P0C063 (GRSB_ANEMI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gramicidin S synthase 2

Alternative name(s):
Gramicidin S synthase II

Including the following 4 domains:

1. ATP-dependent proline adenylase
   Short name=ProA
   Alternative name(s):
   Proline activase
2. ATP-dependent valine adenylase
   Short name=ValA
   Alternative name(s):
   Valine activase
3. ATP-dependent ornithine adenylase
   Short name=OrnA
   Alternative name(s):
   Ornithine activase
4. ATP-dependent leucine adenylase
   Short name=LeuA
   Alternative name(s):
   Leucine activase

Gene names

Name:	grsB
Synonyms:	grs2

Organism

Aneurinibacillus migulanus (Bacillus migulanus)

Taxonomic identifier

47500 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Firmicutes › Bacilli › Bacillales › Paenibacillaceae › Aneurinibacillus group › Aneurinibacillus

Protein attributes

Sequence length	4451 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Inferred from homology

General annotation (Comments)

Function	This protein is a multifunctional enzyme, able to activate and polymerize the amino acids Pro, Val, Orn and Leu. Activation sites for these AA consist of individual domains.
Cofactor	Binds 4 phosphopantetheines covalently.
Pathway	Antibiotic biosynthesis; gramicidin S biosynthesis.
Subunit structure	Large multienzyme complex of GrsA and GrsB.
Domain	Consists of four modules, and harbors a putative thioesterase domain at its C-terminal end. Each module incorporates one amino acid into the peptide product and can be further subdivided into domains responsible for substrate adenylation, thiolation, condensation (not for the initiation module), and epimerization (optional), and N methylation (optional).
Sequence similarities	Belongs to the ATP-dependent AMP-binding enzyme family. Contains 4 acyl carrier domains.

Ontologies

Keywords
Biological process	Antibiotic biosynthesis
Domain	Repeat
Ligand	Phosphopantetheine
Molecular function	Hydrolase Ligase
Technical term	Multifunctional enzyme
Gene Ontology (GO)
Biological_process	antibiotic biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	hydrolase activity, acting on ester bonds Inferred from electronic annotation. Source: InterPro ligase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 4451	4450	Gramicidin S synthase 2		PRO_0000193087
Regions
	Domain	976 – 1043	68	Acyl carrier 1
	Domain	2011 – 2078	68	Acyl carrier 2
	Domain	3057 – 3124	68	Acyl carrier 3
	Domain	4095 – 4162	68	Acyl carrier 4
	Region	467 – 1044	578	Domain 1 (proline-activating) By similarity
	Region	1521 – 2080	560	Domain 2 (valine-activating) By similarity
	Region	2538 – 3135	598	Domain 3 (ornithine-activating) By similarity
	Region	3591 – 4173	583	Domain 4 (leucine-activating)
Amino acid modifications
	Modified residue	1006	1	O-(pantetheine 4'-phosphoryl)serine By similarity
	Modified residue	2041	1	O-(pantetheine 4'-phosphoryl)serine By similarity
	Modified residue	3087	1	O-(pantetheine 4'-phosphoryl)serine By similarity
	Modified residue	4125	1	O-(pantetheine 4'-phosphoryl)serine By similarity
Experimental info
	Sequence conflict	655 – 665	11	TCSFDVCYQEI → NAVLTCVTKKF in CAA43838. Ref.1
	Sequence conflict	942 – 947	6	QLPLTP → HVRLHL in CAA43838. Ref.1
	Sequence conflict	1240 – 1304	65	YWLNV…AAYNV → SLAERICRRDSSIESTDRLP KYQPFKALMVKDLHSVQESS LWMIYTRWQQKQEQHYIWFY LLRIMF in CAA43838. Ref.1
	Sequence conflict	1504 – 1520	17	HMQTI…VEKTP → LCKQFKDYLRNRWRRRA in CAA43838. Ref.1
	Sequence conflict	2842 – 2849	8	CIDSSYYE → ALILAIMN in CAA43838. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P0C063 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 1C6DBA8B27636121	FASTA	4,451	509,254
	10 20 30 40 50 60 MSTFKKEHVQ DMYRLSPMQE GMLFHALLDK DKNAHLVQMS IAIEGIVDVE LLSESLNILI 70 80 90 100 110 120 DRYDVFRTTF LHEKIKQPLQ VVLKERPVQL QFKDISSLDE EKREQAIEQY KYQDGETVFD 130 140 150 160 170 180 LTRDPLMRVA IFQTGKVNYQ MIWSFHHILM DGWCFNIIFN DLFNIYLSLK EKKPLQLEAV 190 200 210 220 230 240 QPYKQFIKWL EKQDKQEALR YWKEHLMNYD QSVTLPKKKA AINNTTYEPA QFRFAFDKVL 250 260 270 280 290 300 TQQLLRIANQ SQVTLNIVFQ TIWGIVLQKY NSTNHVVYGS VVSGRPSEIS GIEKMVGLFI 310 320 330 340 350 360 NTLPLRIQTQ KDQSFIELVK TVHQNVLFSQ QHEYFPLYEI QNHTELKQNL IDHIMVIENY 370 380 390 400 410 420 PLVEELQKNS IMQKVGFTVR DVKMFEPTNY DMTVMVLPRD EISVRLDYNA AVYDIDFIKK 430 440 450 460 470 480 IEGHMKEVAL CVANNPHVLV QDVPLLTKQE KQHLLVELHD SITEYPDKTI HQLFTEQVEK 490 500 510 520 530 540 TPEHVAVVFE DEKVTYRELH ERSNQLARFL REKGVKKESI IGIMMERSVE MIVGILGILK 550 560 570 580 590 600 AGGAFVPIDP EYPKERIGYM LDSVRLVLTQ RHLKDKFAFT KETIVIEDPS ISHELTEEID 610 620 630 640 650 660 YINESEDLFY IIYTSGTTGK PKGVMLEHKN IVNLLHFTFE KTNINFSDKV LQYTTCSFDV 670 680 690 700 710 720 CYQEIFSTLL SGGQLYLIRK ETQRDVEQLF DLVKRENIEV LSFPVAFLKF IFNEREFINR 730 740 750 760 770 780 FPTCVKHIIT AGEQLVVNNE FKRYLHEHNV HLHNHYGPSE THVVTTYTIN PEAEIPELPP 790 800 810 820 830 840 IGKPISNTWI YILDQEQQLQ PQGIVGELYI SGANVGRGYL NNQELTAEKF FADPFRPNER 850 860 870 880 890 900 MYRTGDLARW LPDGNIEFLG RADHQVKIRG HRIELGEIEA QLLNCKGVKE AVVIDKADDK 910 920 930 940 950 960 GGKYLCAYVV MEVEVNDSEL REYLGKALPD YMIPSFFVPL DQLPLTPNGK IDRKSLPNLE 970 980 990 1000 1010 1020 GIVNTNAKYV VPTNELEEKL AKIWEEVLGI SQIGIQDNFF SLGGHSLKAI TLISRMNKEC 1030 1040 1050 1060 1070 1080 NVDIPLRLLF EAPTIQEISN YINGAKKESY VAIQPVPEQE YYPVSSVQKR MFILNEFDRS 1090 1100 1110 1120 1130 1140 GTAYNLPGVM FLDGKLNYRQ LEAAVKKLVE RHEALRTSFH SINGEPVQRV HQNVELQIAY 1150 1160 1170 1180 1190 1200 SESTEDQVER IIAEFMQPFA LEVRPLLRVG LVKLEAERHL FIMDMHHIIS DGVSMQIMIQ 1210 1220 1230 1240 1250 1260 EIADLYKEKE LPTLGIQYKD FTVWHNRLLQ SDVIEKQEAY WLNVFTEEIP VLNLPTDYPR 1270 1280 1290 1300 1310 1320 PTIQSFDGKR FTFSTGKQLM DDLYKVATET GTTLYMVLLA AYNVFLSKYS GQDDIVVGTP 1330 1340 1350 1360 1370 1380 IAGRSHADVE NMLGMFVNTL AIRSRLNNED TFKDFLANVK QTALHAYENP DYPFDTLVEK 1390 1400 1410 1420 1430 1440 LGIQRDLSRN PLFDTMFVLQ NTDRKSFEVE QITITPYVPN SRHSKFDLTL EVSEEQNEIL 1450 1460 1470 1480 1490 1500 LCLEYCTKLF TDKTVERMAG HFLQILHAIV GNPTIIISEI EILSEEEKQH ILFEFNDTKT 1510 1520 1530 1540 1550 1560 TYPHMQTIQG LFEEQVEKTP DHVAVGWKDQ TLTYRELNER ANQVARVLRQ KGVQPDNIVG 1570 1580 1590 1600 1610 1620 LLVERSPEML VGIMGILKAG GAYLPLDPEY PADRISYMIQ DCGVRIMLTQ QHLLSLVHDE 1630 1640 1650 1660 1670 1680 FDCVILDEDS LYKGDSSNLA PVNQAGDLAY IMYTSGSTGK PKGVMVEHRN VIRLVKNTNY 1690 1700 1710 1720 1730 1740 VQVREDDRII QTGAIGFDAL TFEVFGSLLH GAELYPVTKD VLLDAEKLHK FLQANQITIM 1750 1760 1770 1780 1790 1800 WLTSPLFNQL SQGTEEMFAG LRSLIVGGDA LSPKHINNVK RKCPNLTMWN GYGPTENTTF 1810 1820 1830 1840 1850 1860 STCFLIDKEY DDNIPIGKAI SNSTVYIMDR YGQLQPVGVP GELCVGGDGV ARGYMNQPAL 1870 1880 1890 1900 1910 1920 TEEKFVPNPF APGERMYRTG DLARWLPDGT IEYLGRIDQQ VKIRGYRIEP GEIETLLVKH 1930 1940 1950 1960 1970 1980 KKVKESVIMV VEDNNGQKAL CAYYVPEEEV TVSELREYIA KELPVYMVPA YFVQIEQMPL 1990 2000 2010 2020 2030 2040 TQNGKVNRSA LPKPDGEFGT ATEYVAPSSD IEMKLAEIWH NVLGVNKIGV LDNFFELGGH 2050 2060 2070 2080 2090 2100 SLRAMTMISQ VHKEFDVELP LKVLFETPTI SALAQYIADG QKGMYLAIQP VTPTDYYPVS 2110 2120 2130 2140 2150 2160 SAQKRMYILY EFEGAGITYN VPNVMFIEGK LDYQRFEYAI KSLVNRHEAL RTSFYSLNGE 2170 2180 2190 2200 2210 2220 PVQRVHQNVE LQIAYSEAKE DEIEQIVESF VQPFDLEIAP LLRVGLVKLA SDRYLFLMDM 2230 2240 2250 2260 2270 2280 HHIISDGVSM QIITKEIADL YKGKELAELH IQYKDFAVWQ NEWFQSDALE KQKTYWLNTF 2290 2300 2310 2320 2330 2340 AEDIPVLNLS TDYPRPTIQS FEGDIVTFSA GKQLAEELKR LAAETGTTLY MLLLAAYNVL 2350 2360 2370 2380 2390 2400 LHKYSGQEEI VVGTPIAGRS HADVENIVGM FVNTLALKNT PIAVRTFHEF LLEVKQNALE 2410 2420 2430 2440 2450 2460 AFENQDYPFE NLIEKLQVRR DLSRNPLFDT MFSLSNIDEQ VEIGIEGLNF SPYEMQYWIA 2470 2480 2490 2500 2510 2520 KFDISFDILE KQDDIQFYFN YCTNLFKKET IERLATHFMH ILQEIVINPE IKLCEINMLS 2530 2540 2550 2560 2570 2580 EEEQQRVLYD FNGTDATYAT NKIFHELFEE QVEKTPDHIA VIDEREKLSY QELNAKANQL 2590 2600 2610 2620 2630 2640 ARVLRQKGVQ PNSMVGIMVD RSLDMIVGML GVLKAGGAYV PIDIDYPQER ISYMMEDSGA 2650 2660 2670 2680 2690 2700 ALLLTQQKLT QQIAFSGDIL YLDQEEWLHE EASNLEPIAR PHYIAYIIYT SGTTGKPKGV 2710 2720 2730 2740 2750 2760 MIEHQSYVNV AMAWKDAYRL DTFPVRLLQM ASFAFAFDVS AGDFARALLT GGQLIVCPNE 2770 2780 2790 2800 2810 2820 VKMDPASLYA IIKKYDITIF EATPALVIPL MEYIYEQKLD ISQLQILIVG SDSCSMEDFK 2830 2840 2850 2860 2870 2880 TLVSRFGSTI RIVNSYGVTE ACIDSSYYEQ PLSSLHVTGT VPIGKPYANM KMYIMNQYLQ 2890 2900 2910 2920 2930 2940 IQPVGVIGEL CIGGAGVARG YLNRPDLTAE KFVPNPFVPG EKLYRTGDLA RWMPDGNVEF 2950 2960 2970 2980 2990 3000 LGRNDHQVKI RGIRIELGEI EAQLRKHDSI KEATVIARED HMKEKYLCAY MVTEGEVNVA 3010 3020 3030 3040 3050 3060 ELRAYLANDR AAMIPSYFVS LEAMPLTANG KIDKRSLPEP DGSISIGTEY DRPRTMLEGK 3070 3080 3090 3100 3110 3120 LEEIWKDVLG LQRVGIHDDF FTIGGHSLKA MAVISQVHKE CQTEVPLRVL FETPTIQGLA 3130 3140 3150 3160 3170 3180 KYIEETDTEQ YMAIQPVSGQ DYYPVSSAQK RMFIVNQFVG VGISYNMPSI MLIEGKLERT 3190 3200 3210 3220 3230 3240 RLESAFKRLI ERHESLRTSF EIINGKPVQK IHEEVDFNMS YQVASNEQVE KMIDEFIQPF 3250 3260 3270 3280 3290 3300 DLSVAPLLRV ELLKLEEDRH VLIFDMHHII SDGISSNILM KELGELYQGN ALPELRIQYK 3310 3320 3330 3340 3350 3360 DFAVWQNEWF QSEAFKKQEE YWVNVFADER PILDIPTDYP RPMQQSFDGA QLTFGTGKQL 3370 3380 3390 3400 3410 3420 MDGLYRVATE TGTTLYMVLL AAYNVLLSKY SGQEDIIVGT PIVGRSHTDL ENIVGMFVNT 3430 3440 3450 3460 3470 3480 LAMRNKPEGE KTFKAFVSEI KQNALAAFEN QDYPFEELIE KLEIQRDLSR NPLFDTLFSL 3490 3500 3510 3520 3530 3540 QNIGEESFEL AELTCKPFDL VSKLEHAKFD LSLVAVVFEE EIAFGLQYCT KLYKEKTVEQ 3550 3560 3570 3580 3590 3600 LAQHFIQIVK AIVENPDVKL SDIDMLSEEE KKQIMLEFND TKIQYTQNQT IQELFEEQVK 3610 3620 3630 3640 3650 3660 KTPEHIAIVW EGQALIYHEL NIKANQLARV LREKGVTPNH PVAIMTERSL EMIVGIFSIL 3670 3680 3690 3700 3710 3720 KAGGAYVPID PAYPQERIQY LLEDSGAALL LTQSHVLNKL PVDIEWLDLT DEQNYVEDGT 3730 3740 3750 3760 3770 3780 NLPFMNQSTD LAYIIYTSGT TGKPKGVMIE HQSIINCLQW RKEEYEFGPG DTALQVFSFA 3790 3800 3810 3820 3830 3840 FDGFVASLFA PILAGATSVL PKEEEAKDPV ALKKLIASEE ITHYYGVPSL FSAILDVSSS 3850 3860 3870 3880 3890 3900 KDLQNLRCVT LGGEKLPAQI VKKIKEKNKE IEVNNEYGPT ENSVVTTIMR DIQVEQEITI 3910 3920 3930 3940 3950 3960 GRPLSNVDVY IVNCNHQLQP VGVVGELCIG GQGLARGYLN KPELTADKFV VNPFVPGERM 3970 3980 3990 4000 4010 4020 YKTGDLAKWR SDGMIEYVGR VDEQVKVRGY RIELGEIESA ILEYEKIKEA VVMVSEHTAS 4030 4040 4050 4060 4070 4080 EQMLCAYIVG EEDVLTLDLR SYLAKLLPSY MIPNYFIQLD SIPLTPNGKV DRKALPEPQT 4090 4100 4110 4120 4130 4140 IGLMAREYVA PRNEIEAQLV LIWQEVLGIE LIGITDNFFE LGGHSLKATL LVAKIYEYMQ 4150 4160 4170 4180 4190 4200 IEMPLNVVFK HSTIMKIAEY ITHQESENNV HQPILVNVEA DREALSLNGE KQRKNIELPI 4210 4220 4230 4240 4250 4260 LLNEETDRNV FLFAPIGAQG VFYKKLAEQI PTASLYGFDF IEDDDRIQQY IESMIQTQSD 4270 4280 4290 4300 4310 4320 GQYVLIGYSS GGNLAFEVAK EMERQGYSVS DLVLFDVYWK GKVFEQTKEE EEENIKIIME 4330 4340 4350 4360 4370 4380 ELRENPGMFN MTREDFELYF ANEFVKQSFT RKMRKYMSFY TQLVNYGEVE ATIHLIQAEF 4390 4400 4410 4420 4430 4440 EEEKIDENEK ADEEEKTYLE EKWNEKAWNK AAKRFVKYNG YGAHSNMLGG DGLERNSSIL 4450 KQILQGTFVV K

References

[1]	"Four homologous domains in the primary structure of GrsB are related to domains in a superfamily of adenylate-forming enzymes." Turgay K., Krause M., Marahiel M.A. Mol. Microbiol. 6:529-546(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 9999 / DSM 2895 / JCM 8504 / NBRC 15520 / NCTC 7096.
[2]	"Gramicidin S biosynthesis operon containing the structural genes grsA and grsB has an open reading frame encoding a protein homologous to fatty acid thioesterases." Kraetzschmar J., Krause M., Marahiel M.A. J. Bacteriol. 171:5422-5429(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-144. Strain: ATCC 9999 / DSM 2895 / JCM 8504 / NBRC 15520 / NCTC 7096.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X61658 Genomic DNA. Translation: CAA43838.1. M29703 Genomic DNA. Translation: AAA58719.1. X15577 Genomic DNA. Translation: CAA33604.1.
PIR	YGBSG2. S20542.
3D structure databases
ProteinModelPortal	P0C063.
SMR	P0C063. Positions 967-1483, 2000-2519, 3048-3566.
ModBase	Search...
Proteomic databases
PRIDE	P0C063.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Enzyme and pathway databases
BioCyc	MetaCyc:MONOMER-14129.
UniPathway	UPA00102.
Family and domain databases
Gene3D	1.10.1200.10. 4 hits.
InterPro	IPR010071. AA_adenyl_domain. IPR009081. Acyl_carrier_prot-like. IPR020845. AMP-binding_CS. IPR000873. AMP-dep_Synth/Lig. IPR001242. Condensatn. IPR006162. PPantetheine_attach_site. IPR001031. Thioesterase. [Graphical view]
Pfam	PF00501. AMP-binding. 4 hits. PF00668. Condensation. 4 hits. PF00550. PP-binding. 4 hits. PF00975. Thioesterase. 1 hit. [Graphical view]
SUPFAM	SSF47336. ACP_like. 4 hits.
TIGRFAMs	TIGR01733. AA-adenyl-dom. 4 hits.
PROSITE	PS50075. ACP_DOMAIN. 4 hits. PS00455. AMP_BINDING. 4 hits. PS00012. PHOSPHOPANTETHEINE. 4 hits. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

GRSB_ANEMI

Accession

Primary (citable) accession number: P0C063
Secondary accession number(s): P14688, Q44928

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 5, 2005
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 42 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program