Reviewed, UniProtKB/Swiss-Prot P49419 (AL7A1_HUMAN)

Names and origin

Protein names

Recommended name:
    Alpha-aminoadipic semialdehyde dehydrogenase
      Short name=Alpha-AASA dehydrogenase
    EC=1.2.1.31
Alternative name(s):
    Delta1-piperideine-6-carboxylate dehydrogenease
      Short name=P6c dehydrogenase
    Aldehyde dehydrogenase family 7 member A1
    Antiquitin-1

Gene names

Name:	ALDH7A1
Synonyms:	ATQ1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	511 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)

Catalytic activity	L-2-aminoadipate 6-semialdehyde + NAD(P)+ + H2O = L-2-aminoadipate + NAD(P)H.
Subunit structure	Homotetramer By similarity.
Tissue specificity	Abundant in hepatoma cells and fetal cochlea, ovary, eye, heart, adrenal gland, liver and kidney. Low levels present in adult peripheral blood leukocytes and fetal brain, thymus, spleen, skeletal muscle, lung and tongue. Ref.1 Ref.4
Involvement in disease	Defects in ALDH7A1 are the cause of pyridoxine-dependent epilepsy (PDE) [MIM:266100]. PDE is characterized by a combination of various seizure types. It usually occurs in the first hours of life and is unresponsive to standard anticonvulsants, responding only to immediate administration of pyridoxine hydrochloride. Ref.6
Sequence similarities	Belongs to the aldehyde dehydrogenase family.
Sequence caution	The sequence AAC51935.1 differs from that shown. Reason: Frameshift at positions 205 and 230.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Disease	Disease mutation Epilepsy
Ligand	NAD
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cellular aldehyde metabolic process Inferred from sequence or structural similarity. Source: UniProtKB oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW sensory perception of sound Ref.4 Traceable author statement. Source: ProtInc
Molecular function	L-aminoadipate-semialdehyde dehydrogenase activity Inferred from electronic annotation. Source: EC aldehyde dehydrogenase (NAD) activity Inferred from sequence or structural similarity. Source: UniProtKB
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 – 511

510

Alpha-aminoadipic semialdehyde dehydrogenase

PRO_0000056490

Regions

Nucleotide binding

246 – 251

6

NAD By similarity

Sites

Active site

268

1

Proton acceptor By similarity

Active site

302

1

Nucleophile By similarity

Site

167

1

Transition state stabilizer By similarity

Natural variations

Natural variant

171

1

A → V in PDE. Ref.6

VAR_031718

Natural variant

384

1

T → A: dbSNP rs2306618.

VAR_028202

Natural variant

399

1

E → Q in PDE. Ref.6

VAR_031719

Natural variant

411

1

K → Q: dbSNP rs12514417. Ref.3

VAR_028203

Secondary structure

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511

Helix Strand Turn

Details...

Helix

5 – 7

3

Helix

9 – 17

9

Beta strand

21 – 24

4

Beta strand

26 – 32

7

Beta strand

37 – 41

5

Turn

43 – 45

3

Beta strand

48 – 53

6

Helix

57 – 74

18

Helix

79 – 95

17

Helix

97 – 107

11

Helix

112 – 132

21

Turn

133 – 135

3

Beta strand

139 – 141

3

Beta strand

148 – 156

9

Beta strand

158 – 163

6

Beta strand

166 – 168

3

Helix

171 – 182

12

Beta strand

186 – 190

5

Helix

193 – 195

3

Helix

196 – 212

17

Helix

217 – 219

3

Beta strand

220 – 223

4

Helix

227 – 235

9

Beta strand

240 – 246

7

Helix

248 – 260

13

Beta strand

264 – 268

5

Beta strand

273 – 277

5

Helix

283 – 295

13

Helix

296 – 299

4

Beta strand

305 – 311

7

Turn

312 – 314

3

Helix

315 – 327

13

Helix

347 – 362

16

Beta strand

366 – 369

4

Beta strand

375 – 379

5

Beta strand

384 – 388

5

Helix

394 – 397

4

Beta strand

401 – 410

10

Helix

413 – 421

9

Beta strand

427 – 432

6

Helix

436 – 443

8

Beta strand

450 – 457

8

Beta strand

466 – 468

3

Helix

472 – 474

3

Beta strand

479 – 481

3

Helix

484 – 488

5

Beta strand

489 – 497

9

Sequences

	Sequence		Length	Mass (Da)
	P49419-1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 08F6F7672C948E2C	FASTA	511	55,366
	10 20 30 40 50 60 MSTLLINQPQ YAWLKELGLR EENEGVYNGS WGGRGEVITT YCPANNEPIA RVRQASVADY 70 80 90 100 110 120 EETVKKAREA WKIWADIPAP KRGEIVRQIG DALREKIQVL GSLVSLEMGK ILVEGVGEVQ 130 140 150 160 170 180 EYVDICDYAV GLSRMIGGPI LPSERSGHAL IEQWNPVGLV GIITAFNFPV AVYGWNNAIA 190 200 210 220 230 240 MICGNVCLWK GAPTTSLISV AVTKIIAKVL EDNKLPGAIC SLTCGGADIG TAMAKDERVN 250 260 270 280 290 300 LLSFTGSTQV GKQVGLMVQE RFGRSLLELG GNNAIIAFED ADLSLVVPSA LFAAVGTAGQ 310 320 330 340 350 360 RCTTARRLFI HESIHDEVVN RLKKAYAQIR VGNPWDPNVL YGPLHTKQAV SMFLGAVEEA 370 380 390 400 410 420 KKEGGTVVYG GKVMDRPGNY VEPTIVTGLG HDASIAHTET FAPILYVFKF KNEEEVFAWN 430 440 450 460 470 480 NEVKQGLSSS IFTKDLGRIF RWLGPKGSDC GIVNVNIPTS GAEIGGAFGG EKHTGGGRES 490 500 510 GSDAWKQYMR RSTCTINYSK DLPLAQGIKF Q

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Homology between a human protein and a protein of the green garden pea." Lee P., Kuhl W., Gelbart T., Kamimura T., West C., Beutler E. Genomics 21:371-378(1994) [PubMed: 8088832] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Kidney, Liver and Placenta.
[2]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Caudate nucleus.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-411. Tissue: Placenta and Uterus.
[4]	"An ancient conserved gene expressed in the human inner ear: identification, expression analysis, and chromosomal mapping of human and mouse antiquitin (ATQ1)." Skvorak A.B., Robertson N.G., Yin Y., Weremowicz S., Her H., Bieber F.R., Beisel K.W., Lynch E.D., Beier D.R., Morton C.C. Genomics 46:191-199(1997) [PubMed: 9417906] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 205-230, TISSUE SPECIFICITY.
[5]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[6]	"Mutations in antiquitin in individuals with pyridoxine-dependent seizures." Mills P.B., Struys E., Jakobs C., Plecko B., Baxter P., Baumgartner M., Willemsen M.A.A.P., Omran H., Tacke U., Uhlenberg B., Weschke B., Clayton P.T. Nat. Med. 12:307-309(2006) [PubMed: 16491085] [Abstract] Cited for: VARIANTS PDE VAL-171 AND GLN-399, FUNCTION.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

S74728 mRNA. Translation: AAB31966.1.
AK312459 mRNA. Translation: BAG35366.1.
BC002515 mRNA. Translation: AAH02515.3.
BC071712 mRNA. Translation: AAH71712.1.
BC073174 mRNA. Translation: AAH73174.1.
AF002696 Genomic DNA. Translation: AAC51935.1. Sequence problems.

IPI

IPI00936002.

PIR

A54676.

RefSeq

NP_001173.2.

UniGene

Hs.483239

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2J6L	X-ray	1.30	A/B/C/D/E/F/G/H	2-498	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P49419. 1 interaction.

STRING

P49419.

Proteomic databases

PRIDE

P49419.

Genome annotation databases

Ensembl

ENST00000297542; ENSP00000297542; ENSG00000164904; Homo sapiens. [Genome view]
ENST00000409134; ENSP00000387123; ENSG00000164904; Homo sapiens. [Genome view]

GeneID

501.

KEGG

hsa:501.

NMPDR

fig|9606.3.peg.25659.

Organism-specific databases

CTD

501.

GeneCards

GC05M125908.

HGNC

HGNC:877. ALDH7A1.

HPA

HPA023296.

MIM

107323. gene.
266100. phenotype.

Orphanet

3006. Epilepsy, pyridoxin-dependent.

PharmGKB

PA24704.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG18966.

HOGENOM

HBG752218.

HOVERGEN

P49419.

InParanoid

P49419.

PhylomeDB

P49419.

Enzyme and pathway databases

BRENDA

1.2.1.31. 247.

Gene expression databases

ArrayExpress

P49419.

Bgee

P49419.

CleanEx

HS_ALDH7A1.

Genevestigator

P49419.

GermOnline

ENSG00000164904. Homo sapiens.

Family and domain databases

InterPro

IPR016161. Ald_DH/histidinol_DH.
IPR016160. Ald_DH_CS.
IPR016162. Ald_DH_N.
IPR015590. Aldehyde_DH.
[Graphical view]

Gene3D

G3DSA:3.40.605.10. Aldehyde_dehydrogenase_N. 1 hit.

PANTHER

PTHR11699. Aldehyde_dehyd. 1 hit.

Pfam

PF00171. Aldedh. 1 hit.
[Graphical view]

PROSITE

PS00070. ALDEHYDE_DEHYDR_CYS. False negative.
PS00687. ALDEHYDE_DEHYDR_GLU. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00157. NADH.
DB00165. Pyridoxine.

SOURCE

Search...

Entry information

Entry name

AL7A1_HUMAN

Accession

Primary (citable) accession number: P49419
Secondary accession number(s): B2R669 , O14619, Q6IPU8, Q9BUL4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	January 23, 2007
Last modified:	January 19, 2010
This is version 104 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.