DUFMech

All families / PF06663

PF06663: CNK2_3_dom

Connector enhancer of kinase suppressor of ras 2/3 domain

Curation status
SEEDED
Seed status
EX DUF
Characterization
UNSCORED

Grounding

PF06663: Connector enhancer of kinase suppressor of ras 2/3 domain
IPR010599: integrated entry for Connector enhancer of kinase suppressor of ras 2/3 domain

Source description

This family represents a conserved region of unknown function within Connector enhancer of kinase suppressor of ras 2 (CNK2, also known MAGUIN) [InterPro reference PUB00012782,InterPro reference PUB00016229], Connector enhancer of kinase suppressor of ras 3 (CNK3) and CNK3/IPCEF1 fusion protein. This region is situated between the PDZ PF00595 (Pfam entry) and PH PF00169 (Pfam entry) domains in CNK2 and CNK3/IPCEF1, and after the PDZ domain in CNK3. All family members also contain an N-terminal PF00536 (Pfam entry) domain. CNK2 is predominantly expressed in neural tissues, being critical for postsynaptic density morphology, implicated in X-linked intellectual disability (ID). CNK2 was first described as a regulator of Ras/MAPK signalling that lead to further studies concluding that it act as a scaffold for multiple signal cascades. It is able to direct the localisation of regulatory proteins within the cell and influences the behaviour of important regulatory molecules [InterPro reference PUB00016229,InterPro reference PUB00097808]. CNK3 regulates aldosterone-induced and epithelial sodium channel (ENaC)-mediated sodium transport through regulation of ENaC cell surface expression, acting as a scaffold protein that coordinates the assembly of an ENaC-regulatory complex (ERC) [InterPro reference PUB00097809]. CNK3/IPCEF1 is required for hepatocyte growth factor (HGF)-dependent activation of Arf6 and HGF-stimulated cell migration [InterPro reference PUB00097810].

Evidence and references

Source descriptions and links are provenance, not independent functional validation.

Evidence counts: not scored.

Curated functional assertions

No curated functional assertions supplied.

Protein sequence examples

4 verified sequence examples. FASTA

UniProtProtein / organismSequenceProvenance
G9CGD6CNK3/IPCEF1 fusion protein
Homo sapiens
899 aa; version 1
UniProt 2026_03
PTM REGISTRY MIRROR
1 sibling references
Q6P9H4Connector enhancer of kinase suppressor of ras 3
Homo sapiens
555 aa; version 1
UniProt 2026_03
UNIPROT FETCH
2 sibling references
Q80YA9Connector enhancer of kinase suppressor of ras 2
Mus musculus
1032 aa; version 1
UniProt 2026_03
UNIPROT FETCH
1 sibling references
Q8WXI2Connector enhancer of kinase suppressor of ras 2
Homo sapiens
1034 aa; version 1
UniProt 2026_03
UNIPROT FETCH
2 sibling references

Pfam membership is not functional evidence. Whole-protein sequences do not establish domain boundaries. A coverage gap here is not absence from UniProt.

Sequences and metadata: UniProt Consortium, CC BY 4.0.

Domain matches

No residue-level domain match evidence is available in this build. Structure and AlphaFold counters do not supply coordinates or establish function.

Snapshot counters

proteins
3,585
matches
3,637
proteomes
735
taxa
2,235
structures
0
alphafold models
3,207
domain architectures
52

Classification basis

pfam previous unknown name

No scoring reasons supplied.

Related Mech records

This family joined the worklist after the frozen cross-Mech scan, so other Mechs were not searched for it. Missing links here are not evidence that other Mechs lack it; rows shown come from mentions of a former DUF/UPF name.

No cross-Mech examples are present in the supplied snapshot.

Curation history and reviews

No retained curation events supplied.

No retained review supplied.

Record source

data/families/PF06663.yaml
Family YAML in this build

Download this family (JSON)

Status and evidence

Seed status
A name-based classification of frozen InterPro/Pfam metadata. UNKNOWN CANDIDATE means the metadata explicitly says the function is unknown. KNOWN HISTORICAL DUF means a DUF name matched without that wording; this heuristic is not proof of a known function and does not establish experimental characterization. EX DUF means Pfam renamed the family away from a DUF/UPF name, as recorded in Pfam's previous identifiers; a rename usually follows published work on some members but is naming history, not proof of function for every member. Some EX DUF families' current names or descriptions still say the function is unknown; their classification basis lists this, and scoring does not treat them as characterized. FALSE POSITIVE TEXT HIT means the naming rules did not match.
Characterization
A separate evidence-scoring result. UNSCORED means no score has been calculated; it is not evidence that the family lacks a known function. Missing scores are not negative evidence. PARTIALLY CHARACTERIZED has partial support; KNOWN HISTORICAL DUF can inherit the seed label or reflect a known-function signal. Neither label implies experimental validation.
Evidence counts
Source-specific signals, not unique proteins, publications, or confidence scores. Known counts Rhea reactions and experimentally supported GO molecular-function annotations. Partial counts functional/domain assignments. Context counts structural, environmental, orthology, interaction and neighborhood signals; context alone does not assign function. Repeated annotations may not be independent.
Curation status
Reported separately from seed classification and characterization. SNAPSHOT ONLY means no curated metadata was supplied for this build. SEEDED denotes a source-derived record, not an expert-reviewed functional claim.
Missing counts
Not available means the source did not supply that counter. A zero is a reported count. Not scored means evidence counts are unavailable.