P27742 (ACVS_EMENI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase
EC=6.3.2.26

Alternative name(s):
Delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase
Short name=ACV synthetase
Short name=ACVS

Gene names

Name:	acvA
ORF Names:	AN2621

Organism

Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) (Aspergillus nidulans)

Taxonomic identifier

227321 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Pezizomycotina › Eurotiomycetes › Eurotiomycetidae › Eurotiales › Trichocomaceae › Emericella

Protein attributes

Sequence length	3770 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Each of the constituent amino acids of the tripeptide acv are activated as aminoacyl-adenylates with peptide bonds formed through the participation of amino acid thioester intermediates.
Catalytic activity	L-2-aminohexanedioate + L-cysteine + L-valine + 3 ATP + H2O = N-(L-5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine + 3 AMP + 3 diphosphate.
Cofactor	Binds 3 phosphopantetheines covalently Potential.
Pathway	Antibiotic biosynthesis; penicillin G biosynthesis; penicillin G from L-alpha-aminoadipate and L-cysteine and L-valine: step 1/3.
Post-translational modification	The N-terminus is blocked. Glycosylated. Ref.1
Sequence similarities	Belongs to the ATP-dependent AMP-binding enzyme family. Contains 3 acyl carrier domains.

Ontologies

Keywords
Biological process	Antibiotic biosynthesis
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding Phosphopantetheine
Molecular function	Ligase
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological process	antibiotic biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase activity Inferred from electronic annotation. Source: EC acyl carrier activity Inferred from electronic annotation. Source: InterPro cofactor binding Inferred from electronic annotation. Source: InterPro hydrolase activity, acting on ester bonds Inferred from electronic annotation. Source: InterPro phosphopantetheine binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 3770	3770	N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase		PRO_0000193057
Regions
	Domain	850 – 919	70	Acyl carrier 1
	Domain	1929 – 2002	74	Acyl carrier 2
	Domain	3020 – 3087	68	Acyl carrier 3
	Region	321 – 910	590	Domain 1 (adipate-activating)
	Region	1413 – 1993	581	Domain 2 (cysteine-activating)
	Region	2494 – 3078	585	Domain 3 (valine-activating)
Sites
	Active site	3623	1	For thioesterase activity By similarity
Amino acid modifications
	Modified residue	882	1	O-(pantetheine 4'-phosphoryl)serine By similarity
	Modified residue	1965	1	O-(pantetheine 4'-phosphoryl)serine By similarity
	Modified residue	3050	1	O-(pantetheine 4'-phosphoryl)serine By similarity
	Glycosylation	88	1	N-linked (GlcNAc...) Potential
	Glycosylation	309	1	N-linked (GlcNAc...) Potential
	Glycosylation	570	1	N-linked (GlcNAc...) Potential
	Glycosylation	596	1	N-linked (GlcNAc...) Potential
	Glycosylation	638	1	N-linked (GlcNAc...) Potential
	Glycosylation	639	1	N-linked (GlcNAc...) Potential
	Glycosylation	655	1	N-linked (GlcNAc...) Potential
	Glycosylation	787	1	N-linked (GlcNAc...) Potential
	Glycosylation	1256	1	N-linked (GlcNAc...) Potential
	Glycosylation	1402	1	N-linked (GlcNAc...) Potential
	Glycosylation	1545	1	N-linked (GlcNAc...) Potential
	Glycosylation	1735	1	N-linked (GlcNAc...) Potential
	Glycosylation	2410	1	N-linked (GlcNAc...) Potential
	Glycosylation	3130	1	N-linked (GlcNAc...) Potential
	Glycosylation	3298	1	N-linked (GlcNAc...) Potential
	Glycosylation	3332	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	1941	1	W → S in AAA03914. Ref.1
	Sequence conflict	1941	1	W → S in CAA38631. Ref.1
	Sequence conflict	1941	1	W → S AA sequence Ref.1
	Sequence conflict	2177 – 2178	2	NE → KQ in AAA03914. Ref.1
	Sequence conflict	2177 – 2178	2	NE → KQ in CAA38631. Ref.1
	Sequence conflict	2335	1	A → P in AAA03914. Ref.1
	Sequence conflict	2335	1	A → P in CAA38631. Ref.1
	Sequence conflict	2869	1	S → C in AAA03914. Ref.1
	Sequence conflict	2869	1	S → C in CAA38631. Ref.1
	Sequence conflict	3116	1	T → I in AAA03914. Ref.1
	Sequence conflict	3116	1	T → I in CAA38631. Ref.1
	Sequence conflict	3116	1	T → I AA sequence Ref.1
	Sequence conflict	3139	1	E → D in CAA38631. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P27742 [UniParc]. Last modified May 26, 2009. Version 2. Checksum: B31873DD4106D7B0	FASTA	3,770	422,502
	10 20 30 40 50 60 MSPPGLLSED GPGYSGGYAD PTVPKVNWKQ SNGKSAGGNG DVDAGNGNID PSKSGVGVQV 70 80 90 100 110 120 CFAGGLEGWK AGISKITERC DLSSIATNST KYQLAVTGFS DGPDDYNEYS VPFPSEVLVA 130 140 150 160 170 180 MEEMCLARDI SMRSVIQFAV HYVLKGFGGG SHTVAASIDV GDDPNNIATS YTITPSIVCH 190 200 210 220 230 240 ESRQGQTVMQ EIQSMEKLNQ LRKQEMHPGE AGLSLIRMGL FDILVIFADA NKCEGLIAGL 250 260 270 280 290 300 PLAVMVCEGG GRLQVRIHFS GSLFRQKTLV DIAEALNVLF AKAASGGATP VRDLELLSAE 310 320 330 340 350 360 QKQQLEEWNK TDGEYPECKR LNHLIEEATQ LHEDKVAIVY KRRQLTYGEL NAQANCFAHY 370 380 390 400 410 420 LRSIGILPEQ LVALFLEKSE NLIVTILGIW KSGAAYVPID PTYPDERVRF VLEDTQAKVI 430 440 450 460 470 480 IASNHLAERL QSEVISDREL SIIRLEHCLS AIDQQPSTFP RANLRDPSLT SKQLAYVTYT 490 500 510 520 530 540 SGTTGFPKGI LKQHTNVVNS ITDLSARYGV TGDHHEAILL FSAYVFEPFV RQMLMALVNG 550 560 570 580 590 600 HLLAMVDDAE KYDAEKLIPF IREHKITYLN GTASVLQEYD FSSCPSLKRL ILVGENLTES 610 620 630 640 650 660 RYLALRRHFK NCILNEYGFT ESAFVTALNV FEPGSARNNT SLGRPVRNVK CYILNKSLKR 670 680 690 700 710 720 VPIGATGELH IGGLGISKGY LNRPDLTPQR FIPNPFQTDH EKELGLNQLM YKTGDLARWL 730 740 750 760 770 780 PNGEIEYLGR ADFQIKLRGI RIEPGEIEST LAGYPGVRTS LVVSKRLRHG EKETTNEHLV 790 800 810 820 830 840 GYYVGDNTSV SETALLQFLE LKLPRYMIPT RLVRVSQIPV TVNGKADLRA LPSVDLIQPK 850 860 870 880 890 900 VSSCELTDEV EIALGKIWAD VLGAHHLSIS RKDNFFRLGG HSITCIQLIA RIRQQLGVII 910 920 930 940 950 960 SIEDVFSSRT LERMAELLRS KESNGTPDER ARPQLKTVAG EVANANVYLA NSLQQGFVYQ 970 980 990 1000 1010 1020 FLKNMGRSEA YVMQSVLRYD VNINPDLFKK AWKQVQHMLP TLRLRFQWGQ DVLQVIDEDQ 1030 1040 1050 1060 1070 1080 PLNWWFLHLA DDSALPEEQK LLELQRRDLA EPYDLAAGSL FRIYLIEHSS TRFSCLFSCH 1090 1100 1110 1120 1130 1140 HAILDGWSLP LLFRKTHGTY LHLLHGHSLR TLEDPYRQSQ QYLQDHREDH LRYWAGIVNQ 1150 1160 1170 1180 1190 1200 IEERCDMNAL LNERSRYKIQ LADYDKVEDQ QQLTLTVPDA SWLSKLRQTC SAQGITLHSI 1210 1220 1230 1240 1250 1260 LQFVWHAVLH AYGGGTHTVT GTTISGRNLP VSGIERSVGL YINTLPLVIN QLAYKNKTVL 1270 1280 1290 1300 1310 1320 EAIRDVQAIV NGMNSRGNVE LGRLQKNELK HGLFDSLFVL ENYPILDKSE EMRQKSELKY 1330 1340 1350 1360 1370 1380 TIEGNIEKLD YPLAVIAREV DLTGGFTFTI CYARELFDEI VISELLQMVR DTLLQVAKHL 1390 1400 1410 1420 1430 1440 DDPVRSLEYL SSAQMAQLDA WNATDAEFPD TTLHAMFEKE AAQKPDKVAV VYEQRSLTYR 1450 1460 1470 1480 1490 1500 QLNERANRMA HQLKSDISPK PNSIIALVVD KSEHMIATIL AVWKTGGAYV PIDPEYPDDR 1510 1520 1530 1540 1550 1560 IRYILEDTSA IAVISDACYL SRIQELAGES VRLYRSDIST QTDGNWSVSN PAPSSTSTDL 1570 1580 1590 1600 1610 1620 AYIIYTSGTT GKPKGVMVEH HGVVNLQISL SKTFGLRDTD DEVILSFSNY VFDHFVEQMT 1630 1640 1650 1660 1670 1680 DAILNGQTLV MLNDAMRSDK ERLYQYIETN RVTYLSGTPS VISMYEFSRF KDHLRRVDCV 1690 1700 1710 1720 1730 1740 GEAFSQPVFD QIRDTFQGLI INGYGPTEIS ITTHKRLYPF PERRTDKSIG QQIGNSTSYV 1750 1760 1770 1780 1790 1800 LNADMKRVPI GAVGELYLGG EGVARGYHNR PEVTAERFLR NPFQTDSERQ NGRNSRLYRT 1810 1820 1830 1840 1850 1860 GDLVRWIPGS NGEIEYLGRN DFQVKIRGLR IELGEIEAVM SSHPDIKQSV VIAKSGKEGD 1870 1880 1890 1900 1910 1920 QKFLVGYFVA SSPLSPGAIR RFMQSRLPGY MIPSSFIPIS SLPVTPSGKL DTKALPTAEE 1930 1940 1950 1960 1970 1980 KGAMNVLAPR NEIESILCGI WAGLLDISAQ TIGSDSDFFT LGGDSLKSTK LSFKIHEVFG 1990 2000 2010 2020 2030 2040 RTISVSALFR HRTIESLAHL IMNNVGDIQE ITPVDYDNRR KIAVSPAQER LLFIHELEGG 2050 2060 2070 2080 2090 2100 GNAYNIDAAF ELPPYIDQSR VEEALYTILS RHEALRTFLL RDQATGTFYQ KILTTDEAKC 2110 2120 2130 2140 2150 2160 MLIIEKSAVS TIDQIDSIVG RLSQHIFRLD SELPWLAHIV THKTGNLYLT LSFHHTCFDA 2170 2180 2190 2200 2210 2220 WSLKIFEREL RVFCASNEKG GNMPILPMPQ VQYKEYAEHH RRRLGKNQIQ KLSDFWLQRL 2230 2240 2250 2260 2270 2280 DGLEPLQLLP DYPRPAQFNY DGGDLSVILD GVVLETLRGI AKDHGVTLYA VLLAVYCLML 2290 2300 2310 2320 2330 2340 STYTHQVDIA VGVPISHRTH PLFQSIVGFF VNMVVVRVDV KDFAVHDLIR RVMKALVDAQ 2350 2360 2370 2380 2390 2400 LHQDMPFQDV TKLLRVDNDA SRHPLVQTVF NFESDMDKEF ETTPSIQDTA TIAPYQSVQR 2410 2420 2430 2440 2450 2460 IKSVAKFDLN ATATESGSAL KINFNYATSL FRKETIQGFL ETYRHLLLQL SYLGSQGLKE 2470 2480 2490 2500 2510 2520 DTKLLLVRPE EMSGPHLPLA GLSNGAETLE AISLSRAFEF EAFRVPDRAA VVQGDKSLSY 2530 2540 2550 2560 2570 2580 TELNKRANQL ARYIQSVAHL RPDDKVLLIL DKSIDMIICI LAIWKTGSAY VPLDPSYPKE 2590 2600 2610 2620 2630 2640 RVQCISEVVQ AKILITESRY ASAWGSQTST ILAIDSPKVS NMVNNQATHN LPNIAGIKNL 2650 2660 2670 2680 2690 2700 AYIIFTSGTS GKPKGVLVEQ GGVLHLRDAL RKRYFGIECN EYHAVLFLSN YVFDFSIEQL 2710 2720 2730 2740 2750 2760 VLSIMSGHKL IIPEGEFVAD DEFYITANGQ RLSYLSGTPS LLQQIDLARL NHLQVVTAAG 2770 2780 2790 2800 2810 2820 EQLHAAQFNK LRSGFRGPIY NAYGITETTV YNIVSEFSAQ SQFENALREL LPGTRAYLLN 2830 2840 2850 2860 2870 2880 HATQPVPMNA VGELYLAGDC VARGYLNQPV LTGDRFIQNP FQTEQDIASG SYPRLYRTGD 2890 2900 2910 2920 2930 2940 LFRCRLDRQH QPYLEYLGRA DLQVKIRGYR IEPSEVQNVL ASCPGVRECA VVAKYENTDA 2950 2960 2970 2980 2990 3000 YSRIAKFLVG YYTPDTETVS DSSILAHMKS KLPAYMVPKY LCRLEGGLPV TINGKLDVRK 3010 3020 3030 3040 3050 3060 LPDIGNPQHQ ISYNPPRDVL EADLCRLWAS ALGTERCGID DDLFRLGGDS ITALHLAAQI 3070 3080 3090 3100 3110 3120 HHQIGRKVTV RDIFDHPTIR GIHDNVMVKL VPHNVPQFQA EQQTVLGDAP LLPIQTWFLS 3130 3140 3150 3160 3170 3180 KSLQHPSHWN HTFYLRTPEL DVTTLSTAVA ELQLYHDAFR MRLRQIDGRT VQCFADDISP 3190 3200 3210 3220 3230 3240 VQLRVLNVKD VDGSAAIDQQ LQKYQSDFDL EKGPICAAAY LHGYEDRSAR VWFSVHHIII 3250 3260 3270 3280 3290 3300 DIVSWQILAR DLQILYEGGT LGRKSSSVRQ WAEALQSYQG SASERAYWEG LLAQTAANIS 3310 3320 3330 3340 3350 3360 ALPPVTGTRT RLARTWSDDR TVILLNEASN QNASIQDLLL AAVGLALQQV TPGSPSMITL 3370 3380 3390 3400 3410 3420 EGHGREEIVD PTLDLSRTLG WFTSMYPFEI PPLNVETLSQ GIASLRECLR QVPARGIGFG 3430 3440 3450 3460 3470 3480 SLYGYCKHQM PQVTFNYLGQ LTSKQSITDQ WALAVGDGEM QYGLTTSPAD RDQSSFAVDI 3490 3500 3510 3520 3530 3540 TASCVNGALS VEMNSAWSLE KSMRFISRIE EVLNMILSGT LAQQATPVLT PQVFNEEMYT 3550 3560 3570 3580 3590 3600 PYFEFSKTPR RGPILFLLPP GEGGAESYFN NIVKHLPTTN MVVFNNYYLH SKSLNTFEKL 3610 3620 3630 3640 3650 3660 AEMYLGHIRQ IQPDGPYHFI GWSFGGTIAM EISRQLVGLG STIGLLGIID TYFNVPGATR 3670 3680 3690 3700 3710 3720 AIGLGDTEVL DPIHHISQPE PADFQCLPAS TDYIILFKAT RVNDKFQSEN QRRLYEYYDK 3730 3740 3750 3760 3770 TLLNDLDWLL PGASNIHLVR LEEDTHFSWA TNPRQIAHVC STIEKFLARY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase from Aspergillus nidulans. Molecular characterization of the acvA gene encoding the first enzyme of the penicillin biosynthetic pathway." Maccabe A.P., van Liempt H., Pallissa H., Unkles S.E., Riach M.B.R., Pfeifer E., von Doehren H., Kinghorn J.R. J. Biol. Chem. 266:12646-12654(1991) [PubMed: 2061333] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 547-561; 944-979; 1928-1944; 2396-2419 AND 3102-3118, GLYCOSYLATION. Strain: G191.
[2]	"Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae." Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S., Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V., Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S., Braus G.H. , Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H., Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K., Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R., Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C., Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L., Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W. Nature 438:1105-1115(2005) [PubMed: 16372000] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139.
[3]	"The 2008 update of the Aspergillus nidulans genome annotation: a community effort." Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J., Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H., Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M., Estrada C.G. , Geysens S., Goldman G., de Groot P.W., Hansen K., Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G., Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L., Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M., van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P., Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J., Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A., Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X., Robson G., Seiboth B., van Solingen P., Specht T., Sun J., Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H., van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y., Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J., Oliver S.G., Turner G. Fungal Genet. Biol. 46:S2-13(2009) [PubMed: 19146970] [Abstract] Cited for: GENOME REANNOTATION. Strain: FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	S40212 Genomic DNA. Translation: AAA03914.1. X54853 Genomic DNA. Translation: CAA38631.1. AACD01000045 Genomic DNA. Translation: EAA62968.1. BN001306 Genomic DNA. Translation: CBF84349.1.
PIR	A40889.
RefSeq	XP_660225.1. XM_655133.1.
3D structure databases
ProteinModelPortal	P27742.
ModBase	Search...
Protein-protein interaction databases
STRING	P27742.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	CADANIAT00010505; CADANIAP00010505; CADANIAG00010505.
GeneID	2874260.
KEGG	ani:AN2621.2.
Phylogenomic databases
OMA	EPADDAY.
OrthoDB	EOG4PZNHM.
PhylomeDB	P27742.
Family and domain databases
InterPro	IPR010071. AA_adenyl_domain. IPR009081. Acyl_carrier_prot-like. IPR020845. AMP-binding_CS. IPR000873. AMP-dep_Synth/Lig. IPR001242. Condensatn. IPR006163. Phsphopanteth-bd. IPR020806. PKS_PP-bd. IPR006162. PPantetheine_attach_site. IPR001031. Thioesterase. [Graphical view]
Gene3D	G3DSA:1.10.1200.10. ACP_like. 3 hits.
KO	K12743.
Pfam	PF00501. AMP-binding. 3 hits. PF00668. Condensation. 3 hits. PF00550. PP-binding. 3 hits. PF00975. Thioesterase. 1 hit. [Graphical view]
SMART	SM00823. PKS_PP. 3 hits. [Graphical view]
SUPFAM	SSF47336. ACP_like. 3 hits.
TIGRFAMs	TIGR01733. AA-adenyl-dom. 3 hits.
PROSITE	PS50075. ACP_DOMAIN. 3 hits. PS00455. AMP_BINDING. 3 hits. PS00012. PHOSPHOPANTETHEINE. 3 hits. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

ACVS_EMENI

Accession

Primary (citable) accession number: P27742
Secondary accession number(s): C8VHS8, Q4J6A8, Q5BA09

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	May 26, 2009
Last modified:	January 25, 2012
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program