4MQW

Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor (P31)

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Protein Modification Annotation

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
E	d4mqwe_	Small proteins	Cystine-knot cytokines	Cystine-knot cytokines	Gonadodropin/Follitropin	Follicle stimulating hormone, follitropin, beta chain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d4mqwb_	Small proteins	Cystine-knot cytokines	Cystine-knot cytokines	Gonadodropin/Follitropin	Follicle stimulating hormone, follitropin, beta chain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
H	d4mqwh_	Small proteins	Cystine-knot cytokines	Cystine-knot cytokines	Gonadodropin/Follitropin	Follicle stimulating hormone, follitropin, beta chain	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d4mqwa_	Small proteins	Cystine-knot cytokines	Cystine-knot cytokines	Gonadodropin/Follitropin	Glycoprotein hormones alpha chain (Gonadotropin A, Follitropin alpha)	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d4mqwd_	Small proteins	Cystine-knot cytokines	Cystine-knot cytokines	Gonadodropin/Follitropin	Glycoprotein hormones alpha chain (Gonadotropin A, Follitropin alpha)	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
G	d4mqwg_	Small proteins	Cystine-knot cytokines	Cystine-knot cytokines	Gonadodropin/Follitropin	Glycoprotein hormones alpha chain (Gonadotropin A, Follitropin alpha)	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
E	SCOP2B Superfamily	Cystine-knot cytokines	8032460	3000846	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Cystine-knot cytokines	8032460	3000846	SCOP2B (2022-06-29)
H	SCOP2B Superfamily	Cystine-knot cytokines	8032460	3000846	SCOP2B (2022-06-29)
C [auth X]	SCOP2B Superfamily	L domain-like	8032461	3001010	SCOP2B (2022-06-29)
F [auth Y]	SCOP2B Superfamily	L domain-like	8032461	3001010	SCOP2B (2022-06-29)
I [auth Z]	SCOP2B Superfamily	L domain-like	8032461	3001010	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Cystine-knot cytokines	8038799	3000846	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Cystine-knot cytokines	8038799	3000846	SCOP2B (2022-06-29)
G	SCOP2B Superfamily	Cystine-knot cytokines	8038799	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)
E	PF00007	e4mqwE1	A: few secondary structure elements	X: Cystine-knot cytokines (From Topology)	H: Cystine-knot cytokines (From Topology)	T: Cystine-knot cytokines	F: PF00007	ECOD (1.6)
B	PF00007	e4mqwB1	A: few secondary structure elements	X: Cystine-knot cytokines (From Topology)	H: Cystine-knot cytokines (From Topology)	T: Cystine-knot cytokines	F: PF00007	ECOD (1.6)
H	PF00007	e4mqwH1	A: few secondary structure elements	X: Cystine-knot cytokines (From Topology)	H: Cystine-knot cytokines (From Topology)	T: Cystine-knot cytokines	F: PF00007	ECOD (1.6)
C [auth X]	PF12369,PF13855	e4mqwX1	A: beta duplicates or obligate multimers	X: Single-stranded right-handed beta-helix	H: Leucine-rich repeats (From Topology)	T: Leucine-rich repeats	F: PF12369,PF13855	ECOD (1.6)
F [auth Y]	PF13855	e4mqwY1	A: beta duplicates or obligate multimers	X: Single-stranded right-handed beta-helix	H: Leucine-rich repeats (From Topology)	T: Leucine-rich repeats	F: PF13855	ECOD (1.6)
I [auth Z]	PF12369,PF13855	e4mqwZ1	A: beta duplicates or obligate multimers	X: Single-stranded right-handed beta-helix	H: Leucine-rich repeats (From Topology)	T: Leucine-rich repeats	F: PF12369,PF13855	ECOD (1.6)
A	PF00236	e4mqwA1	A: few secondary structure elements	X: Cystine-knot cytokines (From Topology)	H: Cystine-knot cytokines (From Topology)	T: Cystine-knot cytokines	F: PF00236	ECOD (1.6)
D	PF00236	e4mqwD1	A: few secondary structure elements	X: Cystine-knot cytokines (From Topology)	H: Cystine-knot cytokines (From Topology)	T: Cystine-knot cytokines	F: PF00236	ECOD (1.6)
G	PF00236	e4mqwG1	A: few secondary structure elements	X: Cystine-knot cytokines (From Topology)	H: Cystine-knot cytokines (From Topology)	T: Cystine-knot cytokines	F: PF00236	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
E	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)
H	2.10.90.10	Mainly Beta	Ribbon	Cystine Knot Cytokines, subunit B	Cystine-knot cytokines	CATH (4.3.0)
C [auth X]	3.80.10.10	Alpha Beta	Alpha-Beta Horseshoe	Leucine-rich repeat, LRR (right-handed beta-alpha superhelix)	Ribonuclease Inhibitor	CATH (4.3.0)
F [auth Y]	3.80.10.10	Alpha Beta	Alpha-Beta Horseshoe	Leucine-rich repeat, LRR (right-handed beta-alpha superhelix)	Ribonuclease Inhibitor	CATH (4.3.0)
I [auth Z]	3.80.10.10	Alpha Beta	Alpha-Beta Horseshoe	Leucine-rich repeat, LRR (right-handed beta-alpha superhelix)	Ribonuclease Inhibitor	CATH (4.3.0)
A	2.10.90.10	Mainly Beta	Ribbon	Cystine Knot Cytokines, subunit B	Cystine-knot cytokines	CATH (4.3.0)
D	2.10.90.10	Mainly Beta	Ribbon	Cystine Knot Cytokines, subunit B	Cystine-knot cytokines	CATH (4.3.0)
G	2.10.90.10	Mainly Beta	Ribbon	Cystine Knot Cytokines, subunit B	Cystine-knot cytokines	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
B, E, H	PF00007	Cystine-knot domain (Cys_knot)	Cystine-knot domain	The family comprises glycoprotein hormones and the C-terminal domain of various extracellular proteins. It is believed to be involved in disulfide-linked dimerisation.	Domain
C [auth X], F [auth Y], I [auth Z]	PF12369	Gonadotropin hormone receptor transmembrane region (GnHR_trans)	Gonadotropin hormone receptor transmembrane region	-	Family
C [auth X], F [auth Y], I [auth Z]	PF13306	BspA type Leucine rich repeat region (6 copies) (LRR_5)	BspA type Leucine rich repeat region (6 copies)	-	Repeat
C [auth X], F [auth Y], I [auth Z]	PF01462	Leucine rich repeat N-terminal domain (LRRNT)	Leucine rich repeat N-terminal domain	-	Family
A, D, G	PF00236	Glycoprotein hormone (Hormone_6)	Glycoprotein hormone	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
B, E, H	Follitropin subunit beta	hormone activity protein binding binding molecular function activator activity signaling receptor binding molecular function regulator activity signaling receptor regulator activity follicle-stimulating hormone activity receptor ligand activity signaling receptor activator activity	developmental process spermatogenesis sexual reproduction reproductive process multicellular organismal reproductive process developmental process involved in reproduction male gamete generation gamete generation multi-multicellular organism process multicellular organismal process female pregnancy multi-organism reproductive process regulation of cellular process cellular biosynthetic process developmental process spermatogenesis sexual reproduction reproductive process multicellular organismal reproductive process developmental process involved in reproduction male gamete generation gamete generation multi-multicellular organism process multicellular organismal process female pregnancy multi-organism reproductive process regulation of cellular process cellular biosynthetic process positive regulation of biological process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process organic substance metabolic process positive regulation of biosynthetic process organic substance biosynthetic process positive regulation of macromolecule metabolic process positive regulation of cellular process regulation of biosynthetic process regulation of biological process cellular metabolic process biological regulation regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process positive regulation of gene expression regulation of macromolecule biosynthetic process metabolic process cellular process macromolecule metabolic process regulation of metabolic process positive regulation of cellular biosynthetic process regulation of steroid biosynthetic process steroid metabolic process regulation of lipid metabolic process lipid biosynthetic process regulation of primary metabolic process positive regulation of lipid metabolic process steroid biosynthetic process regulation of steroid metabolic process primary metabolic process organic cyclic compound metabolic process positive regulation of steroid biosynthetic process positive regulation of lipid biosynthetic process organic cyclic compound biosynthetic process positive regulation of steroid metabolic process regulation of lipid biosynthetic process lipid metabolic process Sertoli cell proliferation cell population proliferation gonad development reproductive system development sex differentiation animal organ development male gonad development male sex differentiation multicellular organism development development of primary male sexual characteristics development of primary sexual characteristics anatomical structure development reproductive structure development epithelial cell proliferation system development cellular response to stimulus ovulation cycle process response to stimulus signaling development of primary female sexual characteristics cell communication ovulation cycle signal transduction ovarian follicle development rhythmic process female gonad development female sex differentiation follicle-stimulating hormone signaling pathway G protein-coupled receptor signaling pathway positive regulation of cell population proliferation regulation of cell population proliferation female gamete generation myeloid leukocyte differentiation regulation of leukocyte differentiation cellular developmental process regulation of developmental process cell development regulation of cell differentiation regulation of cell development regulation of osteoclast differentiation cell differentiation osteoclast differentiation regulation of immune system process regulation of multicellular organismal process regulation of multicellular organismal development hemopoiesis regulation of myeloid cell differentiation regulation of myeloid leukocyte differentiation myeloid cell differentiation immune system process regulation of hemopoiesis leukocyte differentiation positive regulation of locomotion regulation of cell motility positive regulation of cell migration regulation of locomotion positive regulation of cell motility regulation of cell migration cell migration cell motility locomotion homeostatic process regulation of bone remodeling tissue homeostasis regulation of tissue remodeling regulation of bone resorption bone resorption multicellular organismal-level homeostasis tissue remodeling bone remodeling anatomical structure homeostasis positive regulation of multicellular organismal process positive regulation of bone resorption regulation of signaling regulation of signaling receptor activity regulation of signal transduction regulation of molecular function regulation of response to stimulus regulation of cell communication nucleobase-containing compound metabolic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II regulation of nucleobase-containing compound metabolic process regulation of transcription by RNA polymerase II positive regulation of nucleobase-containing compound metabolic process positive regulation of transcription by RNA polymerase II positive regulation of RNA metabolic process regulation of DNA-templated transcription positive regulation of DNA-templated transcription RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process regulation of RNA biosynthetic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process positive regulation of RNA biosynthetic process cellular response to growth factor stimulus cell surface receptor protein serine/threonine kinase signaling pathway cell surface receptor signaling pathway cellular response to transforming growth factor beta stimulus response to endogenous stimulus cellular response to endogenous 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 enzyme-linked receptor protein signaling pathway C21-steroid hormone metabolic process cellular ketone metabolic process progesterone metabolic process small molecule metabolic process regulation of biological quality hormone biosynthetic process steroid hormone biosynthetic process olefinic compound biosynthetic process small molecule biosynthetic process progesterone biosynthetic process regulation of hormone levels C21-steroid hormone biosynthetic process hormone metabolic process olefinic compound metabolic process ketone biosynthetic process	intracellular anatomical structure cytoplasm cellular anatomical entity extracellular region extracellular space protein-containing complex follicle-stimulating hormone complex pituitary gonadotropin complex
C [auth X], F [auth Y], I [auth Z]	Follicle-stimulating hormone receptor	peptide receptor activity molecular transducer activity G protein-coupled receptor activity G protein-coupled peptide receptor activity transmembrane signaling receptor activity signaling receptor activity follicle-stimulating hormone receptor activity protein-hormone receptor activity	developmental process multicellular organismal process gonad development reproductive system development reproductive process sex differentiation animal organ development developmental process involved in reproduction male gonad development male sex differentiation multicellular organism development development of primary male sexual characteristics development of primary sexual characteristics anatomical structure development reproductive structure development developmental process multicellular organismal process gonad development reproductive system development reproductive process sex differentiation animal organ development developmental process involved in reproduction male gonad development male sex differentiation multicellular organism development development of primary male sexual characteristics development of primary sexual characteristics anatomical structure development reproductive structure development system development spermatogenesis sexual reproduction multicellular organismal reproductive process male gamete generation gamete generation cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction response to stimulus signaling positive regulation of biological process regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus positive regulation of ERK1 and ERK2 cascade regulation of intracellular signal transduction intracellular signaling cassette signal transduction positive regulation of cellular process regulation of biological process regulation of signaling positive regulation of MAPK cascade biological regulation positive regulation of intracellular signal transduction regulation of MAPK cascade regulation of response to stimulus MAPK cascade regulation of cell communication cellular process ERK1 and ERK2 cascade regulation of ERK1 and ERK2 cascade positive regulation of signaling response to organic substance response to endogenous stimulus hormone-mediated signaling pathway cellular response to endogenous stimulus cellular response to chemical stimulus response to hormone response to chemical cellular response to organic substance cellular response to hormone stimulus ovulation cycle process development of primary female sexual characteristics ovulation cycle ovarian follicle development rhythmic process female gonad development female sex differentiation follicle-stimulating hormone signaling pathway G protein-coupled receptor signaling pathway regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction phosphatidylinositol 3-kinase/protein kinase B signal transduction adenylate cyclase-activating G protein-coupled receptor signaling pathway adenylate cyclase-modulating G protein-coupled receptor signaling pathway regulation of protein kinase A signaling protein kinase A signaling female gamete generation cellular response to gonadotropin stimulus response to gonadotropin cellular response to follicle-stimulating hormone stimulus response to follicle-stimulating hormone	membrane cellular anatomical entity cell periphery plasma membrane protein-containing complex receptor complex
A, D, G	Glycoprotein hormones, alpha polypeptide	hormone activity protein binding binding molecular function activator activity signaling receptor binding molecular function regulator activity signaling receptor regulator activity follicle-stimulating hormone activity receptor ligand activity signaling receptor activator activity	regulation of biological process cell population proliferation regulation of cellular process positive regulation of cell population proliferation regulation of cell population proliferation biological regulation positive regulation of biological process cellular process positive regulation of cellular process multicellular organismal process system process gonadotropin secretion transport signaling regulation of biological process cell population proliferation regulation of cellular process positive regulation of cell population proliferation regulation of cell population proliferation biological regulation positive regulation of biological process cellular process positive regulation of cellular process multicellular organismal process system process gonadotropin secretion transport signaling hormone secretion cell communication localization secretion by cell signal release regulation of biological quality secretion regulation of hormone levels follicle-stimulating hormone secretion cell-cell signaling export from cell establishment of localization endocrine hormone secretion endocrine process hormone transport organonitrogen compound metabolic process organic hydroxy compound metabolic process cellular metabolic process hormone metabolic process cellular modified amino acid metabolic process thyroid hormone metabolic process organic cyclic compound metabolic process organic substance metabolic process phenol-containing compound metabolic process metabolic process thyroid hormone generation developmental process developmental growth growth organ growth multicellular organism development thyroid gland development endocrine system development gland development animal organ development anatomical structure development system development positive regulation of locomotion regulation of cell motility positive regulation of cell migration regulation of locomotion positive regulation of cell motility regulation of cell migration cell migration cell motility locomotion cellular response to stimulus response to organic substance response to stimulus response to endogenous stimulus hormone-mediated signaling pathway cellular response to endogenous stimulus cellular response to chemical stimulus response to hormone response to chemical signal transduction cellular response to organic substance cellular response to hormone stimulus regulation of signaling regulation of signaling receptor activity regulation of signal transduction regulation of molecular function regulation of response to stimulus regulation of cell communication regulation of steroid biosynthetic process steroid metabolic process regulation of lipid metabolic process lipid biosynthetic process regulation of primary metabolic process positive regulation of metabolic process positive regulation of biosynthetic process positive regulation of lipid metabolic process organic substance biosynthetic process steroid biosynthetic process regulation of biosynthetic process regulation of steroid metabolic process primary metabolic process positive regulation of steroid biosynthetic process biosynthetic process positive regulation of lipid biosynthetic process organic cyclic compound biosynthetic process positive regulation of steroid metabolic process regulation of lipid biosynthetic process regulation of metabolic process lipid metabolic process G protein-coupled receptor signaling pathway regulation of growth regulation of developmental growth regulation of developmental process negative regulation of developmental process negative regulation of biological process negative regulation of organ growth negative regulation of developmental growth negative regulation of growth regulation of organ growth regulation of multicellular organismal process negative regulation of multicellular organismal process luteinizing hormone secretion ovulation cycle process reproductive process sex differentiation development of primary female sexual characteristics developmental process involved in reproduction ovulation cycle development of primary sexual characteristics reproductive structure development ovarian follicle development rhythmic process gonad development reproductive system development female gonad development multicellular organismal reproductive process female sex differentiation follicle-stimulating hormone signaling pathway positive regulation of macromolecule biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II positive regulation of macromolecule metabolic process regulation of nucleobase-containing compound metabolic process regulation of transcription by RNA polymerase II positive regulation of nucleobase-containing compound metabolic process regulation of cellular metabolic process positive regulation of transcription by RNA polymerase II positive regulation of RNA metabolic process regulation of gene expression 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 regulation of RNA 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	membrane-bounded organelle intracellular anatomical structure Golgi apparatus membrane-enclosed lumen cellular anatomical entity intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen Golgi lumen intracellular organelle organelle lumen organelle cytoplasm protein-containing complex membrane-bounded organelle intracellular anatomical structure Golgi apparatus membrane-enclosed lumen cellular anatomical entity intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen Golgi lumen intracellular organelle organelle lumen organelle cytoplasm protein-containing complex extracellular region pituitary gonadotropin complex extracellular space follicle-stimulating hormone complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
B, E, H	IPR029034	Cystine-knot cytokine	Homologous Superfamily
B, E, H	IPR001545	Gonadotropin, beta subunit	Family
B, E, H	IPR006208	Glycoprotein hormone subunit beta	Domain
B, E, H	IPR018245	Gonadotropin, beta subunit, conserved site	Conserved Site
C [auth X], F [auth Y], I [auth Z]	IPR024635	Gonadotropin hormone receptor, transmembrane domain	Domain
C [auth X], F [auth Y], I [auth Z]	IPR002272	Follicle stimulating hormone receptor	Family
C [auth X], F [auth Y], I [auth Z]	IPR000372	Leucine-rich repeat N-terminal domain	Domain
C [auth X], F [auth Y], I [auth Z]	IPR000276	G protein-coupled receptor, rhodopsin-like	Family
C [auth X], F [auth Y], I [auth Z]	IPR002131	Glycoprotein hormone receptor family	Family
C [auth X], F [auth Y], I [auth Z]	IPR026906	BspA-type LRR region	Repeat
C [auth X], F [auth Y], I [auth Z]	IPR017452	GPCR, rhodopsin-like, 7TM	Domain
C [auth X], F [auth Y], I [auth Z]	IPR032675	Leucine-rich repeat domain superfamily	Homologous Superfamily
A, D, G	IPR000476	Glycoprotein hormone alpha chain	Family
A, D, G	IPR029034	Cystine-knot cytokine	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
B, E, H	Pharos: P01225	hypogonadotropic hypogonadism 24 without anosmia lateral medullary syndrome oligospermia alcohol abuse amenorrhea hypogonadism Fever male infertility polycystic ovary syndrome female infertility Klinefelter syndrome endometriosis hypogonadotropic hypogonadism
C [auth X], F [auth Y], I [auth Z]	Pharos: P23945	polycystic ovary syndrome ovarian hyperstimulation syndrome ovarian dysgenesis 1 46 XX gonadal dysgenesis Ovulation induction prostate carcinoma erectile dysfunction psoriasis infertility disorder primary ovarian failure
A, D, G	Pharos: P01215	oligospermia ovarian disease uterine disease hemiplegia atrial fibrillation ovarian cancer psoriasis thyroid cancer, nonmedullary, 2 adrenal gland disease Disease Exacerbation lung cancer spina bifida lung carcinoma osteosarcoma pituitary cancer oligospermia ovarian disease uterine disease hemiplegia atrial fibrillation ovarian cancer psoriasis thyroid cancer, nonmedullary, 2 adrenal gland disease Disease Exacerbation lung cancer spina bifida lung carcinoma osteosarcoma pituitary cancer interstitial lung disease

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
C [auth X], F [auth Y], I [auth Z]	TYS	Parent Component: TYR RESID: AA0172 PSI-MOD : O4'-sulfo-L-tyrosine MOD:00181

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.