNVNH TTSKISWEFP ESSSSEEEEN LDDYDWFAGN 310 320 330 340 350 360 ISRSQSEQLL RQKGKEGAFM VRNSSQVGMY TVSLFSKAVN DKKGTVKHYH VHTNAENKLY 370 380 390 400 410 420 LAENYCFDSI PKLIHYHQHN SAGMITRLRH PVSTKANKVP DSVSLGNGIW ELKREEITLL 430 440 450 460 470 480 KELGSGQFGV VQLGKWKGQY DVAVKMIKEG SMSEDEFFQE AQTMMKLSHP KLVKFYGVCS 490 500 510 520 530 540 KEYPIYIVTE YISNGCLLNY LRSHGKGLEP SQLLEMCYDV CEGMAFLESH QFIHRDLAAR 550 560 570 580 590 600 NCLVDRDLCV KVSDFGMTRY VLDDQYVSSV GTKFPVKWSA PEVFHYFKYS SKSDVWAFGI 610 620 630 640 650 660 LMWEVFSLGK QPYDLYDNSQ VVLKVSQGHR LYRPHLASDT IYQIMYSCWH ELPEKRPTFQ 670 QLLSSIEPLR EKDKH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"BMX, a novel nonreceptor tyrosine kinase gene of the BTK/ITK/TEC/TXK family located in chromosome Xp22.2." Tamagnone L., Lahtinen I., Mustonen T., Virtaneva K., Francis F., Muscatelli F., Alitalo R.P., Smith C.I., Larsson C., Alitalo K. Oncogene 9:3683-3688(1994) [PubMed: 7970727] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Bone marrow.
[2]	"Etk/Bmx, a tyrosine kinase with a pleckstrin-homology domain, is an effector of phosphatidylinositol 3'-kinase and is involved in interleukin 6-induced neuroendocrine differentiation of prostate cancer cells." Qiu Y., Robinson D., Pretlow T., Kung H.-J. Proc. Natl. Acad. Sci. U.S.A. 95:3644-3649(1998) [PubMed: 9520419] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION. Tissue: Prostate.
[3]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases 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: Skin.
[6]	"Identification of phosphorylation sites within the SH3 domains of Tec family tyrosine kinases." Nore B.F., Mattsson P.T., Antonsson P., Backesjo C.-M., Westlund A., Lennartsson J., Hansson H., Low P., Ronnstrand L., Smith C.I.E. Biochim. Biophys. Acta 1645:123-132(2003) [PubMed: 12573241] [Abstract] Cited for: PROTEIN SEQUENCE OF 207-220 AND 223-236, PHOSPHORYLATION AT TYR-216 AND TYR-224.
[7]	Fuortes M. Thesis (1994), Cornell University, United States Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 536-599. Tissue: Blood.
[8]	"Interaction between tyrosine kinase Etk and a RUN-domain and FYVE-domain containing protein RUFY1. A possible role of Etk in regulation of vesicle trafficking." Yang J., Kim O., Wu J., Qiu Y. J. Biol. Chem. 277:30219-30226(2002) [PubMed: 11877430] [Abstract] Cited for: INTERACTION WITH RUFY1 AND RUFY2.
[9]	"Solution structure of the human BMX SH2 domain and of the BTK motif of human cytoplasmic tyrosine-protein kinase BMX." RIKEN structural genomics initiative (RSGI) Submitted (OCT-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 112-393.
[10]	"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] LEU-284 AND TRP-670.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X83107 mRNA. Translation: CAA58169.1.
AF045459 mRNA. Translation: AAC08966.1. Different initiation.
AC097625 Genomic DNA. No translation available.
CH471074 Genomic DNA. Translation: EAW98889.1.
BC016652 mRNA. Translation: AAH16652.1.
U08341 mRNA. Translation: AAA17744.1.

IPI

IPI00020899.

PIR

S60612.

RefSeq

NP_001712.1.
NP_975010.1.

UniGene

Hs.495731

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EKX	NMR	-	A	291-393	[»]
2YS2	NMR	-	A	113-149	[»]

SMR

P51813. Positions 1-111, 5-147, 415-666.

ModBase

Search...

Protein-protein interaction databases

IntAct

P51813. 4 interactions.

STRING

P51813.

PTM databases

PhosphoSite

P51813.

Proteomic databases

PRIDE

P51813.

Genome annotation databases

Ensembl

ENST00000342014; ENSP00000340082; ENSG00000102010; Homo sapiens. [Genome view]
ENST00000348343; ENSP00000308774; ENSG00000102010; Homo sapiens. [Genome view]
ENST00000357607; ENSP00000350224; ENSG00000102010; Homo sapiens. [Genome view]

GeneID

660.

KEGG

hsa:660.

UCSC

uc004cww.1. human.

Organism-specific databases

CTD

660.

GeneCards

GC0XP015392.

H-InvDB

HIX0016669.

HGNC

HGNC:1079. BMX.

HPA

HPA001048.

MIM

300101. gene.

PharmGKB

PA25389.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13898.

HOGENOM

HBG755340.

HOVERGEN

P51813.

InParanoid

P51813.

OMA

YEYDKMK.

OrthoDB

EOG9M0HKZ.

PhylomeDB

P51813.

Enzyme and pathway databases

BRENDA

2.7.10.2. 247.

Pathway_Interaction_DB

angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

P51813.

Bgee

P51813.

CleanEx

HS_BMX.

Genevestigator

P51813.

GermOnline

ENSG00000102010. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR011993. PH_type.
IPR001849. Pleckstrin_homology.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR000980. SH2.
IPR020635. Tyr_Pkinase_cat_dom.
IPR020685. Tyr_prot_kinase.
IPR008266. Tyr_prot_kinase_AS.
IPR001562. Znf_Btk_motif.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 1 hit.
G3DSA:3.30.505.10. SH2. 1 hit.

PANTHER

PTHR23256. Tyr_prot_kinase. 1 hit.

Pfam

PF00779. BTK. 1 hit.
PF00169. PH. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.
PR00402. TECBTKDOMAIN.

SMART

SM00107. BTK. 1 hit.
SM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

PROSITE

PS50003. PH_DOMAIN. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 1 hit.
PS51113. ZF_BTK. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

2684.

PMAP-CutDB

P51813.

SOURCE

Search...

Entry information

Entry name

BMX_HUMAN

Accession

Primary (citable) accession number: P51813
Secondary accession number(s): A6NIH9, O60564, Q12871

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	February 9, 2010
This is version 103 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.