Keratin-associated protein 3-2 (Krtap3-2) is a small (99 aa) high-sulfur keratin-associated protein of the KAP3 family (Keratin_matx domain), one of the mammal-specific cysteine-rich matrix proteins of the hair fibre. Like its ovine and human KAP3 orthologues, which were first isolated as high-sulfur proteins of wool and are expressed in the hair cortex, it is synthesized in differentiating cortical keratinocytes of the hair follicle and becomes part of the interfilamentous matrix that surrounds the hair keratin intermediate filaments. There, its abundant cysteine residues form inter- and intramolecular disulfide bonds with the head and tail domains of hair keratins and with other KAPs, cross-linking the keratinized hair shaft and contributing to its rigidity and mechanical resistance. No gene-specific functional study of the mouse protein has been reported.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003674 molecular_function | ND GO_REF:0000015 | MODIFY | Summary: Root MF placeholder (ND) for Krtap3-2; the structural matrix role of this high-sulfur (HS) 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. Proposed replacements: structural constituent of cutaneous appendage Supporting Evidence: file:mouse/Krtap3-2/Krtap3-2-uniprot.txt In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. 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:0005198 structural molecule activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO structural molecule activity; correct but general for a hair matrix protein. Reason: Structural molecule activity is true of KAPs, but the evidence supports the more specific child GO:0030281 structural constituent of cutaneous appendage, which names the hair/wool fibre as the structure whose integrity the protein supports. Correct-but-general terms are refined rather than kept. Proposed replacements: structural constituent of cutaneous appendage Supporting Evidence: file:mouse/Krtap3-2/Krtap3-2-uniprot.txt In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. 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 Krtap3-2; 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. Proposed replacements: keratin filament Supporting Evidence: file:mouse/Krtap3-2/Krtap3-2-uniprot.txt In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. 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:0005829 cytosol | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA-rule cytosol placement; KAPs are synthesized in the cytoplasm of keratinizing cortical cells but act in the keratin matrix. Reason: Keratin-associated proteins are non-membrane proteins synthesized in the cytoplasm of differentiating (keratinizing) hair or wool cortical cells, so a cytoplasmic/cytosolic placement is true of the newly made protein. It is not the site of function: KAPs act in the interfilamentous matrix around trichocyte keratin intermediate filaments of the keratinized cell, which this review captures with keratin filament (GO:0045095). The placement is correct but peripheral, so it is kept as non-core rather than marked as over-annotated; ARBA IEA and Reactome TAS cytosol rows are treated identically across the KRTAP family reviews. Supporting Evidence: file:mouse/Krtap3-2/Krtap3-2-uniprot.txt In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. 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 Krtap3-2; 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. Proposed replacements: keratinization Supporting Evidence: file:mouse/Krtap3-2/Krtap3-2-uniprot.txt In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. 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:0045095 keratin filament | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO keratin filament; KAPs are embedded in and cross-linked to the hair keratin filament network. Reason: KAP proteins form the interfilamentous matrix of the hair cortex and are covalently disulfide-bonded to the head and tail domains of hair keratins, so they are integral to the keratin filament assembly of the fibre. This is the standard CC for the family and is as specific as GO allows (there is no separate 'keratin filament matrix' term). Supporting Evidence: file:mouse/Krtap3-2/Krtap3-2-uniprot.txt In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. 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 Krtap3-2 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 Krtap3-2 functionally redundant with its paralogues in the same KAP cluster, or does its loss change fibre mechanics, diameter or curvature?
Experiment: Generate a Krtap3-2 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: Krtap3-2 contributes non-redundantly to fibre mechanics or morphology.
Type: knockout phenotyping
Experiment: Map Krtap3-2-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: Krtap3-2 associates with specific keratin head/tail domains.
Type: biochemical binding / XL-MS
Experiment: Define the follicular compartment and hair-cycle timing of Krtap3-2 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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