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Protein

Cytoplasmic tyrosine-protein kinase BMX

Gene

BMX

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.7 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Enzyme regulationi

TEK and vascular endothelial growth factor receptor 1 (FLT1) stimulate BMX tyrosine kinase activity (By similarity). Activated by integrins through the mediation of PTK2/FAK1. Activated by TNF through the mediation of TNFRSF1B.By similarity3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi121ZincBy similarity1
Metal bindingi132ZincBy similarity1
Metal bindingi133ZincBy similarity1
Metal bindingi143ZincBy similarity1
Binding sitei445ATPPROSITE-ProRule annotation1
Active sitei536Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri113 – 149Btk-typePROSITE-ProRule annotationAdd BLAST37
Nucleotide bindingi423 – 431ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
  • protein tyrosine kinase activity Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
Biological processApoptosis, Cell adhesion, Stress response
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.10.2 2681
ReactomeiR-HSA-111465 Apoptotic cleavage of cellular proteins
R-HSA-1660499 Synthesis of PIPs at the plasma membrane
SignaLinkiP51813
SIGNORiP51813

Names & Taxonomyi

Protein namesi
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 namesi
Name:BMX
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000102010.14
HGNCiHGNC:1079 BMX
MIMi300101 gene
neXtProtiNX_P51813

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi566Y → F: Abolishes almost completely the SRC-induced phosphorylation of BMX. 1 Publication1

Organism-specific databases

DisGeNETi660
OpenTargetsiENSG00000102010
PharmGKBiPA25389

Chemistry databases

ChEMBLiCHEMBL3834
GuidetoPHARMACOLOGYi1942

Polymorphism and mutation databases

BioMutaiBMX
DMDMi1705489

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000880631 – 675Cytoplasmic tyrosine-protein kinase BMXAdd BLAST675

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei216Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei224Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei566Phosphotyrosine; by SRC and autocatalysis1 Publication1

Post-translational modificationi

Phosphorylated in response to protein I/II and to LPS. Phosphorylation at Tyr-566 by SRC and by autocatalysis leads to activation and is required for STAT3 phosphorylation by BMX.4 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP51813
MaxQBiP51813
PaxDbiP51813
PeptideAtlasiP51813
PRIDEiP51813
ProteomicsDBi56409

PTM databases

iPTMnetiP51813
PhosphoSitePlusiP51813

Miscellaneous databases

PMAP-CutDBiP51813

Expressioni

Tissue specificityi

Highly expressed in cells with great migratory potential, including endothelial cells and metastatic carcinoma cell lines.

Inductioni

Activated by IL6/interleukin-6 through phosphatidylinositol 3-kinase (PI3-kinase) pathway. It is likely that activation occurs through binding of phosphoinositides to the PH domain.2 Publications

Gene expression databases

BgeeiENSG00000102010
CleanExiHS_BMX
GenevisibleiP51813 HS

Organism-specific databases

HPAiCAB032495
HPA001048

Interactioni

Subunit structurei

Interacts with BCAR1, CAV1, MYD88, PTK2/FAK1, RUFY1, RUFY2, STAT3, TIRAP and TNFRSF1B.7 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi107128, 27 interactors
IntActiP51813, 13 interactors
MINTiP51813
STRINGi9606.ENSP00000308774

Chemistry databases

BindingDBiP51813

Structurei

Secondary structure

1675
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi129 – 133Combined sources5
Beta strandi136 – 139Combined sources4
Beta strandi294 – 297Combined sources4
Helixi303 – 312Combined sources10
Beta strandi318 – 323Combined sources6
Beta strandi330 – 334Combined sources5
Beta strandi347 – 350Combined sources4
Beta strandi359 – 362Combined sources4
Helixi370 – 379Combined sources10
Beta strandi383 – 385Combined sources3
Helixi414 – 416Combined sources3
Beta strandi417 – 426Combined sources10
Beta strandi429 – 436Combined sources8
Turni437 – 439Combined sources3
Beta strandi440 – 447Combined sources8
Helixi454 – 466Combined sources13
Beta strandi475 – 479Combined sources5
Beta strandi481 – 490Combined sources10
Helixi497 – 504Combined sources8
Helixi505 – 507Combined sources3
Helixi510 – 529Combined sources20
Beta strandi532 – 536Combined sources5
Helixi539 – 541Combined sources3
Beta strandi542 – 544Combined sources3
Beta strandi550 – 552Combined sources3
Turni555 – 557Combined sources3
Beta strandi558 – 560Combined sources3
Beta strandi566 – 568Combined sources3
Helixi576 – 578Combined sources3
Helixi581 – 586Combined sources6
Beta strandi587 – 590Combined sources4
Helixi593 – 606Combined sources14
Turni607 – 609Combined sources3
Turni612 – 615Combined sources4
Helixi618 – 626Combined sources9
Helixi639 – 647Combined sources9
Helixi653 – 655Combined sources3
Helixi659 – 666Combined sources8
Helixi667 – 669Combined sources3

3D structure databases

ProteinModelPortaliP51813
SMRiP51813
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP51813

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 111PHPROSITE-ProRule annotationAdd BLAST108
Domaini296 – 392SH2PROSITE-ProRule annotationAdd BLAST97
Domaini417 – 675Protein kinasePROSITE-ProRule annotationAdd BLAST259

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi596 – 603CAV1-binding8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi251 – 255Poly-Ser5
Compositional biasi282 – 285Poly-Ser4
Compositional biasi286 – 289Poly-Glu4

Domaini

SH2 domain mediates interaction with RUFY1.1 Publication

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri113 – 149Btk-typePROSITE-ProRule annotationAdd BLAST37

Keywords - Domaini

SH2 domain, Zinc-finger

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000119011
HOGENOMiHOG000233859
HOVERGENiHBG008761
InParanoidiP51813
KOiK08896
OMAiKLIHYHQ
OrthoDBiEOG091G0D46
PhylomeDBiP51813
TreeFamiTF351634

Family and domain databases

CDDicd10399 SH2_Tec_Bmx, 1 hit
Gene3Di2.30.29.30, 1 hit
3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR028840 BMX
IPR035875 BMX_SH2
IPR011009 Kinase-like_dom_sf
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR001562 Znf_Btk_motif
PANTHERiPTHR24418:SF91 PTHR24418:SF91, 2 hits
PfamiView protein in Pfam
PF00779 BTK, 1 hit
PF00169 PH, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00402 TECBTKDOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00107 BTK, 1 hit
SM00233 PH, 1 hit
SM00252 SH2, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in 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

Sequencei

Sequence statusi: Complete.

P51813-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDTKSILEEL LLKRSQQKKK MSPNNYKERL FVLTKTNLSY YEYDKMKRGS
60 70 80 90 100
RKGSIEIKKI RCVEKVNLEE QTPVERQYPF QIVYKDGLLY VYASNEESRS
110 120 130 140 150
QWLKALQKEI RGNPHLLVKY HSGFFVDGKF LCCQQSCKAA PGCTLWEAYA
160 170 180 190 200
NLHTAVNEEK HRVPTFPDRV LKIPRAVPVL KMDAPSSSTT LAQYDNESKK
210 220 230 240 250
NYGSQPPSSS TSLAQYDSNS KKIYGSQPNF NMQYIPREDF PDWWQVRKLK
260 270 280 290 300
SSSSSEDVAS SNQKERNVNH TTSKISWEFP ESSSSEEEEN LDDYDWFAGN
310 320 330 340 350
ISRSQSEQLL RQKGKEGAFM VRNSSQVGMY TVSLFSKAVN DKKGTVKHYH
360 370 380 390 400
VHTNAENKLY LAENYCFDSI PKLIHYHQHN SAGMITRLRH PVSTKANKVP
410 420 430 440 450
DSVSLGNGIW ELKREEITLL KELGSGQFGV VQLGKWKGQY DVAVKMIKEG
460 470 480 490 500
SMSEDEFFQE AQTMMKLSHP KLVKFYGVCS KEYPIYIVTE YISNGCLLNY
510 520 530 540 550
LRSHGKGLEP SQLLEMCYDV CEGMAFLESH QFIHRDLAAR NCLVDRDLCV
560 570 580 590 600
KVSDFGMTRY VLDDQYVSSV GTKFPVKWSA PEVFHYFKYS SKSDVWAFGI
610 620 630 640 650
LMWEVFSLGK QPYDLYDNSQ VVLKVSQGHR LYRPHLASDT IYQIMYSCWH
660 670
ELPEKRPTFQ QLLSSIEPLR EKDKH
Length:675
Mass (Da):78,011
Last modified:October 1, 1996 - v1
Checksum:iCB22382A3BD02599
GO

Sequence cautioni

The sequence AAC08966 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti207P → G AA sequence (PubMed:12573241).Curated1
Sequence conflicti597A → S in AAA17744 (Ref. 7) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041674284S → L1 PublicationCorresponds to variant dbSNP:rs35353387Ensembl.1
Natural variantiVAR_041675670R → W in a lung large cell carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1029888196Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS14168.1
PIRiS60612
RefSeqiNP_001307795.1, NM_001320866.1
NP_001712.1, NM_001721.6
NP_975010.1, NM_203281.2
UniGeneiHs.495731

Genome annotation databases

EnsembliENST00000342014; ENSP00000340082; ENSG00000102010
ENST00000348343; ENSP00000308774; ENSG00000102010
ENST00000357607; ENSP00000350224; ENSG00000102010
GeneIDi660
KEGGihsa:660
UCSCiuc004cww.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiBMX_HUMAN
AccessioniPrimary (citable) accession number: P51813
Secondary accession number(s): A6NIH9, O60564, Q12871
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 18, 2018
This is version 187 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

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