ACV1B_HUMAN » Activin receptor type-1B

ACV1B_HUMAN » Activin receptor type-1B
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Topology in Plasma membrane
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ACV1B_HUMAN » Activin receptor type-1B » Activin receptor type IB;ACTR-IB; Activin receptor-like kinase 4;ALK-4; Serine/threonine-protein kinase receptor R2;SKR2;
Hydrophobic Thickness 33.6 ± 4.8 Å
Tilt Angle 41 ± 0°
ΔGtransfer -35.6 kcal/mol
ΔGfold -27.2 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB
Topology Out
TM Segments 124-152 (124-160)
Pathways

Cytokine-cytokine receptor interaction (KEGG)

Developmental Biology (Reactome)

Signal Transduction (Reactome)

TGF-beta signaling pathway (KEGG)

PDB none
OPM none
Complexes none
Interactions

ACV1C, Complex: ACV1C:GDF11:ACV1B:AVR2B:TGFR1, PubMed

ACVR1, Complex: ACV1B:ACVR1, PubMed

AVR2A, Complex: AVR2A:ACV1B, PubMed

AVR2B, Complex: AVR2B:ACV1B, PubMed

BAMBI, Complex: ACV1B:BAMBI, PubMed

BMPR2, Complex: BMPR2:ACV1B, PubMed

Domains

AA: 32-105, PDBID: 2L5S, Subunit A, Seq Identity:41%, Activin types I and II receptor domain

AA: 178-205, PDBID: 1B6C, Subunit B, Seq Identity:79%, Transforming growth factor beta type I GS-motif

AA: 207-494, PDBID: 1B6C, Subunit D, Seq Identity:92%, Protein kinase domain

UniProt annotation for ACV1B_HUMAN » Activin receptor type-1B
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.

CATALYTIC ACTIVITY: ATP + [receptor-protein] = ADP + [receptor- protein] phosphate.

ENZYME REGULATION: Activin receptor type-2 (ACVR2A or ACVR2B) activates the type-1 receptor through phosphorylation of its regulatory GS domain.

SUBUNIT: Forms an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Interacts with TDP2 (By similarity). Interacts with AIP1, FKBP1A, IGSF1, TDGF1, SMAD2, SMAD3 and SMAD7.

TISSUE SPECIFICITY: Expressed in many tissues, most strongly in kidney, pancreas, brain, lung, and liver.

DOMAIN: The GS domain is a 30-amino-acid sequence adjacent to the N-terminal boundary of the kinase domain and highly conserved in all other known type-1 receptors but not in type-2 receptors. The GS domain is the site of activation through phosphorylation by the II receptors.

DISEASE: Note=ACVRIB is abundantly expressed in systemic sclerosis patient fibroblasts and production of collagen is also induced by activin-A/INHBA. This suggests that the activin/ACRV1B signaling mechanism is involved in systemic sclerosis.

UniProt features for ACV1B_HUMAN » Activin receptor type-1B
SIGNAL 1 23 Potential.
CHAIN 24 505 Activin receptor type-1B.
DOMAIN 177 206 GS.
DOMAIN 207 497 Protein kinase.
ACT_SITE 335 335 Proton acceptor (By similarity).
Amino Acid Sequence for ACV1B_HUMAN » Activin receptor type-1B
MAESAGASSF FPLVVLLLAG SGGSGPRGVQ ALLCACTSCL QANYTCETDG ACMVSIFNLD GMEHHVRTCI PKVELVPAGK PFYCLSSEDL RNTHCCYTDY CNRIDLRVPS GHLKEPEHPS MWGPVELVGI IAGPVFLLFL IIIIVFLVIN YHQRVYHNRQ RLDMEDPSCE MCLSKDKTLQ DLVYDLSTSG SGSGLPLFVQ RTVARTIVLQ EIIGKGRFGE VWRGRWRGGD VAVKIFSSRE ERSWFREAEI YQTVMLRHEN ILGFIAADNK DNGTWTQLWL VSDYHEHGSL FDYLNRYTVT IEGMIKLALS AASGLAHLHM EIVGTQGKPG IAHRDLKSKN ILVKKNGMCA IADLGLAVRH DAVTDTIDIA PNQRVGTKRY MAPEVLDETI NMKHFDSFKC ADIYALGLVY WEIARRCNSG GVHEEYQLPY YDLVPSDPSI EEMRKVVCDQ KLRPNIPNWW QSYEALRVMG KMMRECWYAN GAARLTALRI KKTLSQLSVQ EDVKI