Annotations: 3HH2

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d3hh2a_	Small proteins	Cystine-knot cytokines	Cystine-knot cytokines	automated matches	automated matches	mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
B	d3hh2b_	Small proteins	Cystine-knot cytokines	Cystine-knot cytokines	automated matches	automated matches	mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2 Family	Transforming growth factor (TGF)-beta	8070306	4003433	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Cystine-knot cytokines	8070307	3000846	SCOP2 (2022-06-29)
B	SCOP2B Superfamily	Cystine-knot cytokines	8070307	3000846	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	PF00019	e3hh2A1	A: few secondary structure elements	X: Cystine-knot cytokines (From Topology)	H: Cystine-knot cytokines (From Topology)	T: Cystine-knot cytokines	F: PF00019	ECOD (1.6)
B	PF00019	e3hh2B1	A: few secondary structure elements	X: Cystine-knot cytokines (From Topology)	H: Cystine-knot cytokines (From Topology)	T: Cystine-knot cytokines	F: PF00019	ECOD (1.6)
C	PF21333	e3hh2C1	A: few secondary structure elements	X: TB module/8-cys domain (From Topology)	H: TB module/8-cys domain (From Topology)	T: TB module/8-cys domain	F: PF21333	ECOD (1.6)
C	PF07648	e3hh2C3	A: few secondary structure elements	X: Kazal-type serine protease inhibitors-like	H: Kazal-type serine protease inhibitors (From Topology)	T: Kazal-type serine protease inhibitors	F: PF07648	ECOD (1.6)
C	F_UNCLASSIFIED	e3hh2C5	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: F_UNCLASSIFIED	ECOD (1.6)
C	PF09289	e3hh2C6	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: PF09289	ECOD (1.6)
D	PF21333	e3hh2D1	A: few secondary structure elements	X: TB module/8-cys domain (From Topology)	H: TB module/8-cys domain (From Topology)	T: TB module/8-cys domain	F: PF21333	ECOD (1.6)
D	PF07648	e3hh2D3	A: few secondary structure elements	X: Kazal-type serine protease inhibitors-like	H: Kazal-type serine protease inhibitors (From Topology)	T: Kazal-type serine protease inhibitors	F: PF07648	ECOD (1.6)
D	F_UNCLASSIFIED	e3hh2D5	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: F_UNCLASSIFIED	ECOD (1.6)
D	PF09289	e3hh2D6	A: few secondary structure elements	X: EGF-like	H: EGF-related	T: EGF/Laminin	F: PF09289	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.10.90.10	Mainly Beta	Ribbon	Cystine Knot Cytokines, subunit B	Cystine-knot cytokines	CATH (4.3.0)
B	2.10.90.10	Mainly Beta	Ribbon	Cystine Knot Cytokines, subunit B	Cystine-knot cytokines	CATH (4.3.0)
C	3.90.290.10	Alpha Beta	Alpha-Beta Complex	Extracellular Matrix Fibrillin	TGF-beta binding (TB) domain	CATH (4.3.0)
C	3.30.60.30	Alpha Beta	2-Layer Sandwich	Wheat Germ Agglutinin (Isolectin 2)	domain 1	CATH (4.3.0)
D	3.90.290.10	Alpha Beta	Alpha-Beta Complex	Extracellular Matrix Fibrillin	TGF-beta binding (TB) domain	CATH (4.3.0)
D	3.30.60.30	Alpha Beta	2-Layer Sandwich	Wheat Germ Agglutinin (Isolectin 2)	domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF00019	Transforming growth factor beta like domain (TGF_beta)	Transforming growth factor beta like domain	-	Domain
C, D	PF09289	Follistatin/Osteonectin-like EGF domain (FOLN)	Follistatin/Osteonectin-like EGF domain	Members of this family are predominantly found in osteonectin and follistatin and adopt an EGF-like fold [1,2].	Domain
C, D	PF21333	Follistatin, N-terminal (FST_N)	Follistatin, N-terminal	Follistatin (FST) is required for normal embryonic and ovarian follicle development. It regulates transforming growth factor-beta superfamily ligands, being described as a ligand antagonist. It consists of a N-terminal domain with a modified TB fold ...	Follistatin (FST) is required for normal embryonic and ovarian follicle development. It regulates transforming growth factor-beta superfamily ligands, being described as a ligand antagonist. It consists of a N-terminal domain with a modified TB fold and three follistatin domains (FSD1-3) each of which is subdivided in EGF-like and Kazal-like subdomains [1-4]. This domain is important for ligand specificity.	Domain
C, D	PF07648	Kazal-type serine protease inhibitor domain (Kazal_2)	Kazal-type serine protease inhibitor domain	Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containi ...	Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Growth/differentiation factor 8	protein binding binding signaling receptor binding molecular function activator activity molecular function regulator activity signaling receptor regulator activity growth factor activity receptor ligand activity signaling receptor activator activity identical protein binding protein homodimerization activity protein dimerization activity cytokine activity heparin binding protein binding binding signaling receptor binding molecular function activator activity molecular function regulator activity signaling receptor regulator activity growth factor activity receptor ligand activity signaling receptor activator activity identical protein binding protein homodimerization activity protein dimerization activity cytokine activity heparin binding glycosaminoglycan binding carbohydrate derivative binding sulfur compound binding	response to stimulus response to activity response to muscle activity muscle hypertrophy multicellular organismal process regulation of biological process system process negative regulation of muscle hypertrophy regulation of system process negative regulation of biological process biological regulation regulation of muscle system process muscle system process regulation of muscle hypertrophy response to stimulus response to activity response to muscle activity muscle hypertrophy multicellular organismal process regulation of biological process system process negative regulation of muscle hypertrophy regulation of system process negative regulation of biological process biological regulation regulation of muscle system process muscle system process regulation of muscle hypertrophy regulation of multicellular organismal process negative regulation of multicellular organismal process response to organic substance response to hormone response to chemical response to endogenous stimulus response to estrogen skeletal muscle cell differentiation developmental process cellular developmental process skeletal muscle tissue development animal organ development tissue development muscle structure development skeletal muscle organ development cell differentiation anatomical structure development cellular process muscle tissue development muscle organ development skeletal muscle satellite cell differentiation regulation of cellular process regulation of developmental process regulation of cell differentiation regulation of skeletal muscle cell differentiation negative regulation of cellular process negative regulation of skeletal muscle cell differentiation negative regulation of cell differentiation negative regulation of developmental process negative regulation of satellite cell differentiation response to ketone response to lipid response to oxygen-containing compound response to testosterone response to organic cyclic compound response to decreased oxygen levels cellular response to stimulus cellular response to oxygen levels cellular response to hypoxia cellular response to decreased oxygen levels cellular response to chemical stimulus cellular response to stress response to hypoxia response to stress response to oxygen levels response to abiotic stimulus negative regulation of myoblast differentiation regulation of myoblast differentiation myoblast differentiation muscle atrophy striated muscle adaptation skeletal muscle atrophy muscle adaptation skeletal muscle adaptation striated muscle atrophy negative regulation of cell population proliferation cell population proliferation negative regulation of skeletal muscle satellite cell proliferation negative regulation of skeletal muscle cell proliferation skeletal muscle satellite cell proliferation regulation of cell population proliferation muscle cell proliferation regulation of skeletal muscle satellite cell proliferation skeletal muscle cell proliferation regulation of skeletal muscle cell proliferation striated muscle cell proliferation regulation of growth developmental growth negative regulation of growth regulation of skeletal muscle tissue growth regulation of developmental growth growth negative regulation of developmental growth skeletal muscle tissue growth negative regulation of skeletal muscle tissue growth cellular response to endogenous stimulus response to steroid hormone cellular response to organic substance cellular response to ketone cellular response to steroid hormone stimulus cellular response to hormone stimulus cellular response to dexamethasone stimulus response to glucocorticoid cellular response to organic cyclic compound cellular response to glucocorticoid stimulus cellular response to oxygen-containing compound cellular response to corticosteroid stimulus response to corticosteroid cellular response to lipid response to dexamethasone cellular response to nitrogen compound negative regulation of signaling signaling response to peptide hormone regulation of signal transduction insulin receptor signaling pathway regulation of cellular response to insulin stimulus negative regulation of cell communication cell surface receptor protein tyrosine kinase signaling pathway cell communication signal transduction enzyme-linked receptor protein signaling pathway regulation of signaling cell surface receptor signaling pathway negative regulation of response to stimulus response to organonitrogen compound regulation of insulin receptor signaling pathway cellular response to peptide hormone stimulus response to nitrogen compound negative regulation of signal transduction negative regulation of cellular response to insulin stimulus cellular response to organonitrogen compound regulation of response to stimulus negative regulation of insulin receptor signaling pathway response to insulin regulation of cell communication cellular response to insulin stimulus regulation of catalytic activity negative regulation of phosphate metabolic process negative regulation of catalytic activity regulation of transferase activity negative regulation of cellular metabolic process negative regulation of kinase activity negative regulation of transferase activity regulation of phosphate metabolic process phosphate-containing compound metabolic process phosphorus metabolic process phosphorylation cellular metabolic process negative regulation of metabolic process negative regulation of molecular function regulation of cellular metabolic process regulation of molecular function regulation of kinase activity negative regulation of phosphorus metabolic process regulation of phosphorylation regulation of phosphorus metabolic process metabolic process negative regulation of phosphorylation regulation of metabolic process response to alcohol response to ethanol positive regulation of locomotion regulation of cell motility macrophage migration positive regulation of chemotaxis positive regulation of cell migration taxis cell migration regulation of immune system process regulation of mononuclear cell migration positive regulation of immune system process chemotaxis regulation of leukocyte chemotaxis positive regulation of macrophage migration regulation of leukocyte migration response to external stimulus positive regulation of leukocyte chemotaxis granulocyte migration leukocyte migration regulation of locomotion regulation of response to external stimulus macrophage chemotaxis positive regulation of biological process positive regulation of response to stimulus regulation of granulocyte chemotaxis regulation of macrophage migration positive regulation of response to external stimulus positive regulation of cell motility regulation of cell migration myeloid leukocyte migration positive regulation of mononuclear cell migration cell motility locomotion positive regulation of cellular process cell chemotaxis regulation of macrophage chemotaxis positive regulation of leukocyte migration regulation of chemotaxis immune system process granulocyte chemotaxis mononuclear cell migration positive regulation of macrophage chemotaxis leukocyte chemotaxis response to electrical stimulus regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction negative regulation of intracellular signal transduction negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction intracellular signal transduction regulation of intracellular signal transduction intracellular signaling cassette phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of macromolecule biosynthetic process regulation of primary metabolic process nucleobase-containing compound metabolic process positive regulation of metabolic process DNA-templated transcription regulation of RNA metabolic process organic substance biosynthetic process positive regulation of macromolecule metabolic process regulation of nucleobase-containing compound metabolic process positive regulation of nucleobase-containing compound metabolic process primary metabolic process positive regulation of RNA metabolic process organic cyclic compound metabolic process regulation of gene expression biosynthetic process organic cyclic compound biosynthetic process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of DNA-templated transcription positive regulation of DNA-templated transcription cellular biosynthetic process RNA metabolic process positive regulation of cellular metabolic process RNA biosynthetic process nucleic acid biosynthetic process organic substance metabolic process positive regulation of biosynthetic process regulation of RNA biosynthetic process regulation of biosynthetic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of cellular biosynthetic process positive regulation of RNA biosynthetic process positive regulation of cellular biosynthetic process tissue regeneration skeletal muscle tissue regeneration regeneration myoblast proliferation regulation of myoblast proliferation negative regulation of myoblast proliferation rhythmic process ovulation cycle ovulation cycle process reproductive process multicellular organismal reproductive process response to gravity regulation of cellular component organization positive regulation of cellular component organization cell projection organization plasma membrane bounded cell projection assembly cellular component biogenesis cellular component organization cellular component assembly regulation of lamellipodium assembly regulation of lamellipodium organization positive regulation of cell projection organization cellular component organization or biogenesis lamellipodium assembly plasma membrane bounded cell projection organization positive regulation of cellular component biogenesis regulation of cell projection organization regulation of cell projection assembly positive regulation of lamellipodium assembly regulation of cellular component biogenesis positive regulation of lamellipodium organization regulation of plasma membrane bounded cell projection assembly lamellipodium organization cell projection assembly regulation of plasma membrane bounded cell projection organization positive regulation of plasma membrane bounded cell projection assembly cellular response to growth factor stimulus cell surface receptor protein serine/threonine kinase signaling pathway cellular response to transforming growth factor beta stimulus response to transforming growth factor beta transforming growth factor beta receptor signaling pathway response to growth factor transforming growth factor beta receptor superfamily signaling pathway cellular homeostasis homeostatic process muscle cell cellular homeostasis myoblast migration involved in skeletal muscle regeneration muscle cell migration myoblast migration	extracellular region cellular anatomical entity extracellular space
C, D	Follistatin	protein-containing complex binding activin binding binding activin receptor antagonist activity molecular function inhibitor activity protein binding signaling receptor binding molecular function regulator activity signaling receptor inhibitor activity receptor antagonist activity signaling receptor regulator activity heparan sulfate proteoglycan binding proteoglycan binding carbohydrate derivative binding protein-containing complex binding activin binding binding activin receptor antagonist activity molecular function inhibitor activity protein binding signaling receptor binding molecular function regulator activity signaling receptor inhibitor activity receptor antagonist activity signaling receptor regulator activity heparan sulfate proteoglycan binding proteoglycan binding carbohydrate derivative binding sulfur compound binding	developmental process multicellular organism development multicellular organismal process anatomical structure development pattern specification process cellular developmental process cell differentiation cellular process cellular response to stimulus cellular response to BMP stimulus regulation of biological process cell surface receptor protein serine/threonine kinase signaling pathway regulation of cellular process cellular response to growth factor stimulus developmental process multicellular organism development multicellular organismal process anatomical structure development pattern specification process cellular developmental process cell differentiation cellular process cellular response to stimulus cellular response to BMP stimulus regulation of biological process cell surface receptor protein serine/threonine kinase signaling pathway regulation of cellular process cellular response to growth factor stimulus cell surface receptor signaling pathway response to stimulus signaling response to endogenous stimulus biological regulation cell communication cellular response to endogenous stimulus response to BMP transforming growth factor beta receptor superfamily signaling pathway signal transduction response to growth factor BMP signaling pathway enzyme-linked receptor protein signaling pathway sexual reproduction reproductive process multicellular organismal reproductive process gamete generation activin receptor signaling pathway negative regulation of signaling regulation of transmembrane receptor protein serine/threonine kinase signaling pathway negative regulation of biological process regulation of signal transduction negative regulation of cell communication negative regulation of activin receptor signaling pathway negative regulation of cellular process regulation of signaling negative regulation of response to stimulus negative regulation of signal transduction regulation of response to stimulus regulation of cell communication regulation of activin receptor signaling pathway negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway anatomical structure morphogenesis odontogenesis of dentin-containing tooth odontogenesis animal organ development animal organ morphogenesis skeletal system development system development cell population proliferation epithelial cell proliferation keratinocyte proliferation regulation of developmental process regulation of cell differentiation epithelial cell differentiation regulation of epithelial cell differentiation regulation of multicellular organismal process negative regulation of cell differentiation epithelium development regulation of multicellular organismal development negative regulation of epithelial cell differentiation negative regulation of developmental process tissue development epidermis development molting cycle process hair cycle epidermis morphogenesis morphogenesis of an epithelium tissue morphogenesis skin development skin epidermis development hair follicle development molting cycle hair cycle process hair follicle morphogenesis regulation of BMP signaling pathway regulation of cellular response to growth factor stimulus positive regulation of biological process regulation of hair cycle positive regulation of developmental process positive regulation of hair follicle development regulation of hair follicle development positive regulation of multicellular organismal process hemopoiesis cell development hematopoietic progenitor cell differentiation negative regulation of cellular metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II organic substance biosynthetic process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II cellular metabolic process negative regulation of metabolic process primary metabolic process regulation of cellular metabolic process negative regulation of cellular biosynthetic process organic cyclic compound metabolic process regulation of gene expression biosynthetic process negative regulation of macromolecule biosynthetic process organic cyclic compound biosynthetic process metabolic process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of DNA-templated transcription regulation of metabolic process negative regulation of RNA metabolic process cellular biosynthetic process RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process organic substance metabolic process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of biosynthetic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of cellular biosynthetic process negative regulation of biosynthetic process response to organic substance response to chemical response to organic cyclic compound ameloblast differentiation columnar/cuboidal epithelial cell differentiation gonad development reproductive system development female gonad development sex differentiation female sex differentiation development of primary female sexual characteristics developmental process involved in reproduction development of primary sexual characteristics reproductive structure development	intracellular anatomical structure cytoplasm cellular anatomical entity extracellular region extracellular space membrane-bounded organelle intracellular organelle organelle nucleus intracellular membrane-bounded organelle

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR029034	Cystine-knot cytokine	Homologous Superfamily
A, B	IPR015615	Transforming growth factor-beta-related	Family
A, B	IPR017948	Transforming growth factor beta, conserved site	Conserved Site
A, B	IPR001111	TGF-beta, propeptide	Domain
A, B	IPR001839	Transforming growth factor-beta, C-terminal	Domain
C, D	IPR015369	Follistatin/Osteonectin EGF domain	Domain
C, D	IPR036058	Kazal domain superfamily	Homologous Superfamily
C, D	IPR002350	Kazal domain	Domain
C, D	IPR003645	Follistatin-like, N-terminal	Domain
C, D	IPR036773	TGF-beta binding (TB) domain superfamily	Homologous Superfamily
C, D	IPR017878	TB domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
C, D	Pharos: P19883	acute liver failure breast cancer liver cancer breast carcinoma Liver carcinoma malignant glioma myopathy ovarian cancer pituitary cancer atypical teratoid rhabdoid tumor psoriasis cystic fibrosis gastric cancer hepatocellular carcinoma large cell medulloblastoma acute liver failure breast cancer liver cancer breast carcinoma Liver carcinoma malignant glioma myopathy ovarian cancer pituitary cancer atypical teratoid rhabdoid tumor psoriasis cystic fibrosis gastric cancer hepatocellular carcinoma large cell medulloblastoma liver neoplasm non-small cell lung carcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia amyotrophic lateral sclerosis polycystic ovary syndrome Duchenne muscular dystrophy gastric neoplasm hereditary diffuse gastric adenocarcinoma lung cancer medulloblastoma osteosarcoma acne pilocytic astrocytoma atopic eczema primitive neuroectodermal tumor ulcerative colitis Emery-Dreifuss muscular dystrophy glioblastoma juvenile dermatomyositis

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.