SPINK5 (Q9NQ38): PANTHER 19 tree placement

Script: panther_tree.py (run 2026-10-21 against the PANTHER 19.0 treeinfo service for PTHR10913);
raw output in panther_tree.out.

Family assignment

PANTHER 19.0 places SPINK5 in PTHR10913 (FOLLISTATIN-RELATED), subfamily PTHR10913:SF71 (SERINE PROTEASE
INHIBITOR KAZAL-TYPE 5), per the PANTHER 19 human classification file. The UniProt record carries an older
cross-reference to PTHR47499:SF1 (SERINE PROTEASE INHIBITOR KAZAL-TYPE 7); the tree analysis below uses the
PANTHER 19 family.

Root-to-leaf path

PTN000099217 (Eukaryota) > PTN000099219 (Eumetazoa duplication) > PTN000857287 > PTN008956881 (Bilateria
duplication) > PTN000857333 (Bilateria speciation) > PTN000857275 (Deuterostomia) > PTN001331258 (Chordata) >
PTN008508634 (Euteleostomi duplication) > PTN000099251 (Theria speciation) > ... > Q9NQ38.

Scope of the serine-type endopeptidase inhibitor IBD

The PAINT node PTN000099251 (Theria, speciation) lies on the SPINK5 path. Its 12 leaves are the therian
SPINK5 orthologs only: human, chimpanzee, gorilla, macaque, mouse, rat, cow, pig, horse, cat, dog and
opossum. The node does not include TMEFF2 (which diverges from SPINK5 at the Euteleostomi duplication
PTN008508634), the follistatins, or any invertebrate member.

Last common ancestors

Member LCA with Q9NQ38 Event
Spink5 (mouse, Q148R4) PTN000099253 Euarchontoglires speciation (ortholog)
TMEFF2 (human) PTN008508634 Euteleostomi duplication (paralog)
CG32354 (fly, Q9VSK1) PTN000857333 Bilateria speciation (co-ortholog, many-to-many)
Fs (fly, Q86NV3) PTN000857333 Bilateria speciation (co-ortholog, many-to-many)
FST (human) PTN000099219 Eumetazoa duplication (distant paralog)

Interpretation: the mouse ortholog sits inside the therian clade that PAINT annotated with serine-type
endopeptidase inhibitor activity, so mouse experimental findings transfer to human SPINK5 at the orthology
level. The fly proteins share only a Bilateria speciation node with SPINK5, well above the Theria IBD node,
so the PAINT curators chose not to project the inhibitor function to them.