BMX_MOUSE
ID BMX_MOUSE Reviewed; 651 AA.
AC P97504;
DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Cytoplasmic tyrosine-protein kinase BMX;
DE EC=2.7.10.2;
DE AltName: Full=Bone marrow tyrosine kinase gene in chromosome X protein homolog;
GN Name=Bmx;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow;
RA Weil D., Power M.A., Catterral M., Li C.L.;
RT "Predominant expression of murine Bmx in granulo-monocytic cells.";
RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=129/Sv;
RX PubMed=9323053; DOI=10.1161/01.cir.96.6.1729;
RA Ekman N., Lymboussaki A., Vastrik I., Sarvas K., Kaipainen A., Alitalo K.;
RT "Bmx tyrosine kinase is specifically expressed in the endocardium and the
RT endothelium of large arteries.";
RL Circulation 96:1729-1732(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Aorta, and Bone;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP ACTIVITY REGULATION, AND FUNCTION.
RX PubMed=11416142; DOI=10.1128/mcb.21.14.4647-4655.2001;
RA Rajantie I., Ekman N., Iljin K., Arighi E., Gunji Y., Kaukonen J.,
RA Palotie A., Dewerchin M., Carmeliet P., Alitalo K.;
RT "Bmx tyrosine kinase has a redundant function downstream of angiopoietin
RT and vascular endothelial growth factor receptors in arterial endothelium.";
RL Mol. Cell. Biol. 21:4647-4655(2001).
RN [5]
RP REVIEW ON FUNCTION.
RX PubMed=11114746; DOI=10.1038/sj.onc.1203958;
RA Qiu Y., Kung H.J.;
RT "Signaling network of the Btk family kinases.";
RL Oncogene 19:5651-5661(2000).
RN [6]
RP REVIEW ON FUNCTION.
RX PubMed=11340625; DOI=10.1002/bies.1062;
RA Smith C.I., Islam T.C., Mattsson P.T., Mohamed A.J., Nore B.F., Vihinen M.;
RT "The Tec family of cytoplasmic tyrosine kinases: mammalian Btk, Bmx, Itk,
RT Tec, Txk and homologs in other species.";
RL Bioessays 23:436-446(2001).
RN [7]
RP REVIEW ON FUNCTION.
RX PubMed=17624943; DOI=10.1111/j.1600-065x.2007.00534.x;
RA Gomez-Rodriguez J., Readinger J.A., Viorritto I.C., Mueller K.L.,
RA Houghtling R.A., Schwartzberg P.L.;
RT "Tec kinases, actin, and cell adhesion.";
RL Immunol. Rev. 218:45-64(2007).
CC -!- FUNCTION: Non-receptor tyrosine kinase that plays central but diverse
CC modulatory roles in various signaling processes involved in the
CC regulation of actin reorganization, cell migration, cell proliferation
CC and survival, cell adhesion, and apoptosis. Participates in signal
CC transduction stimulated by growth factor receptors, cytokine receptors,
CC G-protein coupled receptors, antigen receptors and integrins. Induces
CC tyrosine phosphorylation of BCAR1 in response to integrin regulation.
CC Activation of BMX by integrins is mediated by PTK2/FAK1, a key mediator
CC of integrin signaling events leading to the regulation of actin
CC cytoskeleton and cell motility. Plays a critical role in TNF-induced
CC angiogenesis, and implicated in the signaling of TEK and FLT1
CC receptors, 2 important receptor families essential for angiogenesis.
CC Required for the phosphorylation and activation of STAT3, a
CC transcription factor involved in cell differentiation. Also involved in
CC interleukin-6 (IL6) induced differentiation. Also plays a role in
CC programming adaptive cytoprotection against extracellular stress in
CC different cell systems, salivary epithelial cells, brain endothelial
CC cells, and dermal fibroblasts. May be involved in regulation of
CC endocytosis through its interaction with an endosomal protein RUFY1.
CC May also play a role in the growth and differentiation of hematopoietic
CC cells; as well as in signal transduction in endocardial and arterial
CC endothelial cells. {ECO:0000269|PubMed:11416142}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: TEK and vascular endothelial growth factor
CC receptor 1 (FLT1) stimulate BMX tyrosine kinase activity. Activated by
CC integrins through the mediation of PTK2/FAK1 (By similarity). Activated
CC by TNF through the mediation of TNFRSF1B (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with BCAR1, CAV1, MYD88, PTK2/FAK1, RUFY1, RUFY2,
CC STAT3, TIRAP and TNFRSF1B. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Note=Localizes to the
CC edges of spreading cells when complexed with BCAR1. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in the endocardium of the
CC developing heart as well as in the endocardium of the left ventricle
CC and in the endothelium of large arteries in adult mice.
CC {ECO:0000269|PubMed:9323053}.
CC -!- DOMAIN: SH2 domain mediates interaction with RUFY1. {ECO:0000250}.
CC -!- PTM: Phosphorylated in response to protein I/II and to LPS.
CC Phosphorylation at Tyr-542 by SRC and by autocatalysis leads to
CC activation and is required for STAT3 phosphorylation by BMX.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. TEC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U88091; AAB47770.1; -; mRNA.
DR EMBL; AF012104; AAC53370.1; -; mRNA.
DR EMBL; AK036707; BAC29542.1; -; mRNA.
DR EMBL; AK040936; BAC30753.1; -; mRNA.
DR RefSeq; NP_033889.2; NM_009759.4.
DR AlphaFoldDB; P97504; -.
DR SMR; P97504; -.
DR BioGRID; 198374; 6.
DR IntAct; P97504; 1.
DR STRING; 10090.ENSMUSP00000107884; -.
DR BindingDB; P97504; -.
DR ChEMBL; CHEMBL2034793; -.
DR iPTMnet; P97504; -.
DR PhosphoSitePlus; P97504; -.
DR MaxQB; P97504; -.
DR PaxDb; P97504; -.
DR PRIDE; P97504; -.
DR ProteomicsDB; 265448; -.
DR Antibodypedia; 412; 655 antibodies from 34 providers.
DR DNASU; 12169; -.
DR Ensembl; ENSMUST00000112263; ENSMUSP00000107882; ENSMUSG00000031377.
DR GeneID; 12169; -.
DR KEGG; mmu:12169; -.
DR CTD; 660; -.
DR MGI; MGI:1101778; Bmx.
DR VEuPathDB; HostDB:ENSMUSG00000031377; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000161172; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; P97504; -.
DR OMA; VPILRMD; -.
DR OrthoDB; 1047190at2759; -.
DR PhylomeDB; P97504; -.
DR Reactome; R-MMU-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-MMU-1660499; Synthesis of PIPs at the plasma membrane.
DR BioGRID-ORCS; 12169; 1 hit in 76 CRISPR screens.
DR PRO; PR:P97504; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; P97504; protein.
DR Bgee; ENSMUSG00000031377; Expressed in granulocyte and 78 other tissues.
DR ExpressionAtlas; P97504; baseline and differential.
DR Genevisible; P97504; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032587; C:ruffle membrane; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; ISO:MGI.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR028840; BMX.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR001562; Znf_Btk_motif.
DR PANTHER; PTHR24418:SF91; PTHR24418:SF91; 1.
DR Pfam; PF00779; BTK; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00402; TECBTKDOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00107; BTK; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS51113; ZF_BTK; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; ATP-binding; Cell adhesion; Cytoplasm; Kinase; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; SH2 domain;
KW Transferase; Tyrosine-protein kinase; Zinc; Zinc-finger.
FT CHAIN 1..651
FT /note="Cytoplasmic tyrosine-protein kinase BMX"
FT /id="PRO_0000088064"
FT DOMAIN 4..111
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 272..368
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 393..646
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ZN_FING 113..149
FT /note="Btk-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT ACT_SITE 512
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 121
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 132
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 133
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 143
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 399..407
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 421
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 542
FT /note="Phosphotyrosine; by SRC and autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P51813"
SQ SEQUENCE 651 AA; 75001 MW; 2E6B79B9491E569C CRC64;
MESKSILEEL LLKKSQQKKK MSPNNYKERL FVLTKTSLSY YEYDKMKRGS RKGSIEIKKI
RCVEKVNLEE QTPVERQYPF QIVYKDGLLY VYASNEESRC QWLKALQKEI RGNPHLLIKY
HSGFFVDGKF LCCQQSCKAA PGCTLWEAYA DLHIAISDEK HRAPTFPERL LKIPRAVPVL
KMDASSSGAI LPQYDSYSKK SCGSQPTSNI RYIPREDCPD WWQVRKLKSE EDIACSNQLE
RNIASHSTSK MSWGFPESSS SEEEENLHAY DWFAGNISRS QSEQLLRQKG KEGAFMVRNS
SQMGMYTVSL FSKAVNDKKG TVKHYHVHTN AENKLYLAEN YCFDSIPKLI HYHQHNSAGM
ITRLRHPVST KANKVPVSVA LGSGIWELKR EEITLLKELG NGQFGVVQLG QWKGQYDVAV
KMIKEGAMSE DEFFQEAQTM MKLSHPKLVK FYGVCSKKYP IYIVTEYITN GCLLNYLKSH
GKGLESCQLL EMCYDVCEGM AFLESHQFIH RDLAARNCLV DSDLSVKVSD FGMTRYVLDD
QYVSSVGTKF PVKWSAPEVF HYFKYSSKSD VWAFGILMWE VFSLGKQPYD LYDNSEVVVK
VSQGHRLYRP QLASDTIYQI MYSCWHELPE KRPTFQQLLS AIEPLREQDK P
