Reviewed, UniProtKB/Swiss-Prot Q9W1L5 (PAL2_DROME)

Names and origin

Protein names

Recommended name:
    Peptidyl-alpha-hydroxyglycine alpha-amidating lyase 2
    EC=4.3.2.5
Alternative name(s):
    Peptidylamidoglycolate lyase 2
      Short name=dPAL2

Gene names

Name:	Pal
Synonyms:	PAL2
ORF Names:	CG5472

Organism

Drosophila melanogaster (Fruit fly) [Complete proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	406 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Probable lyase that catalyzes an essential reaction in C-terminal alpha-amidation of peptides. Mediates the dismutation of the unstable peptidyl(2-hydroxyglycine) intermediate to glyoxylate and the corresponding desglycine peptide amide. C-terminal amidation of peptides such as neuropeptides is essential for full biological activity. Ref.5
Catalytic activity	Peptidylamidoglycolate = peptidyl amide + glyoxylate.
Cofactor	Zinc By similarity.
Subcellular location	Secreted Probable.
Tissue specificity	Only found in a subset of neurons distributed throughout all levels of the central nervous system (CNS). Present in at least some neuroendocrine cells. In adult brains, it is only present in a small handful of cells, the majority of which being distributed in distal parts of the medulla, with a higher expression in the posterior surface of the brain (at protein level). Ref.5
Post-translational modification	N-glycosylated Probable.
Sequence similarities	Belongs to the peptidyl-alpha-hydroxyglycine alpha-amidating lyase family. Contains 4 NHL repeats.
Biophysicochemical properties	Kinetic parameters: KM=70 µM for peptidyl-alpha-hydroxyglycine

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal
Ligand	Metal-binding Zinc
Molecular function	Lyase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	cellular metabolic process Ref.5 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	extracellular region Ref.5 Inferred from direct assay. Source: UniProtKB
Molecular function	peptidylamidoglycolate lyase activity Ref.5 Inferred from mutant phenotype. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: Q9W1L5-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform B (identifier: Q9W1L5-2)

Also known as: C;

The sequence of this isoform differs from the canonical sequence as follows:
     204-205: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Chain	20 – 406	387	Peptidyl-alpha-hydroxyglycine alpha-amidating lyase 2		PRO_0000248574
Regions
	Repeat	168 – 209	42	NHL 1
	Repeat	218 – 261	44	NHL 2
	Repeat	264 – 308	45	NHL 3
	Repeat	358 – 402	45	NHL 4
Amino acid modifications
	Disulfide bond	231 ↔ 251		By similarity
	Disulfide bond	293 ↔ 304		By similarity
Natural variations
	Alternative sequence	204 – 205	2	Missing in isoform B.		VSP_020314
Experimental info
	Sequence conflict	13	1	S → T in AAG01895. Ref.1
	Sequence conflict	16	1	Y → C in AAG01895. Ref.1
	Sequence conflict	40	1	N → S in AAG01895. Ref.1
	Sequence conflict	382	1	N → S in AAG01895. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified October 1, 2002. Version 2. Checksum: 47E6037A41071DF9	FASTA	406	44,712
	10 20 30 40 50 60 MSRLLFVALL AISLGYVASS SSNHLPAGLA MDLGPGVNLN ERFFDQVRAL IKRRLQEKGL 70 80 90 100 110 120 AKPEQPELAM PLTDDDAVAL QNQRSYDNVP LPAASVPTPV LVENWPTEQH SFGQVTAVAV 130 140 150 160 170 180 DPQGSPVVFH RAERYWDVNT FNESNIYYLI EYGPIKENTI YVLDAKTGAI KSGWGSNMFY 190 200 210 220 230 240 MPHGLTIDLH GNYWITDVAM HQAFKFKPFS NKPLLTIGKR FRPGSSVKHL CKPTSIAVAT 250 260 270 280 290 300 TGEFFIADGY CNSRILKFNA AGKLLRTIPQ PPEFLSLQVP HAITLLEHLD LLCIADRENM 310 320 330 340 350 360 RVVCPKAGLI SSHGEGEPAA TIQEPDLGRV FGVASFGDIV FAVNGPTSML PVRGFTIDPR 370 380 390 400 SETIIGHWGE FKNPHSMAVS VNGSALYVTE IGTNHQTNRV WKYVLA
	Isoform B (C). Checksum: D35498E1637038DE	FASTA	404	44,437
	10 20 30 40 50 60 MSRLLFVALL AISLGYVASS SSNHLPAGLA MDLGPGVNLN ERFFDQVRAL IKRRLQEKGL 70 80 90 100 110 120 AKPEQPELAM PLTDDDAVAL QNQRSYDNVP LPAASVPTPV LVENWPTEQH SFGQVTAVAV 130 140 150 160 170 180 DPQGSPVVFH RAERYWDVNT FNESNIYYLI EYGPIKENTI YVLDAKTGAI KSGWGSNMFY 190 200 210 220 230 240 MPHGLTIDLH GNYWITDVAM HQAFKPFSNK PLLTIGKRFR PGSSVKHLCK PTSIAVATTG 250 260 270 280 290 300 EFFIADGYCN SRILKFNAAG KLLRTIPQPP EFLSLQVPHA ITLLEHLDLL CIADRENMRV 310 320 330 340 350 360 VCPKAGLISS HGEGEPAATI QEPDLGRVFG VASFGDIVFA VNGPTSMLPV RGFTIDPRSE 370 380 390 400 TIIGHWGEFK NPHSMAVSVN GSALYVTEIG TNHQTNRVWK YVLA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a peptidyl-alpha-hydroxyglycine alpha-amidating lyase from Drosophila melanogaster." Williamson M., Grimmelikhuijzen C.J.P. Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
[2]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[3]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING.
[4]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed: 12537569] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). Strain: Berkeley. Tissue: Head.
[5]	"Drosophila uses two distinct neuropeptide amidating enzymes, dPAL1 and dPAL2." Han M., Park D., Vanderzalm P.J., Mains R.E., Eipper B.A., Taghert P.H. J. Neurochem. 90:129-141(2004) [PubMed: 15198673] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, GLYCOSYLATION, TISSUE SPECIFICITY.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AY007228 mRNA. Translation: AAG01895.1. AE013599 Genomic DNA. Translation: AAF47043.2. AE013599 Genomic DNA. Translation: AAS64762.1. AE013599 Genomic DNA. Translation: AAS64763.1. AY119165 mRNA. Translation: AAM51025.1.
RefSeq	NP_525118.2. NP_995929.1. NP_995930.1.
UniGene	Dm.1661
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9W1L5. 2 interactions.
Genome annotation databases
Ensembl	FBgn0020623. Drosophila melanogaster. [Contig view]
GeneID	37746.
KEGG	dme:Dmel_CG5472.
Organism-specific databases
FlyBase	FBgn0020623. Pal.
Phylogenomic databases
OMA	Q9W1L5. GFTIDPR.
Enzyme and pathway databases
BRENDA	4.3.2.5. 48.
Gene expression databases
ArrayExpress	Q9W1L5.
GermOnline	CG5472. Drosophila melanogaster.
Family and domain databases
InterPro	IPR011042. 6-blade_b-propeller_TolB-like. IPR001258. NHL_repeat. IPR013017. NHL_repeat_subgr. [Graphical view]
Gene3D	G3DSA:2.120.10.30. 6-blade_b-propeller_TolB-like. 1 hit.
Pfam	PF01436. NHL. 4 hits. [Graphical view]
PROSITE	PS51125. NHL. 4 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	805215.

Entry information

Entry name

PAL2_DROME

Accession

Primary (citable) accession number: Q9W1L5
Secondary accession number(s): A4UZT8, Q7KVI0, Q9GPF3

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 5, 2006
Last sequence update:	October 1, 2002
Last modified:	June 16, 2009
This is version 53 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project