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Conserved domains on  [gi|1034608298|ref|XP_016882389|]
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glutaminyl-peptide cyclotransferase-like protein isoform X2 [Homo sapiens]

Protein Classification

zinc-binding metallopeptidase family protein( domain architecture ID 56613)

zinc-binding metallopeptidase family protein

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Zinc_peptidase_like super family cl14876
Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and ...
 79-263 2.25e-83

Zinc peptidases M18, M20, M28, and M42; Zinc peptidases play vital roles in metabolic and signaling pathways throughout all kingdoms of life. This hierarchy contains zinc peptidases that correspond to the MH clan in the MEROPS database, which contains 4 families (M18, M20, M28, M42). The peptidase M20 family includes carboxypeptidases such as the glutamate carboxypeptidase from Pseudomonas, the thermostable carboxypeptidase Ss1 of broad specificity from archaea and yeast Gly-X carboxypeptidase. The dipeptidases include bacterial dipeptidase, peptidase V (PepV), a non-specific eukaryotic dipeptidase, and two Xaa-His dipeptidases (carnosinases). There is also the bacterial aminopeptidase, peptidase T (PepT) that acts only on tripeptide substrates and has therefore been termed a tripeptidase. Peptidase family M28 contains aminopeptidases and carboxypeptidases, and has co-catalytic zinc ions. However, several enzymes in this family utilize other first row transition metal ions such as cobalt and manganese. Each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. The aminopeptidases in this family are also called bacterial leucyl aminopeptidases, but are able to release a variety of N-terminal amino acids. IAP aminopeptidase and aminopeptidase Y preferentially release basic amino acids while glutamate carboxypeptidase II preferentially releases C-terminal glutamates. Glutamate carboxypeptidase II and plasma glutamate carboxypeptidase hydrolyze dipeptides. Peptidase families M18 and M42 contain metallo-aminopeptidases. M18 is widely distributed in bacteria and eukaryotes. However, only yeast aminopeptidase I and mammalian aspartyl aminopeptidase have been characterized in detail. Some M42 (also known as glutamyl aminopeptidase) enzymes exhibit aminopeptidase specificity while others also have acylaminoacyl-peptidase activity (i.e. hydrolysis of acylated N-terminal residues).


The actual alignment was detected with superfamily member cd03880:

Pssm-ID: 472712 [Multi-domain]  Cd Length: 305  Bit Score: 251.77  E-value: 2.25e-83
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034608298  79 ARLRRVVGQLDPQRLWSTYLRPLLVVRTPGSPGNLQVRKFLEATLRSLTAGWHVELDPFTASTPLGPVDFGNVVATLDPR 158
Cdd:cd03880     1 STLRHLPELSDDNEHFNNLLAPILIPRVPGSPGHREVRNFIIDFLKSLLAGWTVELDNFTEKTPIGEVTFTNIIATLNPP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034608298 159 AARHLTLACHYDSKLFPPGstPFVGATDSAVPCALLLELAQALDLELSRA--KKQAAPVTLQLLFLDGEEALKEWGPKDS 236
Cdd:cd03880    81 AKRYLVLACHYDSKYFPEG--EFIGATDSAVPCAMLLYLARSLDAALTRKwpKSKKSDLGLQLIFFDGEEAFEEWSDTDS 158

                         170       180       190
                  ....*....|....*....|....*....|
gi 1034608298 237 LYGSRHLAQLMESIPHSPG---PTRIQAIS 263
Cdd:cd03880   159 LYGSRHLAAKWESTPYPPGsrySGRLDRID 188
 
Name Accession Description Interval E-value
M28_QC_like cd03880
M28 Zn-peptidase glutaminyl cyclase; Peptidase M28 family, glutaminyl cyclase (QC; EC 2.3.2.5) ...
 79-263 2.25e-83

M28 Zn-peptidase glutaminyl cyclase; Peptidase M28 family, glutaminyl cyclase (QC; EC 2.3.2.5) subfamily. QC is involved in N-terminal glutamine cyclization of many endocrine peptides and is typically abundant in brain tissue. N-terminal glutamine residue cyclization is an important post-translational event in the processing of numerous bioactive proteins, including neuropeptides, hormones, and cytokines during their maturation in the secretory pathway. The N-terminal pGlu protects them from exopeptidase degradation and/or enables them to have proper conformation for binding to their receptors. QCs are highly conserved from yeast to human. In humans, several genetic diseases, such as osteoporosis, appear to result from mutations of the QC gene. N-terminal glutamate cyclization into pyroglutamate (pGlu) is a reaction that may be related to the formation of several plaque-forming peptides, such as amyloid-(A) peptides and collagen-like Alzheimer amyloid plaque component, which play a pivotal role in Alzheimer's disease.


Pssm-ID: 349876 [Multi-domain]  Cd Length: 305  Bit Score: 251.77  E-value: 2.25e-83
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034608298  79 ARLRRVVGQLDPQRLWSTYLRPLLVVRTPGSPGNLQVRKFLEATLRSLTAGWHVELDPFTASTPLGPVDFGNVVATLDPR 158
Cdd:cd03880     1 STLRHLPELSDDNEHFNNLLAPILIPRVPGSPGHREVRNFIIDFLKSLLAGWTVELDNFTEKTPIGEVTFTNIIATLNPP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034608298 159 AARHLTLACHYDSKLFPPGstPFVGATDSAVPCALLLELAQALDLELSRA--KKQAAPVTLQLLFLDGEEALKEWGPKDS 236
Cdd:cd03880    81 AKRYLVLACHYDSKYFPEG--EFIGATDSAVPCAMLLYLARSLDAALTRKwpKSKKSDLGLQLIFFDGEEAFEEWSDTDS 158

                         170       180       190
                  ....*....|....*....|....*....|
gi 1034608298 237 LYGSRHLAQLMESIPHSPG---PTRIQAIS 263
Cdd:cd03880   159 LYGSRHLAAKWESTPYPPGsrySGRLDRID 188
Peptidase_M28 pfam04389
Peptidase family M28;
150-245 4.43e-12

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 63.07  E-value: 4.43e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034608298 150 NVVATLDPRA-ARHLTLACHYDSKLFPPGstpfvgATDSAVPCalllelaqALDLELSR--AKKQAAPVTLQLLFLDGEE 226
Cdd:pfam04389   1 NVIAKLPGKApDEVVLLSAHYDSVGTGPG------ADDNASGV--------AALLELARvlAAGQRPKRSVRFLFFDAEE 66

                          90
                  ....*....|....*....
gi 1034608298 227 AlkewgpkdSLYGSRHLAQ 245
Cdd:pfam04389  67 A--------GLLGSHHFAK 77
 
Name Accession Description Interval E-value
M28_QC_like cd03880
M28 Zn-peptidase glutaminyl cyclase; Peptidase M28 family, glutaminyl cyclase (QC; EC 2.3.2.5) ...
 79-263 2.25e-83

M28 Zn-peptidase glutaminyl cyclase; Peptidase M28 family, glutaminyl cyclase (QC; EC 2.3.2.5) subfamily. QC is involved in N-terminal glutamine cyclization of many endocrine peptides and is typically abundant in brain tissue. N-terminal glutamine residue cyclization is an important post-translational event in the processing of numerous bioactive proteins, including neuropeptides, hormones, and cytokines during their maturation in the secretory pathway. The N-terminal pGlu protects them from exopeptidase degradation and/or enables them to have proper conformation for binding to their receptors. QCs are highly conserved from yeast to human. In humans, several genetic diseases, such as osteoporosis, appear to result from mutations of the QC gene. N-terminal glutamate cyclization into pyroglutamate (pGlu) is a reaction that may be related to the formation of several plaque-forming peptides, such as amyloid-(A) peptides and collagen-like Alzheimer amyloid plaque component, which play a pivotal role in Alzheimer's disease.


Pssm-ID: 349876 [Multi-domain]  Cd Length: 305  Bit Score: 251.77  E-value: 2.25e-83
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034608298  79 ARLRRVVGQLDPQRLWSTYLRPLLVVRTPGSPGNLQVRKFLEATLRSLTAGWHVELDPFTASTPLGPVDFGNVVATLDPR 158
Cdd:cd03880     1 STLRHLPELSDDNEHFNNLLAPILIPRVPGSPGHREVRNFIIDFLKSLLAGWTVELDNFTEKTPIGEVTFTNIIATLNPP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034608298 159 AARHLTLACHYDSKLFPPGstPFVGATDSAVPCALLLELAQALDLELSRA--KKQAAPVTLQLLFLDGEEALKEWGPKDS 236
Cdd:cd03880    81 AKRYLVLACHYDSKYFPEG--EFIGATDSAVPCAMLLYLARSLDAALTRKwpKSKKSDLGLQLIFFDGEEAFEEWSDTDS 158

                         170       180       190
                  ....*....|....*....|....*....|
gi 1034608298 237 LYGSRHLAQLMESIPHSPG---PTRIQAIS 263
Cdd:cd03880   159 LYGSRHLAAKWESTPYPPGsrySGRLDRID 188
Peptidase_M28 pfam04389
Peptidase family M28;
150-245 4.43e-12

Peptidase family M28;


Pssm-ID: 461288 [Multi-domain]  Cd Length: 192  Bit Score: 63.07  E-value: 4.43e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034608298 150 NVVATLDPRA-ARHLTLACHYDSKLFPPGstpfvgATDSAVPCalllelaqALDLELSR--AKKQAAPVTLQLLFLDGEE 226
Cdd:pfam04389   1 NVIAKLPGKApDEVVLLSAHYDSVGTGPG------ADDNASGV--------AALLELARvlAAGQRPKRSVRFLFFDAEE 66

                          90
                  ....*....|....*....
gi 1034608298 227 AlkewgpkdSLYGSRHLAQ 245
Cdd:pfam04389  67 A--------GLLGSHHFAK 77
M28 cd02690
M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also ...
 150-249 2.84e-06

M28 Zn-peptidases include aminopeptidases and carboxypeptidases; Peptidase M28 family (also called aminopeptidase Y family) contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions. The aminopeptidases in this family are also called bacterial leucyl aminopeptidases, but are able to release a variety of N-terminal amino acids. IAP aminopeptidase and aminopeptidase Y preferentially release basic amino acids while glutamate carboxypeptidase II preferentially releases C-terminal glutamates. Plasma glutamate carboxypeptidase (PGCP) and glutamate carboxypeptidase II (NAALADase) hydrolyze dipeptides. Several members of the M28 peptidase family have PA domain inserts which may participate in substrate binding and/or in promoting conformational changes, which influence the stability and accessibility of the site to substrate. These include prostate-specific membrane antigen (PSMA), yeast aminopeptidase S (SGAP), human transferrin receptors (TfR1 and TfR2), plasma glutamate carboxypeptidase (PGCP) and several predicted aminopeptidases where relatively little is known about them. Also included in the M28 family are glutaminyl cyclases (QC), which are involved in N-terminal glutamine cyclization of many endocrine peptides. Nicastrin and nicalin belong to this family but lack the amino-acid conservation required for catalytically active aminopeptidases.


Pssm-ID: 349868 [Multi-domain]  Cd Length: 202  Bit Score: 46.95  E-value: 2.84e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034608298 150 NVVATLDPRAA--RHLTLACHYDSKLFPPGstpfvgATDSAVPCalllelaqALDLELSRA---KKQAAPVTLQLLFLDG 224
Cdd:cd02690     3 NVIATIKGSDKpdEVILIGAHYDSVPLSPG------ANDNASGV--------AVLLELARVlskLQLKPKRSIRFAFWDA 68

                          90       100
                  ....*....|....*....|....*
gi 1034608298 225 EealkEWGpkdsLYGSRHLAQLMES 249
Cdd:cd02690    69 E----ELG----LLGSKYYAEQLLS 85
M28_like cd08656
M28 Zn-peptidase; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase ...
 105-226 1.51e-05

M28 Zn-peptidase; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions.


Pssm-ID: 349943 [Multi-domain]  Cd Length: 287  Bit Score: 45.21  E-value: 1.51e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034608298 105 RTPGSPGNLQVRKFLEATLRSLTA---GWHVELDPFTASTplgpVDFGNVVATLDPRAARHLTLACHYDSKLF------- 174
Cdd:cd08656    17 RVPNTAAHKACGEYLAGKLEAFGAkvyNQYADLIAYDGTI----LKARNIIGAYNPESKKRVLLCAHWDSRPYadndadp 92

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1034608298 175 PPGSTPFVGATDSAvpcallleLAQALDLELSRAKKQAAP-VTLQLLFLDGEE 226
Cdd:cd08656    93 KKHHTPILGANDGA--------SGVGALLEIARQIQQQAPaIGIDIIFFDAED 137
M28_like cd05642
M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called ...
 75-245 1.86e-04

M28 Zn-peptidase-like; uncharacterized subfamily; Peptidase family M28 (also called aminopeptidase Y family), uncharacterized subfamily. The M28 family contains aminopeptidases as well as carboxypeptidases. They have co-catalytic zinc ions; each zinc ion is tetrahedrally co-ordinated, with three amino acid ligands plus activated water; one aspartate residue binds both metal ions.


Pssm-ID: 349894 [Multi-domain]  Cd Length: 347  Bit Score: 42.09  E-value: 1.86e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034608298  75 SLPEARLRRVVGQLDPQRLWSTY-------LRPLLVVRTPGSPGNLQVRKFLEATLRSLTAG----WHVELDPFT---AS 140
Cdd:cd05642     1 QLPDDELQAILSEVDPKRIEATIrklvsfgTRHTLSTQTDPTRGIGAARDWIAEEFREYAAAsggrMTVEVPSYVqgpAS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034608298 141 TPLGPVDFGNVVATL----DPRaaRHLTLACHYDSKLFPP----GSTPfvGATDSAvpcallleLAQALDLELSR--AKK 210
Cdd:cd05642    81 RIPFPVNISNVVATLkgseDPD--RVYVVSGHYDSRVSDVmdyeSDAP--GANDDA--------SGVAVSMELARifAKH 148

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1034608298 211 QaAPVTLQLLFLDGEEalkewgpkDSLYGSRHLAQ 245
Cdd:cd05642   149 R-PKATIVFTAVAGEE--------QGLYGSTFLAQ 174
M28_Fxna_like cd03875
M28 Zn-peptidase Endoplasmic reticulum metallopeptidase 1; Peptidase family M28; Endoplasmic ...
 105-241 1.10e-03

M28 Zn-peptidase Endoplasmic reticulum metallopeptidase 1; Peptidase family M28; Endoplasmic reticulum metallopeptidase 1 (ERMP1; Felix-ina, FXNA or Fxna peptidase; KIAA1815) subfamily. ERMP1 is a multi-pass membrane protein located in the endoplasmic reticulum membrane. In humans, Fxna may play a crucial role in processing proteins required for the organization of somatic cells and oocytes into discrete follicular structures, although which proteins are hydrolyzed has not yet been determined. Another member of this subfamily is the 24-kDa vacuolar protein (VP24) which is probably involved in the formation of intravacuolar pigmented globules (cyanoplasts) in highly anthocyanin-containing vacuoles; however, the biological function of the C-terminal region which includes the putative transmembrane metallopeptidase domain is unknown.


Pssm-ID: 349872 [Multi-domain]  Cd Length: 307  Bit Score: 39.49  E-value: 1.10e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034608298 105 RTPGSPGNLQVRKFLEATLRSLTAGWHVELDPFTASTPLGPVDFG--------------NVVATLDPRAARHLT---LAC 167
Cdd:cd03875    22 HPYGSHNNDKVRDYLLARVEEIKERANANGLEVEVQDDTGSGSFNflssgmtlvyfevtNIVVRISGKNSNSLPallLNA 101

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034608298 168 HYDSKlfpPGStpfVGATDSAVPCalllelaqALDLELSR--AKKQAAP-VTLQLLFLDGEEalkewgpkDSLYGSR 241
Cdd:cd03875   102 HFDSV---PTS---PGATDDGMGV--------AVMLEVLRylSKSGHQPkRDIIFLFNGAEE--------NGLLGAH 156
 
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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