mkt.schema.constants
Constants for KLIFS regions, Pfam kinase domains, and kinase groups/families.
Defines the canonical KLIFS region orderings, Pfam kinase-domain accessions, and the controlled vocabularies for kinase groups and families referenced throughout the schema and databases packages.
Module Attributes
List of Pfam kinase domain names. |
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List of KLIFS region, including intra and inter regions in order. |
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Mapping KLIFS pocket region to start and end indices, boolean denoting if subsequent regions are contiguous, and colors. |
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List of string of all KLIFS pocket regions in format region:idx. |
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KLIFS region:idx of the canonical VAIK beta3 catalytic lysine. |
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KLIFS region:idx of the beta2 lysine used as the catalytic lysine by the WNK ("With No K [lysine]") family in place of the absent beta3 lysine -- Xu et al., J Biol Chem 2000 (WNK1 lacks the subdomain-II lysine); Min et al., Structure 2004 (WNK1 Lys233 sits in beta2). |
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KLIFS region:idx of the HRD catalytic aspartate. |
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KLIFS region:idx of the DFG-motif aspartate. |
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Curated pseudokinases that retain an intact VAIK-K / HRD-D / DFG-D triad and are therefore NOT caught by the catalytic-residue heuristic (false negatives); they are catalytically dead for other reasons (degraded regulatory spine, glycine-rich loop, or nucleotide binding). |
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Kinases the catalytic-residue heuristic flags as pseudokinases but that are (debatably) catalytically active -- false positives held out for review. |
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Dictionary mapping kinase groups to colors. |
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Dictionary mapping KLIFS pocket region:idx to the corresponding canonical molecular brake residue (N, E, K). |
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Per-position UniProt index offset (relative to the KLIFS2UniProt-mapped index) to reach the molecular brake residue in |
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ConSurf conservation-grade bands as inclusive (low, high) grade ranges. |
- mkt.schema.constants.DICT_CONSURF_GRADE_BANDS = {'Conserved': (7, 9), 'Intermediate': (4, 6), 'Variable': (1, 3)}
ConSurf conservation-grade bands as inclusive (low, high) grade ranges. The nine ConSurf nonile grades collapse into three qualitative bands – variable (1-3), intermediate (4-6), conserved (7-9) – used to bracket-label the grade legend on the conservation dot heatmap.
- Type:
dict[str, tuple[int, int]]
- mkt.schema.constants.DICT_KINASE_GROUP_COLORS = {'AGC': '#5B8DBE', 'Atypical': '#7A7A7A', 'CAMK': '#D4A574', 'CK1': '#8B7355', 'CMGC': '#C17B7B', 'Lipid': '#8B6F84', 'NEK': '#E5A672', 'Other': '#9B8AB8', 'RGC': '#A67C52', 'STE': '#D39EB7', 'TK': '#6BAFB8', 'TKL': '#B8AE6E'}
Dictionary mapping kinase groups to colors. Keys are kinase group names, and values are hex color codes. This dictionary can be used to look up colors for kinase groups in visualizations.
- Type:
dict[str, str]
- mkt.schema.constants.DICT_MOLECULAR_BRAKE = {'VIII:79': 'K', 'b.l:37': 'N', 'hinge:46': 'E'}
Dictionary mapping KLIFS pocket region:idx to the corresponding canonical molecular brake residue (N, E, K). The molecular brake is a conserved triad that latches the active site into an autoinhibited state, characterized in FGFR (Asn-Glu-Lys; Chen et al., Mol Cell 2007). This dictionary can be used to identify the molecular brake residues in kinases based on their KLIFS pocket region and index. Some positions require an index offset before lookup – see
DICT_MOLECULAR_BRAKE_OFFSET.- Type:
dict[str, str]
- mkt.schema.constants.DICT_MOLECULAR_BRAKE_OFFSET = {'VIII:79': -1}
Per-position UniProt index offset (relative to the KLIFS2UniProt-mapped index) to reach the molecular brake residue in
DICT_MOLECULAR_BRAKE. The brake lysine sits one residue N-terminal to the VIII:79 KLIFS-aligned position, so a -1 offset is applied there (e.g. FGFR2 K641 maps to VIII:79 idx 642). Positions absent from this dict use no offset.- Type:
dict[str, int]
- mkt.schema.constants.DICT_POCKET_KLIFS_REGIONS = {'GK': {'color': 'orange', 'contiguous': True, 'end': 45, 'start': 45}, 'I': {'color': 'khaki', 'contiguous': True, 'end': 3, 'start': 1}, 'II': {'color': 'khaki', 'contiguous': True, 'end': 13, 'start': 10}, 'III': {'color': 'khaki', 'contiguous': False, 'end': 19, 'start': 14}, 'IV': {'color': 'khaki', 'contiguous': False, 'end': 41, 'start': 38}, 'V': {'color': 'khaki', 'contiguous': True, 'end': 44, 'start': 42}, 'VI': {'color': 'khaki', 'contiguous': True, 'end': 67, 'start': 65}, 'VII': {'color': 'khaki', 'contiguous': False, 'end': 78, 'start': 76}, 'VIII': {'color': 'khaki', 'contiguous': True, 'end': 79, 'start': 79}, 'a.l': {'color': 'cornflowerblue', 'contiguous': False, 'end': 85, 'start': 84}, 'b.l': {'color': 'green', 'contiguous': True, 'end': 37, 'start': 31}, 'c.l': {'color': 'darkorange', 'contiguous': True, 'end': 75, 'start': 68}, 'g.l': {'color': 'green', 'contiguous': True, 'end': 9, 'start': 4}, 'hinge': {'color': 'magenta', 'contiguous': True, 'end': 48, 'start': 46}, 'linker': {'color': 'cyan', 'contiguous': True, 'end': 52, 'start': 49}, 'xDFG': {'color': 'cornflowerblue', 'contiguous': True, 'end': 83, 'start': 80}, 'αC': {'color': 'red', 'contiguous': True, 'end': 30, 'start': 20}, 'αD': {'color': 'red', 'contiguous': False, 'end': 59, 'start': 53}, 'αE': {'color': 'red', 'contiguous': True, 'end': 64, 'start': 60}}
Mapping KLIFS pocket region to start and end indices, boolean denoting if subsequent regions are contiguous, and colors.
- Type:
dict[str, dict[str, int | bool | str]]
- mkt.schema.constants.LIST_FULL_KLIFS_REGION = ['I', 'g.l', 'II', 'II:III', 'III', 'III:αC', 'αC', 'b.l_1', 'b.l_intra', 'b.l_2', 'IV', 'IV:V', 'V', 'GK', 'hinge', 'hinge:linker', 'linker_1', 'linker_intra', 'linker_2', 'αD', 'αD:αE', 'αE', 'αE:VI', 'VI', 'c.l', 'VII', 'VII:VIII', 'VIII', 'xDFG', 'a.l']
List of KLIFS region, including intra and inter regions in order.
- Type:
list[str]
- mkt.schema.constants.LIST_KLIFS_REGION = ['I:1', 'I:2', 'I:3', 'g.l:4', 'g.l:5', 'g.l:6', 'g.l:7', 'g.l:8', 'g.l:9', 'II:10', 'II:11', 'II:12', 'II:13', 'III:14', 'III:15', 'III:16', 'III:17', 'III:18', 'III:19', 'αC:20', 'αC:21', 'αC:22', 'αC:23', 'αC:24', 'αC:25', 'αC:26', 'αC:27', 'αC:28', 'αC:29', 'αC:30', 'b.l:31', 'b.l:32', 'b.l:33', 'b.l:34', 'b.l:35', 'b.l:36', 'b.l:37', 'IV:38', 'IV:39', 'IV:40', 'IV:41', 'V:42', 'V:43', 'V:44', 'GK:45', 'hinge:46', 'hinge:47', 'hinge:48', 'linker:49', 'linker:50', 'linker:51', 'linker:52', 'αD:53', 'αD:54', 'αD:55', 'αD:56', 'αD:57', 'αD:58', 'αD:59', 'αE:60', 'αE:61', 'αE:62', 'αE:63', 'αE:64', 'VI:65', 'VI:66', 'VI:67', 'c.l:68', 'c.l:69', 'c.l:70', 'c.l:71', 'c.l:72', 'c.l:73', 'c.l:74', 'c.l:75', 'VII:76', 'VII:77', 'VII:78', 'VIII:79', 'xDFG:80', 'xDFG:81', 'xDFG:82', 'xDFG:83', 'a.l:84', 'a.l:85']
List of string of all KLIFS pocket regions in format region:idx.
- Type:
list[str]
- mkt.schema.constants.LIST_PFAM_KD = ['Protein kinase domain', 'Protein tyrosine and serine/threonine kinase', 'Serine/threonine-protein kinase mTOR domain']
List of Pfam kinase domain names.
- Type:
list[str]
- mkt.schema.constants.LIST_PSEUDOKINASE_HEURISTIC_FALSE_POSITIVE = ['CAMKK1', 'STYK1']
Kinases the catalytic-residue heuristic flags as pseudokinases but that are (debatably) catalytically active – false positives held out for review. is_pseudokinase() force-returns False for these. Status is genuinely contested in the literature.
- Citations / rationale:
STYK1 (NOK, “Novel Oncogene with Kinase domain”) – fails only DFG-D (xDFG:81 = G); reported as an active oncogenic kinase by some and as catalytically deficient by others, i.e. unresolved: Reiterer et al., Trends Cell Biol 2014; Kung & Jura, Structure 2016.
CAMKK1 – a well-established active Ca2+/calmodulin-dependent kinase kinase (Haribabu et al., EMBO J 1995) whose KLIFS pocket is anomalously degraded here (III:17=M, c.l:70=R, xDFG:81=A), most consistent with a pocket alignment/annotation artifact rather than true loss of catalysis.
NOTE (WNK4): WNK4 also trips the heuristic (no beta3 or beta2 lysine; III:17=C, II:13=R) and is NOT rescued by the beta2-lysine alternative, unlike WNK1/2/3. WNK4 is the most divergent, weakly/debatably active WNK – left flagged pending review rather than added here.
- Type:
list[str]
- mkt.schema.constants.LIST_PSEUDOKINASE_TRIAD_INTACT = ['BUB1B', 'PDIK1L', 'ROR1', 'ROR2', 'RYK', 'SBK3']
Curated pseudokinases that retain an intact VAIK-K / HRD-D / DFG-D triad and are therefore NOT caught by the catalytic-residue heuristic (false negatives); they are catalytically dead for other reasons (degraded regulatory spine, glycine-rich loop, or nucleotide binding). is_pseudokinase() force-returns True for these.
- Citations:
BUB1B (BUBR1) – a bona fide pseudokinase despite an intact catalytic triad: Suijkerbuijk et al., Dev Cell 2012; Murphy et al., Biochem J 2014.
ROR1, ROR2, RYK – Wnt-receptor pseudokinases that retain catalytic residues but lack activity: Boudeau et al., Trends Cell Biol 2006; Reiterer et al., Trends Cell Biol 2014; Mendrola et al., Biochem Soc Trans 2013.
PDIK1L, SBK3 – annotated pseudokinases with intact triads; classified pseudo on nucleotide-binding / catalytic grounds (Murphy et al., Biochem J 2014). Lower confidence than the above; revisit if a more authoritative list is adopted.
- Type:
list[str]
- mkt.schema.constants.STR_KLIFS_BETA2_LYSINE = 'II:13'
KLIFS region:idx of the beta2 lysine used as the catalytic lysine by the WNK (“With No K [lysine]”) family in place of the absent beta3 lysine – Xu et al., J Biol Chem 2000 (WNK1 lacks the subdomain-II lysine); Min et al., Structure 2004 (WNK1 Lys233 sits in beta2). Verified to rescue WNK1/2/3 (K at II:13) without rescuing the genuine pseudokinases KSR1/2 or STRADA, which carry no beta2 lysine.
- Type:
str
- mkt.schema.constants.STR_KLIFS_BETA3_LYSINE = 'III:17'
KLIFS region:idx of the canonical VAIK beta3 catalytic lysine.
- Type:
str
- mkt.schema.constants.STR_KLIFS_CATALYTIC_ASP = 'c.l:70'
KLIFS region:idx of the HRD catalytic aspartate. Note the catalytic loop is reverse-ordered in lipid/PIKK-like kinases (DRH rather than HRD), but the aspartate stays at c.l:70 – so this column is robust to that reversal.
- Type:
str
- mkt.schema.constants.STR_KLIFS_DFG_ASP = 'xDFG:81'
KLIFS region:idx of the DFG-motif aspartate.
- Type:
str