NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|41406057|ref|NP_958817|]
View 

amyloid-beta precursor protein isoform c precursor [Homo sapiens]

Protein Classification

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
A4_EXTRA smart00006
amyloid A4; amyloid A4 precursor of Alzheimers disease
 24-188 5.16e-113

amyloid A4; amyloid A4 precursor of Alzheimers disease


:

Pssm-ID: 128326 [Multi-domain]  Cd Length: 165  Bit Score: 337.17  E-value: 5.16e-113
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406057     24 GNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRK 103
Cdd:smart00006   1 GAAGALAEPQIAMLCGRLNMHMNVQTGRWETDPSRTKTCLRDKEDILQYCRKAYPELQITNVVEASQPVTIQNWCRRGRS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406057    104 QCKTHPHFVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVE 183
Cdd:smart00006  81 QCKTHHHFVIPFRCLVGEFVSDALLVPEGCQFLHQERMDQCETHQRWHQEAKEACSEKGMILHSFGMLLPCGIDKFRGVE 160


                   ....*
gi 41406057    184 FVCCP 188
Cdd:smart00006 161 FVCCP 165
APP_E2 pfam12925
E2 domain of amyloid precursor protein; The E2 domain is the largest of the conserved domains ...
 291-473 9.95e-100

E2 domain of amyloid precursor protein; The E2 domain is the largest of the conserved domains of the amyloid precursor protein. The structure of E2 consists of two coiled-coil sub-structures connected through a continuous helix, and bears an unexpected resemblance to the spectrin family of protein structures.E 2 can reversibly dimerize in solution, and the dimerization occurs along the longest dimension of the molecule in an antiparallel orientation, which enables the N-terminal substructure of one monomer to pack against the C-terminal substructure of a second monomer. The high degree of conservation of residues at the putative dimer interface suggests that the E2 dimer observed in the crystal could be physiologically relevant. Heparin sulfate proteoglycans, the putative ligands for the precursor present in extracellular matrix, bind to E2 at a conserved and positively charged site near the dimer interface.


:

Pssm-ID: 463752  Cd Length: 190  Bit Score: 303.88  E-value: 9.95e-100
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406057   291 TTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKAD-------KKAVIQHFQEK 363
Cdd:pfam12925   1 TTTPPPTDAVDPYFEHPDPRNEHESFKKAKKRLEEKHRERMTKVMKEWEEAEERYQNLPKADpkaaekfKKAMTARFQET 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406057   364 VESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMV 443
Cdd:pfam12925  81 VEALEEEAAAERQQLVETHQQRVEAHLNDRRRDALECYLQALQENPPNPHRILKALKKLLRAEQKDRRHTLRHYRHLLAS 160

                         170       180       190
                  ....*....|....*....|....*....|
gi 41406057   444 DPKKAAQIRSQVMTHLRVIYERMNQSLSLL 473
Cdd:pfam12925 161 DPEKAEQMKPQVLTHLRVIDRRMNQSLTLL 190
JMTM_Notch_APP super family cl41775
juxtamembrane and transmembrane (JMTM) domain found in Notch and APP family proteins; The ...
 618-692 3.25e-31

juxtamembrane and transmembrane (JMTM) domain found in Notch and APP family proteins; The substrates of gamma-secretase include amyloid precursor protein (APP) and the Notch receptor. APP, also called APPI, or Alzheimer disease amyloid protein (ABPP), or amyloid precursor protein, or amyloid-beta A4 protein, or cerebral vascular amyloid peptide (CVAP), or PreA4, or protease nexin-II (PN-II), functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Notch proteins are a family of type-1 transmembrane proteins that form a core component of the Notch signaling pathway. They operate in a variety of different tissues and play a role in a variety of developmental processes by controlling cell fate decisions. Successive cleavage of the APP carboxyl-terminal fragment generates amyloid-beta (Abeta) peptides of varying lengths. Accumulation of Abeta peptides such as Abeta42 and Abeta43 leads to formation of amyloid plaques in the brain, a hallmark of Alzheimer's disease. Notch cleavage is involved in cell-fate determination during development and neurogenesis. The model corresponds to the juxtamembrane and transmembrane (JMTM) domain found in Notch and APP family proteins. It comprises a transmembrane helix (TM) with adjacent juxtamembrane (JM) regions. The JMTM domain is likely to be recognized by gamma-secretase in a similar fashion to both Notch and APP family proteins.


The actual alignment was detected with superfamily member cd21709:

Pssm-ID: 425406  Cd Length: 81  Bit Score: 116.56  E-value: 3.25e-31
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 41406057 618 EDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQ 692
Cdd:cd21709   7 DDFSFSSSALIGLLVIAVAIATVIVISLVLLRKRQYGTISHGIVEVDPMLTPEERHLNKMQNHGYENPTYKYLEQ 81
 
Name Accession Description Interval E-value
A4_EXTRA smart00006
amyloid A4; amyloid A4 precursor of Alzheimers disease
 24-188 5.16e-113

amyloid A4; amyloid A4 precursor of Alzheimers disease


Pssm-ID: 128326 [Multi-domain]  Cd Length: 165  Bit Score: 337.17  E-value: 5.16e-113
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406057     24 GNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRK 103
Cdd:smart00006   1 GAAGALAEPQIAMLCGRLNMHMNVQTGRWETDPSRTKTCLRDKEDILQYCRKAYPELQITNVVEASQPVTIQNWCRRGRS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406057    104 QCKTHPHFVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVE 183
Cdd:smart00006  81 QCKTHHHFVIPFRCLVGEFVSDALLVPEGCQFLHQERMDQCETHQRWHQEAKEACSEKGMILHSFGMLLPCGIDKFRGVE 160


                   ....*
gi 41406057    184 FVCCP 188
Cdd:smart00006 161 FVCCP 165
APP_E2 pfam12925
E2 domain of amyloid precursor protein; The E2 domain is the largest of the conserved domains ...
 291-473 9.95e-100

E2 domain of amyloid precursor protein; The E2 domain is the largest of the conserved domains of the amyloid precursor protein. The structure of E2 consists of two coiled-coil sub-structures connected through a continuous helix, and bears an unexpected resemblance to the spectrin family of protein structures.E 2 can reversibly dimerize in solution, and the dimerization occurs along the longest dimension of the molecule in an antiparallel orientation, which enables the N-terminal substructure of one monomer to pack against the C-terminal substructure of a second monomer. The high degree of conservation of residues at the putative dimer interface suggests that the E2 dimer observed in the crystal could be physiologically relevant. Heparin sulfate proteoglycans, the putative ligands for the precursor present in extracellular matrix, bind to E2 at a conserved and positively charged site near the dimer interface.


Pssm-ID: 463752  Cd Length: 190  Bit Score: 303.88  E-value: 9.95e-100
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406057   291 TTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKAD-------KKAVIQHFQEK 363
Cdd:pfam12925   1 TTTPPPTDAVDPYFEHPDPRNEHESFKKAKKRLEEKHRERMTKVMKEWEEAEERYQNLPKADpkaaekfKKAMTARFQET 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406057   364 VESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMV 443
Cdd:pfam12925  81 VEALEEEAAAERQQLVETHQQRVEAHLNDRRRDALECYLQALQENPPNPHRILKALKKLLRAEQKDRRHTLRHYRHLLAS 160

                         170       180       190
                  ....*....|....*....|....*....|
gi 41406057   444 DPKKAAQIRSQVMTHLRVIYERMNQSLSLL 473
Cdd:pfam12925 161 DPEKAEQMKPQVLTHLRVIDRRMNQSLTLL 190
APP_N pfam02177
Amyloid A4 N-terminal heparin-binding; This N-terminal domain of APP, amyloid precursor ...
 31-131 1.08e-64

Amyloid A4 N-terminal heparin-binding; This N-terminal domain of APP, amyloid precursor protein, is the heparin-binding domain of the protein. this region is also responsible for stimulation of neurite outgrowth. The structure reveals both a highly charged basic surface that may interact with glycosaminoglycans in the brain and an abutting hydrophobic surface that is proposed to play an important functional role such as in dimerization or ligand-binding. Structural similarities with cysteine-rich growth factors, taken together with its known growth-promoting properties, suggest the APP N-terminal domain could function as a growth factor in vivo.


Pssm-ID: 460474  Cd Length: 100  Bit Score: 209.08  E-value: 1.08e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406057    31 EPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHpH 110
Cdd:pfam02177   1 EPQVAMFCGKLNQHMDLETGRWEPDPSGKATCFKDKEEILDYCQKVYPELDITNIVEASQPVTIDNWCKKGRKKCKGH-H 79

                          90       100
                  ....*....|....*....|.
gi 41406057   111 FVIPYRCLVGEFVSDALLVPD 131
Cdd:pfam02177  80 IVKPYRCLVGEFVSDALLVPE 100
JMTM_APLP2 cd21709
juxtamembrane and transmembrane (JMTM) domain found in amyloid-like protein 2 (APLP-2) and ...
 618-692 3.25e-31

juxtamembrane and transmembrane (JMTM) domain found in amyloid-like protein 2 (APLP-2) and similar proteins; Amyloid-like protein 2 (APLP-2), also called amyloid protein homolog (APPH), or CDEI box-binding protein (CDEBP), may play a role in the regulation of hemostasis. Its soluble form may have inhibitory properties towards coagulation factors. APLP-2 may bind to the DNA 5'-GTCACATG-3'(CDEI box). It inhibits trypsin, chymotrypsin, plasmin, factor XIA, and plasma and glandular kallikrein. This model corresponds to juxtamembrane and transmembrane (JMTM) domain of APLP-2, which consists of the intact transmembrane (TM) domain with adjacent N-terminal juxtamembrane (JM) region.


Pssm-ID: 411992  Cd Length: 81  Bit Score: 116.56  E-value: 3.25e-31
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 41406057 618 EDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQ 692
Cdd:cd21709   7 DDFSFSSSALIGLLVIAVAIATVIVISLVLLRKRQYGTISHGIVEVDPMLTPEERHLNKMQNHGYENPTYKYLEQ 81
APP_amyloid pfam10515
Beta-amyloid precursor protein C-terminus; This is the amyloid, C-terminal, protein of the ...
 641-691 4.57e-24

Beta-amyloid precursor protein C-terminus; This is the amyloid, C-terminal, protein of the beta-Amyloid precursor protein (APP) which is a conserved and ubiquitous transmembrane glycoprotein strongly implicated in the pathogenesis of Alzheimer's disease but whose normal biological function is unknown. The C-terminal 100 residues are released and aggregate into amyloid deposits which are strongly implicated in the pathology of Alzheimer's disease plaque-formation. The domain is associated with family A4_EXTRA, pfam02177, further towards the N-terminus.


Pssm-ID: 463129  Cd Length: 52  Bit Score: 95.09  E-value: 4.57e-24
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 41406057   641 IVITLVMLKKK-QYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFE 691
Cdd:pfam10515   1 IVVGMALLRRRaARSPSAHGFVEVDPNVTPEERHVANMQVNGYENPTYKYFE 52
PRK05035 PRK05035
electron transport complex protein RnfC; Provisional
 318-449 2.72e-03

electron transport complex protein RnfC; Provisional


Pssm-ID: 235334 [Multi-domain]  Cd Length: 695  Bit Score: 41.09  E-value: 2.72e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406057  318 KAKERLEAKhRERMsqvmrEWEEAERQAK------NLPKADKKAViqhfQEKVESLEQEAANERQQLVETHMAR-----V 386
Cdd:PRK05035 450 EAKARFEAR-QARL-----EREKAAREARhkkaaeARAAKDKDAV----AAALARVKAKKAAATQPIVIKAGARpdnsaV 519

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 41406057  387 EAMLNDRRRLALENYITALQAVPPRPRhvfnmlKKYV-----RAEQKDRQHTLKHFEHVRMVDPKKAA 449
Cdd:PRK05035 520 IAAREARKAQARARQAEKQAAAAADPK------KAAVaaaiaRAKAKKAAQQAANAEAEEEVDPKKAA 581
 
Name Accession Description Interval E-value
A4_EXTRA smart00006
amyloid A4; amyloid A4 precursor of Alzheimers disease
 24-188 5.16e-113

amyloid A4; amyloid A4 precursor of Alzheimers disease


Pssm-ID: 128326 [Multi-domain]  Cd Length: 165  Bit Score: 337.17  E-value: 5.16e-113
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406057     24 GNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRK 103
Cdd:smart00006   1 GAAGALAEPQIAMLCGRLNMHMNVQTGRWETDPSRTKTCLRDKEDILQYCRKAYPELQITNVVEASQPVTIQNWCRRGRS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406057    104 QCKTHPHFVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVE 183
Cdd:smart00006  81 QCKTHHHFVIPFRCLVGEFVSDALLVPEGCQFLHQERMDQCETHQRWHQEAKEACSEKGMILHSFGMLLPCGIDKFRGVE 160


                   ....*
gi 41406057    184 FVCCP 188
Cdd:smart00006 161 FVCCP 165
APP_E2 pfam12925
E2 domain of amyloid precursor protein; The E2 domain is the largest of the conserved domains ...
 291-473 9.95e-100

E2 domain of amyloid precursor protein; The E2 domain is the largest of the conserved domains of the amyloid precursor protein. The structure of E2 consists of two coiled-coil sub-structures connected through a continuous helix, and bears an unexpected resemblance to the spectrin family of protein structures.E 2 can reversibly dimerize in solution, and the dimerization occurs along the longest dimension of the molecule in an antiparallel orientation, which enables the N-terminal substructure of one monomer to pack against the C-terminal substructure of a second monomer. The high degree of conservation of residues at the putative dimer interface suggests that the E2 dimer observed in the crystal could be physiologically relevant. Heparin sulfate proteoglycans, the putative ligands for the precursor present in extracellular matrix, bind to E2 at a conserved and positively charged site near the dimer interface.


Pssm-ID: 463752  Cd Length: 190  Bit Score: 303.88  E-value: 9.95e-100
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406057   291 TTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKAD-------KKAVIQHFQEK 363
Cdd:pfam12925   1 TTTPPPTDAVDPYFEHPDPRNEHESFKKAKKRLEEKHRERMTKVMKEWEEAEERYQNLPKADpkaaekfKKAMTARFQET 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406057   364 VESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMV 443
Cdd:pfam12925  81 VEALEEEAAAERQQLVETHQQRVEAHLNDRRRDALECYLQALQENPPNPHRILKALKKLLRAEQKDRRHTLRHYRHLLAS 160

                         170       180       190
                  ....*....|....*....|....*....|
gi 41406057   444 DPKKAAQIRSQVMTHLRVIYERMNQSLSLL 473
Cdd:pfam12925 161 DPEKAEQMKPQVLTHLRVIDRRMNQSLTLL 190
APP_N pfam02177
Amyloid A4 N-terminal heparin-binding; This N-terminal domain of APP, amyloid precursor ...
 31-131 1.08e-64

Amyloid A4 N-terminal heparin-binding; This N-terminal domain of APP, amyloid precursor protein, is the heparin-binding domain of the protein. this region is also responsible for stimulation of neurite outgrowth. The structure reveals both a highly charged basic surface that may interact with glycosaminoglycans in the brain and an abutting hydrophobic surface that is proposed to play an important functional role such as in dimerization or ligand-binding. Structural similarities with cysteine-rich growth factors, taken together with its known growth-promoting properties, suggest the APP N-terminal domain could function as a growth factor in vivo.


Pssm-ID: 460474  Cd Length: 100  Bit Score: 209.08  E-value: 1.08e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406057    31 EPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHpH 110
Cdd:pfam02177   1 EPQVAMFCGKLNQHMDLETGRWEPDPSGKATCFKDKEEILDYCQKVYPELDITNIVEASQPVTIDNWCKKGRKKCKGH-H 79

                          90       100
                  ....*....|....*....|.
gi 41406057   111 FVIPYRCLVGEFVSDALLVPD 131
Cdd:pfam02177  80 IVKPYRCLVGEFVSDALLVPE 100
JMTM_APLP2 cd21709
juxtamembrane and transmembrane (JMTM) domain found in amyloid-like protein 2 (APLP-2) and ...
 618-692 3.25e-31

juxtamembrane and transmembrane (JMTM) domain found in amyloid-like protein 2 (APLP-2) and similar proteins; Amyloid-like protein 2 (APLP-2), also called amyloid protein homolog (APPH), or CDEI box-binding protein (CDEBP), may play a role in the regulation of hemostasis. Its soluble form may have inhibitory properties towards coagulation factors. APLP-2 may bind to the DNA 5'-GTCACATG-3'(CDEI box). It inhibits trypsin, chymotrypsin, plasmin, factor XIA, and plasma and glandular kallikrein. This model corresponds to juxtamembrane and transmembrane (JMTM) domain of APLP-2, which consists of the intact transmembrane (TM) domain with adjacent N-terminal juxtamembrane (JM) region.


Pssm-ID: 411992  Cd Length: 81  Bit Score: 116.56  E-value: 3.25e-31
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 41406057 618 EDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQ 692
Cdd:cd21709   7 DDFSFSSSALIGLLVIAVAIATVIVISLVLLRKRQYGTISHGIVEVDPMLTPEERHLNKMQNHGYENPTYKYLEQ 81
APP_Cu_bd pfam12924
Copper-binding of amyloid precursor, CuBD; This short domain, part of the extra-cellular ...
 133-188 3.84e-31

Copper-binding of amyloid precursor, CuBD; This short domain, part of the extra-cellular N-terminus of the amyloid precursor protein, APP, can bind both copper and zinc, CuBD. The structure of Cu2+-bound CuBD reveals that the metal ligands are His147, His151, Tyr168 and two water molecules, which are arranged in a square pyramidal geometry. The structure of Cu+-bound CuBD is almost identical to the Cu2+-bound structure except for the loss of one of the water ligands. The geometry of the site is unfavourable for Cu+, thus providing a mechanism by which CuBD could readily transfer Cu ions to other proteins.


Pssm-ID: 463751  Cd Length: 56  Bit Score: 115.45  E-value: 3.84e-31
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 41406057   133 CKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCP 188
Cdd:pfam12924   1 CKFDHKHNMDVCESHQHWHATAKEACAARGMVLHSFGMLLPCGIDLFTGVEFVCCP 56
JMTM_APLP1 cd21708
juxtamembrane and transmembrane (JMTM) domain found in amyloid-like protein 1 (APLP-1) and ...
 620-692 8.42e-29

juxtamembrane and transmembrane (JMTM) domain found in amyloid-like protein 1 (APLP-1) and similar proteins; Amyloid-like protein 1 (APLP-1), also called APLP, may play a role in postsynaptic function. It couples to JIP signal transduction through C-terminal binding. APLP-1 may interact with cellular G-protein signaling pathways. It can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I. This model corresponds to the juxtamembrane and transmembrane (JMTM) domain of APLP-1, which consists of the intact transmembrane (TM) domain with adjacent N-terminal juxtamembrane (JM) region.


Pssm-ID: 411991  Cd Length: 85  Bit Score: 109.91  E-value: 8.42e-29
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 41406057 620 VGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQ 692
Cdd:cd21708  13 VTFNRGALIGLLVVAVAVAMVIVISLLLVRRKPYGTISHGIVEVDPMLTPEERQLSKMQNHGYENPTYRFLEE 85
APP_amyloid pfam10515
Beta-amyloid precursor protein C-terminus; This is the amyloid, C-terminal, protein of the ...
 641-691 4.57e-24

Beta-amyloid precursor protein C-terminus; This is the amyloid, C-terminal, protein of the beta-Amyloid precursor protein (APP) which is a conserved and ubiquitous transmembrane glycoprotein strongly implicated in the pathogenesis of Alzheimer's disease but whose normal biological function is unknown. The C-terminal 100 residues are released and aggregate into amyloid deposits which are strongly implicated in the pathology of Alzheimer's disease plaque-formation. The domain is associated with family A4_EXTRA, pfam02177, further towards the N-terminus.


Pssm-ID: 463129  Cd Length: 52  Bit Score: 95.09  E-value: 4.57e-24
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 41406057   641 IVITLVMLKKK-QYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFE 691
Cdd:pfam10515   1 IVVGMALLRRRaARSPSAHGFVEVDPNVTPEERHVANMQVNGYENPTYKYFE 52
JMTM_APP cd21707
juxtamembrane and transmembrane (JMTM) domain found in amyloid-beta precursor protein (APP) ...
 612-651 2.41e-17

juxtamembrane and transmembrane (JMTM) domain found in amyloid-beta precursor protein (APP) and similar proteins; Amyloid-beta precursor protein (APP), also called APPI, ABPP, Alzheimer disease amyloid protein, amyloid precursor protein, amyloid-beta A4 protein, cerebral vascular amyloid peptide (CVAP), PreA4, or protease nexin-II (PN-II), functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity; they bind transient metals such as copper, zinc and iron. This model corresponds to juxtamembrane and transmembrane (JMTM) domain of APP, which consists of the intact transmembrane (TM) domain with adjacent N-terminal juxtamembrane (JM) region. More than half of all familial APP mutations of Alzheimer's disease are seen in its JMTM domain region.


Pssm-ID: 411990  Cd Length: 40  Bit Score: 75.76  E-value: 2.41e-17
                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 41406057 612 KLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKK 651
Cdd:cd21707   1 KLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKK 40
Beta-APP pfam03494
Beta-amyloid peptide (beta-APP);
601-638 1.85e-16

Beta-amyloid peptide (beta-APP);


Pssm-ID: 427335  Cd Length: 39  Bit Score: 73.33  E-value: 1.85e-16
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 41406057   601 RHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA 638
Cdd:pfam03494   2 RQSAGYEVYHEKLVFLAEDMGSNKGAIIGLMVGGVVIA 39
JMTM_APP_like cd21699
juxtamembrane and transmembrane (JMTM) domain found in the amyloid-beta precursor protein (APP) ...
 612-651 6.38e-10

juxtamembrane and transmembrane (JMTM) domain found in the amyloid-beta precursor protein (APP) family; The amyloid-beta precursor protein (APP) family includes amyloid-like proteins APLP-1 and APLP-2. APP (also called ABPP, APPI, Alzheimer disease (AD) amyloid protein, amyloid precursor protein, amyloid-beta A4 protein, cerebral vascular amyloid peptide (CVAP), PreA4, or protease nexin-II (PN-II)) functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity; they bind transient metals such as copper, zinc and iron. APLP-1, also called APLP, may play a role in postsynaptic function. It couples to JIP signal transduction through C-terminal binding. APLP-1 may interact with cellular G-protein signaling pathways. It can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I. APLP-2 (also called amyloid protein homolog (APPH), or CDEI box-binding protein (CDEBP)) may play a role in the regulation of hemostasis. Its soluble form may have inhibitory properties towards coagulation factors. APLP-2 may bind to the DNA 5'-GTCACATG-3'(CDEI box). It inhibits trypsin, chymotrypsin, plasmin, factor XIA, and plasma and glandular kallikrein. This model corresponds to juxtamembrane and transmembrane (JMTM) domain of APP, which consists of the intact transmembrane (TM) domain with adjacent N-terminal juxtamembrane (JM) region. More than half of all familial APP mutations of Alzheimer's disease are seen in its JMTM domain region.


Pssm-ID: 411982  Cd Length: 41  Bit Score: 54.60  E-value: 6.38e-10
                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 41406057 612 KLVFFAEDVG-SNKGAIIGLMVGGVVIATVIVITLVMLKKK 651
Cdd:cd21699   1 ERVFLAEDSSnSSFGAVIGLAVGGVAVAIVIVVAVVMLRRR 41
JMTM_Notch_APP cd21700
juxtamembrane and transmembrane (JMTM) domain found in Notch and APP family proteins; The ...
 613-651 1.14e-06

juxtamembrane and transmembrane (JMTM) domain found in Notch and APP family proteins; The substrates of gamma-secretase include amyloid precursor protein (APP) and the Notch receptor. APP, also called APPI, or Alzheimer disease amyloid protein (ABPP), or amyloid precursor protein, or amyloid-beta A4 protein, or cerebral vascular amyloid peptide (CVAP), or PreA4, or protease nexin-II (PN-II), functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Notch proteins are a family of type-1 transmembrane proteins that form a core component of the Notch signaling pathway. They operate in a variety of different tissues and play a role in a variety of developmental processes by controlling cell fate decisions. Successive cleavage of the APP carboxyl-terminal fragment generates amyloid-beta (Abeta) peptides of varying lengths. Accumulation of Abeta peptides such as Abeta42 and Abeta43 leads to formation of amyloid plaques in the brain, a hallmark of Alzheimer's disease. Notch cleavage is involved in cell-fate determination during development and neurogenesis. The model corresponds to the juxtamembrane and transmembrane (JMTM) domain found in Notch and APP family proteins. It comprises a transmembrane helix (TM) with adjacent juxtamembrane (JM) regions. The JMTM domain is likely to be recognized by gamma-secretase in a similar fashion to both Notch and APP family proteins.


Pssm-ID: 411983  Cd Length: 41  Bit Score: 45.47  E-value: 1.14e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 41406057 613 LVFFAEDVGSNKGAIIGLMVGGVVIATVIVITL--VMLKKK 651
Cdd:cd21700   1 LPFFALDDGSGKGAIIGLLVGAVVILLVFVITGglVAARKK 41
PRK05035 PRK05035
electron transport complex protein RnfC; Provisional
 318-449 2.72e-03

electron transport complex protein RnfC; Provisional


Pssm-ID: 235334 [Multi-domain]  Cd Length: 695  Bit Score: 41.09  E-value: 2.72e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406057  318 KAKERLEAKhRERMsqvmrEWEEAERQAK------NLPKADKKAViqhfQEKVESLEQEAANERQQLVETHMAR-----V 386
Cdd:PRK05035 450 EAKARFEAR-QARL-----EREKAAREARhkkaaeARAAKDKDAV----AAALARVKAKKAAATQPIVIKAGARpdnsaV 519

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 41406057  387 EAMLNDRRRLALENYITALQAVPPRPRhvfnmlKKYV-----RAEQKDRQHTLKHFEHVRMVDPKKAA 449
Cdd:PRK05035 520 IAAREARKAQARARQAEKQAAAAADPK------KAAVaaaiaRAKAKKAAQQAANAEAEEEVDPKKAA 581
TPH pfam13868
Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of ...
 309-399 3.54e-03

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.


Pssm-ID: 464007 [Multi-domain]  Cd Length: 341  Bit Score: 40.29  E-value: 3.54e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41406057   309 DENEHAHFQKAKERLEAKHRERMS------QVMREWEEAERQAKNLPKADKKAVIQHFQEKVEsLEQEAANERQQLVETH 382
Cdd:pfam13868 213 EEQERKERQKEREEAEKKARQRQElqqareEQIELKERRLAEEAEREEEEFERMLRKQAEDEE-IEQEEAEKRRMKRLEH 291

                          90
                  ....*....|....*..
gi 41406057   383 MARVEAMLNDRRRLALE 399
Cdd:pfam13868 292 RRELEKQIEEREEQRAA 308
PRK14475 PRK14475
F0F1 ATP synthase subunit B; Provisional
 321-388 3.85e-03

F0F1 ATP synthase subunit B; Provisional


Pssm-ID: 184697 [Multi-domain]  Cd Length: 167  Bit Score: 38.77  E-value: 3.85e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 41406057  321 ERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEqEAANERQQLVETHMARVEA 388
Cdd:PRK14475  54 QRLREEAQALLADVKAEREEAERQAAAMLAAAKADARRMEAEAKEKLE-EQIKRRAEMAERKIAQAEA 120
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH