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Reviewed, UniProtKB/Swiss-Prot P32322 (P5CR1_HUMAN)

Last modified February 9, 2010. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length319 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Involved in the cellular response to oxidative stress. Ref.7

Catalytic activity

L-proline + NAD(P)+ = 1-pyrroline-5-carboxylate + NAD(P)H.

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.8

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.9

Sequence similarities

Belongs to the pyrroline-5-carboxylate reductase family.

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Ontologies

Keywords
   Biological processAmino-acid biosynthesis
Proline biosynthesis
Stress response
   Cellular componentMitochondrion
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   LigandNADP
   Molecular functionOxidoreductase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Gene Ontology (GO)
   Biological processcellular response to oxidative stress Ref.7

Inferred from mutant phenotype. Source: UniProtKB

oxidation reduction

Inferred from electronic annotation. Source: UniProtKB-KW

proline biosynthetic process Ref.1

Traceable author statement. Source: ProtInc

   Cellular componentmitochondrion Ref.7

Inferred from direct assay. Source: UniProtKB

   Molecular functionbinding

Inferred from electronic annotation. Source: InterPro

pyrroline-5-carboxylate reductase activity Ref.1

Traceable author statement. Source: ProtInc

Complete GO annotation...

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.4 Ref.5
Chain2 – 319318Pyrroline-5-carboxylate reductase 1, mitochondrial
PRO_0000187314

Amino acid modifications

Modified residue21N-acetylserine Ref.4 Ref.5

Natural variations

Natural variant1191R → G in ARCL2B. Ref.7
VAR_059068
Natural variant1191R → H in ARCL2B. Ref.7
VAR_059069
Natural variant1791A → T in ARCL2B. Ref.7
VAR_059070
Natural variant1891A → V
VAR_059071
Natural variant2061G → R in ARCL2B. Ref.7
VAR_059072
Natural variant2061G → W in ARCL2B. Ref.7
VAR_059073
Natural variant2511R → H in ARCL2B. Ref.7
VAR_059074
Natural variant2571A → T in ARCL2B. Ref.7
VAR_059075
Natural variant2661R → Q in ARCL2B; may cause skipping of exon 6. Ref.9
VAR_059076

Experimental info

Sequence conflict1551S → T in AAA36407. Ref.1
Sequence conflict3171G → S in CAG46568. Ref.2

Secondary structure

1 ............................................... 319
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
P32322-1 [UniParc].

Last modified March 1, 2005. Version 2.
Checksum: 9E8C4DED0638EFC5

FASTA31933,361
        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

« Hide

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References

« Hide '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]"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.
[4]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.
[5]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.
[6]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[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. expand/collapse author list , 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]"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 (3.1 ANGSTROMS), SUBUNIT.
[9]"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.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		M77836 mRNA. Translation: AAA36407.1.
CR541769 mRNA. Translation: CAG46568.1.
BC001504 mRNA. Translation: AAH01504.1.
BC071842 mRNA. Translation: AAH71842.1.
IPIIPI00941557.
PIRA41770.
RefSeqNP_008838.2.
UniGeneHs.163451

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2GERX-ray3.10A/B/C/D/E1-319[»]
2GR9X-ray3.10A/B/C/D/E1-275[»]
2GRAX-ray3.10A/B/C/D/E1-275[»]
2IZZX-ray1.95A/B/C/D/E1-300[»]
ModBaseSearch...

Protein-protein interaction databases

STRINGP32322.

PTM databases

PhosphoSiteP32322.

Proteomic databases

PRIDEP32322.

Genome annotation databases

EnsemblENST00000329875; ENSP00000328858; ENSG00000183010; Homo sapiens. [Genome view]
ENST00000405481; ENSP00000386002; ENSG00000183010; Homo sapiens. [Genome view]
ENST00000432920; ENSP00000414068; ENSG00000183010; Homo sapiens. [Genome view]
GeneID5831.
KEGGhsa:5831.
UCSCuc002kcr.1. human.

Organism-specific databases

CTD5831.
GeneCardsGC17M077484.
H-InvDBHIX0014258.
HGNCHGNC:9721. PYCR1.
MIM179035. gene.
612940. phenotype.
Orphanet90350. Cutis laxa, recessive type 2.
2078. Geroderma osteodysplastica.
2962. Progeroid syndrome, De Barsy type.
2834. Wrinkly skin syndrome.
PharmGKBPA34064.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG18642.
HOVERGENP32322.
InParanoidP32322.
OrthoDBEOG9W3W6S.
PhylomeDBP32322.

Enzyme and pathway databases

BioCycMetaCyc:MONOMER-11444.
BRENDA1.5.1.2. 247.
ReactomeREACT_13. Metabolism of amino acids.

Gene expression databases

ArrayExpressP32322.
BgeeP32322.
CleanExHS_PYCR1.
GenevestigatorP32322.
GermOnlineENSG00000183010. Homo sapiens.

Family and domain databases

InterProIPR016040. NAD(P)-bd_dom.
IPR004455. NADP_OxRdtase_F420.
IPR000304. P5CR.
[Graphical view]
Gene3DG3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
PANTHERPTHR11645. P5CR. 1 hit.
PfamPF03807. F420_oxidored. 1 hit.
[Graphical view]
PIRSFPIRSF000193. Pyrrol-5-carb_rd. 1 hit.
TIGRFAMsTIGR00112. proC. 1 hit.
PROSITEPS00521. P5CR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00172. L-Proline.
DB00157. NADH.
NextBio22720.
SOURCESearch...

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Entry information

Entry nameP5CR1_HUMAN
AccessionPrimary (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: February 9, 2010
This is version 91 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny 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.

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Index of human polymorphisms and disease mutations

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Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents