Q8CHT0 (AL4A1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial
Short name=P5C dehydrogenase
EC=1.5.1.12

Alternative name(s):
Aldehyde dehydrogenase family 4 member A1

Gene names

Name:

Aldh4a1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	562 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	Irreversible conversion of delta-1-pyrroline-5-carboxylate (P5C), derived either from proline or ornithine, to glutamate. This is a necessary step in the pathway interconnecting the urea and tricarboxylic acid cycles. The preferred substrate is glutamic gamma-semialdehyde, other substrates include succinic, glutaric and adipic semialdehydes By similarity.
Catalytic activity	(S)-1-pyrroline-5-carboxylate + NAD(P)+ + 2 H2O = L-glutamate + NAD(P)H.
Pathway	Amino-acid degradation; L-proline degradation into L-glutamate; L-glutamate from L-proline: step 2/2.
Subunit structure	Homodimer. Ref.7
Subcellular location	Mitochondrion matrix By similarity.
Post-translational modification	Acetylation of Lys-98, Lys-113 and Lys-401 is observed in liver mitochondria from fasted mice but not from fed mice.
Sequence similarities	Belongs to the aldehyde dehydrogenase family.

Ontologies

Keywords
Biological process	Proline metabolism
Cellular component	Mitochondrion
Domain	Transit peptide
Ligand	NAD
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	proline biosynthetic process Inferred from electronic annotation. Source: InterPro proline catabolic process to glutamate Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from direct assay PubMed 14651853PubMed 18614015. Source: MGI
Molecular_function	1-pyrroline-5-carboxylate dehydrogenase activity Inferred from electronic annotation. Source: EC oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 23

23

Mitochondrion By similarity

Chain

24 – 562

539

Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial

PRO_0000007174

Regions

Nucleotide binding

285 – 289

5

NAD

Sites

Active site

313

1

Proton acceptor Ref.7

Active site

347

1

Nucleophile Ref.7

Binding site

207

1

NAD

Binding site

232

1

NAD

Binding site

446

1

NAD

Binding site

512

1

Substrate

Site

210

1

Transition state stabilizer By similarity

Amino acid modifications

Modified residue

98

1

N6-acetyllysine Ref.5

Modified residue

113

1

N6-acetyllysine Ref.5

Modified residue

401

1

N6-acetyllysine Ref.5

Experimental info

Sequence conflict

18

1

G → S in BAC32045. Ref.1

Sequence conflict

18

1

G → S in AAH56226. Ref.4

Sequence conflict

18

1

G → S in AAH39281. Ref.4

Sequence conflict

18

1

G → S in AAH24133. Ref.4

Sequence conflict

32

1

T → A in BAC32045. Ref.1

Sequence conflict

32

1

T → A in AAH56226. Ref.4

Sequence conflict

32

1

T → A in AAH39281. Ref.4

Sequence conflict

32

1

T → A in AAH24133. Ref.4

Sequence conflict

47

1

D → G in BAC32045. Ref.1

Sequence conflict

60

1

M → T in BAC32045. Ref.1

Sequence conflict

60

1

M → T in AAH56226. Ref.4

Sequence conflict

60

1

M → T in AAH39281. Ref.4

Sequence conflict

60

1

M → T in AAH24133. Ref.4

Sequence conflict

467

1

Q → K in BAC32045. Ref.1

Sequence conflict

467

1

Q → K in AAH56226. Ref.4

Sequence conflict

467

1

Q → K in AAH39281. Ref.4

Sequence conflict

467

1

Q → K in AAH24133. Ref.4

Sequence conflict

467

1

Q → K in AAH26589. Ref.4

Secondary structure

1

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562

Helix Strand Turn

Details...

Helix

44 – 54

11

Turn

55 – 58

4

Beta strand

65 – 67

3

Beta strand

70 – 72

3

Beta strand

77 – 82

6

Beta strand

85 – 94

10

Helix

98 – 117

20

Helix

120 – 135

16

Turn

136 – 138

3

Helix

139 – 150

12

Helix

154 – 160

7

Helix

163 – 179

17

Beta strand

190 – 195

6

Beta strand

200 – 206

7

Helix

212 – 224

13

Beta strand

229 – 232

4

Helix

235 – 237

3

Helix

238 – 250

13

Beta strand

257 – 260

4

Helix

265 – 272

8

Beta strand

278 – 285

8

Helix

287 – 299

13

Turn

300 – 303

4

Beta strand

309 – 313

5

Beta strand

318 – 322

5

Helix

328 – 340

13

Helix

341 – 344

4

Beta strand

350 – 356

7

Helix

357 – 359

3

Helix

360 – 372

13

Turn

379 – 381

3

Helix

393 – 408

16

Beta strand

412 – 416

5

Beta strand

423 – 425

3

Beta strand

431 – 436

6

Helix

441 – 443

3

Beta strand

449 – 457

9

Helix

459 – 461

3

Helix

462 – 471

10

Beta strand

472 – 482

11

Helix

486 – 495

10

Turn

496 – 499

4

Beta strand

501 – 507

7

Turn

514 – 516

3

Helix

536 – 540

5

Beta strand

544 – 549

6

Helix

559 – 561

3

Sequences

	Sequence		Length	Mass (Da)
	Q8CHT0 [UniParc]. Last modified July 27, 2011. Version 3. Checksum: 4D8A0C9C68A99478	FASTA	562	61,841
	10 20 30 40 50 60 MLPLPSLRRS LLSHAWRGAG LRWKHTSSLK VTNEPILAFS QGSPERDALQ KALKDLKGQM 70 80 90 100 110 120 EAIPCVVGDE EVWTSDIQYQ LSPFNHAHKV AKFCYADKAL LNRAIDAALA ARKEWDLKPM 130 140 150 160 170 180 ADRAQVFLKA ADMLSGPRRA EVLAKTMVGQ GKTVIQAEID AAAELIDFFR FNAKFAVELE 190 200 210 220 230 240 GEQPISVPPS TNHTVYRGLE GFVAAISPFN FTAIGGNLAG APALMGNVVL WKPSDTAMLA 250 260 270 280 290 300 SYAVYRILRE AGLPPNIIQF VPADGPTFGD TVTSSEHLCG INFTGSVPTF KHLWRQVAQN 310 320 330 340 350 360 LDRFRTFPRL AGECGGKNFH FVHSSADVDS VVSGTLRSAF EYGGQKCSAC SRLYVPKSLW 370 380 390 400 410 420 PQIKGRLLEE HSRIKVGDPA EDFGTFFSAV IDAKAFARIK KWLEHARSSP SLSILAGGQC 430 440 450 460 470 480 NESVGYYVEP CIIESKDPQE PIMKEEIFGP VLTVYVYPDD KYRETLQLVD STTSYGLTGA 490 500 510 520 530 540 VFAQDKAIVQ EATRMLRNAA GNFYINDKST GSVVGQQPFG GARASGTNDK PGGPHYILRW 550 560 TSPQVIKETH KPLGDWRYSY MQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Retina.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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]. Strain: FVB/N. Tissue: Kidney and Liver.
[5]	"Substrate and functional diversity of lysine acetylation revealed by a proteomics survey." Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y. Mol. Cell 23:607-618(2006) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-98; LYS-113 AND LYS-401, MASS SPECTROMETRY. Tissue: Liver.
[6]	"Proline: Mother Nature's cryoprotectant applied to protein crystallography." Pemberton T.A., Still B.R., Christensen E.M., Singh H., Srivastava D., Tanner J.J. Acta Crystallogr. D 68:1010-1018(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.24 ANGSTROMS) OF 21-562.
[7]	"The three-dimensional structural basis of type II hyperprolinemia." Srivastava D., Singh R.K., Moxley M.A., Henzl M.T., Becker D.F., Tanner J.J. J. Mol. Biol. 420:176-189(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 21-562 IN COMPLEXES WITH GLUTAMATE AND NAD, SUBUNIT, ACTIVE SITE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AK044712 mRNA. Translation: BAC32045.1.
AL831790 Genomic DNA. Translation: CAM21310.1.
CH466615 Genomic DNA. Translation: EDL13315.1.
BC024133 mRNA. Translation: AAH24133.1.
BC026589 mRNA. Translation: AAH26589.1.
BC039281 mRNA. Translation: AAH39281.2.
BC056226 mRNA. Translation: AAH56226.1.

IPI

IPI00405699.

RefSeq

NP_780647.3. NM_175438.4.

UniGene

Mm.273571.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3V9J	X-ray	1.30	A/B	21-562	[»]
3V9K	X-ray	1.50	A/B	21-562	[»]
3V9L	X-ray	1.50	A/B	21-562	[»]
4E3X	X-ray	1.24	A/B	21-562	[»]

ProteinModelPortal

Q8CHT0.

SMR

Q8CHT0. Positions 21-562.

ModBase

Search...

PTM databases

PhosphoSite

Q8CHT0.

Proteomic databases

PaxDb

Q8CHT0.

PRIDE

Q8CHT0.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000039818; ENSMUSP00000043821; ENSMUSG00000028737.

GeneID

212647.

KEGG

mmu:212647.

Organism-specific databases

CTD

8659.

MGI

MGI:2443883. Aldh4a1.

Phylogenomic databases

eggNOG

COG1012.

GeneTree

ENSGT00560000077335.

HOGENOM

HOG000271511.

HOVERGEN

HBG050484.

InParanoid

B1AXW8.

KO

K00294.

OMA

YVNDKST.

OrthoDB

EOG4ZCT3Q.

Enzyme and pathway databases

UniPathway

UPA00261; UER00374.

Gene expression databases

ArrayExpress

Q8CHT0.

Bgee

Q8CHT0.

CleanEx

MM_ALDH4A1.

Genevestigator

Q8CHT0.

GermOnline

ENSMUSG00000028737. Mus musculus.

Family and domain databases

Gene3D

3.40.309.10. 1 hit.
3.40.605.10. 1 hit.

InterPro

IPR005931. 1-pyrroline-5-COlate_DH.
IPR016161. Ald_DH/histidinol_DH.
IPR016163. Ald_DH_C.
IPR016160. Ald_DH_CS.
IPR016162. Ald_DH_N.
IPR015590. Aldehyde_DH_dom.
[Graphical view]

Pfam

PF00171. Aldedh. 1 hit.
[Graphical view]

SUPFAM

SSF53720. Aldehyde_DH/Histidinol_DH. 1 hit.

TIGRFAMs

TIGR01236. D1pyr5carbox1. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

ChiTaRS

ALDH4A1. mouse.

NextBio

373656.

SOURCE

Search...

Entry information

Entry name

AL4A1_MOUSE

Accession

Primary (citable) accession number: Q8CHT0
Secondary accession number(s): B1AXW8 , Q7TND0, Q8BXM3, Q8R0N1, Q8R1S2

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 2005
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 98 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program