Secretin receptor family (class B

GPCR G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...

subfamily) consists of

secretin receptor The secretin receptor is a protein that in humans is encoded by the SCTR gene. This protein is a G protein-coupled receptor which binds secretin Secretin is a hormone that regulates water homeostasis throughout the body and influences the enviro ...

s regulated by

peptide hormones Peptide hormones are hormones composed of peptide molecules. These hormones influence the endocrine system of animals, including humans. Most hormones are classified as either amino-acid-based hormones (amines, peptides, or proteins) or steroid h ...

from the

glucagon hormone family Glucagon/gastric inhibitory polypeptide/secretin/vasoactive intestinal peptide hormones are a family of evolutionarily related peptide hormones that regulate activity of G-protein-coupled receptors from the secretin receptor family. A number of ...

. The family is different from

adhesion G protein-coupled receptors Adhesion G protein-coupled receptors (adhesion GPCRs) are a class of 33 human protein receptors with a broad distribution in embryonic and larval cells, cells of the reproductive tract, neurons, leukocytes, and a variety of tumours. Adhesion GPC ...

. The secretin-receptor family of GPCRs include

vasoactive intestinal peptide receptor There are two known receptors for the vasoactive intestinal peptide (VIP) termed VPAC1 and VPAC2. These receptors bind both VIP and pituitary adenylate cyclase-activating polypeptide (PACAP) to some degree. Both receptors are members of the 7 t ...

s and receptors for

secretin Secretin is a hormone that regulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. It is a peptide hormone produced in the S cells of the duodenum ...

calcitonin Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the ...

and

parathyroid hormone Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates serum calcium and phosphate through its actions on the bone, kidneys, and small intestine. PTH incre ...

/parathyroid hormone-related peptides. These receptors activate

adenylyl cyclase Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :A ...

and the phosphatidyl-inositol-calcium pathway. The receptors in this family have seven

transmembrane A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently u ...

helices A helix (; ) is a shape like a cylindrical coil spring or the thread of a machine screw. It is a type of smoothness (mathematics), smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as ...

,; ; like rhodopsin-like GPCRs. However, there is no significant sequence identity between these two GPCR families and the secretin-receptor family has its own characteristic 7TM signature. The secretin-receptor family GPCRs exist in many animal species. Data mining with the

Pfam Pfam is a database of protein families that includes their annotations and multiple sequence alignments generated using hidden Markov models. The latest version of Pfam, 37.0, was released in June 2024 and contains 21,979 families. It is cur ...

signature has identified members in fungi, although due to their presumed non-hormonal function they are more commonly referred to as Adhesion G protein-coupled receptors, making the ''Adhesion'' subfamily the more basal group. Three distinct sub-families (B1-B3) are recognized.

Subfamily B1

Subfamily B1 contains classical

hormone receptor A hormone receptor is a receptor molecule that binds to a specific hormone. Hormone receptors are a wide family of proteins made up of receptors for thyroid and steroid hormones, retinoids and Vitamin D, and a variety of other receptors for various ...

s, such as receptors for

and

glucagon Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises the concentration of glucose and fatty acids in the bloodstream and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medic ...

, that are all involved in cAMP-mediated signalling pathways. * Pituitary adenylate cyclase-activating polypeptide type 1 receptor ** PACAPR (ADCYAP1R1) * Calcitonin receptor ** CALCR * Calcitonin receptor-like receptor **

CALCRL Calcitonin receptor-like (CALCRL), also known as the calcitonin receptor-like receptor (CRLR), is a human protein; it is a receptor for calcitonin gene-related peptide. Function The protein encoded by the CALCRL gene is a G protein-coupled rece ...

* Corticotropin-releasing hormone receptor ** CRHR1; CRHR2 * Glucose-dependent insulinotropic polypeptide receptor/Gastric inhibitory polypeptide receptor **

GIPR The gastric inhibitory polypeptide receptor (GIP-R), also known as the glucose-dependent insulinotropic polypeptide receptor, is a protein that in humans is encoded by the ''GIPR'' gene. GIP-R is a member of the class B family of G protein� ...

Glucagon receptor The glucagon receptor is a 62 kDa protein that is activated by glucagon and is a member of the class B G-protein coupled family of receptors ( secretin receptor family), coupled to G alpha i, Gs and to a lesser extent G alpha q. Stimulation o ...

** GCGR * Glucagon receptor-related ** GLP1R;

GLP2R Glucagon-like peptide-2 receptor (GLP-2R) is a protein that in human is encoded by the ''GLP2R'' gene located on chromosome 17. Function The GLP2 receptor (GLP2R) is a G protein-coupled receptor superfamily member closely related to the glucago ...

; * Growth hormone releasing hormone receptor ** GHRHR * Parathyroid hormone receptor ** PTHR1; PTHR2 * Secretin receptor ** SCTR *

Vasoactive intestinal peptide receptor There are two known receptors for the vasoactive intestinal peptide (VIP) termed VPAC1 and VPAC2. These receptors bind both VIP and pituitary adenylate cyclase-activating polypeptide (PACAP) to some degree. Both receptors are members of the 7 t ...

VIPR1 Vasoactive intestinal polypeptide receptor 1 also known as VPAC1, is a protein, that in humans is encoded by the ''VIPR1'' gene. VPAC1 is expressed in the brain (cerebral cortex, hippocampus, amygdala), lung, prostate, peripheral blood leukocytes ...

;

VIPR2 Vasoactive intestinal peptide receptor 2 also known as VPAC2, is a G-protein coupled receptor that in humans is encoded by the ''VIPR2'' gene. Tissue distribution VIPR2 is expressed in the uterus, prostate, smooth muscle of the gastrointesti ...

Subfamily B2

Subfamily B2 contains receptors with long extracellular N-termini, such as the leukocyte cell-surface antigen

CD97 Cluster of differentiation 97 is a protein also known as BL-Ac 2encoded by the ''ADGRE5'' gene. CD97 is a member of the adhesion G protein-coupled receptor (GPCR) family. Adhesion GPCRs are characterized by an extended extracellular region oft ...

; calcium-independent receptors for latrotoxin and brain-specific angiogenesis inhibitor receptors amongst others. They are otherwise known as Adhesion G protein-coupled receptors. * Brain-specific angiogenesis inhibitor ** BAI1; BAI2; BAI3 * CD97 antigen **

* EMR hormone receptor **

CELSR1 Cadherin EGF LAG seven-pass G-type receptor 1 also known as flamingo homolog 2 or cadherin family member 9 is a protein that in humans is encoded by the ''CELSR1'' gene. Function The protein encoded by this gene is a member of the flamingo su ...

;

CELSR2 Cadherin EGF LAG seven-pass G-type receptor 2 is a protein that in humans is encoded by the ''CELSR2'' gene. The protein encoded by this gene is a member of the flamingo subfamily, part of the cadherin superfamily. The flamingo subfamily consis ...

;

CELSR3 Cadherin EGF LAG seven-pass G-type receptor 3 is a protein that in humans is encoded by the ''CELSR3'' gene. The protein encoded by this gene is a member of the flamingo subfamily, part of the cadherin superfamily. The flamingo subfamily consist ...

; EMR1; EMR2;

EMR3 EGF-like module-containing mucin-like hormone receptor-like 3 is a protein encoded by the ''ADGRE3'' gene. EMR3 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-term ...

;

EMR4 The EGF module-containing Mucin-like hormone Receptors (EMRs) are closely related subgroup of G protein-coupled receptors (GPCRs). These receptors have a unique hybrid structure in which an extracellular epidermal growth factor (EGF)-like dom ...

* GPR56 orphan receptor **

GPR56 G protein-coupled receptor 56 also known as TM7XN1 is a protein encoded by the ''ADGRG1'' gene. GPR56 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal prote ...

; GPR64; GPR97; GPR110; GPR111; GPR112; GPR113; GPR114; GPR115;

GPR123 Probable G-protein coupled receptor 123 is a protein that in humans is encoded by the ''GPR123'' gene. It is a member of the adhesion-GPCR Adhesion G protein-coupled receptors (adhesion GPCRs) are a class of 33 human protein Receptor (biochemi ...

;

GPR125 Adhesion G-protein coupled receptor A3 (ADGRA3), also known as GPR125, is an adhesion GPCR that in humans is encoded by the ''Adgra3'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The mo ...

; GPR126; GPR128;

GPR133 Probable G-protein coupled receptor 133 is a protein that in humans is encoded by the ''GPR133'' gene. This gene encodes a member of the adhesion-GPCR family of receptors. Family members are characterized by an extended extracellular region with ...

;

GPR144 Probable G-protein coupled receptor 144 is a protein that in humans is encoded by the ''GPR144'' gene. This gene encodes a member of the adhesion-GPCR Adhesion G protein-coupled receptors (adhesion GPCRs) are a class of 33 human protein Rece ...

; GPR157 * Latrophilin receptor **

ELTD1 Adhesion G protein-coupled receptor L4 is a latrophilin-like orphan receptor of the adhesion G protein-coupled receptor family. In humans this protein is encoded by the ''ADGRL4'' gene. ADGRL4 appears to have a role in angiogenesis, both physiol ...

; LPHN1; LPHN2; LPHN3 * Ig-hepta receptor ** GPR116

Subfamily B3

Subfamily B3 includes

Methuselah Methuselah (; ''Məṯūšélaḥ'', in pausa ''Məṯūšālaḥ'', "His death shall send" or "Man of the javelin" or "Death of sword"; ''Mathousalas'') was a biblical patriarch and a figure in Judaism, Christianity, and Islam. He is clai ...

and other

Drosophila ''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...

proteins. Other than the typical seven-transmembrane region, characteristic structural features include an amino-terminal extracellular domain involved in ligand binding, and an intracellular loop (IC3) required for specific G-protein coupling. * Diuretic hormone receptor

Unclassified members

HCTR-5; HCTR-6; KPG 006; KPG 008

References

{{G protein-coupled receptors Protein domains Protein families G protein-coupled receptors