Keratin-associated protein 29-1 (Krtap29-1; also Kap29.2) is a large (342 aa) cysteine-rich keratin-associated protein classified with the KRTAP type 10 family of ultra-high-sulfur KAPs, built largely from cysteine-rich pentapeptide repeats. Its existence is inferred from the mouse genome sequence and homology. By family membership it is predicted to be an ultra-high-sulfur matrix protein of the keratinizing hair fibre that becomes extensively disulfide cross-linked with hair keratin intermediate filaments and other matrix proteins; its expression pattern and follicular compartment have not been described.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003674 molecular_function | ND GO_REF:0000015 | MODIFY | Summary: Root MF placeholder (ND) for Krtap29-1; the structural matrix role of this ultra-high-sulfur (UHS) KAP is now describable with a specific term. Reason: The ND row records that no MF was annotated when MGI last searched, but KAP-family literature establishes that KAPs are structural matrix components of the hair fibre that cross-link hair keratin intermediate filaments. GO:0030281 structural constituent of cutaneous appendage ('contributes to the structural integrity of cutaneous epidermal structures such as hairs') captures this. The root term is replaced rather than kept, and no binding term is proposed: KAP-keratin association is the mechanism of the structural role, not a separable activity, and keratin-binding data exist only for other family members. Krtap29-1 is supported only by family classification (PE 3), so this is a family-level inference. Proposed replacements: structural constituent of cutaneous appendage Supporting Evidence: file:mouse/Krtap29-1/Krtap29-1-uniprot.txt Belongs to the KRTAP type 10 family PMID:16382671 Hair keratin-associated proteins (KAP) are a major component of the hair fiber, and play crucial roles in forming a strong hair shaft through a cross-linked network with keratin intermediate filaments (KIF), which are produced from hair keratins. PMID:22298953 These filaments have a matrix surrounding them, that contains the keratin-associated proteins (KAPs), which cross-link with the IFs through extensive disulfide bonding PMID:29797274 Thus it is the crosslinking that occurs between the cysteines in the keratins and KAPs that is an important determinant in the functionality of wool and hair fibres. |
| GO:0005575 cellular_component | ND GO_REF:0000015 | MODIFY | Summary: Root CC placeholder (ND) for Krtap29-1; KAPs reside in the keratin filament matrix. Reason: KAPs are synthesized in differentiating hair cortex/cuticle cells and are embedded in, and covalently cross-linked to, the hair keratin intermediate filament network. GO keratin filament (GO:0045095), the CC used for the KAP family by InterPro2GO, is the appropriate replacement for the uninformative root. Krtap29-1 is supported only by family classification (PE 3), so this is a family-level inference. Proposed replacements: keratin filament Supporting Evidence: file:mouse/Krtap29-1/Krtap29-1-uniprot.txt Belongs to the KRTAP type 10 family PMID:16382671 Hair keratin-associated proteins (KAP) are a major component of the hair fiber, and play crucial roles in forming a strong hair shaft through a cross-linked network with keratin intermediate filaments (KIF), which are produced from hair keratins. PMID:22298953 These filaments have a matrix surrounding them, that contains the keratin-associated proteins (KAPs), which cross-link with the IFs through extensive disulfide bonding |
| GO:0008150 biological_process | ND GO_REF:0000015 | MODIFY | Summary: Root BP placeholder (ND) for Krtap29-1; KAPs are structural participants in hair keratinization. Reason: The process in which KAPs do work is the terminal keratinization of hair cortical (or cuticle) cells: KAPs are deposited around the keratin intermediate filaments and disulfide cross-linked into the insoluble keratin-matrix composite that fills the keratinized cell. This is structural participation (the KAP is a constituent of the product), not mere dependence. GO:0031424 keratinization explicitly covers hair. Hair cycle or hair follicle development terms were not chosen: KAP expression tracks anagen, but KAPs are downstream structural products and do not drive follicle cycling or morphogenesis. Krtap29-1 is supported only by family classification (PE 3), so this is a family-level inference. Proposed replacements: keratinization Supporting Evidence: file:mouse/Krtap29-1/Krtap29-1-uniprot.txt Belongs to the KRTAP type 10 family PMID:16382671 Hair keratin-associated proteins (KAP) are a major component of the hair fiber, and play crucial roles in forming a strong hair shaft through a cross-linked network with keratin intermediate filaments (KIF), which are produced from hair keratins. PMID:22298953 These filaments have a matrix surrounding them, that contains the keratin-associated proteins (KAPs), which cross-link with the IFs through extensive disulfide bonding |
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Download this section (compressed HTML)Q: Which keratin residues or domains does Krtap29-1 cross-link or bind in the fibre, and does it pair preferentially with particular type I/type II trichocyte keratins or other KAPs?
Q: Is Krtap29-1 functionally redundant with its paralogues in the same KAP cluster, or does its loss change fibre mechanics, diameter or curvature?
Experiment: Generate a Krtap29-1 knockout (CRISPR, ideally together with close paralogues) and measure fibre tensile strength, diameter, curvature and ortho/para-cortex organization, with keratin/KAP proteomics of the fibre.
Hypothesis: Krtap29-1 contributes non-redundantly to fibre mechanics or morphology.
Type: knockout phenotyping
Experiment: Map Krtap29-1-keratin cross-links in native fibres by cross-linking mass spectrometry, and test binding of recombinant protein to trichocyte keratin head domains (ITC/pull-down) under non-reducing and reducing conditions.
Hypothesis: Krtap29-1 associates with specific keratin head/tail domains.
Type: biochemical binding / XL-MS
Experiment: Define the follicular compartment and hair-cycle timing of Krtap29-1 expression by RNA in situ hybridization or single-cell RNA-seq of anagen follicles, with an antibody to confirm protein in the keratinized shaft.
Type: expression localization
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