Definition of L-histidine catabolism

GapMind for catabolism of small carbon sources

Definition of L-histidine catabolism

# Histidine utilization in GapMind is based on MetaCyc pathways
# L-histidine degradation I (metacyc:HISDEG-PWY)
# or II (metacyc:PWY-5028).
# These pathways are very similar.
# Other pathways in MetaCyc (III-VI) are not complete or are not reported in prokaryotes, so they are not included.


# ABC transporters:
# E. coli hisPMQJ (hisPMQ can also act with another SBP, argT, but argT does not bind arginine)
# Salmonella has a very similar system
# Pseudomonas aeruginosa PA5125-PA5155 (which is related to hisPMQJ)
#   and also PA5503-PA5505 (MetIQN in TCDB)
# Acidovorax GW101-3H11 has a system with two permease subunits and two SBPs
# NatABCDE (TC 3.A.1.4.2) is described as a possible his transporter
# Rhizobium leguminosarum has aapJQMP
# Sinorhizobium meliloti has hutWVX and also a 4-component system related to aapJQMP
# Pseudomonas fluorescens FW300-N2E3 has a system similar to hutWVX
# Synechocystis has bgtAB  (bgtB has fused SBP and permease components)
# Burkholderia phytofirmans PsJN has BPHYT_RS24000:BPHYT_RS24015

# hisPMQJ from E.coli/Salmonella and PA5125-PA5155 from Pseudomona aeruginosa.
# A similar system in Pseudomonas fluorescens FW300-N2C3 is annotated as a lysine transporter
# but may well transport histidine, so it is ignored.
hisP	L-histidine ABC transporter, ATPase component HisP	curated:CharProtDB::CH_003210	curated:SwissProt::P02915	curated:TCDB::Q9HU32	ignore:reanno::pseudo5_N2C3_1:AO356_09895
hisM	L-histidine ABC transporter, permease component 1 (HisM)	curated:SwissProt::P0A2I7	curated:SwissProt::P0AEU3	curated:TCDB::Q9HU29	ignore:reanno::pseudo5_N2C3_1:AO356_09910
hisQ	L-histidine ABC transporter, permease component 2 (HisQ)	curated:SwissProt::P0A2I9	curated:SwissProt::P52094	curated:TCDB::Q9HU30	ignore:reanno::pseudo5_N2C3_1:AO356_09905
hisJ	L-histidine ABC transporter, substrate-binding component HisJ	curated:CharProtDB::CH_014295	curated:CharProtDB::CH_018185	curated:TCDB::Q9HU31	ignore:reanno::pseudo5_N2C3_1:AO356_09900

# Transporters were identified using
# query: transporter:histidine:L-histidine:his
histidine-transport: hisP hisM hisQ hisJ

# PA5503-PA5505 in P. aeruginosa (MetIQN in TCDB)
PA5503	L-histidine ABC transporter, ATPase component	curated:TCDB::Q9HT70
PA5504	L-histidine ABC transporter, permease component	curated:TCDB::Q9HT69
PA5505	L-histidine ABC transporter, substrate-binding component	curated:TCDB::Q9HT68
histidine-transport: PA5503 PA5504 PA5505

# 5-component 2-SBP system in Acidovorax sp. GW101-3H11
Ac3H11_2562	L-histidine ABC transporter, substrate-binding component 1	curated:reanno::acidovorax_3H11:Ac3H11_2562
Ac3H11_2561	L-histidine ABC transporter, permease component 1	curated:reanno::acidovorax_3H11:Ac3H11_2561
Ac3H11_2560	L-histidine ABC transporter, ATPase component	curated:reanno::acidovorax_3H11:Ac3H11_2560
Ac3H11_2555	L-histidine ABC transporter, substrate-binding component 2	curated:reanno::acidovorax_3H11:Ac3H11_2555 
Ac3H11_2554	ABC transporter for L-Histidine, permease component 2	curated:reanno::acidovorax_3H11:Ac3H11_2554 
histidine-transport: Ac3H11_2562 Ac3H11_2561 Ac3H11_2560 Ac3H11_2555 Ac3H11_2554

# Synechocystis sp. NatABCDE; a similar system in Anabaena is not included as it appears to use
# some other SBP for histidine (but the non-SPB components are marked ignore)
natA	L-histidine ABC transporter, ATPase component 1 (NatA)	curated:TCDB::Q55164	ignore:TCDB::Q7A2H0
natB	L-histidine ABC transporter, substrate-binding component NatB	curated:TCDB::Q55387
natC	L-histidine ABC transporter, permease component 1 (NatC)	curated:TCDB::P74455	ignore:TCDB::Q8YY08
natD	L-histidine ABC transporter, permease component 2 (NatD)	curated:TCDB::P74318	ignore:TCDB::Q8YXD0
natE	L-histidine ABC transporter, ATPase component 2 (NatE)	curated:TCDB::P73650	ignore:TCDB::Q8YT15
histidine-transport: natA natB natC natD natE

# aapJQMP from Rhizobium leguminosarum and Sinorhizobium meliloti
aapJ	L-histidine ABC transporter, substrate-binding component AapJ	curated:reanno::Smeli:SMc02118	curated:TCDB::Q52812
aapQ	L-histidine ABC transporter, permease component 1 (AapQ)	curated:reanno::Smeli:SMc02119	curated:TCDB::Q52813
aapM	L-histidine ABC transporter, permease component 2 (AapM)	curated:reanno::Smeli:SMc02120	curated:TCDB::Q52814
aapP	L-histidine ABC transporter, ATPase component AapP	curated:reanno::Smeli:SMc02121	curated:TCDB::Q52815
histidine-transport: aapJ aapQ aapM aapP

# braCDEFG from Rhizobium leguminosarum is described in glutamate.steps
import glutamate.steps:braC braD braE braF braG
histidine-transport: braC braD braE braF braG

# hutVWX from Sinorhizobium meliloti and Pseudomonas fluorescens FW300-N2C3
hutV	L-histidine ABC transporter, ATPase component HutV	curated:TCDB::Q9KKE1	curated:reanno::pseudo5_N2C3_1:AO356_09610
hutW	L-histidine ABC transporter, permease component HutW	curated:reanno::pseudo5_N2C3_1:AO356_09615	curated:TCDB::Q9KKE2
hutX	L-histidine ABC transporter, substrate-binding component HutX	curated:TCDB::Q9KKE3	curated:reanno::pseudo5_N2C3_1:AO356_09620
histidine-transport: hutV hutW hutX

# bgtAB from Synechocystis
bgtA	L-histidine ABC transporter, ATPase component BgtA	curated:TCDB::P73721
bgtB	L-histidine ABC transporter, fused substrate-binding and permease components (BgtB/BgtAB)	curated:TCDB::P73544	curated:TCDB::Q8YSA2
histidine-transport: bgtA bgtB

# BPHYT_RS24000:BPHYT_RS24015 from Burkholderia phytofirmans PsJN is specifically
# important for histidine utilization. (There's no fitness data for _RS24015.)
BPHYT_RS24000	L-histidine ABC transporter, substrate-binding component	uniprot:B2TBJ6
BPHYT_RS24005	L-histidine ABC transporter, permease component 1	uniprot:B2TBJ7
BPHYT_RS24010	L-histidine ABC transporter, permease component 2	uniprot:B2TBJ8
BPHYT_RS24015	L-histidine ABC transporter, ATPase component	uniprot:B2TBJ9
histidine-transport: BPHYT_RS24000 BPHYT_RS24005 BPHYT_RS24010 BPHYT_RS24015

# Homomeric transporters

permease	L-histidine permease	curated:SwissProt::A2RI97	curated:CharProtDB::CH_091109	curated:CharProtDB::CH_091412	curated:TCDB::P43059	curated:TCDB::Q46065	curated:reanno::pseudo3_N2E3:AO353_12275
histidine-transport: permease

Ga0059261_1577	L-histidine transporter	curated:reanno::Korea:Ga0059261_1577
histidine-transport: Ga0059261_1577

S15A3	L-histidine transporter	curated:SwissProt::O09014	curated:SwissProt::Q8BPX9	curated:SwissProt::Q8IY34	curated:SwissProt::Q8N697	curated:SwissProt::Q924V4
histidine-transport: S15A3

LAT2	L-histidine transporter	curated:SwissProt::Q9WVR6	curated:SwissProt::O34739	curated:TCDB::Q26594	curated:TCDB::Q9NA91
histidine-transport: LAT2

LHT	L-histidine transporter	curated:SwissProt::Q9FKS8	curated:SwissProt::Q9LRB5	curated:SwissProt::Q9SX98	curated:TCDB::Q84WE9
histidine-transport: LHT

SLC38A3	L-histidine:Na+ symporter	curated:CharProtDB::CH_091437	curated:CharProtDB::CH_091510
histidine-transport: SLC38A3

PTR2	L-histidine:H+ symporter	curated:SwissProt::P46032	curated:TCDB::Q43390
histidine-transport: PTR2

# Ignored exporters and porins, and vacuolar transporters, and mitochondrial amino acid carriers
# MctP (TC 2.A.21.4.1) is described as a potential histidine transporter, but the evidence is weak, and homologs
#   with fitness data do not have a relevant phenotype, so do not include.

hutH	histidine ammonia-lyase	EC:4.3.1.3
hutU	urocanase	EC:4.2.1.49
hutI	imidazole-5-propionate hydrolase	EC:3.5.2.7
hutG	N-formiminoglutamate formiminohydrolase	EC:3.5.3.8

# In pathway I, hutH deaminates histidine to urocanate,
# hutU hydrates it to 4-imidazolone-5-propanoate, hutI hydrolyzes it
# to N-formiminoglutamate, and hutG hydrolyzes it to formamide and
# glutamate. Formamide can be cleaved to formate and ammonia, but it
# could also be secreted, so this is not described. Similarly, formate
# may be oxidized to CO2 or secreted.
all: histidine-transport hutH hutU hutI hutG

hutF	N-formiminoglutamate deiminase	EC:3.5.3.13
hutG'	N-formylglutamate amidohydrolase	EC:3.5.1.68

# Pathway II also involves conversion
# to N-formiminoglutamate, but then it is deaminated to
# N-formylglutamate by hutF, and hydrolyzed to formate and glutamate by hutG'.
all: histidine-transport hutH hutU hutI hutH hutF hutG'

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About GapMind

Each pathway is defined by a set of rules based on individual steps or genes. Candidates for each step are identified by using ublast (a fast alternative to protein BLAST) against a database of manually-curated proteins (most of which are experimentally characterized) or by using HMMer with enzyme models (usually from TIGRFam). Ublast hits may be split across two different proteins.

A candidate for a step is "high confidence" if either:

ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.

where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").

Otherwise, a candidate is "medium confidence" if either:

ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
HMMer finds a hit (regardless of coverage or other bits).

Other blast hits with at least 50% coverage are "low confidence."

Steps with no high- or medium-confidence candidates may be considered "gaps." For the typical bacterium that can make all 20 amino acids, there are 1-2 gaps in amino acid biosynthesis pathways. For diverse bacteria and archaea that can utilize a carbon source, there is a complete high-confidence catabolic pathway (including a transporter) just 38% of the time, and there is a complete medium-confidence pathway 63% of the time. Gaps may be due to:

our ignorance of proteins' functions,
omissions in the gene models,
frame-shift errors in the genome sequence, or
the organism lacks the pathway.

GapMind relies on the predicted proteins in the genome and does not search the six-frame translation. In most cases, you can search the six-frame translation by clicking on links to Curated BLAST for each step definition (in the per-step page).

For more information, see:

the paper from 2019 on GapMind for amino acid biosynthesis
the paper from 2022 on GapMind for carbon sources
the source code
instructions for running GapMind on your computer

If you notice any errors or omissions in the step descriptions, or any questionable results, please let us know

by Morgan Price, Arkin group, Lawrence Berkeley National Laboratory

GapMind for catabolism of small carbon sources