# HISTORY
26 Mar 2016: Updated by: TOUCHUP-v1.15
18 Nov 2015: redistribution of PTN000003938 from PTHR10032 to PTHR16516
16 Mar 2016: Updated by: TOUCHUP-v1.14

# molecular_function

# cellular_component

# biological_process
20130211: Bilateria_PTN000003938 participates in oligodendrocyte development (GO:0014003) 

# WARNINGS - THE FOLLOWING HAVE BEEN REMOVED FOR THE REASONS NOTED

# NOTES
This is a widely divergent family that shares only zinc finger domains overall.  There are several main subfamilies that have greater conservation based on MSA: ZNF518B-related (vertebrates, other members are questionable); PLAG1-related (deuterostomes, the arthropod members are questionable); ZNF488-related, hb(D.mel.)-related; ovo(D.mel.)-related-- this SubFamily is massively duplicated and diverged in vertebrates).  There are a few fungal outgroup sequences and one plant subfamily, but these are only related in the zinc finger domain.  There's a small subfamily after an apparent duplication at the root (mostly frog sequences) that doesn't look like it aligns well, so prune this clade, i.e. "root" below actually refers to PTN000003381.
Molecular Function
1) transcription factor related terms are found in all groups, including the plant outgroup, so propagate this term to the root PTN000003381: sequence-specific DNA binding RNAP II transcription factor activity.
There are some interesting outlier annotations:
2) neurotrophin p75 receptor binding: propagate to placental mammal clade after duplication (Eutheria_PTN000003506) since this is critical for its involvement in apoptosis.
3) transcription co-activator: propagate to orthologous clade Eutheria_PTN000003572 -- this family is SCAN domain only and interacts with nuclear receptors, so also put NOT transcription factor as it does not interact directly with DNA.
Additional outlier annotations:
- identical protein binding and protein homodimerization activity and protein self-association (ignore)
- outward rectifier potassium channel activity annotated to Human_REST (http://www.uniprot.org/uniprot/Q13127) (scanned PMID1857091, this maybe a misannotation)
- protein kinase binding (there are no clear orthologs of CkIIalphai-1)
Cellular Component
1) nucleus widespread and consistent with MF: propagate to root.
other CC annotations:
- several proteins are annotated to NOT nucleolus but not widespread enough (or informative enough) to propagate
- Transcription repressor complex is a function, so do not propagate
- Actin cytoskeleton and extracellular region are singletons and based on high throughput papers so do not propagate
- cytosol only for mouse REST, this is correct but according to the paper the cytosolic location is to regulate function and function actually occurs in nucleus so do not propagate cytosol.
Biological Process
- do not propagate any terms like 'regulation of transcription' as this is not a coordinated process and is covered by MF.
* Plag clade
1) annotations in multiple paralogous groups of involvement in induction of apoptosis (mechanism known), so annotate to PTN000798650 (root of clade)
2) cell differentiation, a parent term (based on skeletal muscle differentiation for plagl1, and PMID 19808959 should really annotate plagl1 to neuronal cell differentiation instead of plag1 to glial cell proliferation which is the abnormal process in this case) to the plagl1 ancestor Mammalia_PTN000003408
3) propagate chylomicron assembly to root of plagl2 Mammalia_PTN000003391clade, but not lipid metabolic process as it does not contribute to chemical synthesis or breakdown of lipids
- Do not propagate cell cycle arrest as it is a singleton and TAS
- All the BPs for plag1 from PMID 15606491 are due to a very general phenotype (overall growth) so do not propagate these BPs.
* ZNF488 clade:
1) propagate oligodendrocyte development (parent of mouse annotation of positive regulation of oligodendrocyte development; don't see justification for regulation in paper).
* hb clade: best-studied gene is D. mel hunchback, but its C. elegans ortholog also has experimental annotations.
1) Regulation of development, heterochronic is annotated in both fly and worm orthologs, propagate to root of clade bilateria_PTN000798667
- All other worm annotations are nonspecific phenotypes that probably result from this more basic function.
- Fly has many BPs but only neuroblast development has experimental evidence, so propagate to arthropod ancestor  PTN000798670 since no evidence for this in worm.
Annotation issues:
1) http://www.uniprot.org/uniprot/Q13127
Annotated to: outward rectifier potassium channel activity based on PMID1857091, this maybe a misannotation.
2) PMID 19808959 should really annotate plagl1 to neuronal cell differentiation instead of plag1 to glial cell proliferation which is the abnormal process in this case

# REFERENCE
Annotation inferences using phylogenetic trees
The goal of the GO Reference Genome Project, described in PMID 19578431, is to provide accurate, complete and consistent GO annotations for all genes in twelve model organism genomes. To this end, GO curators are annotating evolutionary trees from the PANTHER database with GO terms describing molecular function, biological process and cellular component. GO terms based on experimental data from the scientific literature are used to annotate ancestral genes in the phylogenetic tree by sequence similarity (ISS), and unannotated descendants of these ancestral genes are inferred to have inherited these same GO annotations by descent. The annotations are done using a tool called PAINT (Phylogenetic Annotation and INference Tool).