Human ABRA, UniProt Q8N0Z2, 381 aa, HGNC:30655. Also called STARS (striated muscle
activator of Rho signaling) and MS1 (myocyte stress 1).
The mechanism is worked out and consistent across three papers from one group plus
independent confirmation, but almost all of it is rodent.
Discovery and actin binding. PMID:11983702 and
PMID:11983702. The SRF effect requires the
actin interaction: PMID:11983702.
UniProt records the binding as being to filaments specifically —
[file:human/ABRA/ABRA-uniprot.txt "Binds F-actin and ABLIM1, ABLIM2 and ABLIM3."] — with
two C-terminal actin-binding regions of which the first is disordered
[file:human/ABRA/ABRA-uniprot.txt "The actin-binding domain 1 (ABD1) is intrinsically disordered,"].
The step that actually links actin to transcription. PMID:15798203 and
PMID:15798203. This is loss-of-function as well as gain-of-function:
PMID:15798203 UniProt's own human FUNCTION line encodes exactly this step:
[file:human/ABRA/ABRA-uniprot.txt "-!- FUNCTION: Acts as an activator of serum response factor (SRF)-dependent"].
Partners. ABLIM2 and ABLIM3 were found with STARS as bait
PMID:17194709 and they amplify the output
PMID:17194709. Note that
none of the ABLIM interactions appear in the human GOA file — the only IPI row is
PPP1R18 from HuRI.
In vivo requirement. Zebrafish knockdown PMID:22815879 rescued by SRF PMID:22815879. Mouse deletion impairs
arteriogenesis PMID:19778941.
A second, MRTF-independent activity. PMID:26903873 Worth flagging: the
canonical MRTF/SRF axis does not account for everything STARS does.
See ABRA-bioinformatics/RESULTS.md for the reproducible audit. Headline numbers: 16 rows,
2 experimental (one Y2H IPI, one LIFEdb IDA), 14 transferred; and of the transfers,
mouse Abra is the WITH/FROM source for 8 rows under four different identifier styles
(UniProtKB:Q8BUZ1, ensembl:ENSMUSP00000051973, MGI:MGI:2444891, InterPro:IPR026111),
rat Abra for 3 more. No human experiment has established any molecular function, biological
process or native localisation for this protein. The mechanism above is entirely mouse,
rat, zebrafish and C2C12; the human contribution to the literature is expression profiling.
The propagation topology is clean, though: PANTHER PTHR22739 has 4 reviewed members, all
named ABRA, all in subfamily SF20, so the IBA node PTN001100454 and the ISS transfers sit
inside a one-to-one ortholog group with no paralog to confuse them.
GO:0005886 IDA under GO_REF:0000054 (LIFEdb GFP-fusion survey) is the one annotation
that is not a rodent transfer, and it is the one I do not believe:
Cytoplasm, myofibril, sarcomere and Cytoplasm, cytoskeleton,GO:0005886 twice, by Ensembl ComparaGO_REF:0000107) and by ISO (GO_REF:0000119), and both cite UniProtKB:Q8N0Z2.Marked MARK_AS_OVER_ANNOTATED rather than REMOVE: the observation itself may be real for
an overexpressed fusion, and GO_REF:0000054 is a pipeline reference with no full text to
read against.
The mechanistic heart of what ABRA does — driving MRTF-A/MRTF-B into the nucleus — has no
human GO annotation. Mouse has GO:0006606 protein import into nucleus IDA from
PMID:15798203, but that term says STARS is imported, which is not what the paper shows;
STARS causes MRTFs to be imported. The correctly-directed term is
GO:0042307 positive regulation of protein import into nucleus. Because the mouse
annotation used the wrong-direction term, the step was never propagated to human, and the
human record jumps straight from actin binding to positive regulation of transcription by
RNA polymerase II with the causal middle missing. Added as a NEW annotation and flagged
for the mouse record too.
self_evaluation_pairwise: win with clear trust gates, all 12 citations are real numeric PMIDs,
and the mechanistic narrative
is accurate. One over-attribution:
"Its actin-cytoskeleton-regulating activity is conserved through the C-terminal Costars
domain, whose function in actin organization and motility is preserved across species
PMID:20940261."
PMID:20940261 is about a different gene. The Costars protein is 82 residues
PMID:20940261 and the rescue used
PMID:20940261. The human counterpart of that 82-residue protein is ABRACL (Q9P1F3,
81 aa) — RESULTS.md Q4 confirms ABRACL and ABRA are the only two reviewed human proteins
carrying Pfam PF14705, and ABRACL is essentially the domain alone. Sharing a domain is not
sharing a phenotype; nothing from that paper is used to support an ABRA annotation here.
GO:0030838 positive regulation of actin filament polymerization. The claim thatGO:0031674 I band. Tempting, but the reports disagree on the sub-compartment —GO:0030017 sarcomere is the honest level.Protein transport,Translocation and Transport, which used to generate GO:0015031 protein transport