AP2S1 (sigma2) dileucine-pocket residues: are they there, and how specific are they?

Generated by check_sigma2_pockets.py; every sequence is fetched live from the
UniProt REST API at run time and no result is hardcoded.

Target: P53680 (AP2S1_HUMAN), length 142 aa.

Q1. Residue identity at the claimed positions in human AP2S1

position	expected	observed in P53680	match	role (Kelly et al. 2008, PMID:19140243)
15	R	R	yes	basic L-4 patch with alpha R21; FHH3 mutational hotspot
63	A	A	yes	pocket floor; A63W fills the pocket and blocks binding
65	L	L	yes	pocket lining; L65S abolishes dileucine binding
88	V	V	yes	pocket lining; V88D reduced binding below detection
92	N	N	yes	pocket lining; N92W fills the pocket and blocks binding
97	N	N	yes	contacts the L-1 position of the motif
98	V	V	yes	pocket lining; V98S abolishes dileucine binding
103	L	L	yes	pocket lining; L103S reduced binding below detection

All eight positions match the literature: True

Q2. Does the crystal structure's numbering transfer to the human protein?

Kelly et al. solved a species-mixed AP2 core; their Methods give the construct as
1-621 mouse alpha-adaptin; 1-591 human beta2-adaptin; 1-435 rat mu2-adaptin, 1-143 mouse sigma2-adaptin, so the sigma2 chain is the mouse protein (P62743).
The residue numbers therefore transfer to human AP2S1 only if the orthologues are
identical over these sites.

accession	entry	length	identical to P53680 over full length	residues at the 8 claimed positions
P53680	AP2S1_HUMAN	142	True	RALVNNVL
P62744	AP2S1_RAT	142	True	RALVNNVL
P62743	AP2S1_MOUSE	142	True	RALVNNVL

Human, rat and mouse sigma2 identical over the full chain: True — so the numbering transfers without an alignment step.

Q3. Conservation across the eight human AP-complex sigma subunits

MAFFT L-INS-i alignment of the eight human sigma subunits (alignment length 257 columns).

AP2S1 pos	AP2S1	AP1S1	AP1S2	AP1S3	AP3S1	AP3S2	AP4S1	AP5S1	identical to AP2S1
15R	R	R	R	R	R	R	R	R	7/7
63A	A	A	A	A	A	A	A	L	6/7
65L	L	L	L	L	L	L	L	L	7/7
88V	V	V	V	V	V	V	V	-	6/7
92N	N	D	D	D	D	D	D	D	0/7
97N	N	S	S	N	N	N	R	L	3/7
98V	V	V	V	V	V	V	V	A	6/7
103L	L	I	I	I	L	L	I	L	3/7

Positions identical in all eight paralogues: 15R, 65L

Restricted to the AP-1 to AP-4 sigma subunits (Kelly's stated scope), the positions invariant across all seven are: 15R, 63A, 65L, 88V, 98V

Positions where AP2S1 differs from every other AP-1 to AP-4 sigma subunit (i.e. AP2-specific): 92N

R15 column across paralogues: {'AP2S1': 'R', 'AP1S1': 'R', 'AP1S2': 'R', 'AP1S3': 'R', 'AP3S1': 'R', 'AP3S2': 'R', 'AP4S1': 'R', 'AP5S1': 'R'}

Machine-readable summary

{
  "target": "P53680",
  "target_length": 142,
  "all_claimed_residues_match": true,
  "human_rat_mouse_identical": true,
  "positions_identical_in_all_8_paralogs": [
    15,
    65
  ],
  "positions_identical_across_AP1_to_AP4_sigmas": [
    15,
    63,
    65,
    88,
    98
  ],
  "positions_specific_to_AP2S1_among_AP1_to_AP4_sigmas": [
    92
  ],
  "r15_column": {
    "AP2S1": "R",
    "AP1S1": "R",
    "AP1S2": "R",
    "AP1S3": "R",
    "AP3S1": "R",
    "AP3S2": "R",
    "AP4S1": "R",
    "AP5S1": "R"
  }
}