Tyrosine-protein kinase Blk

Details

Name

Tyrosine-protein kinase Blk

Synonyms

• 2.7.10.2
• B lymphocyte kinase
• p55-Blk

Gene Name

BLK

Organism

Humans

Amino acid sequence

>lcl|BSEQ0051704|Tyrosine-protein kinase Blk
MGLVSSKKPDKEKPIKEKDKGQWSPLKVSAQDKDAPPLPPLVVFNHLTPPPPDEHLDEDK
HFVVALYDYTAMNDRDLQMLKGEKLQVLKGTGDWWLARSLVTGREGYVPSNFVARVESLE
MERWFFRSQGRKEAERQLLAPINKAGSFLIRESETNKGAFSLSVKDVTTQGELIKHYKIR
CLDEGGYYISPRITFPSLQALVQHYSKKGDGLCQRLTLPCVRPAPQNPWAQDEWEIPRQS
LRLVRKLGSGQFGEVWMGYYKNNMKVAIKTLKEGTMSPEAFLGEANVMKALQHERLVRLY
AVVTKEPIYIVTEYMARGCLLDFLKTDEGSRLSLPRLIDMSAQIAEGMAYIERMNSIHRD
LRAANILVSEALCCKIADFGLARIIDSEYTAQEGAKFPIKWTAPEAIHFGVFTIKADVWS
FGVLLMEVVTYGRVPYPGMSNPEVIRNLERGYRMPRPDTCPPELYRGVIAECWRSRPEER
PTFEFLQSVLEDFYTATERQYELQP

Number of residues

505

Molecular Weight

57706.01

Theoretical pI

Not Available

GO Classification

Functions

ATP binding / non-membrane spanning protein tyrosine kinase activity / protein tyrosine kinase activity / receptor binding

Processes

B cell receptor signaling pathway / cell differentiation / cell migration / innate immune response / intracellular signal transduction / peptidyl-tyrosine autophosphorylation / positive regulation of insulin secretion / regulation of B cell receptor signaling pathway / regulation of cell proliferation / transmembrane receptor protein tyrosine kinase signaling pathway

Components

cytosol / extrinsic component of cytoplasmic side of plasma membrane

General Function

Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling. B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor. Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207'. Phosphorylates also the immunoglobulin G receptors FCGR2A, FCGR2B and FCGR2C. With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation. Contributes also to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation. In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose.

Specific Function

Atp binding

Pfam Domain Function

• PK_Tyr_Ser-Thr (PF07714)
• SH2 (PF00017)
• SH3_1 (PF00018)

Transmembrane Regions

Not Available

Cellular Location

Cell membrane

Gene sequence

>lcl|BSEQ0051705|Tyrosine-protein kinase Blk (BLK)
ATGGGGCTGGTAAGTAGCAAAAAGCCGGACAAGGAAAAGCCGATCAAAGAGAAGGACAAG
GGCCAATGGAGCCCCCTGAAGGTCAGCGCCCAAGACAAGGACGCCCCGCCACTGCCGCCC
CTGGTTGTCTTCAACCACCTTACTCCTCCACCGCCCGATGAACACCTGGATGAAGACAAG
CATTTCGTGGTGGCTCTGTATGACTACACCGCTATGAATGATCGGGACCTGCAGATGCTG
AAGGGGGAGAAGCTACAGGTCCTGAAGGGAACTGGAGACTGGTGGCTGGCCAGGTCACTC
GTCACAGGAAGAGAAGGCTATGTGCCCAGTAACTTTGTGGCCCGAGTGGAGAGCCTGGAA
ATGGAAAGGTGGTTCTTTAGATCACAGGGTCGGAAGGAGGCTGAGAGGCAGCTTCTTGCT
CCAATCAACAAGGCCGGCTCCTTTCTTATCAGAGAGAGTGAAACCAACAAAGGTGCCTTC
TCCCTGTCTGTGAAGGATGTCACCACCCAGGGGGAGCTGATCAAGCACTATAAGATCCGC
TGCCTGGATGAAGGGGGCTACTACATCTCCCCCCGGATCACCTTCCCCTCGCTCCAGGCC
CTGGTGCAGCACTATTCTAAGAAGGGGGATGGTCTATGCCAGAGGCTGACCCTGCCCTGT
GTGCGCCCGGCCCCGCAGAATCCCTGGGCCCAGGATGAATGGGAGATCCCCCGGCAGTCT
CTCAGGCTGGTCAGGAAACTCGGGTCTGGACAATTCGGCGAAGTCTGGATGGGTTACTAC
AAAAACAACATGAAGGTGGCCATTAAGACGCTGAAGGAGGGAACCATGTCTCCAGAAGCC
TTTCTGGGTGAGGCCAACGTGATGAAGGCTCTGCAGCACGAGCGGCTGGTCCGACTCTAC
GCAGTGGTCACCAAGGAGCCCATCTACATTGTCACCGAGTACATGGCCAGAGGATGCCTG
CTGGATTTCCTGAAGACAGATGAAGGGAGCAGATTGTCACTCCCAAGGCTGATTGACATG
TCGGCGCAGATTGCTGAAGGGATGGCATACATTGAGCGCATGAATTCCATCCACCGCGAC
CTGCGGGCGGCCAACATCCTGGTGTCTGAGGCCTTGTGCTGCAAAATTGCTGATTTTGGC
TTGGCTCGAATCATCGACAGTGAATACACGGCCCAAGAGGGGGCCAAGTTCCCCATCAAG
TGGACAGCCCCGGAAGCCATCCACTTCGGGGTCTTCACCATCAAAGCAGACGTGTGGTCG
TTTGGAGTCCTCCTGATGGAAGTTGTCACTTATGGGCGGGTGCCATACCCAGGGATGAGC
AACCCCGAGGTCATCCGCAACCTGGAGCGCGGCTACCGCATGCCGCGCCCCGACACCTGC
CCGCCCGAGCTGTACCGCGGCGTCATCGCCGAGTGCTGGCGCAGCCGGCCCGAGGAGCGG
CCCACCTTCGAGTTCCTGCAGTCGGTGCTGGAGGACTTCTACACGGCCACCGAGCGGCAG
TACGAGCTGCAGCCCTAG

Chromosome Location

8

Locus

8p23.1

External Identifiers

Resource	Link
UniProtKB ID	P51451
UniProtKB Entry Name	BLK_HUMAN
HGNC ID	HGNC:1057

General References

1. Islam KB, Rabbani H, Larsson C, Sanders R, Smith CI: Molecular cloning, characterization, and chromosomal localization of a human lymphoid tyrosine kinase related to murine Blk. J Immunol. 1995 Feb 1;154(3):1265-72. [Article]
2. Drebin JA, Hartzell SW, Griffin C, Campbell MJ, Niederhuber JE: Molecular cloning and chromosomal localization of the human homologue of a B-lymphocyte specific protein tyrosine kinase (blk). Oncogene. 1995 Feb 2;10(3):477-86. [Article]
3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
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5. Donovan JA, Wange RL, Langdon WY, Samelson LE: The protein product of the c-cbl protooncogene is the 120-kDa tyrosine-phosphorylated protein in Jurkat cells activated via the T cell antigen receptor. J Biol Chem. 1994 Sep 16;269(37):22921-4. [Article]
6. Bewarder N, Weinrich V, Budde P, Hartmann D, Flaswinkel H, Reth M, Frey J: In vivo and in vitro specificity of protein tyrosine kinases for immunoglobulin G receptor (FcgammaRII) phosphorylation. Mol Cell Biol. 1996 Sep;16(9):4735-43. [Article]
7. Akerblad P, Sigvardsson M: Early B cell factor is an activator of the B lymphoid kinase promoter in early B cell development. J Immunol. 1999 Nov 15;163(10):5453-61. [Article]
8. Lang ML, Chen YW, Shen L, Gao H, Lang GA, Wade TK, Wade WF: IgA Fc receptor (FcalphaR) cross-linking recruits tyrosine kinases, phosphoinositide kinases and serine/threonine kinases to glycolipid rafts. Biochem J. 2002 Jun 1;364(Pt 2):517-25. [Article]
9. Borowiec M, Liew CW, Thompson R, Boonyasrisawat W, Hu J, Mlynarski WM, El Khattabi I, Kim SH, Marselli L, Rich SS, Krolewski AS, Bonner-Weir S, Sharma A, Sale M, Mychaleckyj JC, Kulkarni RN, Doria A: Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction. Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14460-5. doi: 10.1073/pnas.0906474106. Epub 2009 Aug 10. [Article]
10. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
11. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, 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 DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB12010	Fostamatinib	approved, investigational	unknown	inhibitor	Details
DB15035	Zanubrutinib	approved, investigational	unknown	inhibitor	Details