Q9NRN7 (ADPPT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase
EC=2.7.8.-

Alternative name(s):
4'-phosphopantetheinyl transferase
Alpha-aminoadipic semialdehyde dehydrogenase-phosphopantetheinyl transferase
Short name=AASD-PPT
LYS5 ortholog

Gene names

Name:	AASDHPPT
ORF Names:	CGI-80, HAH-P, HSPC223, x0005

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	309 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the post-translational modification of target proteins by phosphopantetheine. Can transfer the 4'-phosphopantetheine moiety from coenzyme A to a serine residue of a broad range of acceptors, such as the acyl carrier domain of FASN. Ref.1 Ref.11 Ref.16
Catalytic activity	CoA-[4'-phosphopantetheine] + apo-[acyl-carrier-protein] = adenosine 3',5'-bisphosphate + holo-[acyl-carrier-protein].
Cofactor	Binds 1 magnesium ion. Ref.11 Ref.16
Subunit structure	Monomer. Interacts with FASN. Ref.11
Subcellular location	Cytoplasm Ref.11.
Tissue specificity	Detected in heart, skeletal muscle, placenta, testis, brain, pancreas, liver and kidney. Ref.1 Ref.11
Sequence similarities	Belongs to the P-Pant transferase superfamily. AcpS family.
Biophysicochemical properties	Kinetic parameters: KM=0.44 mM for magnesium Ref.16 KM=0.025 mM for coenzyme A
Sequence caution	The sequence AAD34075.1 differs from that shown. Reason: Frameshift at positions 34 and 63. The sequence AAF86879.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	Magnesium Metal-binding
Molecular function	Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	macromolecule biosynthetic process Inferred from electronic annotation. Source: InterPro pantothenate metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	holo-[acyl-carrier-protein] synthase activity Inferred from direct assay Ref.16. Source: UniProtKB magnesium ion binding Inferred from direct assay Ref.16. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 309

309

L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase

PRO_0000175736

Regions

Region

86 – 91

6

Coenzyme A binding

Region

108 – 111

4

Coenzyme A binding

Region

181 – 185

5

Coenzyme A binding

Sites

Metal binding

129

1

Magnesium

Metal binding

181

1

Magnesium

Binding site

47

1

Coenzyme A

Amino acid modifications

Modified residue

258

1

Phosphoserine Ref.12 Ref.13 Ref.14

Experimental info

Mutagenesis

47

1

R → A: Reduces affinity for magnesium 7-fold, and enzyme activity 2-fold. Ref.16

Mutagenesis

86

1

R → A: Reduces affinity for magnesium and coenzyme A, and reduces enzyme activity 7-fold. Ref.16

Mutagenesis

111

1

H → A: Reduces affinity for magnesium 75-fold, and enzyme activity 150-fold. Ref.16

Mutagenesis

112

1

Q → E: Reduces affinity for magnesium 200-fold and abolishes enzyme activity; when associated with Q-181. Ref.16

Mutagenesis

129

1

D → A: Reduces affinity for magnesium 10-fold, and enzyme activity 30000-fold. Ref.16

Mutagenesis

181

1

E → A: Reduces affinity for magnesium 40-fold, and enzyme activity 32000-fold. Ref.16

Mutagenesis

181

1

E → Q: Reduces affinity for magnesium 20-fold, and enzyme activity 6500-fold. Ref.16

Mutagenesis

185

1

K → A: Reduces enzyme activity 2000-fold, with only minor change in the affinity for magnesium and coenzyme A. Ref.16

Sequence conflict

136 – 141

6

PGRGSI → FQVVVQF in AAG49439. Ref.4

Sequence conflict

307 – 309

3

TKS → YKVMMIP in AAG49439. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

309

Helix Strand Turn

Details...

Beta strand

17 – 21

5

Helix

23 – 25

3

Helix

30 – 38

9

Helix

42 – 49

8

Helix

54 – 74

21

Helix

79 – 81

3

Beta strand

84 – 86

3

Beta strand

92 – 94

3

Beta strand

102 – 104

3

Beta strand

106 – 112

7

Beta strand

115 – 132

18

Beta strand

137 – 139

3

Helix

141 – 147

7

Helix

149 – 151

3

Helix

154 – 160

7

Beta strand

163 – 165

3

Helix

166 – 187

22

Helix

190 – 192

3

Helix

195 – 197

3

Beta strand

198 – 201

4

Beta strand

203 – 206

4

Beta strand

217 – 220

4

Beta strand

228 – 236

9

Beta strand

239 – 246

8

Beta strand

270 – 272

3

Helix

274 – 277

4

Turn

278 – 280

3

Helix

289 – 291

3

Helix

298 – 300

3

Turn

305 – 307

3

Sequences

	Sequence		Length	Mass (Da)
	Q9NRN7 [UniParc]. Last modified November 8, 2005. Version 2. Checksum: 6263E302600FDDED	FASTA	309	35,776
	10 20 30 40 50 60 MVFPAKRFCL VPSMEGVRWA FSCGTWLPSR AEWLLAVRSI QPEEKERIGQ FVFARDAKAA 70 80 90 100 110 120 MAGRLMIRKL VAEKLNIPWN HIRLQRTAKG KPVLAKDSSN PYPNFNFNIS HQGDYAVLAA 130 140 150 160 170 180 EPELQVGIDI MKTSFPGRGS IPEFFHIMKR KFTNKEWETI RSFKDEWTQL DMFYRNWALK 190 200 210 220 230 240 ESFIKAIGVG LGFELQRLEF DLSPLNLDIG QVYKETRLFL DGEEEKEWAF EESKIDEHHF 250 260 270 280 290 300 VAVALRKPDG SRHQDVPSQD DSKPTQRQFT ILNFNDLMSS AVPMTPEDPS FWDCFCFTEE IPIRNGTKS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of the alpha-aminoadipic semialdehyde dehydrogenase-phosphopantetheinyl transferase gene, the human ortholog of the yeast LYS5 gene." Praphanphoj V., Sacksteder K.A., Gould S.J., Thomas G.H., Geraghty M.T. Mol. Genet. Metab. 72:336-342(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
[2]	"Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics." Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C. Genome Res. 10:703-713(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. , Gu J., Chen S.-J., Chen Z. Genome Res. 10:1546-1560(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Umbilical cord blood.
[4]	"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning." Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L. Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Adrenal gland.
[5]	"Novel genes expressed in human dendritic cell." Li N., Peng Y., Li Y., Gu W., Han Z., Fu G., Chen Z. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Dendritic cell.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Tongue.
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Urinary bladder and Uterus.
[9]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 99-309. Tissue: Kidney.
[10]	Lubec G., Afjehi-Sadat L. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 235-246, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[11]	"Cloning, expression, and characterization of a human 4'-phosphopantetheinyl transferase with broad substrate specificity." Joshi A.K., Zhang L., Rangan V.S., Smith S. J. Biol. Chem. 278:33142-33149(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, COFACTOR, MASS SPECTROMETRY, TISSUE SPECIFICITY.
[12]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]	"Mechanism and substrate recognition of human holo ACP synthase." Bunkoczi G., Pasta S., Joshi A., Wu X., Kavanagh K.L., Smith S., Oppermann U. Chem. Biol. 14:1243-1253(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 14-309 IN COMPLEXES WITH COENZYME A; MAGNESIUM IONS AND FASN, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, MUTAGENESIS OF ARG-47; ARG-86; HIS-111; GLN-112; ASP-129; GLU-181 AND LYS-185.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF302110 mRNA. Translation: AAG30872.1.
AF151838 mRNA. Translation: AAD34075.1. Frameshift.
AF151057 mRNA. Translation: AAF36143.1.
AF136978 mRNA. Translation: AAG49439.1.
AF201943 mRNA. Translation: AAF86879.1. Different initiation.
AK312529 mRNA. Translation: BAG35428.1.
CH471065 Genomic DNA. Translation: EAW67078.1.
BC015470 mRNA. Translation: AAH15470.1.
BC016728 mRNA. Translation: AAH16728.1.
AL050073 mRNA. Translation: CAB43257.1.

IPI

IPI00250297.

PIR

T08733.

RefSeq

NP_056238.2. NM_015423.2.

UniGene

Hs.524009.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BYD	X-ray	2.00	A	14-309	[»]
2C43	X-ray	1.93	A	14-309	[»]
2CG5	X-ray	2.70	A	14-309	[»]

ProteinModelPortal

Q9NRN7.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NRN7. 6 interactions.

MINT

MINT-5005661.

STRING

9606.ENSP00000278618.

PTM databases

PhosphoSite

Q9NRN7.

Polymorphism databases

DMDM

81170356.

Proteomic databases

PaxDb

Q9NRN7.

PeptideAtlas

Q9NRN7.

PRIDE

Q9NRN7.

Protocols and materials databases

DNASU

60496.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000278618; ENSP00000278618; ENSG00000149313.

GeneID

60496.

KEGG

hsa:60496.

UCSC

uc001pjc.1. human.

Organism-specific databases

CTD

60496.

GeneCards

GC11P105982.

HGNC

HGNC:14235. AASDHPPT.

HPA

HPA026687.

MIM

607756. gene.

neXtProt

NX_Q9NRN7.

PharmGKB

PA24368.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2091.

HOGENOM

HOG000265195.

HOVERGEN

HBG080822.

InParanoid

Q9NRN7.

KO

K06133.

OMA

VRWAFRC.

OrthoDB

EOG46HGB4.

Enzyme and pathway databases

BioCyc

MetaCyc:HS14278-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

Q9NRN7.

Gene expression databases

ArrayExpress

Q9NRN7.

Bgee

Q9NRN7.

CleanEx

HS_AASDHPPT.

Genevestigator

Q9NRN7.

GermOnline

ENSG00000149313. Homo sapiens.

Family and domain databases

Gene3D

3.90.470.20. 2 hits.

InterPro

IPR008278. 4-PPantetheinyl_Trfase_SF.
[Graphical view]

Pfam

PF01648. ACPS. 1 hit.
[Graphical view]

SUPFAM

SSF56214. 4-PPT_transf. 2 hits.

ProtoNet

Search...

Other

EvolutionaryTrace

Q9NRN7.

GenomeRNAi

60496.

NextBio

65403.

SOURCE

Search...

Entry information

Entry name

ADPPT_HUMAN

Accession

Primary (citable) accession number: Q9NRN7
Secondary accession number(s): B2R6D1 , Q9C068, Q9P0Q3, Q9UG80, Q9Y389

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2005
Last sequence update:	November 8, 2005
Last modified:	May 1, 2013
This is version 91 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.