P32322 (P5CR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pyrroline-5-carboxylate reductase 1, mitochondrial
Short name=P5C reductase 1
Short name=P5CR 1
EC=1.5.1.2

Gene names

Name:

PYCR1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	319 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	Housekeeping enzyme that catalyzes the last step in proline biosynthesis. Can utilize both NAD and NADP, but has higher affinity for NAD. Involved in the cellular response to oxidative stress. Ref.7 Ref.9
Catalytic activity	L-proline + NAD(P)+ = 1-pyrroline-5-carboxylate + NAD(P)H. Ref.9
Enzyme regulation	Subject to competitive inhibition by the reaction product proline. Subject to competitive inhibition by stearoyl coenzyme A. Ref.9
Pathway	Amino-acid biosynthesis; L-proline biosynthesis; L-proline from L-glutamate 5-semialdehyde: step 1/1.
Subunit structure	Homodecamer; composed of 5 homodimers. Ref.9
Subcellular location	Mitochondrion Ref.7.
Involvement in disease	Defects in PYCR1 are the cause of cutis laxa autosomal recessive type 2B (ARCL2B) [MIM:612940]. A multisystem disorder characterized by the appearance of premature aging, wrinkled and lax skin with reduced elasticity, joint laxity, craniofacial dysmorphic features, intrauterine growth retardation with some degree of postnatal growth deficiency, and developmental delay. Ref.7 Ref.11
Sequence similarities	Belongs to the pyrroline-5-carboxylate reductase family.
Biophysicochemical properties	Kinetic parameters: KM=0.151 mM for NAD+ Ref.9 KM=3.06 mM for NADP+

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Proline biosynthesis Stress response
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cellular response to oxidative stress Inferred from mutant phenotype Ref.7. Source: UniProtKB proline biosynthetic process Inferred from direct assay Ref.9. Source: UniProtKB
Cellular component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular function	identical protein binding Inferred from physical interaction. Source: IntAct nucleotide binding Inferred from electronic annotation. Source: InterPro oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor Inferred from electronic annotation. Source: InterPro pyrroline-5-carboxylate reductase activity Inferred from direct assay Ref.9. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		5	EBI-848624,EBI-848624

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.5 Ref.6

Chain

2 – 319

318

Pyrroline-5-carboxylate reductase 1, mitochondrial

PRO_0000187314

Regions

Nucleotide binding

6 – 11

6

NADP

Nucleotide binding

69 – 72

4

NADP

Nucleotide binding

95 – 97

3

NADP

Sites

Binding site

34

1

NADP; via carbonyl oxygen

Binding site

56

1

NADP

Amino acid modifications

Modified residue

2

1

N-acetylserine Ref.5 Ref.6

Natural variations

Natural variant

119

1

R → G in ARCL2B. Ref.7

VAR_059068

Natural variant

119

1

R → H in ARCL2B. Ref.7

VAR_059069

Natural variant

179

1

A → T in ARCL2B. Ref.7

VAR_059070

Natural variant

189

1

A → V. Ref.7

VAR_059071

Natural variant

206

1

G → R in ARCL2B. Ref.7

VAR_059072

Natural variant

206

1

G → W in ARCL2B. Ref.7

VAR_059073

Natural variant

251

1

R → H in ARCL2B. Ref.7

VAR_059074

Natural variant

257

1

A → T in ARCL2B. Ref.7

VAR_059075

Natural variant

266

1

R → Q in ARCL2B; may cause skipping of exon 6. Ref.11

VAR_059076

Experimental info

Mutagenesis

221

1

E → A: Reduced enzyme activity. Ref.9

Sequence conflict

155

1

S → T in AAA36407. Ref.1

Sequence conflict

317

1

G → S in CAG46568. Ref.2

Secondary structure

1

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319

Helix Strand Turn

Details...

Beta strand

3 – 7

5

Helix

10 – 21

12

Helix

27 – 29

3

Beta strand

30 – 33

4

Helix

40 – 48

9

Beta strand

51 – 54

4

Helix

56 – 62

7

Beta strand

64 – 68

5

Helix

72 – 74

3

Helix

75 – 82

8

Helix

83 – 85

3

Beta strand

91 – 94

4

Helix

101 – 109

9

Beta strand

116 – 121

6

Helix

124 – 128

5

Beta strand

131 – 137

7

Helix

143 – 154

12

Beta strand

157 – 161

5

Helix

164 – 166

3

Helix

167 – 173

7

Turn

174 – 176

3

Helix

177 – 194

18

Helix

199 – 219

21

Helix

224 – 231

8

Helix

237 – 247

11

Helix

250 – 270

21

Sequences

	Sequence		Length	Mass (Da)
	P32322 [UniParc]. Last modified March 1, 2005. Version 2. Checksum: 9E8C4DED0638EFC5	FASTA	319	33,361
	10 20 30 40 50 60 MSVGFIGAGQ LAFALAKGFT AAGVLAAHKI MASSPDMDLA TVSALRKMGV KLTPHNKETV 70 80 90 100 110 120 QHSDVLFLAV KPHIIPFILD EIGADIEDRH IVVSCAAGVT ISSIEKKLSA FRPAPRVIRC 130 140 150 160 170 180 MTNTPVVVRE GATVYATGTH AQVEDGRLME QLLSSVGFCT EVEEDLIDAV TGLSGSGPAY 190 200 210 220 230 240 AFTALDALAD GGVKMGLPRR LAVRLGAQAL LGAAKMLLHS EQHPGQLKDN VSSPGGATIH 250 260 270 280 290 300 ALHVLESGGF RSLLINAVEA SCIRTRELQS MADQEQVSPA AIKKTILDKV KLDSPAGTAL 310 SPSGHTKLLP RSLAPAGKD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning human pyrroline-5-carboxylate reductase cDNA by complementation in Saccharomyces cerevisiae." Dougherty K.M., Brandriss M.C., Valle D. J. Biol. Chem. 267:871-875(1992) [PubMed: 1730675] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed: 16625196] [Abstract] 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lymph and Placenta.
[5]	Bienvenut W.V., Zebisch A., Kolch W. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-17 AND 205-215, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, MASS SPECTROMETRY. Tissue: Colon carcinoma.
[6]	Bienvenut W.V., Waridel P., Quadroni M. Submitted (MAR-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-46; 130-147; 205-215 AND 252-264, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[7]	"Mutations in PYCR1 cause cutis laxa with progeroid features." Reversade B., Escande-Beillard N., Dimopoulou A., Fischer B., Chng S.C., Li Y., Shboul M., Tham P.-Y., Kayserili H., Al-Gazali L., Shahwan M., Brancati F., Lee H., O'Connor B.D., Schmidt-von Kegler M., Merriman B., Nelson S.F., Masri A. , Alkazaleh F., Guerra D., Ferrari P., Nanda A., Rajab A., Markie D., Gray M., Nelson J., Grix A., Sommer A., Savarirayan R., Janecke A.R., Steichen E., Sillence D., Hausser I., Budde B., Nuernberg G., Nuernberg P., Seemann P., Kunkel D., Zambruno G., Dallapiccola B., Schuelke M., Robertson S., Hamamy H., Wollnik B., Van Maldergem L., Mundlos S., Kornak U. Nat. Genet. 41:1016-1021(2009) [PubMed: 19648921] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANTS ARCL2B GLY-119; HIS-119; THR-179; TRP-206; ARG-206; HIS-251 AND THR-257, VARIANT VAL-189.
[8]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"Crystal structure of human pyrroline-5-carboxylate reductase." Meng Z., Lou Z., Liu Z., Li M., Zhao X., Bartlam M., Rao Z. J. Mol. Biol. 359:1364-1377(2006) [PubMed: 16730026] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF APOENZYME AND IN COMPLEXES WITH NAD; NADP AND SUBSTRATE ANALOG GLU, CATALYTIC ACTIVITY, FUNCTION, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF GLU-221, SUBUNIT.
[10]	"Crystal structure of human pyrroline-5-carboxylate reductase." Structural genomics consortium (SGC) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 1-300 IN COMPLEX WITH NAD.
[11]	"Mutation in pyrroline-5-carboxylate reductase 1 gene in families with cutis laxa type 2." Guernsey D.L., Jiang H., Evans S.C., Ferguson M., Matsuoka M., Nightingale M., Rideout A.L., Provost S., Bedard K., Orr A., Dube M.-P., Ludman M., Samuels M.E. Am. J. Hum. Genet. 85:120-129(2009) [PubMed: 19576563] [Abstract] Cited for: VARIANT ARCL2B GLN-266.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M77836 mRNA. Translation: AAA36407.1.
CR541769 mRNA. Translation: CAG46568.1.
AC145207 Genomic DNA. No translation available.
BC001504 mRNA. Translation: AAH01504.1.
BC071842 mRNA. Translation: AAH71842.1.

IPI

IPI00941557.

PIR

A41770.

RefSeq

NP_008838.2. NM_006907.2.

UniGene

Hs.163451.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2GER	X-ray	3.10	A/B/C/D/E	1-319	[»]
2GR9	X-ray	3.10	A/B/C/D/E	1-275	[»]
2GRA	X-ray	3.10	A/B/C/D/E	1-275	[»]
2IZZ	X-ray	1.95	A/B/C/D/E	1-300	[»]

ProteinModelPortal

P32322.

SMR

P32322. Positions 1-275.

ModBase

Search...

Protein-protein interaction databases

IntAct

P32322. 2 interactions.

STRING

P32322.

PTM databases

PhosphoSite

P32322.

Polymorphism databases

DMDM

60416434.

Proteomic databases

PRIDE

P32322.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000329875; ENSP00000328858; ENSG00000183010.
ENST00000405481; ENSP00000386002; ENSG00000183010.
ENST00000432920; ENSP00000414068; ENSG00000183010.

GeneID

5831.

KEGG

hsa:5831.

UCSC

uc002kcr.1. human.

Organism-specific databases

CTD

5831.

GeneCards

GC01M226075.
GC17M079890.

H-InvDB

HIX0014258.

HGNC

HGNC:9721. PYCR1.

MIM

179035. gene.
612940. phenotype.

neXtProt

NX_P32322.

Orphanet

90350. Autosomal recessive cutis laxa type 2.
2962. De Barsy syndrome.
2078. Geroderma osteodysplastica.
2834. Wrinkly skin syndrome.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG18642.

HOVERGEN

HBG053399.

InParanoid

P32322.

PhylomeDB

P32322.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-11444.

BRENDA

1.5.1.2. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P32322.

Bgee

P32322.

CleanEx

HS_PYCR1.

Genevestigator

P32322.

GermOnline

ENSG00000183010. Homo sapiens.

Family and domain databases

InterPro

IPR008927. 6-PGluconate_DH_C-like.
IPR016040. NAD(P)-bd_dom.
IPR004455. NADP_OxRdtase_F420.
IPR000304. Pyrroline-COOH_reductase.
[Graphical view]

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.

KO

K00286.

PANTHER

PTHR11645. P5CR. 1 hit.

Pfam

PF03807. F420_oxidored. 1 hit.
[Graphical view]

PIRSF

PIRSF000193. Pyrrol-5-carb_rd. 1 hit.

SUPFAM

SSF48179. 6DGDH_C_like. 1 hit.

TIGRFAMs

TIGR00112. ProC. 1 hit.

PROSITE

PS00521. P5CR. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00172. L-Proline.
DB00157. NADH.

NextBio

22720.

SOURCE

Search...

Entry information

Entry name

P5CR1_HUMAN

Accession

Primary (citable) accession number: P32322
Secondary accession number(s): Q6FHI4, Q96DI6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	March 1, 2005
Last modified:	January 25, 2012
This is version 110 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.