P97504 (BMX_MOUSE) Reviewed, UniProtKB/Swiss-Prot

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 homolog

Gene names

Name:

Bmx

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	651 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Non-receptor tyrosine kinase that plays central but diverse modulatory roles in various signaling processes involved in the regulation of actin reorganization, cell migration, cell proliferation and survival, cell adhesion, and apoptosis. Participates in signal transduction stimulated by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen receptors and integrins. Induces tyrosine phosphorylation of BCAR1 in response to integrin regulation. Activation of BMX by integrins is mediated by PTK2/FAK1, a key mediator of integrin signaling events leading to the regulation of actin cytoskeleton and cell motility. Plays a critical role in TNF-induced angiogenesis, and implicated in the signaling of TEK and FLT1 receptors, 2 important receptor families essential for angiogenesis. Required for the phosphorylation and activation of STAT3, a transcription factor involved in cell differentiation. Also involved in interleukin-6 (IL6) induced differentiation. Plays also a role in programming adaptive cytoprotection against extracellular stress in different cell systems, salivary epithelial cells, brain endothelial cells, and dermal fibroblasts. May be involved in regulation of endocytosis through its interaction with an endosomal protein RUFY1. May also play a role in the growth and differentiation of hematopoietic cells; as well as in signal transduction in endocardial and arterial endothelial cells. Ref.4
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Enzyme regulation	TEK and vascular endothelial growth factor receptor 1 (FLT1) stimulate BMX tyrosine kinase activity. Activated by integrins through the mediation of PTK2/FAK1 By similarity. Activated by TNF through the mediation of TNFRSF1B By similarity. Ref.4
Subunit structure	Interacts with BCAR1, CAV1, MYD88, PTK2/FAK1, RUFY1, RUFY2, STAT3, TIRAP and TNFRSF1B By similarity.
Subcellular location	Cytoplasm By similarity. Note: Localizes to the edges of spreading cells when complexed with BCAR1 By similarity.
Tissue specificity	Specifically expressed in the endocardium of the developing heart as well as in the endocardium of the left ventricle and in the endothelium of large arteries in adult mice. Ref.2
Domain	SH2 domain mediates interaction with RUFY1 By similarity.
Post-translational modification	Phosphorylated in response to protein I/II and to LPS By similarity. Phosphorylation at Tyr-542 by SRC and by autocatalysis leads to activation and is required for STAT3 phosphorylation by BMX By similarity.
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
Biological process	Apoptosis Cell adhesion
Cellular component	Cytoplasm
Domain	SH2 domain Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW intracellular signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC phospholipid binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 651	651	Cytoplasmic tyrosine-protein kinase BMX		PRO_0000088064
Regions
	Domain	4 – 111	108	PH
	Domain	272 – 368	97	SH2
	Domain	393 – 646	254	Protein kinase
	Zinc finger	113 – 149	37	Btk-type
	Nucleotide binding	399 – 407	9	ATP By similarity
Sites
	Active site	512	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	421	1	ATP By similarity
Amino acid modifications
	Modified residue	542	1	Phosphotyrosine; by SRC and autocatalysis By similarity

Sequences

	Sequence		Length	Mass (Da)
	P97504 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 2E6B79B9491E569C	FASTA	651	75,001
	10 20 30 40 50 60 MESKSILEEL LLKKSQQKKK MSPNNYKERL FVLTKTSLSY YEYDKMKRGS RKGSIEIKKI 70 80 90 100 110 120 RCVEKVNLEE QTPVERQYPF QIVYKDGLLY VYASNEESRC QWLKALQKEI RGNPHLLIKY 130 140 150 160 170 180 HSGFFVDGKF LCCQQSCKAA PGCTLWEAYA DLHIAISDEK HRAPTFPERL LKIPRAVPVL 190 200 210 220 230 240 KMDASSSGAI LPQYDSYSKK SCGSQPTSNI RYIPREDCPD WWQVRKLKSE EDIACSNQLE 250 260 270 280 290 300 RNIASHSTSK MSWGFPESSS SEEEENLHAY DWFAGNISRS QSEQLLRQKG KEGAFMVRNS 310 320 330 340 350 360 SQMGMYTVSL FSKAVNDKKG TVKHYHVHTN AENKLYLAEN YCFDSIPKLI HYHQHNSAGM 370 380 390 400 410 420 ITRLRHPVST KANKVPVSVA LGSGIWELKR EEITLLKELG NGQFGVVQLG QWKGQYDVAV 430 440 450 460 470 480 KMIKEGAMSE DEFFQEAQTM MKLSHPKLVK FYGVCSKKYP IYIVTEYITN GCLLNYLKSH 490 500 510 520 530 540 GKGLESCQLL EMCYDVCEGM AFLESHQFIH RDLAARNCLV DSDLSVKVSD FGMTRYVLDD 550 560 570 580 590 600 QYVSSVGTKF PVKWSAPEVF HYFKYSSKSD VWAFGILMWE VFSLGKQPYD LYDNSEVVVK 610 620 630 640 650 VSQGHRLYRP QLASDTIYQI MYSCWHELPE KRPTFQQLLS AIEPLREQDK P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Predominant expression of murine Bmx in granulo-monocytic cells." Weil D., Power M.A., Catterral M., Li C.L. Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6. Tissue: Bone marrow.
[2]	"Bmx tyrosine kinase is specifically expressed in the endocardium and the endothelium of large arteries." Ekman N., Lymboussaki A., Vastrik I., Sarvas K., Kaipainen A., Alitalo K. Circulation 96:1729-1732(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Strain: 129/Sv.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Aorta and Bone.
[4]	"Bmx tyrosine kinase has a redundant function downstream of angiopoietin and vascular endothelial growth factor receptors in arterial endothelium." Rajantie I., Ekman N., Iljin K., Arighi E., Gunji Y., Kaukonen J., Palotie A., Dewerchin M., Carmeliet P., Alitalo K. Mol. Cell. Biol. 21:4647-4655(2001) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, FUNCTION.
[5]	"Signaling network of the Btk family kinases." Qiu Y., Kung H.J. Oncogene 19:5651-5661(2000) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[6]	"The Tec family of cytoplasmic tyrosine kinases: mammalian Btk, Bmx, Itk, Tec, Txk and homologs in other species." Smith C.I., Islam T.C., Mattsson P.T., Mohamed A.J., Nore B.F., Vihinen M. Bioessays 23:436-446(2001) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[7]	"Tec kinases, actin, and cell adhesion." Gomez-Rodriguez J., Readinger J.A., Viorritto I.C., Mueller K.L., Houghtling R.A., Schwartzberg P.L. Immunol. Rev. 218:45-64(2007) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U88091 mRNA. Translation: AAB47770.1. AF012104 mRNA. Translation: AAC53370.1. AK036707 mRNA. Translation: BAC29542.1. AK040936 mRNA. Translation: BAC30753.1.
IPI	IPI00126519.
RefSeq	NP_033889.2. NM_009759.4.
UniGene	Mm.504.
3D structure databases
ProteinModelPortal	P97504.
SMR	P97504. Positions 6-150, 219-649.
ModBase	Search...
Protein-protein interaction databases
IntAct	P97504. 1 interaction.
PTM databases
PhosphoSite	P97504.
Proteomic databases
PRIDE	P97504.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000112263; ENSMUSP00000107882; ENSMUSG00000031377.
GeneID	12169.
KEGG	mmu:12169.
Organism-specific databases
CTD	660.
MGI	MGI:1101778. Bmx.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00640000091347.
HOGENOM	HOG000233859.
HOVERGEN	HBG008761.
InParanoid	P97504.
KO	K08896.
OrthoDB	EOG48WC1J.
Gene expression databases
ArrayExpress	P97504.
Bgee	P97504.
CleanEx	MM_BMX.
Genevestigator	P97504.
GermOnline	ENSMUSG00000031377. Mus musculus.
Family and domain databases
Gene3D	2.30.29.30. 1 hit. 3.30.505.10. 1 hit.
InterPro	IPR011009. Kinase-like_dom. IPR011993. PH_like_dom. IPR001849. Pleckstrin_homology. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR000980. SH2. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. IPR001562. Znf_Btk_motif. [Graphical view]
Pfam	PF00779. BTK. 1 hit. PF00169. PH. 1 hit. PF07714. Pkinase_Tyr. 1 hit. PF00017. SH2. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN. PR00402. TECBTKDOMAIN. PR00109. TYRKINASE.
SMART	SM00107. BTK. 1 hit. SM00233. PH. 1 hit. SM00252. SH2. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
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
NextBio	280543.
SOURCE	Search...

Entry information

Entry name

BMX_MOUSE

Accession

Primary (citable) accession number: P97504

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 4, 2005
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program