Multi-Level Structural and Functional Annotation of Neuropilin-2 (NRP2)

Workflow

Click a stage to see what was done and which tools were used.

Tools per analysis layer

NRP2 domain architecture

Multi-track map: signal peptide, extracellular a1/a2 (CUB), b1/b2 (FV/VIII) and c (MAM) domains, the transmembrane helix and cytoplasmic tail, with ligand-binding brackets, partner lollipops, topology bar and residue ruler. Boundaries are approximate (≈930 residues); replace with your InterProScan / CDD output. Hover any block.

Network topology analytics

Adjacency-matrix view of the interactome (rows and columns grouped by partner class) with a degree profile and graph metrics computed live from the network model: density, clustering coefficient and characteristic path length.

Interactors

Well-characterised NRP2 partners grouped by class. Filter below.

Domain × function map

Qualitative map of which region contributes most to each function.

Evolutionary context

Live UPGMA dendrogram built from the alignment in the MSA Conservation Studio below (distance = 1 − fractional identity; node tooltips give divergence). Paste your own alignment there and the tree re-roots.

Live Sequence Lab interactive

Paste any protein sequence (e.g. NRP2 from UniProt) to compute ProtParam-style properties, a hydropathy plot with TM-candidate regions, and protease site counts, all in your browser.

Evidence integration flow

How the eight analysis layers feed the three biological conclusions. Ribbon width is qualitative contribution. Hover a layer.

Force-directed interactome

Live physics simulation of NRP2 and its partners, including secondary links (semaphorin–plexin, VEGF–receptor, NRP1 crosstalk). Drag any node.

Tool directory

All 20 tools and databases used. Search or filter by method type.

Method landscape

3D domain explorer

Drag to rotate. A schematic bead model of NRP2 showing the extracellular a1/a2, b1/b2 and MAM globules, the transmembrane rod crossing the membrane plane, and the cytoplasmic tail. Click a chip to isolate a region. For real coordinates, open the PDB entries in Mol*.

Circular interaction map

Circos-style view: the outer ring is the NRP2 domain layout, and each chord links a partner to the region it engages. Hover a chord.

Cell-surface signalling

Animated schematic of the two best-known NRP2 signalling routes: semaphorin–plexin repulsion and VEGF-driven angiogenesis.

Live interactor builder

Add your own partner and watch it join the network in real time. Type a protein name, pick its class, press Add. Drag nodes; double-click a node to remove it. Published pages cannot query STRING directly, so the button opens the live STRING network for everything currently on the canvas.

MSA Conservation Studio

Paste an aligned FASTA (e.g. exported from Clustal Omega or COBALT). Computes gap-weighted Shannon conservation per column, a pairwise identity matrix and a conservation-shaded alignment.

Methods in depth

Algorithmic basis, what each analysis contributes, and its main limitation.

Protein Sigil generative

A unique visual fingerprint generated from the loaded sequence. Spiral = golden-angle phyllotaxis packing sized and coloured by hydropathy; Bloom = hydropathy petal curve with a charge ring; Mandala = dipeptide-driven 6-fold symmetry. Rose = hydrophobic, blue = hydrophilic. Paste a different sequence in the Live Sequence Lab and watch the sigil change.

Hydropathy Ridgeline generative

The sequence folded into rows, each drawn as a smoothed hydropathy ridge in the style of a pulsar plot. Pink dots mark TM-grade peaks (mean KD above 1.6). Row labels give the first residue of each line.

Protein Constellation generative

Each residue becomes a glowing star on a walk whose turns depend on residue class. Star size follows hydropathy magnitude, strongly hydrophobic or hydrophilic residues get a sparkle, every 10th residue is numbered, the chain is a faint backbone and runs of hydrophobic residues are joined in bright constellation lines.

Protein Soundscape audio

Hear the sequence. Each residue becomes a pentatonic note: higher pitch for more hydrophobic residues, with a different timbre per residue class. Plays the first 120 residues; press play (sound on).

Chaos Game Representation generative

A classic alignment-free sequence signature: the 20 amino acids sit on the vertices of a regular icosagon (ordered by physicochemical similarity). Start at the centre and, for each residue, jump halfway towards its vertex. The resulting trajectory is a fractal fingerprint of the protein. Colour runs from rose (N-terminus) to teal-blue (C-terminus) and the path redraws continuously.

Hydropathy Spectrogram signal analysis

Sliding-window Fourier analysis of the hydropathy signal (window 32). Rows are periodicities in residues: a bright band near 3.6 flags amphipathic α-helices, near 2.0 alternating β-strand patterns. Lower lane = relative 3.6-residue power along the sequence.

Residue Cellular Automaton generative

The first 150 residues seed a one-dimensional cellular automaton (hydrophobic = 1, otherwise 0) which then evolves downward under an elementary rule. Different rules turn the same sequence into different emergent textures.

Window Scanner interactive

Slide or auto-play a window along the sequence and read its local biophysics live: mean hydropathy, hydrophobic moment (100° helical periodicity, shown as the arrow on the helical wheel), net charge and disorder propensity, with a heuristic verdict. Thresholds are illustrative.

Dipeptide Landscape statistics

20 × 20 map of adjacent residue pairs, coloured by log₂(observed / expected) where expected comes from single-residue composition. Rose = over-represented, blue = under-represented. Hover a cell. Short sequences are sparse; full-length NRP2 gives a much richer map.

Residue Solar System generative

Every residue is a planet orbiting the protein on the ring of its class: hydrophobic innermost, then polar, basic and acidic. Planet size follows hydropathy magnitude, colour follows hydropathy sign, and outer rings move slower (Kepler-style).

Hydropathy Scale-Space multi-scale

Mean hydropathy at every position for window sizes 5–41 (small windows at the bottom, large at the top). Segments that stay rose across many scales are robust hydrophobic stretches such as TM helices; white dots mark windows above the 1.6 TM threshold.

Residue Arc Diagram contacts

Candidate residue relationships along the chain. Above the line: cysteine pairs (possible disulfides, amber) and hydrophobic i→i+4 pairs on the same helical face (rose). Below: opposite-charge pairs at i→i+3/4 (possible helical salt bridges, teal). Heuristic candidates, not predicted contacts.

Secondary-Structure Cartoon Chou–Fasman

Classic Chou–Fasman propensity analysis drawn as a cartoon: helices as coils, strands as arrows, coil as a thin line, with the smoothed α and β propensity curves below. This is a simplified 1970s-style heuristic (roughly 60% accurate), for illustration only.

Sequence Logo information content

Information-content logo (bits, with small-sample correction) of the alignment loaded in the MSA Conservation Studio. Letter height = residue frequency × information at that column; colours follow residue class. Use the slider to scroll through long alignments.

3D Helix Viewer geometry

The most amphipathic 28-residue window of the sequence, modelled as an ideal α-helix (100° per residue) and rotated in 3D. Watch the hydrophobic (rose) and hydrophilic (blue) faces swing in and out of view. Idealised geometry, not a predicted structure.

Self Dot Plot repeats

Classic internal-repeat finder: the sequence compared with itself in 5-residue windows (3+ identities, 4+ for long sequences). The grey diagonal is the sequence itself; off-diagonal rose streaks reveal internal repeats and duplications.

Motif & PTM Scanner sequence motifs

PROSITE-style consensus scan along the sequence: N-glycosylation sequons (relevant to the heavily glycosylated extracellular region), kinase consensus sites, furin-like cleavage sites, RGD, plus a check of the C-terminal tripeptide for a PDZ-binding motif. Consensus matches only; they overpredict real modification.

Surface & Antigenicity Profile Hopp–Woods

Hopp–Woods hydrophilicity averaged over a 7-residue window. Peaks (rose) are hydrophilic, likely solvent-exposed stretches and classic candidate antigenic determinants; the top non-overlapping peaks are numbered.

Eisenberg Hydrophobic-Moment Plot classification

Every 18-residue window plotted by mean hydropathy (x) against hydrophobic moment (y), coloured from N-terminus (rose) to C-terminus (blue). Shaded zones are illustrative: transmembrane-like (teal), amphipathic-helix-like (amber) and surface-like (blue).

Physicochemical profile (ProtParam)

Biological significance