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Conserved domains on  [gi|1802446916|ref|NP_001365018|]
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integral membrane protein GPR137 isoform 7 [Homo sapiens]

Protein Classification

G protein-coupled receptor family protein( domain architecture ID 705710)

G protein-coupled receptor family protein is a seven-transmembrane G protein-coupled receptor (7TM-GPCR) family protein which typically transmits an extracellular signal into the cell by the conformational rearrangement of the 7TM helices and by the subsequent binding and activation of an intracellular heterotrimeric G protein; GPCR ligands include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
7tm_GPCRs super family cl28897
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
16-273 6.61e-144

seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary model represents the seven-transmembrane (7TM) receptors, often referred to as G protein-coupled receptors (GPCRs), which transmit physiological signals from the outside of the cell to the inside via G proteins. GPCRs constitute the largest known superfamily of transmembrane receptors across the three kingdoms of life that respond to a wide variety of extracellular stimuli including peptides, lipids, neurotransmitters, amino acids, hormones, and sensory stimuli such as light, smell and taste. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. However, some 7TM receptors, such as the type 1 microbial rhodopsins, do not activate G proteins. Based on sequence similarity, GPCRs can be divided into six major classes: class A (the rhodopsin-like family), class B (the Methuselah-like, adhesion and secretin-like receptor family), class C (the metabotropic glutamate receptor family), class D (the fungal mating pheromone receptors), class E (the cAMP receptor family), and class F (the frizzled/smoothened receptor family). Nearly 800 human GPCR genes have been identified and are involved essentially in all major physiological processes. Approximately 40% of clinically marketed drugs mediate their effects through modulation of GPCR function for the treatment of a variety of human diseases including bacterial infections.


The actual alignment was detected with superfamily member cd21474:

Pssm-ID: 475119  Cd Length: 310  Bit Score: 409.15  E-value: 6.61e-144
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916  16 PALPPAVTLGLTAAYTTLYALLFFSVYAQLWLVLLYGHKRLSYQTVFLALCLLWAALRTTLFSFYFRDTPRANRLGPLPF 95
Cdd:cd21474     1 PAVPPAVKLGLTALYTTLYALLFLSVYAQLWLVLLYRHKRLSYQTVFLFLCLLWAALRTTLFSFYFRDTLKANHLGPFLF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916  96 WLLYCCPVCLQFFTLTLMNLYFAQVVFKAKVKRRPEMSRGF------------------------GSQGVEEAGSLLSLR 151
Cdd:cd21474    81 WLLYCCPVCLQFFTLTLMNLYFAQVVFKAKAKFRPEMSKGLlavrgaclgasllfllvnvacavlVRMRRAEPWALVLVR 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916 152 VL---------------CCYL-------------CQGTSVCQAAAMGGAMVLLYASRACYNLTALALAPQSRLDTFDYDW 203
Cdd:cd21474   161 VLindslfvlcavslaaCLCLvarrspstsiyleAKGTTVCQTAAMGGAVILLYASRACYNLAALALSPRTRLDAFDYDW 240
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916 204 YNVSDQADLVNDLGNKGYLVFGLILFVWELLPTTLLVGFFRVHRPPQDLSTSHILNGQVFASRSYFFDRA 273
Cdd:cd21474   241 YNVSDQADLITDLGDKGYLVFGLILFVWELLPTALLVGFFRVRRPPQDLSASRIINGQSFGSRSYFFDNP 310
 
Name Accession Description Interval E-value
7tm_GPR137A cd21474
Integral membrane protein GPR137A, an orphan receptor member of the seven-transmembrane G ...
16-273 6.61e-144

Integral membrane protein GPR137A, an orphan receptor member of the seven-transmembrane G protein-coupled receptor superfamily; GPR137A, also called GPR137 or transmembrane 7 superfamily member 1-like 1 protein (TM7SF1L1), is an orphan G protein-coupled receptor (GPCR) expressed in the central nervous system (CNS), endocrine gland, thymus, and lung. It is associated with different cancers including gastric cancer, pancreatic cancer, colon cancer, and malignant glioma. It is highly expressed in ovarian cancer and plays a pro-oncogenic role in the disease, promoting cell proliferation and metastasis through regulation of the PI3K/AKT pathway. GPCRs transmit physiological signals from the outside of the cell to the inside via G proteins. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.


Pssm-ID: 410551  Cd Length: 310  Bit Score: 409.15  E-value: 6.61e-144
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916  16 PALPPAVTLGLTAAYTTLYALLFFSVYAQLWLVLLYGHKRLSYQTVFLALCLLWAALRTTLFSFYFRDTPRANRLGPLPF 95
Cdd:cd21474     1 PAVPPAVKLGLTALYTTLYALLFLSVYAQLWLVLLYRHKRLSYQTVFLFLCLLWAALRTTLFSFYFRDTLKANHLGPFLF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916  96 WLLYCCPVCLQFFTLTLMNLYFAQVVFKAKVKRRPEMSRGF------------------------GSQGVEEAGSLLSLR 151
Cdd:cd21474    81 WLLYCCPVCLQFFTLTLMNLYFAQVVFKAKAKFRPEMSKGLlavrgaclgasllfllvnvacavlVRMRRAEPWALVLVR 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916 152 VL---------------CCYL-------------CQGTSVCQAAAMGGAMVLLYASRACYNLTALALAPQSRLDTFDYDW 203
Cdd:cd21474   161 VLindslfvlcavslaaCLCLvarrspstsiyleAKGTTVCQTAAMGGAVILLYASRACYNLAALALSPRTRLDAFDYDW 240
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916 204 YNVSDQADLVNDLGNKGYLVFGLILFVWELLPTTLLVGFFRVHRPPQDLSTSHILNGQVFASRSYFFDRA 273
Cdd:cd21474   241 YNVSDQADLITDLGDKGYLVFGLILFVWELLPTALLVGFFRVRRPPQDLSASRIINGQSFGSRSYFFDNP 310
 
Name Accession Description Interval E-value
7tm_GPR137A cd21474
Integral membrane protein GPR137A, an orphan receptor member of the seven-transmembrane G ...
16-273 6.61e-144

Integral membrane protein GPR137A, an orphan receptor member of the seven-transmembrane G protein-coupled receptor superfamily; GPR137A, also called GPR137 or transmembrane 7 superfamily member 1-like 1 protein (TM7SF1L1), is an orphan G protein-coupled receptor (GPCR) expressed in the central nervous system (CNS), endocrine gland, thymus, and lung. It is associated with different cancers including gastric cancer, pancreatic cancer, colon cancer, and malignant glioma. It is highly expressed in ovarian cancer and plays a pro-oncogenic role in the disease, promoting cell proliferation and metastasis through regulation of the PI3K/AKT pathway. GPCRs transmit physiological signals from the outside of the cell to the inside via G proteins. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.


Pssm-ID: 410551  Cd Length: 310  Bit Score: 409.15  E-value: 6.61e-144
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916  16 PALPPAVTLGLTAAYTTLYALLFFSVYAQLWLVLLYGHKRLSYQTVFLALCLLWAALRTTLFSFYFRDTPRANRLGPLPF 95
Cdd:cd21474     1 PAVPPAVKLGLTALYTTLYALLFLSVYAQLWLVLLYRHKRLSYQTVFLFLCLLWAALRTTLFSFYFRDTLKANHLGPFLF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916  96 WLLYCCPVCLQFFTLTLMNLYFAQVVFKAKVKRRPEMSRGF------------------------GSQGVEEAGSLLSLR 151
Cdd:cd21474    81 WLLYCCPVCLQFFTLTLMNLYFAQVVFKAKAKFRPEMSKGLlavrgaclgasllfllvnvacavlVRMRRAEPWALVLVR 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916 152 VL---------------CCYL-------------CQGTSVCQAAAMGGAMVLLYASRACYNLTALALAPQSRLDTFDYDW 203
Cdd:cd21474   161 VLindslfvlcavslaaCLCLvarrspstsiyleAKGTTVCQTAAMGGAVILLYASRACYNLAALALSPRTRLDAFDYDW 240
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916 204 YNVSDQADLVNDLGNKGYLVFGLILFVWELLPTTLLVGFFRVHRPPQDLSTSHILNGQVFASRSYFFDRA 273
Cdd:cd21474   241 YNVSDQADLITDLGDKGYLVFGLILFVWELLPTALLVGFFRVRRPPQDLSASRIINGQSFGSRSYFFDNP 310
7tm_GPR137 cd21464
GPR137 family belonging to the seven-transmembrane G protein-coupled receptor superfamily; The ...
16-271 3.44e-112

GPR137 family belonging to the seven-transmembrane G protein-coupled receptor superfamily; The GPR137 family includes GPR137A, GPR137B, and GPR137C, which are all orphan G protein-coupled receptors (GPCRs). GPR137A, also called GPR137 or transmembrane 7 superfamily member 1-like 1 protein (TM7SF1L1), is expressed in the central nervous system (CNS), endocrine gland, thymus, and lung. It is associated with different cancers including gastric cancer, pancreatic cancer, colon cancer, and malignant glioma. GPR137B, also called transmembrane 7 superfamily member 1 (TM7SF1), is a lysosome integral membrane protein that is strongly expressed in the heart, liver, kidney, and brain. It is associated with M2 macrophage polarization, and has been shown to perform a regulatory function in controlling dynamic Rag and mTORC1 localization and activity, as well as lysosome morphology. GPR137C, also called transmembrane 7 superfamily member 1-like 2 protein (TM7SF1L2), may be a key player in the prognosis of small cell lung cancer. GPCRs transmit physiological signals from the outside of the cell to the inside via G proteins. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.


Pssm-ID: 410550  Cd Length: 310  Bit Score: 328.42  E-value: 3.44e-112
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916  16 PALPPAVTLGLTAAYTTLYALLFFSVYAQLWLVLLYGHKRLSYQTVFLALCLLWAALRTTLFSFYFRDTPRANRLGPLPF 95
Cdd:cd21464     1 PALSPAVHLGLTIVFTVLYALLFIFVYVQLWLILYYRHKRLSYQTVFLFLCLLWSGLRTTLFSFYFKNCILANNLSFFPY 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916  96 WLLYCCPVCLQFFTLTLMNLYFAQVVFKAKVKRRpEMSRGF--------------------------GSQGVEEAG--SL 147
Cdd:cd21464    81 WLLYCFPVCLQFLTLCLLVLYFAQVVFKARAKYY-EPSRYKkplrllfvlanllflatnitcavlvrEYQATDRSVlkAL 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916 148 LSLRV-------------LCCYLC--------------QGTSVCQAAAMGGAMVLLYASRACYNLTALALaPQSRLDTFD 200
Cdd:cd21464   160 VLTRViindllfvlaaivLSICIYkitkmssanvlleaKGTTVCQAIAVCIIIILLYVSRAVYNIIAVSP-SSSKLPSFG 238
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1802446916 201 YDWYNVSDQADLVNDLGNKGYLVFGLILFVWELLPTTLLVGFFRVHRPPQDLSTSHILNGQVFASRSYFFD 271
Cdd:cd21464   239 YGWINVSDQADLVNLLSGYAYISFGVVLFVWEFLPTFIVVLFFRVRRPQTDLLLSSDISSSSTNSRSYFFD 309
7tm_GPR137B cd21476
Integral membrane protein GPR137B, an orphan receptor member of the seven-transmembrane G ...
16-271 3.39e-98

Integral membrane protein GPR137B, an orphan receptor member of the seven-transmembrane G protein-coupled receptor superfamily; GPR137B, also called transmembrane 7 superfamily member 1 (TM7SF1), is a lysosome integral membrane protein that is strongly expressed in the heart, liver, kidney, and brain. It is an orphan G protein-coupled receptor (GPCR) associated with M2 macrophage polarization, and has been shown to perform a regulatory function in controlling dynamic Rag and mTORC1 localization and activity, as well as lysosome morphology. It also plays a role in bone remodeling in mouse and zebrafish, functioning as a negative regulator of osteoclast activity essential for normal resorption and patterning of the skeleton. GPCRs transmit physiological signals from the outside of the cell to the inside via G proteins. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.


Pssm-ID: 410553  Cd Length: 320  Bit Score: 293.26  E-value: 3.39e-98
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916  16 PALPPAVTLGLTAAYTTLYALLFFSVYAQLWLVLLYGHKRLSYQTVFLALCLLWAALRTTLFSFYFRDTPRANRLGPLPF 95
Cdd:cd21476     1 PAVPPYVKLGLTAVYTVFYALLFVFIYVQLWLVLRYRHKRFSYQTVFLFLCLFWASLRTVLFSFYFRDFVAANSLSPFVF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916  96 WLLYCCPVCLQFFTLTLMNLYFAQVVFKAKVKRRPEMSR-----GFGSQGVE-------------------EAGSLLSLR 151
Cdd:cd21476    81 WLLYCFPVCLQFFTLTLMNLYFTQVIFKAKSKYSPELLKyrlplYLASLFISllfllvnltcavlvktgnwERKVIVSVR 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916 152 --------VLCC------------------YL-CQGTSVCQAAAMGGAMVLLYASRACYNLTALALAPQSRLDTFDYDWY 204
Cdd:cd21476   161 vaindtlfVLCAvslsiclykiskmslaniYLeSKGSSVCQVTAIGVTVILLYTSRACYNLFILSFSQIKSVHSFDYDWY 240
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1802446916 205 NVSDQADLVNDLGNKGYLVFGLILFVWELLPTTLLVGFFRVHRPPQDLSTSHILNGQVFASRSYFFD 271
Cdd:cd21476   241 NVSDQADLKSQLGDAGYVVFGVILFVWELLPTTLVVYFFRVRNPTKDLTNPGMVPSHGFSPRSYFFD 307
7tm_GPR137C cd21475
Integral membrane protein GPR137C, an orphan receptor member of the seven-transmembrane G ...
16-271 4.69e-93

Integral membrane protein GPR137C, an orphan receptor member of the seven-transmembrane G protein-coupled receptor superfamily; GPR137C, also called transmembrane 7 superfamily member 1-like 2 protein (TM7SF1L2), is an orphan G protein-coupled receptor (GPCR) of unknown function. Bioinformatics analysis identified it as a likely key player in the prognosis of small cell lung cancer. GPCRs transmit physiological signals from the outside of the cell to the inside via G proteins. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.


Pssm-ID: 410552  Cd Length: 319  Bit Score: 280.13  E-value: 4.69e-93
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916  16 PALPPAVTLGLTAAYTTLYALLFFSVYAQLWLVLLYGHKRLSYQTVFLALCLLWAALRTTLFSFYFRDTPRANRLGPLPF 95
Cdd:cd21475     1 AAVPPSVELGLTVLYTVLYSALFLFAYLQLWLLLHYRHKRLSYQSLFLFLCLLWAALRTTLFSFYFKNCVQANQLQPFPH 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916  96 WLLYCCPVCLQFFTLTLMNLYFAQVVFKAKVKrrPEMSR-------GFGSQG-----------------VEE-------- 143
Cdd:cd21475    81 WLLYCFPVCLQFFTLCLLNLYFAQVIFKAKCA--PELNKykiplrlGFLLASllflvvnltcamlvhgdVPEnqlkwtvl 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802446916 144 AGSLL--SLRVLC-----CYLC--------------QGTSVCQAAAMGGAMVLLYASRACYNLTALALAPQSRLDTFDYD 202
Cdd:cd21475   159 ARVLIndSLFVLCaislaCCIFkiakmssanvylesKGTSVCQAVAVGSVVILLYSSRACYNLVVVAISPEDRPSPFNYG 238
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1802446916 203 WYNVSDQADlVNDLGNKGYLVFGLILFVWELLPTTLLVGFFRVHRPPQDLSTSHILNGQVFASRSYFFD 271
Cdd:cd21475   239 WDNVSDQAD-VEKISGEEYVVFGIVLFFWELLPTSLVVLFFRAQRLNQNLAPAGMINSHSFSSRAYFFD 306
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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