General Information of Binding Target of SBP (BTS) (ID: ST00083)
BTS Name
Activin receptor type-1B
Synonyms
EC 2.7.11.30; Activin receptor type IB; ACTR-IB; Activin receptor-like kinase 4; ALK-4; Serine/threonine-protein kinase receptor R2; SKR2
BTS Type
Protein
Family
Protein kinase superfamily;
TKL Ser/Thr protein kinase family;
TGFB receptor subfamily
Gene Name
ACVR1B
Organism
Homo sapiens (Human)
Function
Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, type-2 receptors (ACVR2A and/or ACVR2B) act as a primary activin receptors whereas the type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine-threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor such as ACVR1B. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor. ACVR1B also phosphorylates TDP2.
UniProt ID
P36896
UniProt Entry
ACV1B_HUMAN
PFam
PF01064 ; PF00069 ; PF08515
Gene ID
91
Sequence
MAESAGASSFFPLVVLLLAGSGGSGPRGVQALLCACTSCLQANYTCETDGACMVSIFNLD
GMEHHVRTCIPKVELVPAGKPFYCLSSEDLRNTHCCYTDYCNRIDLRVPSGHLKEPEHPS
MWGPVELVGIIAGPVFLLFLIIIIVFLVINYHQRVYHNRQRLDMEDPSCEMCLSKDKTLQ
DLVYDLSTSGSGSGLPLFVQRTVARTIVLQEIIGKGRFGEVWRGRWRGGDVAVKIFSSRE
ERSWFREAEIYQTVMLRHENILGFIAADNKDNGTWTQLWLVSDYHEHGSLFDYLNRYTVT
IEGMIKLALSAASGLAHLHMEIVGTQGKPGIAHRDLKSKNILVKKNGMCAIADLGLAVRH
DAVTDTIDIAPNQRVGTKRYMAPEVLDETINMKHFDSFKCADIYALGLVYWEIARRCNSG
GVHEEYQLPYYDLVPSDPSIEEMRKVVCDQKLRPNIPNWWQSYEALRVMGKMMRECWYAN
GAARLTALRIKKTLSQLSVQEDVKI
Sequence Length
505
Synthetic Binding Protein (SBP) Targeting This BTS
SBP Name Highest Status Mechanism Affinity Application Details Ref
Bicyclic peptide anti-ALK4 B3 Research Binder Kd: 62-168 nM Tumors [ICD-11: XH1N44]
SBP Info
[1]
References
1 Structure-based design of small bicyclic peptide inhibitors of Cripto-1 activity. Biochem J. 2020 Apr 30;477(8):1391-1407.