Get all kinase domain sequences

Setup

from katlas.data import *
from katlas.utils import *
import pandas as pd
from fastcore.all import L
import re

pd.set_option('display.max_rows', 20)
pd.set_option('display.max_columns', 100)

Kinase domain info of current human kinome

df = Data.get_kinase_info()

df.kinasecom_domain.notna().sum()

# df.uniprot.to_csv('kinase_uniprot.csv')

Query the uniprot id in ID mapping in uniprot. Add domain [FT] and region in the columns

uniprot=pd.read_excel('raw/idmapping_kinase_info_2025_05_27.xlsx')

uniprot['Domain [FT]'].head()

0    DOMAIN 46..315; /note="Protein kinase"; /evide...
1    DOMAIN 61..121; /note="SH3"; /evidence="ECO:00...
2    DOMAIN 107..167; /note="SH3"; /evidence="ECO:0...
3    DOMAIN 126..385; /note="Protein kinase"; /evid...
4    DOMAIN 192..485; /note="Protein kinase"; /evid...
Name: Domain [FT], dtype: object

FAM20C does not have Domain[FT] but contains Region to indicate kinase domain

uniprot[uniprot['Domain [FT]'].isna()].Region.tolist()

['REGION 62..81; /note="Disordered"; /evidence="ECO:0000256|SAM:MobiDB-lite"; REGION 94..159; /note="Disordered"; /evidence="ECO:0000256|SAM:MobiDB-lite"; REGION 354..565; /note="Kinase domain"; /evidence="ECO:0000305|PubMed:22582013"']

uniprot = uniprot.dropna(subset='Domain [FT]')

def extract_kinase_domains1(text):
    """
    Extracts domain or region annotations from text using regex.
    Includes entries where the note contains either 'kinase' or 'PI3K/PI4K catalytic'.
    Returns a list of [note, region, evidence] where evidence is set to 'nan' if not present.
    """
    pattern = r'(?:REGION|DOMAIN) [<>]?(\d+)\.\.[<>]?(\d+); /note="([^"]*?(?:kinase|PI3K/PI4K catalytic)[^"]*?)"(?:; /evidence="([^"]*?)")?'
    matches = re.findall(pattern, text, flags=re.IGNORECASE)
    
    return [[note.strip(), evidence if evidence else 'nan']
            for start, end, note, evidence in matches]

out = uniprot['Domain [FT]'].apply(extract_kinase_domains1)

The rest of the kinases have domain info:

out.explode().value_counts()

Domain [FT]
[Protein kinase, ECO:0000255|PROSITE-ProRule:PRU00159]                                  454
[AGC-kinase C-terminal, ECO:0000255|PROSITE-ProRule:PRU00618]                            55
[Protein kinase 2, ECO:0000255|PROSITE-ProRule:PRU00159]                                 14
[Protein kinase 1, ECO:0000255|PROSITE-ProRule:PRU00159]                                 14
[Protein kinase, nan]                                                                     7
[Alpha-type protein kinase, ECO:0000255|PROSITE-ProRule:PRU00501]                         6
[PI3K/PI4K catalytic, ECO:0000255|PROSITE-ProRule:PRU00269]                               6
[Histidine kinase, ECO:0000255|PROSITE-ProRule:PRU00107]                                  4
[Protein kinase, ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000305]                       4
[Guanylate kinase-like, ECO:0000255|PROSITE-ProRule:PRU00100]                             1
[Protein kinase; inactive, ECO:0000255|PROSITE-ProRule:PRU00159]                          1
[Protein kinase, ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000269|PubMed:15194684]       1
[Protein kinase, ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000269|PubMed:9092543]        1
[Protein kinase, ECO:0000250|UniProtKB:Q5VT25, ECO:0000255|PROSITE-ProRule:PRU00159]      1
[Protein kinase, ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000312|EMBL:CAA84485.1]       1
[Protein kinase, ECO:0000305]                                                             1
Name: count, dtype: int64

We’ll search uniprot across species based on the info above to get all kinases and their kinase domains.

Download kinase domain info from Uniprot

Uniprot reviewed –> search advanced

–> domain: “Protein kinase”, or “PI3K PI4K catalytic” or “Histidine kinase”

or –> region: “Kinase domain”

kd1=pd.read_excel('raw/uniprotkb_ft_domain_Protein_kinase_AND_2025_05_25.xlsx')
kd2=pd.read_excel('raw/uniprotkb_ft_domain_PI3K_PI4K_catalytic_2025_05_25.xlsx')
kd3=pd.read_excel('raw/uniprotkb_ft_domain_Histidine_kinase_AN_2025_05_25.xlsx')
kd4=pd.read_excel('raw/uniprotkb_ft_region_Kinase_domain_2025_05_26.xlsx')

kd_all = pd.concat([kd1,kd2,kd3,kd4],ignore_index=True)

kd_human = kd_all[kd_all.Organism.str.contains('Homo')]

Check if how it overlap with current kinome

kinase domain query vs. kinome tree kinases

kinase_info = Data.get_kinase_info()

a,b = get_diff(kd_human,kinase_info,'Uniprot','uniprot')

b.iloc[:,:5] # special for kinome tree

	kinase	ID_coral	uniprot	ID_HGNC	group
44	BRD2	BRD2	P25440	BRD2	Atypical
45	BRD3	BRD3	Q15059	BRD3	Atypical
46	BRD4	BRD4	O60885	BRD4	Atypical
47	BRDT	BRDT	Q58F21	BRDT	Atypical
472	TRIM24	TIF1a	O15164	TRIM24	Atypical
473	TRIM28	TIF1b	Q13263	TRIM28	Atypical
474	TRIM33	TIF1g	Q9UPN9	TRIM33	Atypical

These kinases does not have clear boundary of kinase domain in the domain[FT] column.

a.iloc[:,:5] # special for kinase domain query

	Uniprot	Reviewed	Entry Name	Protein names	Gene Names
895	P21675	reviewed	TAF1_HUMAN	Transcription initiation factor TFIID subunit ...	TAF1 BA2R CCG1 CCGS TAF2A
1982	Q496M5	reviewed	PLK5_HUMAN	Inactive serine/threonine-protein kinase PLK5 ...	PLK5 PLK5P FG060302
2448	Q6A1A2	reviewed	PDPK2_HUMAN	Putative 3-phosphoinositide-dependent protein ...	PDPK2P PDPK2
2894	Q8NEV1	reviewed	CSK23_HUMAN	Casein kinase II subunit alpha 3 (CK II alpha ...	CSNK2A3 CSNK2A1P
3624	Q9UQ88	reviewed	CD11A_HUMAN	Cyclin-dependent kinase 11A (EC 2.7.11.22) (Ce...	CDK11A CDC2L2 CDC2L3 PITSLREB
...	...	...	...	...	...
4761	Q9UBF8	reviewed	PI4KB_HUMAN	Phosphatidylinositol 4-kinase beta (PI4K-beta)...	PI4KB PIK4CB
4790	A4QPH2	reviewed	PI4P2_HUMAN	Putative phosphatidylinositol 4-kinase alpha-l...	PI4KAP2
4812	A4D2B8	reviewed	PM2P1_HUMAN	Putative postmeiotic segregation increased 2-l...	PMS2P1 PMS2L1 PMS2L13 PMS2L6 PMS2L8 PMS3 PMS8 ...
4878	Q15119	reviewed	PDK2_HUMAN	[Pyruvate dehydrogenase (acetyl-transferring)]...	PDK2 PDHK2
5441	Q8N159	reviewed	NAGS_HUMAN	N-acetylglutamate synthase, mitochondrial (EC ...	NAGS

21 rows × 5 columns

Kinase keyword query contains a lot of non-serine/thronine/tyrosine kinases.

kinase domain query vs. kinase keyword query

all_kinase = pd.read_excel('raw/uniprot_human_keyword_kinase.xlsx').rename(columns={'Entry':'Uniprot'})

a,b = get_diff(kd_human,all_kinase,'Uniprot')

a.iloc[:,:5] # special for kd domain query

	Uniprot	Reviewed	Entry Name	Protein names	Gene Names
1982	Q496M5	reviewed	PLK5_HUMAN	Inactive serine/threonine-protein kinase PLK5 ...	PLK5 PLK5P FG060302
5441	Q8N159	reviewed	NAGS_HUMAN	N-acetylglutamate synthase, mitochondrial (EC ...	NAGS

kd domain query also include inactive kinase (PLK5), which is not marked with ‘kinase’ in the keywords.

Another one is NAGS, which contains Amino-acid kinase domain (AAK), and not marked with ‘kinase’ in the keywords.

b.iloc[:,:5] # special for kinase keyword query

	Uniprot	Entry Name	Protein names	Gene Names	uniprot_keyword_kinase
0	A2RU49	HYKK_HUMAN	Hydroxylysine kinase (5-hydroxy-L-lysine kinas...	HYKK AGPHD1	1
3	O00142	KITM_HUMAN	Thymidine kinase 2, mitochondrial (EC 2.7.1.21...	TK2	1
11	O00746	NDKM_HUMAN	Nucleoside diphosphate kinase, mitochondrial (...	NME4 NM23D	1
13	O00764	PDXK_HUMAN	Pyridoxal kinase (EC 2.7.1.35) (Pyridoxine kin...	PDXK C21orf124 C21orf97 PKH PNK PRED79	1
23	O14986	PI51B_HUMAN	Phosphatidylinositol 4-phosphate 5-kinase type...	PIP5K1B STM7	1
...	...	...	...	...	...
638	O60885	BRD4_HUMAN	Bromodomain-containing protein 4 (Protein HUNK1)	BRD4 HUNK1	0
639	Q58F21	BRDT_HUMAN	Bromodomain testis-specific protein (Cancer/te...	BRDT	0
663	O15164	TIF1A_HUMAN	Transcription intermediary factor 1-alpha (TIF...	TRIM24 RNF82 TIF1 TIF1A	0
664	Q13263	TIF1B_HUMAN	Transcription intermediary factor 1-beta (TIF1...	TRIM28 KAP1 RNF96 TIF1B	0
665	Q9UPN9	TRI33_HUMAN	E3 ubiquitin-protein ligase TRIM33 (EC 2.3.2.2...	TRIM33 KIAA1113 RFG7 TIF1G	0

151 rows × 5 columns

Kinase keyword query contains a lot of non-serine/thronine/tyrosine kinases.

Extract kinase domain info

Get residue start, end, and evidence info.

def extract_kinase_domains(text):
    """
    Extracts domain or region annotations from text using regex.
    Includes entries where the note contains either 'kinase' or 'PI3K/PI4K catalytic'.
    Returns a list of [note, region, evidence] where evidence is set to 'nan' if not present.
    """
    pattern = r'(?:REGION|DOMAIN) [<>]?(\d+)\.\.[<>]?(\d+); /note="([^"]*?(?:kinase|PI3K/PI4K catalytic)[^"]*?)"(?:; /evidence="([^"]*?)")?'
    matches = re.findall(pattern, text, flags=re.IGNORECASE)
    
    return [[note.strip(),int(start),int(end), evidence if evidence else 'nan']
            for start, end, note, evidence in matches]

Region column

Specific for kd4, without domain info but with region info

kd4['kd_info'] = kd4['Region'].apply(extract_kinase_domains)

kd4['kd_info']

0     [[Amino-acid kinase domain (AAK), 40, 361, ECO...
1     [[Kinase domain, 349, 560, ECO:0000250|UniProt...
2     [[Kinase domain, 354, 565, ECO:0000305|PubMed:...
3      [[Amino-acid kinase domain (AAK), 19, 376, nan]]
4     [[Amino-acid kinase domain (AAK), 19, 369, ECO...
5        [[HWE histidine kinase domain, 160, 236, nan]]
6        [[HWE histidine kinase domain, 285, 367, nan]]
7        [[HWE histidine kinase domain, 260, 303, nan]]
8        [[HWE histidine kinase domain, 259, 341, nan]]
9        [[HWE histidine kinase domain, 259, 341, nan]]
10       [[HWE histidine kinase domain, 286, 368, nan]]
11       [[HWE histidine kinase domain, 285, 367, nan]]
12       [[HWE histidine kinase domain, 285, 367, nan]]
13       [[HWE histidine kinase domain, 285, 367, nan]]
14       [[HWE histidine kinase domain, 254, 336, nan]]
15       [[HWE histidine kinase domain, 259, 341, nan]]
Name: kd_info, dtype: object

Domain

Most kinases contain domain info for kinase domain.

kd = pd.concat([kd1,kd2,kd3])

kd = kd.drop_duplicates('Uniprot').reset_index(drop=True)

kd['kd_info'] = kd['Domain [FT]'].apply(extract_kinase_domains)

kd['kd_info'].str.len().value_counts() # check non-zero

kd_info
1    5015
2     397
3      22
Name: count, dtype: int64

Some kinase contain 3 kinase domains

kd[kd['kd_info'].str.len()==3]['Domain [FT]'].tolist()[0]

'DOMAIN 49..318; /note="Protein kinase 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"; DOMAIN 319..387; /note="AGC-kinase C-terminal"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"; DOMAIN 426..687; /note="Protein kinase 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"'

After check, it seems it includes C-terminal domain. We will later remove them

kd_final = pd.concat([kd,kd4])

df = kd_final.explode('kd_info', ignore_index=True)

df

	Uniprot	Reviewed	Entry Name	Protein names	Gene Names	Gene Names (primary)	Organism	Length	Domain [FT]	Domain [CC]	Motif	Protein families	Reactome	ComplexPortal	Subcellular location [CC]	Gene Ontology (biological process)	Tissue specificity	Interacts with	Subunit structure	Function [CC]	Activity regulation	Mass	Sequence	kd_info	Region
0	A0A075F7E9	reviewed	LERK1_ORYSI	G-type lectin S-receptor-like serine/threonine...	LECRK1 LECRK OsI_14840	LECRK1	Oryza sativa subsp. indica (Rice)	813	DOMAIN 22..149; /note="Bulb-type lectin"; /evi...	NaN	NaN	Protein kinase superfamily, Ser/Thr protein ki...	NaN	NaN	SUBCELLULAR LOCATION: Membrane {ECO:0000255}; ...	defense response [GO:0006952]; response to oth...	TISSUE SPECIFICITY: Expressed in plumules, rad...	NaN	SUBUNIT: Interacts (via kinase domain) with AD...	FUNCTION: Involved in innate immunity. Require...	NaN	90770	MVALLLFPMLLQLLSPTCAQTQKNITLGSTLAPQGPASSWLSPSGD...	[Protein kinase, 523, 797, ECO:0000255\|PROSITE...	NaN
1	A0A078CGE6	reviewed	M3KE1_BRANA	MAP3K epsilon protein kinase 1 (BnM3KE1) (EC 2...	M3KE1 BnaA03g30290D GSBRNA2T00111755001	M3KE1	Brassica napus (Rape)	1299	DOMAIN 20..274; /note="Protein kinase"; /evide...	NaN	NaN	Protein kinase superfamily, Ser/Thr protein ki...	NaN	NaN	SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton,...	cell division [GO:0051301]; protein autophosph...	TISSUE SPECIFICITY: Expressed in both the spor...	NaN	NaN	FUNCTION: Serine/threonine-protein kinase invo...	NaN	143609	MARQMTSSQFHKSKTLDNKYMLGDEIGKGAYGRVYIGLDLENGDFV...	[Protein kinase, 20, 274, ECO:0000255\|PROSITE-...	NaN
2	A0A0H3MBJ2	reviewed	PKN1_CHLT2	Serine/threonine-protein kinase Pkn1 (EC 2.7.1...	pkn1 CTL0400	pkn1	Chlamydia trachomatis serovar L2 (strain ATCC ...	614	DOMAIN 13..276; /note="Protein kinase"; /evide...	NaN	NaN	Protein kinase superfamily, Ser/Thr protein ki...	NaN	NaN	NaN	NaN	NaN	NaN	SUBUNIT: Interacts with PknD, interacts with a...	FUNCTION: Together with the serine/threonine k...	NaN	69638	MEERAAVEYWGDYKVIAELGHGLWSRDVLAEHRFIKKRYILKILPS...	[Protein kinase, 13, 276, ECO:0000255\|PROSITE-...	NaN
3	A0A0K3AV08	reviewed	MLK1_CAEEL	Mitogen-activated protein kinase kinase kinase...	mlk-1 K11D12.10	mlk-1	Caenorhabditis elegans	1059	DOMAIN 69..130; /note="SH3"; /evidence="ECO:00...	NaN	MOTIF 937..940; /note="NPQY motif"; /evidence=...	Protein kinase superfamily, STE Ser/Thr protei...	NaN	NaN	NaN	axon regeneration [GO:0031103]; defense respon...	TISSUE SPECIFICITY: Expressed in pharynx, inte...	NaN	SUBUNIT: Interacts with max-2; the interaction...	FUNCTION: Serine/threonine-protein kinase whic...	ACTIVITY REGULATION: Activated by phosphorylat...	117635	MEQASVPSYVNIPPIAKTRSTSHLAPTPEHHRSVSYEDTTTASTST...	[Protein kinase, 150, 454, ECO:0000255\|PROSITE...	NaN
4	A0A0P0VIP0	reviewed	LRSK7_ORYSJ	L-type lectin-domain containing receptor kinas...	LECRKS7 DAF1 Os02g0459600 LOC_Os02g26160	LECRKS7	Oryza sativa subsp. japonica (Rice)	695	DOMAIN 389..661; /note="Protein kinase"; /evid...	NaN	NaN	Leguminous lectin family; Protein kinase super...	NaN	NaN	SUBCELLULAR LOCATION: Cell membrane {ECO:00002...	pollen aperture formation [GO:0062075]; pollen...	TISSUE SPECIFICITY: Expressed in roots, leaves...	NaN	SUBUNIT: Interacts with INP1 (PubMed:32284546)...	FUNCTION: Legume-lectin receptor-like kinase r...	NaN	74135	MPPRCRRLPLLFILLLAVRPLSAAAASSIAAAPASSYRRISWASNL...	[Protein kinase, 389, 661, ECO:0000255\|PROSITE...	NaN
...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...
5886	A9MBM8	reviewed	LOVHK_BRUC2	Blue-light-activated histidine kinase (EC 2.7....	BCAN_B0589	NaN	Brucella canis (strain ATCC 23365 / NCTC 10854...	489	DOMAIN 19..93; /note="PAS"; /evidence="ECO:000...	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	FUNCTION: Photosensitive kinase that is involv...	NaN	54874	MAIDLRPFIPFGRGALSQATDPFRAAVEFTLMPMLITNPHLPDNPI...	[HWE histidine kinase domain, 285, 367, nan]	REGION 285..367; /note="HWE histidine kinase d...
5887	A9WYQ7	reviewed	LOVHK_BRUSI	Blue-light-activated histidine kinase (EC 2.7....	BSUIS_B0585	NaN	Brucella suis (strain ATCC 23445 / NCTC 10510)	489	DOMAIN 19..93; /note="PAS"; /evidence="ECO:000...	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	FUNCTION: Photosensitive kinase that is involv...	NaN	54874	MAIDLRPFIPFGRGALSQATDPFRAAVEFTLMPMLITNPHLPDNPI...	[HWE histidine kinase domain, 285, 367, nan]	REGION 285..367; /note="HWE histidine kinase d...
5888	B2SB67	reviewed	LOVHK_BRUA1	Blue-light-activated histidine kinase (EC 2.7....	BAbS19_II06090	NaN	Brucella abortus (strain S19)	489	DOMAIN 19..93; /note="PAS"; /evidence="ECO:000...	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	FUNCTION: Photosensitive kinase that is involv...	NaN	54902	MAIDLRPFIPFGRGALSQATDPFRAAVEFTLMPMLITNPHLPDNPI...	[HWE histidine kinase domain, 285, 367, nan]	REGION 285..367; /note="HWE histidine kinase d...
5889	Q577Y7	reviewed	LOVHK_BRUAB	Blue-light-activated histidine kinase (EC 2.7....	BruAb2_0636	NaN	Brucella abortus biovar 1 (strain 9-941)	489	DOMAIN 19..93; /note="PAS"; /evidence="ECO:000...	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	FUNCTION: Photosensitive kinase that is involv...	NaN	54874	MAIDLRPFIPFGRGALSQATDPFRAAVEFTLMPMLITNPHLPDNPI...	[HWE histidine kinase domain, 254, 336, nan]	REGION 254..336; /note="HWE histidine kinase d...
5890	Q8FW73	reviewed	LOVHK_BRUSU	Blue-light-activated histidine kinase (EC 2.7....	BRA0588 BS1330_II0583	NaN	Brucella suis biovar 1 (strain 1330)	489	DOMAIN 19..93; /note="PAS"; /evidence="ECO:000...	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	FUNCTION: Photosensitive kinase that is involv...	NaN	54874	MAIDLRPFIPFGRGALSQATDPFRAAVEFTLMPMLITNPHLPDNPI...	[HWE histidine kinase domain, 259, 341, nan]	REGION 259..341; /note="HWE histidine kinase d...

5891 rows × 25 columns

df[['domain_note', 'domain_start','domain_end', 'domain_evidence']] = df.kd_info.apply(pd.Series)

df

	Uniprot	Reviewed	Entry Name	Protein names	Gene Names	Gene Names (primary)	Organism	Length	Domain [FT]	Domain [CC]	Motif	Protein families	Reactome	ComplexPortal	Subcellular location [CC]	Gene Ontology (biological process)	Tissue specificity	Interacts with	Subunit structure	Function [CC]	Activity regulation	Mass	Sequence	kd_info	Region	domain_note	domain_start	domain_end	domain_evidence
0	A0A075F7E9	reviewed	LERK1_ORYSI	G-type lectin S-receptor-like serine/threonine...	LECRK1 LECRK OsI_14840	LECRK1	Oryza sativa subsp. indica (Rice)	813	DOMAIN 22..149; /note="Bulb-type lectin"; /evi...	NaN	NaN	Protein kinase superfamily, Ser/Thr protein ki...	NaN	NaN	SUBCELLULAR LOCATION: Membrane {ECO:0000255}; ...	defense response [GO:0006952]; response to oth...	TISSUE SPECIFICITY: Expressed in plumules, rad...	NaN	SUBUNIT: Interacts (via kinase domain) with AD...	FUNCTION: Involved in innate immunity. Require...	NaN	90770	MVALLLFPMLLQLLSPTCAQTQKNITLGSTLAPQGPASSWLSPSGD...	[Protein kinase, 523, 797, ECO:0000255\|PROSITE...	NaN	Protein kinase	523	797	ECO:0000255\|PROSITE-ProRule:PRU00159
1	A0A078CGE6	reviewed	M3KE1_BRANA	MAP3K epsilon protein kinase 1 (BnM3KE1) (EC 2...	M3KE1 BnaA03g30290D GSBRNA2T00111755001	M3KE1	Brassica napus (Rape)	1299	DOMAIN 20..274; /note="Protein kinase"; /evide...	NaN	NaN	Protein kinase superfamily, Ser/Thr protein ki...	NaN	NaN	SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton,...	cell division [GO:0051301]; protein autophosph...	TISSUE SPECIFICITY: Expressed in both the spor...	NaN	NaN	FUNCTION: Serine/threonine-protein kinase invo...	NaN	143609	MARQMTSSQFHKSKTLDNKYMLGDEIGKGAYGRVYIGLDLENGDFV...	[Protein kinase, 20, 274, ECO:0000255\|PROSITE-...	NaN	Protein kinase	20	274	ECO:0000255\|PROSITE-ProRule:PRU00159
2	A0A0H3MBJ2	reviewed	PKN1_CHLT2	Serine/threonine-protein kinase Pkn1 (EC 2.7.1...	pkn1 CTL0400	pkn1	Chlamydia trachomatis serovar L2 (strain ATCC ...	614	DOMAIN 13..276; /note="Protein kinase"; /evide...	NaN	NaN	Protein kinase superfamily, Ser/Thr protein ki...	NaN	NaN	NaN	NaN	NaN	NaN	SUBUNIT: Interacts with PknD, interacts with a...	FUNCTION: Together with the serine/threonine k...	NaN	69638	MEERAAVEYWGDYKVIAELGHGLWSRDVLAEHRFIKKRYILKILPS...	[Protein kinase, 13, 276, ECO:0000255\|PROSITE-...	NaN	Protein kinase	13	276	ECO:0000255\|PROSITE-ProRule:PRU00159
3	A0A0K3AV08	reviewed	MLK1_CAEEL	Mitogen-activated protein kinase kinase kinase...	mlk-1 K11D12.10	mlk-1	Caenorhabditis elegans	1059	DOMAIN 69..130; /note="SH3"; /evidence="ECO:00...	NaN	MOTIF 937..940; /note="NPQY motif"; /evidence=...	Protein kinase superfamily, STE Ser/Thr protei...	NaN	NaN	NaN	axon regeneration [GO:0031103]; defense respon...	TISSUE SPECIFICITY: Expressed in pharynx, inte...	NaN	SUBUNIT: Interacts with max-2; the interaction...	FUNCTION: Serine/threonine-protein kinase whic...	ACTIVITY REGULATION: Activated by phosphorylat...	117635	MEQASVPSYVNIPPIAKTRSTSHLAPTPEHHRSVSYEDTTTASTST...	[Protein kinase, 150, 454, ECO:0000255\|PROSITE...	NaN	Protein kinase	150	454	ECO:0000255\|PROSITE-ProRule:PRU00159
4	A0A0P0VIP0	reviewed	LRSK7_ORYSJ	L-type lectin-domain containing receptor kinas...	LECRKS7 DAF1 Os02g0459600 LOC_Os02g26160	LECRKS7	Oryza sativa subsp. japonica (Rice)	695	DOMAIN 389..661; /note="Protein kinase"; /evid...	NaN	NaN	Leguminous lectin family; Protein kinase super...	NaN	NaN	SUBCELLULAR LOCATION: Cell membrane {ECO:00002...	pollen aperture formation [GO:0062075]; pollen...	TISSUE SPECIFICITY: Expressed in roots, leaves...	NaN	SUBUNIT: Interacts with INP1 (PubMed:32284546)...	FUNCTION: Legume-lectin receptor-like kinase r...	NaN	74135	MPPRCRRLPLLFILLLAVRPLSAAAASSIAAAPASSYRRISWASNL...	[Protein kinase, 389, 661, ECO:0000255\|PROSITE...	NaN	Protein kinase	389	661	ECO:0000255\|PROSITE-ProRule:PRU00159
...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...	...
5886	A9MBM8	reviewed	LOVHK_BRUC2	Blue-light-activated histidine kinase (EC 2.7....	BCAN_B0589	NaN	Brucella canis (strain ATCC 23365 / NCTC 10854...	489	DOMAIN 19..93; /note="PAS"; /evidence="ECO:000...	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	FUNCTION: Photosensitive kinase that is involv...	NaN	54874	MAIDLRPFIPFGRGALSQATDPFRAAVEFTLMPMLITNPHLPDNPI...	[HWE histidine kinase domain, 285, 367, nan]	REGION 285..367; /note="HWE histidine kinase d...	HWE histidine kinase domain	285	367	nan
5887	A9WYQ7	reviewed	LOVHK_BRUSI	Blue-light-activated histidine kinase (EC 2.7....	BSUIS_B0585	NaN	Brucella suis (strain ATCC 23445 / NCTC 10510)	489	DOMAIN 19..93; /note="PAS"; /evidence="ECO:000...	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	FUNCTION: Photosensitive kinase that is involv...	NaN	54874	MAIDLRPFIPFGRGALSQATDPFRAAVEFTLMPMLITNPHLPDNPI...	[HWE histidine kinase domain, 285, 367, nan]	REGION 285..367; /note="HWE histidine kinase d...	HWE histidine kinase domain	285	367	nan
5888	B2SB67	reviewed	LOVHK_BRUA1	Blue-light-activated histidine kinase (EC 2.7....	BAbS19_II06090	NaN	Brucella abortus (strain S19)	489	DOMAIN 19..93; /note="PAS"; /evidence="ECO:000...	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	FUNCTION: Photosensitive kinase that is involv...	NaN	54902	MAIDLRPFIPFGRGALSQATDPFRAAVEFTLMPMLITNPHLPDNPI...	[HWE histidine kinase domain, 285, 367, nan]	REGION 285..367; /note="HWE histidine kinase d...	HWE histidine kinase domain	285	367	nan
5889	Q577Y7	reviewed	LOVHK_BRUAB	Blue-light-activated histidine kinase (EC 2.7....	BruAb2_0636	NaN	Brucella abortus biovar 1 (strain 9-941)	489	DOMAIN 19..93; /note="PAS"; /evidence="ECO:000...	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	FUNCTION: Photosensitive kinase that is involv...	NaN	54874	MAIDLRPFIPFGRGALSQATDPFRAAVEFTLMPMLITNPHLPDNPI...	[HWE histidine kinase domain, 254, 336, nan]	REGION 254..336; /note="HWE histidine kinase d...	HWE histidine kinase domain	254	336	nan
5890	Q8FW73	reviewed	LOVHK_BRUSU	Blue-light-activated histidine kinase (EC 2.7....	BRA0588 BS1330_II0583	NaN	Brucella suis biovar 1 (strain 1330)	489	DOMAIN 19..93; /note="PAS"; /evidence="ECO:000...	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	NaN	FUNCTION: Photosensitive kinase that is involv...	NaN	54874	MAIDLRPFIPFGRGALSQATDPFRAAVEFTLMPMLITNPHLPDNPI...	[HWE histidine kinase domain, 259, 341, nan]	REGION 259..341; /note="HWE histidine kinase d...	HWE histidine kinase domain	259	341	nan

5891 rows × 29 columns

df = df.drop(columns=['kd_info'])

Remove non kinase domains:

df = df[df.domain_note!='AGC-kinase C-terminal'].reset_index(drop=True)

df.domain_note.value_counts()

domain_note
Protein kinase                    4530
Histidine kinase                   625
PI3K/PI4K catalytic                168
Protein kinase 2                    73
Protein kinase 1                    73
Alpha-type protein kinase           22
Protein kinase; inactive            13
HWE histidine kinase domain         11
Guanylate kinase-like                5
Histidine kinase 2                   4
Histidine kinase 1                   4
Amino-acid kinase domain (AAK)       3
Kinase domain                        2
Protein kinase; truncated            1
Histidine kinase; first part         1
Histidine kinase; second part        1
Name: count, dtype: int64

Download uniprot sequence

The big TITIN proteins (A2ASS6 for mouse, and Q8WZ42 for human) is truncated when downloaded online.

from tqdm.contrib.concurrent import thread_map
from kdock.core.protein import get_uniprot_seq

df = df.rename(columns={'Sequence':'full_protein_seq'})

full_seq = thread_map(get_uniprot_seq,df.Uniprot, max_workers=5)

CPU times: user 28.3 s, sys: 4.08 s, total: 32.4 s
Wall time: 13min 6s

df['full_seq']=full_seq

df[df['full_seq']!=df['full_protein_seq']]

	KD_ID	Uniprot	Entry Name	Protein names	Gene Names	Gene Names (primary)	Organism	domain_note	domain_evidence	domain_start	...	ComplexPortal	Subcellular location [CC]	Gene Ontology (biological process)	Tissue specificity	Interacts with	Subunit structure	Function [CC]	Activity regulation	full_protein_seq	full_seq
91	A2ASS6_TITIN_MOUSE_KD1	A2ASS6	TITIN_MOUSE	Titin (EC 2.7.11.1) (Connectin)	Ttn	Ttn	Mus musculus (Mouse)	Protein kinase	ECO:0000255\|PROSITE-ProRule:PRU00159	33040	...	CPX-127;	SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}....	adult heart development [GO:0007512]; cardiac ...	NaN	Q70IV5	SUBUNIT: Interacts with MYOM1, MYOM2, tropomyo...	FUNCTION: Key component in the assembly and fu...	ACTIVITY REGULATION: Full activation of the pr...	MTTQAPMFTQPLQSVVVLEGSTATFEAHVSGSPVPEVSWFRDGQVI...	MTTQAPMFTQPLQSVVVLEGSTATFEAHVSGSPVPEVSWFRDGQVI...
4500	Q8WZ42_TITIN_HUMAN_KD1	Q8WZ42	TITIN_HUMAN	Titin (EC 2.7.11.1) (Connectin) (Rhabdomyosarc...	TTN	TTN	Homo sapiens (Human)	Protein kinase	ECO:0000255\|PROSITE-ProRule:PRU00159	32178	...	CPX-101;	SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305\|P...	cardiac muscle cell development [GO:0055013]; ...	TISSUE SPECIFICITY: Isoforms 3, 7 and 8 are ex...	P12814; P35609; P62158; P20807; O75953; O75923...	SUBUNIT: Interacts with MYOM1, MYOM2, tropomyo...	FUNCTION: Key component in the assembly and fu...	ACTIVITY REGULATION: Full activation of the pr...	MTTQAPTFTQPLQSVVVLEGSTATFEAHISGFPVPEVSWFRDGQVI...	MTTQAPTFTQPLQSVVVLEGSTATFEAHISGFPVPEVSWFRDGQVI...

2 rows × 28 columns

Seems the uniprot online download have limits length in downloading.

Get domain sequence

def get_region(seq,start,end): return seq[start-1:end]

df['domain_seq'] = df.apply(lambda r: get_region(r['full_seq'],r['domain_start'],r['domain_end']),axis=1)

df['domain_seq']

0       AGFHEILGAGASGVVYKGQLEDELKTNIAVKTIHKLQPETEKEFMV...
1       RVSTISTARASYSSIFSGNVAEHAIVNKQKVSVKRHVQRRAITFSR...
2       YMLGDEIGKGAYGRVYIGLDLENGDFVAIKQVSLENIVQEDLNTIM...
3       RLEECRIMSSAKRPLWLNWENPDIMSELLFQNNEIIFKNGDDLRQD...
4       GASHELKTPLASLRIILENMQHNIGDYKDHPKYIAKSINKIDQMSH...
                              ...                        
5531    YILKDLLGTGAFSQVRLAEVKEDPSRVVAIKIIDKKALKGKEDSLE...
5532    YTVEKEIGKGSFAIVYKGVSLRDGRNIAIKAVSRSKLKNKKLLENL...
5533    LETERIIGRGTFGTVKLVHHKPTKIRYALKCVSKRSIINLNQQNNI...
5534    LKFDEELGRGSFKTVFRGLDTETGVAVAWCELQESKLNKTERQRFR...
5535    EASQRSFASGPSTSTKLTVESRTETTRFIFYIYQVRNNEVVAANKH...
Name: domain_seq, Length: 5536, dtype: object

df['domain_seq'].isna().sum()

Arrange columns & save

df = df.sort_values(['Uniprot','domain_start']).reset_index(drop=True)

df['KD_ID']=df['Uniprot']+'_'+df['Entry Name']+'_KD'+(df.Uniprot.duplicated().astype(int)+1).astype(str)

col = ['KD_ID','Uniprot',  'Entry Name', 'Protein names', 'Gene Names','Gene Names (primary)',
     'Organism', 'domain_note','domain_evidence', 'domain_start', 'domain_end','domain_seq' , 'Domain [FT]',
       'Domain [CC]', 'Region', 'Motif', 'Protein families', 'Reactome', 'ComplexPortal',
       'Subcellular location [CC]', 'Gene Ontology (biological process)',
       'Tissue specificity', 'Interacts with', 'Subunit structure',
       'Function [CC]', 'Activity regulation',  'full_seq', 
       ]

df = df[col]

# df[df.KD_ID.str.contains('JAK1')] # check JAK1 to see if KD1 and KD2 is assigned correctly

new_colname=['kd_ID','Uniprot',  'Entry Name', 'Protein names', 'Gene Names','Gene Names (primary)',
     'Organism', 'kd_note','kd_evidence', 'kd_start', 'kd_end','kd_seq' , 'Domain [FT]',
       'Domain [CC]', 'Region', 'Motif', 'Protein families', 'Reactome', 'ComplexPortal',
       'Subcellular location [CC]', 'Gene Ontology (biological process)',
       'Tissue specificity', 'Interacts with', 'Subunit structure',
       'Function [CC]', 'Activity regulation',  'full_seq', 
       ]

df.columns=new_colname

# df.to_excel('out/uniprot_kd.xlsx',index=False)

df.shape

(5536, 27)

Kinases with 1-2 kinase domains

out = df.groupby('Uniprot').agg({'domain_note':list})

out.domain_note.value_counts()

domain_note
[Protein kinase]                            4521
[Histidine kinase]                           621
[PI3K/PI4K catalytic]                        168
[Protein kinase 1, Protein kinase 2]          73
[Alpha-type protein kinase]                   22
[Protein kinase; inactive]                    13
[HWE histidine kinase domain]                 11
[Protein kinase, Guanylate kinase-like]        5
[Histidine kinase 1, Histidine kinase 2]       4
[Protein kinase, Histidine kinase]             4
[Amino-acid kinase domain (AAK)]               3
[Kinase domain]                                2
[Histidine kinase; first part]                 1
[Histidine kinase; second part]                1
[Protein kinase; truncated]                    1
Name: count, dtype: int64

Some kinases contain two kinase domains. Some are both protein kinase domains, while some have the first to be protein kinase and the second to be histidine kinase.

Duplicates among kinase domains

Across species

def get_dup(df):
    dup = df[df.kd_seq.duplicated(keep=False)].sort_values('kd_seq')
    return dup.groupby('kd_seq').agg({'kd_ID':lambda x: ','.join(x)}).reset_index()

dup_unique = get_dup(df)

dup_unique[dup_unique.kd_ID.str.contains("HUMAN")]

	kd_seq	kd_ID
26	EPWQEKVRRIREGSPYGHLPNWRLLSVIVKCGDDLRQELLAFQVLK...	B4UT09_PI4KB_OTOGA_KD1,A9X1A0_PI4KB_PAPAN_KD1,...
30	EYEGCKVGRGTYGHVYKARRKDGKDEKEYALKQIEGTGISMSACRE...	Q8BWD8_CDK19_MOUSE_KD1,Q9BWU1_CDK19_HUMAN_KD1
31	FDFLKVIGKGSFGKVLLAKRKLDGKFYAVKVLQKKIVLNRKEQKHI...	Q96BR1_SGK3_HUMAN_KD1,Q5R7A7_SGK3_PONAB_KD1
33	FDIIGIIGEGTYGQVYKARDKDTGEMVALKKVRLDNEKEGFPITAI...	E1BB52_CDK13_BOVIN_KD1,Q14004_CDK13_HUMAN_KD1,...
34	FDLIRVIGRGSYAKVLLVRLKKNDQIYAMKVVKKELVHDDEDIDWV...	P09217_KPCZ_RAT_KD1,Q05513_KPCZ_HUMAN_KD1,Q029...
...	...	...
271	YTLKDEIGKGSYGVVKLAYNENDNTYYAMKVLSKKKLIRQAGFPRR...	Q96RR4_KKCC2_HUMAN_KD1,O88831_KKCC2_RAT_KD1
274	YTNLSYIGEGAYGMVCSAYDNVNKVRVAIKKISPFEHQTYCQRTLR...	P46196_MK01_BOVIN_KD1,P28482_MK01_HUMAN_KD1
276	YTRFEKIGQGASGTVYTALDIATGQEVAIKQMNLQQQPKKELIINE...	Q7YQL4_PAK3_PANTR_KD1,Q7YQL3_PAK3_PONPY_KD1,O7...
277	YTRFEKIGQGASGTVYTAMDVATGQEVAIKQMNLQQQPKKELIINE...	Q13153_PAK1_HUMAN_KD1,P35465_PAK1_RAT_KD1,Q08E...
278	YTRYEKIGQGASGTVFTATDVALGQEVAIKQINLQKQPKKELIINE...	Q13177_PAK2_HUMAN_KD1,Q8CIN4_PAK2_MOUSE_KD1

90 rows × 2 columns

Duplicates within human

human=df[df.Organism=='Homo sapiens (Human)']

dup_human = get_dup(human)

dup_human

	kd_seq	kd_ID

Check duplicates within other species

species = df.Organism.value_counts().head().index

for s in species:
    df_species=df[df.Organism==s]
    print(s)
    print(get_dup(df_species))

Arabidopsis thaliana (Mouse-ear cress)
Empty DataFrame
Columns: [kd_seq, kd_ID]
Index: []
Mus musculus (Mouse)
                                              kd_seq  \
0  YVMLETIGHGGCATVKLAQHRLTGTHVAVKTIRKREYWCNRVISEV...   

                                           kd_ID  
0  C0HKC8_SMK3A_MOUSE_KD1,C0HKC9_SMK3B_MOUSE_KD1  
Homo sapiens (Human)
Empty DataFrame
Columns: [kd_seq, kd_ID]
Index: []
Dictyostelium discoideum (Social amoeba)
Empty DataFrame
Columns: [kd_seq, kd_ID]
Index: []
Rattus norvegicus (Rat)
Empty DataFrame
Columns: [kd_seq, kd_ID]
Index: []

only mouse SMK3A/3B duplicates in the top 5 species