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Conserved domains on  [gi|540344584|ref|NP_001269370|]
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guanine nucleotide-binding protein subunit alpha-12 isoform 3 [Homo sapiens]

Protein Classification

guanine nucleotide-binding protein subunit alpha( domain architecture ID 10048024)

guanine nucleotide-binding protein subunit alpha contains the guanine nucleotide binding site of heterotrimeric G protein, which functions as a modulator or transducer in various transmembrane signaling systems

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
G-alpha cd00066
Alpha subunit of G proteins (guanine nucleotide binding); The alpha subunit of G proteins ...
45-316 5.57e-143

Alpha subunit of G proteins (guanine nucleotide binding); The alpha subunit of G proteins contains the guanine nucleotide binding site. The heterotrimeric GNP-binding proteins are signal transducers that communicate signals from many hormones, neurotransmitters, chemokines, and autocrine and paracrine factors. Extracellular signals are received by receptors, which activate the G proteins, which in turn route the signals to several distinct intracellular signaling pathways. The alpha subunit of G proteins is a weak GTPase. In the resting state, heterotrimeric G proteins are associated at the cytosolic face of the plasma membrane and the alpha subunit binds to GDP. Upon activation by a receptor GDP is replaced with GTP, and the G-alpha/GTP complex dissociates from the beta and gamma subunits. This results in activation of downstream signaling pathways, such as cAMP synthesis by adenylyl cyclase, which is terminated when GTP is hydrolized and the heterotrimers reconstitute.


:

Pssm-ID: 206639 [Multi-domain]  Cd Length: 315  Bit Score: 405.76  E-value: 5.57e-143
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584  45 GSRVLVDARDKLGIPWQYSENEKHGMFLMAFENKAglpVEPATFQLYVPALSALWRDSGIREAFSRRSEFQLGESVKYFL 124
Cdd:cd00066   47 SMKALLRAMETLNIPYGDPENEKDAKKILSLAPRA---EEGPLPPELAEAIKRLWKDPGIQACYDRRNEYQLNDSAKYFL 123
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 125 DNLDRIGQLNYFPSKQDILLARKATKGIVEHDFVIKKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSEYDQVLME 204
Cdd:cd00066  124 DNLDRISDPDYIPTEQDILRSRVKTTGIIETDFSIKNLKFRMFDVGGQRSERKKWIHCFEDVTAIIFVVALSEYDQVLVE 203
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 205 DRRTNRLVESMNIFETIVNNKLFFNVSIILFLNKMDLLVEKVKTVSIKKHFPDFRGDPHRLEDVQRYLVQCFDRKRRNRS 284
Cdd:cd00066  204 DESVNRMQESLKLFDSICNSRWFANTSIILFLNKKDLFEEKIKKSPLTDYFPDYTGPPNDYEEAAKYIKKKFLDLNRNPN 283
                        250       260       270
                 ....*....|....*....|....*....|..
gi 540344584 285 KPLFHHFTTAIDTENVRFVFHAVKDTILQENL 316
Cdd:cd00066  284 KEIYPHFTCATDTENIRFVFDAVKDIILQNNL 315
 
Name Accession Description Interval E-value
G-alpha cd00066
Alpha subunit of G proteins (guanine nucleotide binding); The alpha subunit of G proteins ...
45-316 5.57e-143

Alpha subunit of G proteins (guanine nucleotide binding); The alpha subunit of G proteins contains the guanine nucleotide binding site. The heterotrimeric GNP-binding proteins are signal transducers that communicate signals from many hormones, neurotransmitters, chemokines, and autocrine and paracrine factors. Extracellular signals are received by receptors, which activate the G proteins, which in turn route the signals to several distinct intracellular signaling pathways. The alpha subunit of G proteins is a weak GTPase. In the resting state, heterotrimeric G proteins are associated at the cytosolic face of the plasma membrane and the alpha subunit binds to GDP. Upon activation by a receptor GDP is replaced with GTP, and the G-alpha/GTP complex dissociates from the beta and gamma subunits. This results in activation of downstream signaling pathways, such as cAMP synthesis by adenylyl cyclase, which is terminated when GTP is hydrolized and the heterotrimers reconstitute.


Pssm-ID: 206639 [Multi-domain]  Cd Length: 315  Bit Score: 405.76  E-value: 5.57e-143
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584  45 GSRVLVDARDKLGIPWQYSENEKHGMFLMAFENKAglpVEPATFQLYVPALSALWRDSGIREAFSRRSEFQLGESVKYFL 124
Cdd:cd00066   47 SMKALLRAMETLNIPYGDPENEKDAKKILSLAPRA---EEGPLPPELAEAIKRLWKDPGIQACYDRRNEYQLNDSAKYFL 123
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 125 DNLDRIGQLNYFPSKQDILLARKATKGIVEHDFVIKKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSEYDQVLME 204
Cdd:cd00066  124 DNLDRISDPDYIPTEQDILRSRVKTTGIIETDFSIKNLKFRMFDVGGQRSERKKWIHCFEDVTAIIFVVALSEYDQVLVE 203
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 205 DRRTNRLVESMNIFETIVNNKLFFNVSIILFLNKMDLLVEKVKTVSIKKHFPDFRGDPHRLEDVQRYLVQCFDRKRRNRS 284
Cdd:cd00066  204 DESVNRMQESLKLFDSICNSRWFANTSIILFLNKKDLFEEKIKKSPLTDYFPDYTGPPNDYEEAAKYIKKKFLDLNRNPN 283
                        250       260       270
                 ....*....|....*....|....*....|..
gi 540344584 285 KPLFHHFTTAIDTENVRFVFHAVKDTILQENL 316
Cdd:cd00066  284 KEIYPHFTCATDTENIRFVFDAVKDIILQNNL 315
G_alpha smart00275
G protein alpha subunit; Subunit of G proteins that contains the guanine nucleotide binding ...
45-320 1.58e-138

G protein alpha subunit; Subunit of G proteins that contains the guanine nucleotide binding site


Pssm-ID: 214595 [Multi-domain]  Cd Length: 342  Bit Score: 395.79  E-value: 1.58e-138
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584    45 GSRVLVDARDKLGIPWQYSENEKHGMFLMAFENKAGLPvEPATFQLYVPALSALWRDSGIREAFSRRSEFQLGESVKYFL 124
Cdd:smart00275  68 SMKALVDAMEELNIPFEDPESILDIRIITEQFNKTDET-ENVLPKEIAKAIKALWKDEGIQECYRRRNEFQLNDSASYFL 146
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584   125 DNLDRIGQLNYFPSKQDILLARKATKGIVEHDFVIKKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSEYDQVLME 204
Cdd:smart00275 147 DNIDRIGDPDYVPTEQDILRSRVPTTGIQETAFIVKKLFFRMFDVGGQRSERKKWIHCFDNVTAIIFCVALSEYDQVLEE 226
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584   205 DRRTNRLVESMNIFETIVNNKLFFNVSIILFLNKMDLLVEKVKTVSIKKHFPDFRGdPHRLEDVQRYLVQCFDRKRRNRS 284
Cdd:smart00275 227 DESTNRMQESLNLFESICNSRWFANTSIILFLNKIDLFEEKIKKVPLVDYFPDYKG-PNDYEAAAKFIKQKFLRLNRNSS 305
                          250       260       270
                   ....*....|....*....|....*....|....*..
gi 540344584   285 -KPLFHHFTTAIDTENVRFVFHAVKDTILQENLKDIM 320
Cdd:smart00275 306 rKSIYHHFTCATDTRNIRVVFDAVKDIILQRNLKDAG 342
G-alpha pfam00503
G-protein alpha subunit; G proteins couple receptors of extracellular signals to intracellular ...
44-311 8.53e-116

G-protein alpha subunit; G proteins couple receptors of extracellular signals to intracellular signaling pathways. The G protein alpha subunit binds guanyl nucleotide and is a weak GTPase. A set of residues that are unique to G-alpha as compared to its ancestor the Arf-like family form a ring of residues centered on the nucleotide binding site. A Ggamma is found fused to an inactive Galpha in the Dictyostelium protein gbqA.


Pssm-ID: 459835 [Multi-domain]  Cd Length: 316  Bit Score: 336.87  E-value: 8.53e-116
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584   44 RGSRVLVDARDKLGIPWQYSENEKHGMFLMAFENKaglPVEPATFQL-YVPALSALWRDSGIREAFSRRSEFQLGESVKY 122
Cdd:pfam00503  51 RSLKTLIEAMERLGIELSNPENKERLDDLLSLDSS---LKNETEFTPeLAEDIKRLWNDPGIQECYERRNEFQLPDSAEY 127
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584  123 FLDNLDRIGQLNYFPSKQDILLARKATKGIVEHDFVIKKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSEYDQVL 202
Cdd:pfam00503 128 FLDNLDRIASPDYVPTDQDILRARVKTTGIIETKFEFKGLKFRLFDVGGQRSERKKWIHCFEDVTAIIFVVSLSEYDQVL 207
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584  203 MEDRRTNRLVESMNIFETIVNNKLFFNVSIILFLNKMDLLVEKVKTVSIKKHFPDFRGDPHRLEDVQRYLVQCFDRKRRN 282
Cdd:pfam00503 208 YEDDSTNRMEESLKLFEEICNSPWFKNTPIILFLNKKDLFEEKLKKSPLSDYFPDYTGNPNDYEEALKYIRNKFLDLNKN 287
                         250       260
                  ....*....|....*....|....*....
gi 540344584  283 RSKPLFHHFTTAIDTENVRFVFHAVKDTI 311
Cdd:pfam00503 288 PNRKIYTHFTCATDTENIRFVFDAVKDII 316
small_GTP TIGR00231
small GTP-binding protein domain; Proteins with a small GTP-binding domain recognized by this ...
160-248 5.32e-04

small GTP-binding protein domain; Proteins with a small GTP-binding domain recognized by this model include Ras, RhoA, Rab11, translation elongation factor G, translation initiation factor IF-2, tetratcycline resistance protein TetM, CDC42, Era, ADP-ribosylation factors, tdhF, and many others. In some proteins the domain occurs more than once.This model recognizes a large number of small GTP-binding proteins and related domains in larger proteins. Note that the alpha chains of heterotrimeric G proteins are larger proteins in which the NKXD motif is separated from the GxxxxGK[ST] motif (P-loop) by a long insert and are not easily detected by this model. [Unknown function, General]


Pssm-ID: 272973 [Multi-domain]  Cd Length: 162  Bit Score: 40.05  E-value: 5.32e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584  160 KKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSS----EYDQVLMEDRRtnrlvesmnifetIVNNKLFFNVSIILF 235
Cdd:TIGR00231  49 KTYKFNLLDTAGQEDYDAIRRLYYPQVERSLRVFDIVilvlDVEEILEKQTK-------------EIIHHADSGVPIILV 115
                          90
                  ....*....|...
gi 540344584  236 LNKMDLLVEKVKT 248
Cdd:TIGR00231 116 GNKIDLKDADLKT 128
PLN00223 PLN00223
ADP-ribosylation factor; Provisional
160-241 7.81e-04

ADP-ribosylation factor; Provisional


Pssm-ID: 165788  Cd Length: 181  Bit Score: 39.95  E-value: 7.81e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 160 KKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSEYDqvlmedrrtnRLVESMNIFETIVNNKLFFNVSIILFLNKM 239
Cdd:PLN00223  59 KNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDRD----------RVVEARDELHRMLNEDELRDAVLLVFANKQ 128

                 ..
gi 540344584 240 DL 241
Cdd:PLN00223 129 DL 130
 
Name Accession Description Interval E-value
G-alpha cd00066
Alpha subunit of G proteins (guanine nucleotide binding); The alpha subunit of G proteins ...
45-316 5.57e-143

Alpha subunit of G proteins (guanine nucleotide binding); The alpha subunit of G proteins contains the guanine nucleotide binding site. The heterotrimeric GNP-binding proteins are signal transducers that communicate signals from many hormones, neurotransmitters, chemokines, and autocrine and paracrine factors. Extracellular signals are received by receptors, which activate the G proteins, which in turn route the signals to several distinct intracellular signaling pathways. The alpha subunit of G proteins is a weak GTPase. In the resting state, heterotrimeric G proteins are associated at the cytosolic face of the plasma membrane and the alpha subunit binds to GDP. Upon activation by a receptor GDP is replaced with GTP, and the G-alpha/GTP complex dissociates from the beta and gamma subunits. This results in activation of downstream signaling pathways, such as cAMP synthesis by adenylyl cyclase, which is terminated when GTP is hydrolized and the heterotrimers reconstitute.


Pssm-ID: 206639 [Multi-domain]  Cd Length: 315  Bit Score: 405.76  E-value: 5.57e-143
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584  45 GSRVLVDARDKLGIPWQYSENEKHGMFLMAFENKAglpVEPATFQLYVPALSALWRDSGIREAFSRRSEFQLGESVKYFL 124
Cdd:cd00066   47 SMKALLRAMETLNIPYGDPENEKDAKKILSLAPRA---EEGPLPPELAEAIKRLWKDPGIQACYDRRNEYQLNDSAKYFL 123
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 125 DNLDRIGQLNYFPSKQDILLARKATKGIVEHDFVIKKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSEYDQVLME 204
Cdd:cd00066  124 DNLDRISDPDYIPTEQDILRSRVKTTGIIETDFSIKNLKFRMFDVGGQRSERKKWIHCFEDVTAIIFVVALSEYDQVLVE 203
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 205 DRRTNRLVESMNIFETIVNNKLFFNVSIILFLNKMDLLVEKVKTVSIKKHFPDFRGDPHRLEDVQRYLVQCFDRKRRNRS 284
Cdd:cd00066  204 DESVNRMQESLKLFDSICNSRWFANTSIILFLNKKDLFEEKIKKSPLTDYFPDYTGPPNDYEEAAKYIKKKFLDLNRNPN 283
                        250       260       270
                 ....*....|....*....|....*....|..
gi 540344584 285 KPLFHHFTTAIDTENVRFVFHAVKDTILQENL 316
Cdd:cd00066  284 KEIYPHFTCATDTENIRFVFDAVKDIILQNNL 315
G_alpha smart00275
G protein alpha subunit; Subunit of G proteins that contains the guanine nucleotide binding ...
45-320 1.58e-138

G protein alpha subunit; Subunit of G proteins that contains the guanine nucleotide binding site


Pssm-ID: 214595 [Multi-domain]  Cd Length: 342  Bit Score: 395.79  E-value: 1.58e-138
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584    45 GSRVLVDARDKLGIPWQYSENEKHGMFLMAFENKAGLPvEPATFQLYVPALSALWRDSGIREAFSRRSEFQLGESVKYFL 124
Cdd:smart00275  68 SMKALVDAMEELNIPFEDPESILDIRIITEQFNKTDET-ENVLPKEIAKAIKALWKDEGIQECYRRRNEFQLNDSASYFL 146
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584   125 DNLDRIGQLNYFPSKQDILLARKATKGIVEHDFVIKKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSEYDQVLME 204
Cdd:smart00275 147 DNIDRIGDPDYVPTEQDILRSRVPTTGIQETAFIVKKLFFRMFDVGGQRSERKKWIHCFDNVTAIIFCVALSEYDQVLEE 226
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584   205 DRRTNRLVESMNIFETIVNNKLFFNVSIILFLNKMDLLVEKVKTVSIKKHFPDFRGdPHRLEDVQRYLVQCFDRKRRNRS 284
Cdd:smart00275 227 DESTNRMQESLNLFESICNSRWFANTSIILFLNKIDLFEEKIKKVPLVDYFPDYKG-PNDYEAAAKFIKQKFLRLNRNSS 305
                          250       260       270
                   ....*....|....*....|....*....|....*..
gi 540344584   285 -KPLFHHFTTAIDTENVRFVFHAVKDTILQENLKDIM 320
Cdd:smart00275 306 rKSIYHHFTCATDTRNIRVVFDAVKDIILQRNLKDAG 342
G-alpha pfam00503
G-protein alpha subunit; G proteins couple receptors of extracellular signals to intracellular ...
44-311 8.53e-116

G-protein alpha subunit; G proteins couple receptors of extracellular signals to intracellular signaling pathways. The G protein alpha subunit binds guanyl nucleotide and is a weak GTPase. A set of residues that are unique to G-alpha as compared to its ancestor the Arf-like family form a ring of residues centered on the nucleotide binding site. A Ggamma is found fused to an inactive Galpha in the Dictyostelium protein gbqA.


Pssm-ID: 459835 [Multi-domain]  Cd Length: 316  Bit Score: 336.87  E-value: 8.53e-116
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584   44 RGSRVLVDARDKLGIPWQYSENEKHGMFLMAFENKaglPVEPATFQL-YVPALSALWRDSGIREAFSRRSEFQLGESVKY 122
Cdd:pfam00503  51 RSLKTLIEAMERLGIELSNPENKERLDDLLSLDSS---LKNETEFTPeLAEDIKRLWNDPGIQECYERRNEFQLPDSAEY 127
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584  123 FLDNLDRIGQLNYFPSKQDILLARKATKGIVEHDFVIKKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSEYDQVL 202
Cdd:pfam00503 128 FLDNLDRIASPDYVPTDQDILRARVKTTGIIETKFEFKGLKFRLFDVGGQRSERKKWIHCFEDVTAIIFVVSLSEYDQVL 207
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584  203 MEDRRTNRLVESMNIFETIVNNKLFFNVSIILFLNKMDLLVEKVKTVSIKKHFPDFRGDPHRLEDVQRYLVQCFDRKRRN 282
Cdd:pfam00503 208 YEDDSTNRMEESLKLFEEICNSPWFKNTPIILFLNKKDLFEEKLKKSPLSDYFPDYTGNPNDYEEALKYIRNKFLDLNKN 287
                         250       260
                  ....*....|....*....|....*....
gi 540344584  283 RSKPLFHHFTTAIDTENVRFVFHAVKDTI 311
Cdd:pfam00503 288 PNRKIYTHFTCATDTENIRFVFDAVKDII 316
Arf_Arl cd00878
ADP-ribosylation factor(Arf)/Arf-like (Arl) small GTPases; Arf (ADP-ribosylation factor)/Arl ...
149-254 2.44e-12

ADP-ribosylation factor(Arf)/Arf-like (Arl) small GTPases; Arf (ADP-ribosylation factor)/Arl (Arf-like) small GTPases. Arf proteins are activators of phospholipase D isoforms. Unlike Ras proteins they lack cysteine residues at their C-termini and therefore are unlikely to be prenylated. Arfs are N-terminally myristoylated. Members of the Arf family are regulators of vesicle formation in intracellular traffic that interact reversibly with membranes of the secretory and endocytic compartments in a GTP-dependent manner. They depart from other small GTP-binding proteins by a unique structural device, interswitch toggle, that implements front-back communication from N-terminus to the nucleotide binding site. Arf-like (Arl) proteins are close relatives of the Arf, but only Arl1 has been shown to function in membrane traffic like the Arf proteins. Arl2 has an unrelated function in the folding of native tubulin, and Arl4 may function in the nucleus. Most other Arf family proteins are so far relatively poorly characterized. Thus, despite their significant sequence homologies, Arf family proteins may regulate unrelated functions.


Pssm-ID: 206644 [Multi-domain]  Cd Length: 158  Bit Score: 63.75  E-value: 2.44e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 149 TKGIVEHDFVIKKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSeydqvlmeDRRtnRLVESMNIFETIVNNKLFF 228
Cdd:cd00878   30 TIGFNVETVEYKNVKFTVWDVGGQDKIRPLWKHYYENTDGLIFVVDSS--------DRE--RIEEAKNELHKLLNEEELK 99
                         90       100       110
                 ....*....|....*....|....*....|....
gi 540344584 229 NVSIILFLNKMDL--------LVEKVKTVSIKKH 254
Cdd:cd00878  100 GAPLLILANKQDLpgalteseLIELLGLESIKGR 133
ARLTS1 cd04156
Arf-like tumor suppressor gene 1 (ARLTS1 or Arl11); ARLTS1 (Arf-like tumor suppressor gene 1), ...
160-241 2.36e-06

Arf-like tumor suppressor gene 1 (ARLTS1 or Arl11); ARLTS1 (Arf-like tumor suppressor gene 1), also known as Arl11, is a member of the Arf family of small GTPases that is believed to play a major role in apoptotic signaling. ARLTS1 is widely expressed and functions as a tumor suppressor gene in several human cancers. ARLTS1 is a low-penetrance suppressor that accounts for a small percentage of familial melanoma or familial chronic lymphocytic leukemia (CLL). ARLTS1 inactivation seems to occur most frequently through biallelic down-regulation by hypermethylation of the promoter. In breast cancer, ARLTS1 alterations were typically a combination of a hypomorphic polymorphism plus loss of heterozygosity. In a case of thyroid adenoma, ARLTS1 alterations were polymorphism plus promoter hypermethylation. The nonsense polymorphism Trp149Stop occurs with significantly greater frequency in familial cancer cases than in sporadic cancer cases, and the Cys148Arg polymorphism is associated with an increase in high-risk familial breast cancer.


Pssm-ID: 133356 [Multi-domain]  Cd Length: 160  Bit Score: 46.64  E-value: 2.36e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 160 KKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSEYDqvlmedrrtnRLVESMNIFETIVNNKLFFNVSIILFLNKM 239
Cdd:cd04156   42 KHLSLTVWDVGGQEKMRTVWKCYLENTDGLVYVVDSSDEA----------RLDESQKELKHILKNEHIKGVPVVLLANKQ 111

                 ..
gi 540344584 240 DL 241
Cdd:cd04156  112 DL 113
Arf6 cd04149
ADP ribosylation factor 6 (Arf6); Arf6 subfamily. Arf6 (ADP ribosylation factor 6) proteins ...
160-241 3.10e-06

ADP ribosylation factor 6 (Arf6); Arf6 subfamily. Arf6 (ADP ribosylation factor 6) proteins localize to the plasma membrane, where they perform a wide variety of functions. In its active, GTP-bound form, Arf6 is involved in cell spreading, Rac-induced formation of plasma membrane ruffles, cell migration, wound healing, and Fc-mediated phagocytosis. Arf6 appears to change the actin structure at the plasma membrane by activating Rac, a Rho family protein involved in membrane ruffling. Arf6 is required for and enhances Rac formation of ruffles. Arf6 can regulate dendritic branching in hippocampal neurons, and in yeast it localizes to the growing bud, where it plays a role in polarized growth and bud site selection. In leukocytes, Arf6 is required for chemokine-stimulated migration across endothelial cells. Arf6 also plays a role in down-regulation of beta2-adrenergic receptors and luteinizing hormone receptors by facilitating the release of sequestered arrestin to allow endocytosis. Arf6 is believed to function at multiple sites on the plasma membrane through interaction with a specific set of GEFs, GAPs, and effectors. Arf6 has been implicated in breast cancer and melanoma cell invasion, and in actin remodelling at the invasion site of Chlamydia infection.


Pssm-ID: 206716  Cd Length: 168  Bit Score: 46.69  E-value: 3.10e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 160 KKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSeydqvlmeDRrtNRLVESMNIFETIVNNKLFFNVSIILFLNKM 239
Cdd:cd04149   51 KNVKFNVWDVGGQDKIRPLWRHYYTGTQGLIFVVDSA--------DR--DRIDEARQELHRIINDREMRDALLLVFANKQ 120

                 ..
gi 540344584 240 DL 241
Cdd:cd04149  121 DL 122
Arfrp1 cd04160
Arf-related protein 1 (Arfrp1); Arfrp1 (Arf-related protein 1), formerly known as ARP, is a ...
168-249 3.35e-06

Arf-related protein 1 (Arfrp1); Arfrp1 (Arf-related protein 1), formerly known as ARP, is a membrane-associated Arf family member that lacks the N-terminal myristoylation motif. Arfrp1 is mainly associated with the trans-Golgi compartment and the trans-Golgi network, where it regulates the targeting of Arl1 and the GRIP domain-containing proteins, golgin-97 and golgin-245, onto Golgi membranes. It is also involved in the anterograde transport of the vesicular stomatitis virus G protein from the Golgi to the plasma membrane, and in the retrograde transport of TGN38 and Shiga toxin from endosomes to the trans-Golgi network. Arfrp1 also inhibits Arf/Sec7-dependent activation of phospholipase D. Deletion of Arfrp1 in mice causes embryonic lethality at the gastrulation stage and apoptosis of mesodermal cells, indicating its importance in development.


Pssm-ID: 206725 [Multi-domain]  Cd Length: 168  Bit Score: 46.57  E-value: 3.35e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 168 DVGGQRSQRQKWFQCFDGITSILFMVSSSEYDqvlmedrrtnRLVESMNIFETIVNNKLFFNVSIILFLNKMD----LLV 243
Cdd:cd04160   57 DLGGQEELRSLWDKYYAESHGVIYVIDSTDRE----------RFNESKSAFEKVINNEALEGVPLLVLANKQDlpdaLSV 126

                 ....*.
gi 540344584 244 EKVKTV 249
Cdd:cd04160  127 AEIKEV 132
Arf pfam00025
ADP-ribosylation factor family; Pfam combines a number of different Prosite families together
149-241 3.43e-06

ADP-ribosylation factor family; Pfam combines a number of different Prosite families together


Pssm-ID: 459636 [Multi-domain]  Cd Length: 160  Bit Score: 46.45  E-value: 3.43e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584  149 TKGIVEHDFVIKKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSeydqvlmeDRrtNRLVESMNIFETIVNNKLFF 228
Cdd:pfam00025  31 TIGFNVETVTYKNVKFTVWDVGGQESLRPLWRNYFPNTDAVIFVVDSA--------DR--DRIEEAKEELHALLNEEELA 100
                          90
                  ....*....|...
gi 540344584  229 NVSIILFLNKMDL 241
Cdd:pfam00025 101 DAPLLILANKQDL 113
Sar1 cd00879
Sar1 is an essential component of COPII vesicle coats; Sar1 is an essential component of COPII ...
157-241 5.99e-06

Sar1 is an essential component of COPII vesicle coats; Sar1 is an essential component of COPII vesicle coats involved in export of cargo from the ER. The GTPase activity of Sar1 functions as a molecular switch to control protein-protein and protein-lipid interactions that direct vesicle budding from the ER. Activation of the GDP to the GTP-bound form of Sar1 involves the membrane-associated guanine nucleotide exchange factor (GEF) Sec12. Sar1 is unlike all Ras superfamily GTPases that use either myristoyl or prenyl groups to direct membrane association and function, in that Sar1 lacks such modification. Instead, Sar1 contains a unique nine-amino-acid N-terminal extension. This extension contains an evolutionarily conserved cluster of bulky hydrophobic amino acids, referred to as the Sar1-N-terminal activation recruitment (STAR) motif. The STAR motif mediates the recruitment of Sar1 to ER membranes and facilitates its interaction with mammalian Sec12 GEF leading to activation.


Pssm-ID: 206645 [Multi-domain]  Cd Length: 191  Bit Score: 46.12  E-value: 5.99e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 157 FVIKKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSEYdqvlmedrrtNRLVESMNIFETIVNNKLFFNVSIILFL 236
Cdd:cd00879   58 LTIGNVKFTTFDLGGHEQARRVWKDYFPEVDGIVFLVDAADP----------ERFQESKEELDSLLNDEELANVPILILG 127

                 ....*
gi 540344584 237 NKMDL 241
Cdd:cd00879  128 NKIDK 132
Arl3 cd04155
Arf-like 3 (Arl3) GTPase; Arl3 (Arf-like 3) is an Arf family protein that differs from most ...
155-242 2.20e-05

Arf-like 3 (Arl3) GTPase; Arl3 (Arf-like 3) is an Arf family protein that differs from most Arf family members in the N-terminal extension. In is inactive, GDP-bound form, the N-terminal extension forms an elongated loop that is hydrophobically anchored into the membrane surface; however, it has been proposed that this region might form a helix in the GTP-bound form. The delta subunit of the rod-specific cyclic GMP phosphodiesterase type 6 (PDEdelta) is an Arl3 effector. Arl3 binds microtubules in a regulated manner to alter specific aspects of cytokinesis via interactions with retinitis pigmentosa 2 (RP2). It has been proposed that RP2 functions in concert with Arl3 to link the cell membrane and the cytoskeleton in photoreceptors as part of the cell signaling or vesicular transport machinery. In mice, the absence of Arl3 is associated with abnormal epithelial cell proliferation and cyst formation.


Pssm-ID: 206721 [Multi-domain]  Cd Length: 174  Bit Score: 44.31  E-value: 2.20e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 155 HDFVIKKIP---FKMV--DVGGQRSQRQKWFQCFDGITSILFMVSSSeydqvlmeDRRtnRLVESMNIFETIVNNKLFFN 229
Cdd:cd04155   47 QGFNIKNVQadgFKLNvwDIGGQRKIRPYWRNYFENTDVLIYVIDSA--------DRK--RFEEAGQELVELLEEEKLAG 116
                         90
                 ....*....|...
gi 540344584 230 VSIILFLNKMDLL 242
Cdd:cd04155  117 VPVLVFANKQDLL 129
ARF smart00177
ARF-like small GTPases; ARF, ADP-ribosylation factor; Ras homologues involved in vesicular ...
160-241 1.06e-04

ARF-like small GTPases; ARF, ADP-ribosylation factor; Ras homologues involved in vesicular transport. Activator of phospholipase D isoforms. Unlike Ras proteins they lack cysteine residues at their C-termini and therefore are unlikely to be prenylated. ARFs are N-terminally myristoylated. Contains ATP/GTP-binding motif (P-loop).


Pssm-ID: 128474 [Multi-domain]  Cd Length: 175  Bit Score: 42.22  E-value: 1.06e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584   160 KKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSEYDqvlmedrrtnRLVESMNIFETIVNNKLFFNVSIILFLNKM 239
Cdd:smart00177  55 KNISFTVWDVGGQDKIRPLWRHYYTNTQGLIFVVDSNDRD----------RIDEAREELHRMLNEDELRDAVILVFANKQ 124

                   ..
gi 540344584   240 DL 241
Cdd:smart00177 125 DL 126
Arf1_5_like cd04150
ADP-ribosylation factor-1 (Arf1) and ADP-ribosylation factor-5 (Arf5); The Arf1-Arf5-like ...
160-241 1.09e-04

ADP-ribosylation factor-1 (Arf1) and ADP-ribosylation factor-5 (Arf5); The Arf1-Arf5-like subfamily contains Arf1, Arf2, Arf3, Arf4, Arf5, and related proteins. Arfs1-5 are soluble proteins that are crucial for assembling coat proteins during vesicle formation. Each contains an N-terminal myristoylated amphipathic helix that is folded into the protein in the GDP-bound state. GDP/GTP exchange exposes the helix, which anchors to the membrane. Following GTP hydrolysis, the helix dissociates from the membrane and folds back into the protein. A general feature of Arf1-5 signaling may be the cooperation of two Arfs at the same site. Arfs1-5 are generally considered to be interchangeable in function and location, but some specific functions have been assigned. Arf1 localizes to the early/cis-Golgi, where it is activated by GBF1 and recruits the coat protein COPI. It also localizes to the trans-Golgi network (TGN), where it is activated by BIG1/BIG2 and recruits the AP1, AP3, AP4, and GGA proteins. Humans, but not rodents and other lower eukaryotes, lack Arf2. Human Arf3 shares 96% sequence identity with Arf1 and is believed to generally function interchangeably with Arf1. Human Arf4 in the activated (GTP-bound) state has been shown to interact with the cytoplasmic domain of epidermal growth factor receptor (EGFR) and mediate the EGF-dependent activation of phospholipase D2 (PLD2), leading to activation of the activator protein 1 (AP-1) transcription factor. Arf4 has also been shown to recognize the C-terminal sorting signal of rhodopsin and regulate its incorporation into specialized post-Golgi rhodopsin transport carriers (RTCs). There is some evidence that Arf5 functions at the early-Golgi and the trans-Golgi to affect Golgi-associated alpha-adaptin homology Arf-binding proteins (GGAs).


Pssm-ID: 206717 [Multi-domain]  Cd Length: 159  Bit Score: 42.01  E-value: 1.09e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 160 KKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSEYDqvlmedrrtnRLVESMNIFETIVNNKLFFNVSIILFLNKM 239
Cdd:cd04150   42 KNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDRE----------RIGEAREELQRMLNEDELRDAVLLVFANKQ 111

                 ..
gi 540344584 240 DL 241
Cdd:cd04150  112 DL 113
Arl6 cd04157
Arf-like 6 (Arl6) GTPase; Arl6 (Arf-like 6) forms a subfamily of the Arf family of small ...
124-241 3.53e-04

Arf-like 6 (Arl6) GTPase; Arl6 (Arf-like 6) forms a subfamily of the Arf family of small GTPases. Arl6 expression is limited to the brain and kidney in adult mice, but it is expressed in the neural plate and somites during embryogenesis, suggesting a possible role for Arl6 in early development. Arl6 is also believed to have a role in cilia or flagella function. Several proteins have been identified that bind Arl6, including Arl6 interacting protein (Arl6ip), and SEC61beta, a subunit of the heterotrimeric conducting channel SEC61p. Based on Arl6 binding to these effectors, Arl6 is also proposed to play a role in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation. At least three specific homozygous Arl6 mutations in humans have been found to cause Bardet-Biedl syndrome, a disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, and hypogenitalism. Older literature suggests that Arl6 is a part of the Arl4/Arl7 subfamily, but analyses based on more recent sequence data place Arl6 in its own subfamily.


Pssm-ID: 206722 [Multi-domain]  Cd Length: 162  Bit Score: 40.49  E-value: 3.53e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 124 LDNLDRIGQLNYF-PSK---QDILlarkATKGIVEHDFVIKKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSeyd 199
Cdd:cd04157    7 LDNSGKTTIINQLkPSNaqsQNIV----PTVGFNVESFKKGNLSFTAFDMSGQGKYRGLWEHYYKNIQGIIFVIDSS--- 79
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 540344584 200 qvlmeDRRtnRLVESMNIFETIVNNKLFFN--VSIILFLNKMDL 241
Cdd:cd04157   80 -----DRL--RMVVAKDELELLLNHPDIKHrrIPILFYANKMDL 116
small_GTP TIGR00231
small GTP-binding protein domain; Proteins with a small GTP-binding domain recognized by this ...
160-248 5.32e-04

small GTP-binding protein domain; Proteins with a small GTP-binding domain recognized by this model include Ras, RhoA, Rab11, translation elongation factor G, translation initiation factor IF-2, tetratcycline resistance protein TetM, CDC42, Era, ADP-ribosylation factors, tdhF, and many others. In some proteins the domain occurs more than once.This model recognizes a large number of small GTP-binding proteins and related domains in larger proteins. Note that the alpha chains of heterotrimeric G proteins are larger proteins in which the NKXD motif is separated from the GxxxxGK[ST] motif (P-loop) by a long insert and are not easily detected by this model. [Unknown function, General]


Pssm-ID: 272973 [Multi-domain]  Cd Length: 162  Bit Score: 40.05  E-value: 5.32e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584  160 KKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSS----EYDQVLMEDRRtnrlvesmnifetIVNNKLFFNVSIILF 235
Cdd:TIGR00231  49 KTYKFNLLDTAGQEDYDAIRRLYYPQVERSLRVFDIVilvlDVEEILEKQTK-------------EIIHHADSGVPIILV 115
                          90
                  ....*....|...
gi 540344584  236 LNKMDLLVEKVKT 248
Cdd:TIGR00231 116 GNKIDLKDADLKT 128
PLN00223 PLN00223
ADP-ribosylation factor; Provisional
160-241 7.81e-04

ADP-ribosylation factor; Provisional


Pssm-ID: 165788  Cd Length: 181  Bit Score: 39.95  E-value: 7.81e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 160 KKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSEYDqvlmedrrtnRLVESMNIFETIVNNKLFFNVSIILFLNKM 239
Cdd:PLN00223  59 KNISFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDRD----------RVVEARDELHRMLNEDELRDAVLLVFANKQ 128

                 ..
gi 540344584 240 DL 241
Cdd:PLN00223 129 DL 130
Ras_like_GTPase cd00882
Rat sarcoma (Ras)-like superfamily of small guanosine triphosphatases (GTPases); Ras-like ...
149-247 2.25e-03

Rat sarcoma (Ras)-like superfamily of small guanosine triphosphatases (GTPases); Ras-like GTPase superfamily. The Ras-like superfamily of small GTPases consists of several families with an extremely high degree of structural and functional similarity. The Ras superfamily is divided into at least four families in eukaryotes: the Ras, Rho, Rab, and Sar1/Arf families. This superfamily also includes proteins like the GTP translation factors, Era-like GTPases, and G-alpha chain of the heterotrimeric G proteins. Members of the Ras superfamily regulate a wide variety of cellular functions: the Ras family regulates gene expression, the Rho family regulates cytoskeletal reorganization and gene expression, the Rab and Sar1/Arf families regulate vesicle trafficking, and the Ran family regulates nucleocytoplasmic transport and microtubule organization. The GTP translation factor family regulates initiation, elongation, termination, and release in translation, and the Era-like GTPase family regulates cell division, sporulation, and DNA replication. Members of the Ras superfamily are identified by the GTP binding site, which is made up of five characteristic sequence motifs, and the switch I and switch II regions.


Pssm-ID: 206648 [Multi-domain]  Cd Length: 161  Bit Score: 38.21  E-value: 2.25e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 149 TKGIVEHDFVI--KKIPFKMVDVGGQRS-----QRQKWFQCFDGITSILFMVSSSEYDqvlmedrrtnrlvESMNIFETI 221
Cdd:cd00882   32 TRDPDVYVKELdkGKVKLVLVDTPGLDEfgglgREELARLLLRGADLILLVVDSTDRE-------------SEEDAKLLI 98
                         90       100
                 ....*....|....*....|....*.
gi 540344584 222 VNNKLFFNVSIILFLNKMDLLVEKVK 247
Cdd:cd00882   99 LRRLRKEGIPIILVGNKIDLLEEREV 124
SAR smart00178
Sar1p-like members of the Ras-family of small GTPases; Yeast SAR1 is an essential gene ...
124-240 4.04e-03

Sar1p-like members of the Ras-family of small GTPases; Yeast SAR1 is an essential gene required for transport of secretory proteins from the endoplasmic reticulum to the Golgi apparatus.


Pssm-ID: 197556 [Multi-domain]  Cd Length: 184  Bit Score: 37.61  E-value: 4.04e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584   124 LDNLDRIGQLNYFpsKQDILLARKATKGIVEHDFVIKKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSEYDqvlm 203
Cdd:smart00178  25 LDNAGKTTLLHML--KNDRLAQHQPTQHPTSEELAIGNIKFTTFDLGGHQQARRLWKDYFPEVNGIVYLVDAYDKE---- 98
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 540344584   204 edrrtnRLVESMNIFETIVNNKLFFNVSIILFLNKMD 240
Cdd:smart00178  99 ------RFAESKRELDALLSDEELATVPFLILGNKID 129
Arl2 cd04154
Arf-like 2 (Arl2) GTPase; Arl2 (Arf-like 2) GTPases are members of the Arf family that bind ...
157-241 6.25e-03

Arf-like 2 (Arl2) GTPase; Arl2 (Arf-like 2) GTPases are members of the Arf family that bind GDP and GTP with very low affinity. Unlike most Arf family proteins, Arl2 is not myristoylated at its N-terminal helix. The protein PDE-delta, first identified in photoreceptor rod cells, binds specifically to Arl2 and is structurally very similar to RhoGDI. Despite the high structural similarity between Arl2 and Rho proteins and between PDE-delta and RhoGDI, the interactions between the GTPases and their effectors are very different. In its GTP bound form, Arl2 interacts with the protein Binder of Arl2 (BART), and the complex is believed to play a role in mitochondrial adenine nucleotide transport. In its GDP bound form, Arl2 interacts with tubulin- folding Cofactor D; this interaction is believed to play a role in regulation of microtubule dynamics that impact the cytoskeleton, cell division, and cytokinesis.


Pssm-ID: 206720 [Multi-domain]  Cd Length: 173  Bit Score: 36.92  E-value: 6.25e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 540344584 157 FVIKKIPFK-----MVDVGGQRSQRQKWFQCFDGITSILFMVSSSeydqvlmeDRRtnRLVESMNIFETIVNNKLFFNVS 231
Cdd:cd04154   48 FNIKTLEYNgyklnIWDVGGQKSLRSYWRNYFESTDALIWVVDSS--------DRA--RLEDCKRELQKLLVEERLAGAT 117
                         90
                 ....*....|
gi 540344584 232 IILFLNKMDL 241
Cdd:cd04154  118 LLIFANKQDL 127
 
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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