ADPRH catalytic-residue census across PANTHER PTHR16222

Members analysed: 31 reviewed (Swiss-Prot) entries out of a family total of 29860 proteins (0.104% of the family). Every statement below is about the reviewed subset only.

Catalytic positions tested (human ADPRH P54922, each a UniProt MUTAGEN with note "Complete loss of activity"): S54, D55, D56, D302, S305.

Cross-tabulation: does GO:0003875 track the residues?

holds GO:0003875 does not
all 5 residues retained 5 see table
>=1 residue lost 11 see table

Members that hold GO:0003875 while missing at least one catalytic residue:

accession gene organism residues retained % identity to ADPRH evidence
B0KTG8 tri1 Pseudomonas putida (strain GB-1) 4/5 31.3 IEA(GO_REF:0000120)
A8GG79 tri1 Serratia proteamaculans (strain 568) 4/5 29.4 IEA(GO_REF:0000120)
P14300 draG Rhodospirillum rubrum 3/5 27.5 IEA(GO_REF:0000116), EXP(PMID:19706507)
A0A168WVR6 tri1 Pseudomonas putida (strain DSM 28064 / B6-2) 3/5 23.2 ISS(GO_REF:0000024), IEA(GO_REF:0000120)
Q3ZBM1 ADPRHL1 Bos taurus 2/5 42.6 IEA(GO_REF:0000120)
Q5XJB9 adprhl1 Danio rerio 2/5 44.4 IEA(GO_REF:0000002)
Q8NDY3 ADPRHL1 Homo sapiens 2/5 46.6 IEA(GO_REF:0000120)
Q8BGK2 Adprhl1 Mus musculus 2/5 46.1 IEA(GO_REF:0000120)
Q5RCJ0 ADPRHL1 Pongo abelii 2/5 46.3 IEA(GO_REF:0000120)
Q5XIB3 Adprhl1 Rattus norvegicus 2/5 45.6 IEA(GO_REF:0000120)
Q6AZR2 adprhl1 Xenopus laevis 1/5 47.7 IEA(GO_REF:0000002)

By clade

clade n % identity to ADPRH catalytic residues retained hold GO:0003875
ADPRH (ARH1) 5 48.4-100.0 5-5 of 5 5/5
ADPRHL1 (ARH2) 7 42.6-47.7 1-2 of 5 7/7
ADPRS (ARH3) 7 25.8-28.1 3-4 of 5 0/7
other / non-vertebrate 12 20.0-32.5 0-4 of 5 4/12

Is a residue loss real, or an alignment artefact?

A single identity threshold was tried first and rejected: a single identity threshold from the largest observed gap; it lands at 65.4% between Dictyostelium ADPRH (48.4%) and mouse Adprh (82.4%), i.e. a taxonomic boundary, and would discard the ADPRHL1 signal.

Percent identity here is computed over aligned columns only (gaps excluded), which runs slightly above the conventional alignment-length denominator. It is applied identically to every member, so no comparison below is affected, but the absolute figures should not be set against externally quoted identities.

Two computed measures are used instead. Clade consistency -- the same substitution at the same column in every member of a clade is not alignment noise. Substitution chemistry -- S<->T (hydroxyl retained); D<->E (carboxylate retained).

clade n disruptive in EVERY member disruptive substitutions example member hold GO:0003875
ADPRH (ARH1) 5 none 0 of 5 none 5/5
ADPRHL1 (ARH2) 7 S305, D56 2-3 of 5 D56->N(disruptive), D302->E(conservative), S305->A(disruptive) 7/7
ADPRS (ARH3) 7 none 0 of 5 S305->T(conservative) 0/7
other / non-vertebrate 12 none 0-5 of 5 S305->T(conservative) 4/12

Positive control -- a member with its own experimental annotation to GO:0003875 despite scoring below 5/5. Its substitutions bound what catalysis tolerates:

accession gene organism % id retained disruptive substitutions evidence
P14300 draG Rhodospirillum rubrum 27.5 3/5 0 S54->T(conservative), S305->T(conservative) IEA(GO_REF:0000116), EXP(PMID:19706507)

Per-member detail

accession entry gene organism % id S54 D55 D56 D302 S305 ident/5 ident+own-site/5 GO:0003875
Q32KR8 ADPRH_BOVIN ADPRH Bos taurus 88.5 S59 D60 D61 D307 S310 5/5 5 ISS(GO_REF:0000024), ISS(GO_REF:0000024), IBA(GO_REF:0000033), IEA(GO_REF:0000120)
Q54H71 ADPRH_DICDI adprh Dictyostelium discoideum 48.4 S79 D80 D81 D348 S351 5/5 5 ISS(GO_REF:0000024), ISS(GO_REF:0000024), IEA(GO_REF:0000120)
P54922 ADPRH_HUMAN ADPRH Homo sapiens 100.0 S54 D55 D56 D302 S305 5/5 5 IBA(GO_REF:0000033), IEA(GO_REF:0000120), IDA(PMID:30472116), IMP(PMID:8349667)
P54923 ADPRH_MOUSE Adprh Mus musculus 82.4 S59 D60 D61 D307 S310 5/5 5 ISS(GO_REF:0000024), ISS(GO_REF:0000024), IBA(GO_REF:0000033), ISO(GO_REF:0000096), ISO(GO_REF:0000119), IEA(GO_REF:0000120), IMP(PMID:8349667)
Q02589 ADPRH_RAT Adprh Rattus norvegicus 82.9 S59 D60 D61 D307 S310 5/5 5 ISS(GO_REF:0000024), IBA(GO_REF:0000033), IEA(GO_REF:0000120), ISO(GO_REF:0000121), ISO(GO_REF:0000121), IDA(PMID:1375222), IMP(PMID:1375222)
Q5UQP4 ADPRL_MIMIV - Acanthamoeba polyphaga mimivirus 30.5 S185 D186 D187 D437 T440* 4/5 n/a -
Q66HT8 ADPRS_DANRE adprs Danio rerio 26.6 S65 D66 D67 D304 T307* 4/5 3 -
B0KTG8 TRI1_PSEPG tri1 Pseudomonas putida (strain GB-1) 31.3 T112* D113 D114 D311 S314 4/5 2 IEA(GO_REF:0000120)
A8GG79 TRI1_SERP5 tri1 Serratia proteamaculans (strain 568) 29.4 T116* D117 D118 D315 S318 4/5 2 IEA(GO_REF:0000120)
Q58588 Y1187_METJA - Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440) 28.8 T60* D61 D62 D253 S256 4/5 n/a -
O28550 Y1724_ARCFU - Archaeoglobus fulgidus (strain ATCC 49558 / DSM 4304 / JCM 9628 / NBRC 100126 / VC-16) 32.5 T54* D55 D56 D254 S257 4/5 n/a -
Q5UQA6 ADPRM_MIMIV - Acanthamoeba polyphaga mimivirus 23.7 T62* D63 D64 D277 T280* 3/5 n/a -
Q3SYV9 ADPRS_BOVIN ADPRS Bos taurus 26.5 T77* D78 D79 D315 T318* 3/5 3 -
Q5ZI51 ADPRS_CHICK ADPRS Gallus gallus 25.8 T79* D80 D81 D317 T320* 3/5 3 -
Q9NX46 ADPRS_HUMAN ADPRS Homo sapiens 27.8 T76* D77 D78 D314 T317* 3/5 3 -
H3BCW1 ADPRS_LATCH adprs Latimeria chalumnae 26.1 T62* D63 D64 D303 T306* 3/5 3 -
Q8CG72 ADPRS_MOUSE Adprs Mus musculus 27.9 T82* D83 D84 D320 T323* 3/5 3 -
Q28FQ6 ADPRS_XENTR adprs Xenopus tropicalis 28.1 T57* D58 D59 D295 T298* 3/5 3 -
P14300 DRAG_RHORU draG Rhodospirillum rubrum 27.5 T59* D60 D61 D243 T246* 3/5 1 IEA(GO_REF:0000116), EXP(PMID:19706507)
A0A168WVR6 TRI1_PSEP8 tri1 Pseudomonas putida (strain DSM 28064 / B6-2) 23.2 L63* S64* D65 D322 S325 3/5 0 ISS(GO_REF:0000024), IEA(GO_REF:0000120)
P76418 YEGU_ECOLI yegU Escherichia coli (strain K12) 27.7 T60* D61 D62 D280 T283* 3/5 n/a -
Q3ZBM1 ARHL1_BOVIN ADPRHL1 Bos taurus 42.6 S56 D57 N58* E304* A307* 2/5 n/a IEA(GO_REF:0000120)
Q5XJB9 ARHL1_DANRE adprhl1 Danio rerio 44.4 S53 D54 G55* E300* A303* 2/5 n/a IEA(GO_REF:0000002)
Q8NDY3 ARHL1_HUMAN ADPRHL1 Homo sapiens 46.6 S56 D57 N58* E304* A307* 2/5 n/a IEA(GO_REF:0000120)
Q8BGK2 ARHL1_MOUSE Adprhl1 Mus musculus 46.1 S55 D56 N57* E303* A306* 2/5 n/a IEA(GO_REF:0000120)
Q5RCJ0 ARHL1_PONAB ADPRHL1 Pongo abelii 46.3 S56 D57 N58* E304* A307* 2/5 n/a IEA(GO_REF:0000120)
Q5XIB3 ARHL1_RAT Adprhl1 Rattus norvegicus 45.6 S55 D56 N57* E303* A306* 2/5 n/a IEA(GO_REF:0000120)
Q6AZR2 ARHL1_XENLA adprhl1 Xenopus laevis 47.7 S56 N57* N58* E304* A307* 1/5 n/a IEA(GO_REF:0000002)
Q03442 CRJ1A_TRICY - Tripedalia cystophora 21.5 Y67* G68* E69* C274* P277* 0/5 n/a -
Q03443 CRJ1B_TRICY - Tripedalia cystophora 20.0 D60* N61* G62* C274* A277* 0/5 n/a -
P40821 CRJ1C_TRICY - Tripedalia cystophora 20.1 Y67* G68* E69* C274* P277* 0/5 n/a -

* = not identical to the ADPRH residue. ident+own-site/5 is n/a where the entry has no
BINDING/ACT_SITE features of its own, so the second condition cannot be evaluated; those
counts are NOT promoted to matches.

Metals actually present in the ADPRH structures

PDB resolution (A) bound non-polymer components MG K PubMed
3HFW 1.92 K, MG yes yes -
6G28 1.23 AR6, MG yes no 30472116
6G2A 1.8 A3R, MG yes no 30472116
6IUX 1.195 AR6, MG yes no -

Magnesium is present in 4 of 4 structures (3HFW, 6G28, 6G2A, 6IUX). Potassium is present in 1 of 4 (3HFW).

Every structure containing potassium is at the worst resolution in the set (1.92 A); all 3 better-resolved structures (6G28, 6G2A, 6IUX) contain none.

InterPro signature membership (the annotation route)

IPR012108 ("ADP-ribosylarginine hydrolase") is the family-specific signature whose interpro2go mapping supplies GO:0000287, GO:0003875 and GO:0051725.