Amyloid beta A4 protein

UniProt data

UniProt name: A4_HUMAN (P05067)

Gene name: APP; Synonyms=A4, AD1

Organism: Homo sapiens (Human).

Function: N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).

Subcellular location: Membrane; Single-pass type I membrane protein. Membrane, clathrin-coated pit. Note=Cell surface protein that rapidly becomes internalized via clathrin-coated pits. During maturation, the immature APP (N-glycosylated in the endoplasmic reticulum) moves to the Golgi complex where complete maturation occurs (O-glycosylated and sulfated). After alpha-secretase cleavage, soluble APP is released into the extracellular space and the C-terminal is internalized to endosomes and lysosomes. Some APP accumulates in secretory transport vesicles leaving the late Golgi compartment and returns to the cell surface. Gamma-CTF(59) peptide is located to both the cytoplasm and nuclei of neurons. It can be translocated to the nucleus through association with APBB1 (Fe65). Beta-APP42 associates with FRPL1 at the cell surface and the complex is then rapidly internalized. APP sorts to the basolateral surface in epithelial cells. During neuronal differentiation, the Thr-743 phosphorylated form is located mainly in growth cones, moderately in neurites and sparingly in the cell body. Casein kinase phosphorylation can occur either at the cell surface or within a post-Golgi compartment. Associates with GPC1 in perinuclear compartments. Colocalizes with SORL1 in a vesicular pattern in cytoplasm and perinuclear regions.

Transmembrane domains:

  1. 700-723, 24 AA, Helical. {ECO:0000255}.

Sequence: 770 AA

10 20 30 40 50 60 MLPGLALLLL AAWTARALEV PTDGNAGLLA EPQIAMFCGR LNMHMNVQNG KWDSDPSGTK 70 80 90 100 110 120 TCIDTKEGIL QYCQEVYPEL QITNVVEANQ PVTIQNWCKR GRKQCKTHPH FVIPYRCLVG 130 140 150 160 170 180 EFVSDALLVP DKCKFLHQER MDVCETHLHW HTVAKETCSE KSTNLHDYGM LLPCGIDKFR 190 200 210 220 230 240 GVEFVCCPLA EESDNVDSAD AEEDDSDVWW GGADTDYADG SEDKVVEVAE EEEVAEVEEE 250 260 270 280 290 300 EADDDEDDED GDEVEEEAEE PYEEATERTT SIATTTTTTT ESVEEVVREV CSEQAETGPC 310 320 330 340 350 360 RAMISRWYFD VTEGKCAPFF YGGCGGNRNN FDTEEYCMAV CGSAMSQSLL KTTQEPLARD 370 380 390 400 410 420 PVKLPTTAAS TPDAVDKYLE TPGDENEHAH FQKAKERLEA KHRERMSQVM REWEEAERQA 430 440 450 460 470 480 KNLPKADKKA VIQHFQEKVE SLEQEAANER QQLVETHMAR VEAMLNDRRR LALENYITAL 490 500 510 520 530 540 QAVPPRPRHV FNMLKKYVRA EQKDRQHTLK HFEHVRMVDP KKAAQIRSQV MTHLRVIYER 550 560 570 580 590 600 MNQSLSLLYN VPAVAEEIQD EVDELLQKEQ NYSDDVLANM ISEPRISYGN DALMPSLTET 610 620 630 640 650 660 KTTVELLPVN GEFSLDDLQP WHSFGADSVP ANTENEVEPV DARPAADRGL TTRPGSGLTN 670 680 690 700 710 720 IKTEEISEVK MDAEFRHDSG YEVHHQKLVF FAEDVGSNKG AIIGLMVGGV VIATVIVITL 730 740 750 760 VMLKKKQYTS IHHGVVEVDA AVTPEERHLS KMQQNGYENP TYKFFEQMQN

CATM prediction

The sequence of A4_HUMAN returned 5 potential models

The positions at the dimer's interface are highlighted in yellow. The position at the crossing point is highlighted in orange.

# Sequence and interface d θ Z' ω' Score
     700       710       720    
   |    +    |    +    |    + 		 (Å) (°) (Å) (°)  
Model 1 SNKGAIIGLMVGGVVIATVIVITLVMLKKK 6.7 -28.2° 6.0 47.0 -30.8
Model 2 SNKGAIIGLMVGGVVIATVIVITLVMLKKK 6.4 -47.2° 3.3 54.0 -27.2
Model 3 SNKGAIIGLMVGGVVIATVIVITLVMLKKK 7.4 -48.1° 0.4 47.0 -23.3
Model 4 SNKGAIIGLMVGGVVIATVIVITLVMLKKK 7.0 -54.1° 3.6 48.9 -14.1
Model 5 SNKGAIIGLMVGGVVIATVIVITLVMLKKK 6.4 -55.1° 5.9 46.8 -10.4

Click on the model number to visualize its details below.

MODEL 1 DETAILS

Precited structure:


Click on the image to enlarge

Download model 1 structure: PDB, PyMOL session

List of hydrogen bonds:

Donor Acceptor Distance
B, 701, ALA, HA A, 700, GLY, O 2.57Å
B, 704, GLY, HA1 A, 701, ALA, O 3.34Å
A, 701, ALA, HA B, 700, GLY, O 2.57Å
A, 704, GLY, HA1 B, 701, ALA, O 3.34Å