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Protein

Cytoplasmic tyrosine-protein kinase BMX

Gene

BMX

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • signal transducer activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Apoptosis, Cell adhesion, Stress response

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS02334-MONOMER.
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

HGNCiHGNC:1079. BMX.

Subcellular locationi

  • Cytoplasm 1 Publication

  • Note: Localizes to the edges of spreading cells when complexed with BCAR1.

GO - Cellular componenti

Complete GO annotation...

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

MaxQBiP51813.
PaxDbiP51813.
PeptideAtlasiP51813.
PRIDEiP51813.

PTM databases

iPTMnetiP51813.
PhosphoSitePlusiP51813.

Miscellaneous databases

PMAP-CutDBP51813.

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

WithEntry#Exp.IntActNotes
PIM1P113094EBI-696657,EBI-696621
STAT3P407636EBI-696657,EBI-518675

Protein-protein interaction databases

BioGridi107128. 27 interactors.
IntActiP51813. 12 interactors.
MINTiMINT-1433284.
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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EKXNMR-A291-393[»]
2YS2NMR-A113-149[»]
3SXRX-ray2.40A/B411-675[»]
3SXSX-ray1.89A411-675[»]
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
Contains 1 Btk-type zinc finger.PROSITE-ProRule annotation
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SH2 domain.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.
OMAiEYISNGC.
OrthoDBiEOG091G0D46.
PhylomeDBiP51813.
TreeFamiTF351634.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR028840. BMX.
IPR011009. Kinase-like_dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000719. Prot_kinase_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]
PANTHERiPTHR24418:SF91. PTHR24418:SF91. 3 hits.
PfamiPF00779. BTK. 1 hit.
PF00169. PH. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00402. TECBTKDOMAIN.
PR00109. TYRKINASE.
SMARTiSM00107. BTK. 1 hit.
SM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50003. 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]

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 → L.1 PublicationCorresponds to variant rs35353387dbSNPEnsembl.1
Natural variantiVAR_041675670R → W in a lung large cell carcinoma sample; somatic mutation. 1 Publication1

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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EKXNMR-A291-393[»]
2YS2NMR-A113-149[»]
3SXRX-ray2.40A/B411-675[»]
3SXSX-ray1.89A411-675[»]
ProteinModelPortaliP51813.
SMRiP51813.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107128. 27 interactors.
IntActiP51813. 12 interactors.
MINTiMINT-1433284.
STRINGi9606.ENSP00000308774.

Chemistry databases

BindingDBiP51813.
ChEMBLiCHEMBL3834.
GuidetoPHARMACOLOGYi1942.

PTM databases

iPTMnetiP51813.
PhosphoSitePlusiP51813.

Polymorphism and mutation databases

BioMutaiBMX.
DMDMi1705489.

Proteomic databases

MaxQBiP51813.
PaxDbiP51813.
PeptideAtlasiP51813.
PRIDEiP51813.

Protocols and materials databases

DNASUi660.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi660.
DisGeNETi660.
GeneCardsiBMX.
HGNCiHGNC:1079. BMX.
HPAiCAB032495.
HPA001048.
MIMi300101. gene.
neXtProtiNX_P51813.
OpenTargetsiENSG00000102010.
PharmGKBiPA25389.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS02334-MONOMER.
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.

Miscellaneous databases

ChiTaRSiBMX. human.
EvolutionaryTraceiP51813.
GeneWikiiBMX_(gene).
GenomeRNAii660.
PMAP-CutDBP51813.
PROiP51813.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000102010.
CleanExiHS_BMX.
GenevisibleiP51813. HS.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR028840. BMX.
IPR011009. Kinase-like_dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000719. Prot_kinase_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]
PANTHERiPTHR24418:SF91. PTHR24418:SF91. 3 hits.
PfamiPF00779. BTK. 1 hit.
PF00169. PH. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00402. TECBTKDOMAIN.
PR00109. TYRKINASE.
SMARTiSM00107. BTK. 1 hit.
SM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50003. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiBMX_HUMAN
AccessioniPrimary (citable) accession number: P51813
Secondary accession number(s): A6NIH9, O60564, Q12871
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 30, 2016
This is version 173 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.