Details of the BTS

General Information of Binding Target of SBP (BTS) (ID: ST00005)
BTS Name	Receptor tyrosine-protein kinase erbB-2
Synonyms	EC 2.7.10.1; Metastatic lymph node gene 19 protein; MLN 19; Proto-oncogene Neu; Proto-oncogene c-ErbB-2; Tyrosine kinase-type cell surface receptor HER2; p185erbB2; CD antigen CD340
BTS Type	Protein
Family	Protein kinase superfamily; Tyr protein kinase family; EGF receptor subfamily
Gene Name	ERBB2
Organism	Homo sapiens (Human)
Function	Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization.; In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth.
UniProt ID	P04626
UniProt Entry	ERBB2_HUMAN
PFam	PF00757 ; PF14843 ; PF07714 ; PF01030
Gene ID	2064
Sequence	MELAALCRWGLLLALLPPGAASTQVCTGTDMKLRLPASPETHLDMLRHLYQGCQVVQGNL ELTYLPTNASLSFLQDIQEVQGYVLIAHNQVRQVPLQRLRIVRGTQLFEDNYALAVLDNG DPLNNTTPVTGASPGGLRELQLRSLTEILKGGVLIQRNPQLCYQDTILWKDIFHKNNQLA LTLIDTNRSRACHPCSPMCKGSRCWGESSEDCQSLTRTVCAGGCARCKGPLPTDCCHEQC AAGCTGPKHSDCLACLHFNHSGICELHCPALVTYNTDTFESMPNPEGRYTFGASCVTACP YNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEKCSKPCARVCYGLGMEHLREVRAVTSAN IQEFAGCKKIFGSLAFLPESFDGDPASNTAPLQPEQLQVFETLEEITGYLYISAWPDSLP DLSVFQNLQVIRGRILHNGAYSLTLQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHTV PWDQLFRNPHQALLHTANRPEDECVGEGLACHQLCARGHCWGPGPTQCVNCSQFLRGQEC VEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVARC PSGVKPDLSYMPIWKFPDEEGACQPCPINCTHSCVDLDDKGCPAEQRASPLTSIISAVVG ILLVVVLGVVFGILIKRRQQKIRKYTMRRLLQETELVEPLTPSGAMPNQAQMRILKETEL RKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSP YVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVR LVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFT HQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWM IDSECRPRFRELVSEFSRMARDPQRFVVIQNEDLGPASPLDSTFYRSLLEDDDMGDLVDA EEYLVPQQGFFCPDPAPGAGGMVHHRHRSSSTRSGGGDLTLGLEPSEEEAPRSPLAPSEG AGSDVFDGDLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCSPQPEYV NQPDVRPQPPSPREGPLPAARPAGATLERPKTLSPGKNGVVKDVFAFGGAVENPEYLTPQ GGAAPQPHPPPAFSPAFDNLYYWDQDPPERGAPPSTFKGTPTAENPEYLGLDVPV
Sequence Length	1255

Synthetic Binding Protein (SBP) Targeting This BTS

SBP Name	Highest Status	Mechanism	Affinity	Application	Details	Ref
ABD-derived affinity protein anti-ERBB2/HSA clone 1	Research	Binder	Kd: 75 nM	Diagnostic reagent; Next generation protein therapeutics	SBP Info	[1]
ABD-derived affinity protein anti-ERBB2/HSA clone 1(A43V)	Research	Binder	Kd: 46 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
ABD-derived affinity protein anti-ERBB2/HSA clone 1(D6A)	Research	Binder	Kd: 148 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
ABD-derived affinity protein anti-ERBB2/HSA clone 1(R14A)	Research	Binder	Kd: 140 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
ABD-derived affinity protein anti-ERBB2/HSA clone 1(R35A)	Research	Binder	Kd: 136 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
ABD-derived affinity protein anti-ERBB2/HSA clone 1(S3A)	Research	Binder	Kd: 41 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
ABD-derived affinity protein anti-ERBB2/HSA clone 1(V15A)	Research	Binder	Kd: 74 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
ABD-derived affinity protein anti-ERBB2/HSA clone FACS-10	Research	Binder	Kd: 0.8 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
ABD-derived affinity protein anti-ERBB2/HSA clone FACS-12	Research	Binder	Kd: 0.3 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
ABD-derived affinity protein anti-ERBB2/HSA clone FACS-12(A8)	Research	Binder	Kd: 1 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
ABD-derived affinity protein anti-ERBB2/HSA clone FACS-17	Research	Binder	Kd: 2.2 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
ABD-derived affinity protein anti-ERBB2/HSA clone FACS-18	Research	Binder	Kd: 1.7 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
ABD-derived affinity protein anti-ERBB2/HSA clone FACS-4	Research	Binder	Kd: 0.6 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
ABD-derived affinity protein anti-ERBB2/HSA clone FACS-5	Research	Binder	Kd: 1.4 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
ABD-derived affinity protein anti-ERBB2/HSA clone mat1	Research	Binder	Kd: 2.3 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
ABD-derived affinity protein anti-ERBB2/HSA clone mat3	Research	Binder	Kd: 1.1 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
ABD-derived affinity protein anti-ERBB2/HSA clone mat6	Research	Binder	Kd: 0.9 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[1]
Affibody ABY-025	Phase III	Binder	Kd: 0.076 nM	Imaging agent for patients with breast cancer	SBP Info	[2]
Anticalin Cinrebafusp alfa	Phase I	Binder	N.A.	Solid tumour/cancer [ICD-11: 2A00-2F9Z]	SBP Info	[3], []
DARPin anti-ERBB2 6L1G	Research	Blocker	N.A.	HER2-positive breast cancer [ICD-11: 2C60-2C65]	SBP Info	[4], [5], [6]
DARPin anti-ERBB2 9L1H	Research	Blocker	N.A.	Tumors [ICD-11: XH1N44]	SBP Info	[6]
DARPin anti-ERBB2 A1	Research	Binder	Kd: 3.8 nM	Research tool	SBP Info	[7]
DARPin anti-ERBB2 C3	Research	Binder	Kd: 4 nM	Research tool	SBP Info	[7]
DARPin anti-ERBB2 clone 28z	Research	Binder	N.A.	Tools for inducing cytokine production by CAR-T cells upon antigen binding	SBP Info	[8]
DARPin anti-ERBB2 clone 9_29	Research	Binder	Kd: 3.8 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[9], [10], [11]
DARPin anti-ERBB2 D4	Research	Binder	Kd: 15 nM	Research tool	SBP Info	[7]
DARPin anti-ERBB2 D72C	Research	Binder	N.A.	Cancers [ICD-11: 2D4Z]	SBP Info	[12]
DARPin anti-ERBB2 F1	Research	Binder	Kd: 0.39 nM	Research tool	SBP Info	[7]
DARPin anti-ERBB2 F3	Research	Binder	Kd: 1.9 nM	Research tool	SBP Info	[7]
DARPin anti-ERBB2 G3-A	Research	Binder	Kd: 1.2 nM	Tools for detecting Her3 in human carcinoma extracts	SBP Info	[13]
DARPin anti-ERBB2 G3-AVD	Research	Binder	Kd: 10.2 nM	Research tool	SBP Info	[13]
DARPin anti-ERBB2 G3-D	Research	Binder	Kd: 1.5 nM	Tools for detecting Her3 in human carcinoma extracts	SBP Info	[13]
DARPin anti-ERBB2 G3-E2_5	Research	Binder	N.A.	Cancers [ICD-11: 2D4Z]	SBP Info	[14]
DARPin anti-ERBB2 G3-G3	Research	Binder	Kd: 0.011 nM	Cancers [ICD-11: 2D4Z]	SBP Info	[14]
DARPin anti-ERBB2 G3-HAVD	Research	Binder	Kd: 269 nM	Research tool	SBP Info	[13]
DARPin anti-ERBB2 H10-2-A2	Research	Binder	Kd: 3.5 nM	Tools for detecting Her5 in human carcinoma extracts	SBP Info	[13]
DARPin anti-ERBB2 H10-2-D11	Research	Binder	Kd: 35.8 nM	Research tool	SBP Info	[13]
DARPin anti-ERBB2 H10-2-D12	Research	Binder	Kd: 93.9 nM	Research tool	SBP Info	[13]
DARPin anti-ERBB2 H10-2-G3	Research	Binder	Kd: 0.091 nM	Tools for detecting Her2 in human carcinoma extracts	SBP Info	[13], [15], [16]
DARPin anti-ERBB2 H10-2-G5	Research	Binder	Kd: 0.67 nM	Tools for detecting Her2 in human carcinoma extracts	SBP Info	[13]
DARPin anti-ERBB2 N69C	Research	Binder	N.A.	Cancers [ICD-11: 2D4Z]	SBP Info	[12]
DARPin MP0274	Phase I	Antagonist	N.A.	Solid tumour/cancer [ICD-11: 2A00-2F9Z]	SBP Info	[17], [2], [18]
Diabody anti-CD40/ERBB2	Research	Inhibitor	N.A.	Tumors [ICD-11: XH1N44]	SBP Info	[19]
Fab anti-ErbB-2	Research	Binder	N.A.	Research tool	SBP Info	[20]
Peptide aptamer anti-ERBB2 AII-7	Research	Binder	N.A.	Breast cancer [ICD-11: 2C6Z]	SBP Info	[21], [22]
scFv Gancotamab	Phase II; Discontinued	Binder	N.A.	Breast cancer [ICD-11: 2C6Z]	SBP Info	[23]

References

1	Engineering of bispecific affinity proteins with high affinity for ERBB2 and adaptable binding to albumin. PLoS One. 2014 Aug 4;9(8):e103094.
2	In vitro-engineered non-antibody protein therapeutics. Protein Cell. 2018 Jan;9(1):3-14.
3	Recent advances in the development of novel protein scaffolds based therapeutics. Int J Biol Macromol. 2017 Sep;102:630-641.
4	Systemic analysis of tyrosine kinase signaling reveals a common adaptive response program in a HER2-positive breast cancer. Sci Signal. 2019 Jan 22;12(565):eaau2875.
5	Designed ankyrin repeat proteins (DARPins) from research to therapy. Methods Enzymol. 2012;503:101-34.
6	Intermolecular biparatopic trapping of ErbB2 prevents compensatory activation of PI3K/AKT via RAS-p110 crosstalk. Nat Commun. 2016 Jun 3;7:11672.
7	Directed evolution of anti-HER2 DARPins by SNAP display reveals stability/function trade-offs in the selection process. Protein Eng Des Sel. 2015 Sep;28(9):269-79.
8	Designed ankyrin repeat proteins are effective targeting elements for chimeric antigen receptors. J Immunother Cancer. 2015 Dec 15;3:55.
9	On the prevention of kidney uptake of radiolabeled DARPins. EJNMMI Res. 2020 Feb 4;10(1):7.
10	Designed Ankyrin Repeat Proteins as Her2 Targeting Domains in Chimeric Antigen Receptor-Engineered T Cells. Hum Gene Ther. 2017 Sep;28(9):726-736.
11	Comparative Evaluation of Radioiodine and Technetium-Labeled DARPin 9_29 for Radionuclide Molecular Imaging of HER2 Expression in Malignant Tumors. Contrast Media Mol Imaging. 2018 Jun 6;2018:6930425.
12	A rapid, site-selective and efficient route to the dual modification of DARPins. Chem Commun (Camb). 2014 May 18;50(38):4898-900.
13	A designed ankyrin repeat protein evolved to picomolar affinity to Her2. J Mol Biol. 2007 Jun 15;369(4):1015-28.
14	Efficient tumor targeting with high-affinity designed ankyrin repeat proteins: effects of affinity and molecular size. Cancer Res. 2010 Feb 15;70(4):1595-605.
15	Development of the designed ankyrin repeat protein (DARPin) G3 for HER2 molecular imaging. Eur J Nucl Med Mol Imaging. 2015 Feb;42(2):288-301.
16	Multifunctional superparamagnetic nanoparticles conjugated with fluorescein-labeled designed ankyrin repeat protein as an efficient HER2-targeted probe in breast cancer. Biomaterials. 2017 Dec;147:86-98.
17	DARPins: Promising Scaffolds for Theranostics. Acta Naturae. Oct-Dec 2019;11(4):42-53.
18	Beyond Antibodies: The DARPin ? Drug Platform. BioDrugs. 2020 Aug;34(4):423-433.
19	A tetravalent single chain diabody (CD40/HER2) efficiently inhibits tumor proliferation through recruitment of T cells and anti-HER2 functions. Mol Immunol. 2019 May;109:149-156.
20	Molecular structural and functional characterization of tumor suppressive anti-ErbB-2 monoclonal antibody by phage display system. J Biochem. 2003 Feb;133(2):239-45.
21	Peptide aptamers with binding specificity for the intracellular domain of the ErbB2 receptor interfere with AKT signaling and sensitize breast cancer cells to Taxol. Mol Cancer Res. 2006 Dec;4(12):983-98.
22	Peptide aptamers with biological and therapeutic applications. Curr Med Chem. 2011;18(27):4215-22.
23	Nanoliposome targeting in breast cancer is influenced by the tumor microenvironment. Nanomedicine. 2019 Apr;17:71-81.