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P00797 (RENI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 153. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Renin

EC=3.4.23.15
Alternative name(s):
Angiotensinogenase
Gene names
Name:REN
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length406 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney.

Catalytic activity

Cleavage of Leu-|-Xaa bond in angiotensinogen to generate angiotensin I.

Enzyme regulation

Interaction with ATP6AP2 results in a 5-fold increased efficiency in angiotensinogen processing.

Subunit structure

Interacts with ATP6AP2. Ref.14

Subcellular location

Secreted. Membrane. Note: Associated to membranes via binding to ATP6AP2.

Involvement in disease

Defects in REN are a cause of renal tubular dysgenesis (RTD) [MIM:267430]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype). Ref.17

Defects in REN are the cause of familial juvenile hyperuricemic nephropathy type 2 (HNFJ2) [MIM:613092]. It is a renal disease characterized by juvenile onset of hyperuricemia, slowly progressive renal failure and anemia. Ref.18

Sequence similarities

Belongs to the peptidase A1 family.

Biophysicochemical properties

Kinetic parameters:

KM=1 µM for angiotensinogen (in absence of ATP6AP2)

KM=0.15 µM for angiotensinogen (in presence of membrane-bound ATP6AP2)

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P00797-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P00797-2)

The sequence of this isoform differs from the canonical sequence as follows:
     231-233: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Ref.13
Propeptide24 – 6643Activation peptide
PRO_0000026081
Chain67 – 406340Renin
PRO_0000026082

Sites

Active site1041
Active site2921

Amino acid modifications

Glycosylation711N-linked (GlcNAc...)
Glycosylation1411N-linked (GlcNAc...)
Disulfide bond117 ↔ 124
Disulfide bond283 ↔ 287
Disulfide bond325 ↔ 362

Natural variations

Alternative sequence231 – 2333Missing in isoform 2.
VSP_012899
Natural variant161L → R in HNFJ2; affects ER translocation and processing of nascent preprorenin, resulting in abolished prorenin and renin biosynthesis and secretion. Ref.18
VAR_063770
Natural variant331R → W.
Corresponds to variant rs11571098 [ dbSNP | Ensembl ].
VAR_020375
Natural variant1041D → N in RTD. Ref.17
VAR_035088
Natural variant1601Q → K.
Corresponds to variant rs11571083 [ dbSNP | Ensembl ].
VAR_029171
Natural variant2171G → R.
Corresponds to variant rs11571117 [ dbSNP | Ensembl ].
VAR_020376
Natural variant2301R → K in RTD. Ref.17
VAR_035087

Experimental info

Sequence conflict551R → S in AAA60364. Ref.2
Sequence conflict1891E → Q in AAA60364. Ref.2
Sequence conflict3041S → C in AAA60364. Ref.2
Sequence conflict3511V → I Ref.9

Secondary structure

........................................................................ 406
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 1, 1988. Version 1.
Checksum: 5AFDF8E973B21EDA

FASTA40645,057
        10         20         30         40         50         60 
MDGWRRMPRW GLLLLLWGSC TFGLPTDTTT FKRIFLKRMP SIRESLKERG VDMARLGPEW 

        70         80         90        100        110        120 
SQPMKRLTLG NTTSSVILTN YMDTQYYGEI GIGTPPQTFK VVFDTGSSNV WVPSSKCSRL 

       130        140        150        160        170        180 
YTACVYHKLF DASDSSSYKH NGTELTLRYS TGTVSGFLSQ DIITVGGITV TQMFGEVTEM 

       190        200        210        220        230        240 
PALPFMLAEF DGVVGMGFIE QAIGRVTPIF DNIISQGVLK EDVFSFYYNR DSENSQSLGG 

       250        260        270        280        290        300 
QIVLGGSDPQ HYEGNFHYIN LIKTGVWQIQ MKGVSVGSST LLCEDGCLAL VDTGASYISG 

       310        320        330        340        350        360 
STSSIEKLME ALGAKKRLFD YVVKCNEGPT LPDISFHLGG KEYTLTSADY VFQESYSSKK 

       370        380        390        400 
LCTLAIHAMD IPPPTGPTWA LGATFIRKFY TEFDRRNNRI GFALAR 

« Hide

Isoform 2 [UniParc].

Checksum: 4DEF0016D9EF5854
Show »

FASTA40344,726

References

« Hide 'large scale' references
[1]"Cloning and sequence analysis of cDNA for human renin precursor."
Imai T., Miyazaki H., Hirose S., Hori H., Hayashi T., Kageyama R., Ohkubo H., Nakanishi S., Murakami K.
Proc. Natl. Acad. Sci. U.S.A. 80:7405-7409(1983) [PubMed: 6324167] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[2]"New possibilities for intracellular renin and inactive renin now that the structure of the human renin gene has been elucidated."
Morris B.J.
Clin. Sci. 71:345-355(1986) [PubMed: 3530608] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
[3]"Primary structure of the human renin gene."
Hardman J.A., Hort Y.J., Catanzaro D.F., Tellam J.T., Baxter J.D., Morris B.J., Shine J.
DNA 3:457-468(1984) [PubMed: 6391881] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Fetal liver.
[4]Rieder M.J., da Ponte S.H., Kuldanek S.A., Rajkumar N., Smith J.D., Toth E.J., Krauss R.M., Nickerson D.A.
Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]NIEHS SNPs program
Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed: 16710414] [Abstract]
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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Colon and Ovary.
[9]"Molecular cloning and nucleotide sequence of a human renin cDNA fragment."
Soubrier F., Panthier J.-J., Corvol P., Rougeon F.
Nucleic Acids Res. 11:7181-7190(1983) [PubMed: 6138751] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 108-406 (ISOFORM 1).
[10]"Human renin gene of renin-secreting tumor."
Fukamizu A., Nishi K., Nishimatsu S., Miyazaki H., Hirose S., Murakami K.
Gene 49:139-145(1986) [PubMed: 3032746] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33.
[11]"Identification of negative and positive regulatory elements in the human renin gene."
Burt D.W., Nakamura N., Kelley P., Dzau V.J.
J. Biol. Chem. 264:7357-7362(1989) [PubMed: 2540188] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33.
[12]"Segmental homology between the promoter region of the human renin gene and the mouse ren1 and ren2 promoter regions."
Soubrier F., Panthier J.J., Houot A.-M., Rougeon F., Corvol P.
Gene 41:85-92(1986) [PubMed: 3516796] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33.
[13]"Isolation and characterization of recombinant human prorenin in Chinese hamster ovary cells."
Ishizuka Y., Shoda A., Yoshida S., Kawamura Y., Haraguchi K., Murakami K.
J. Biochem. 109:30-35(1991) [PubMed: 2016271] [Abstract]
Cited for: PROTEIN SEQUENCE OF 24-42 AND 67-86.
[14]"Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin."
Nguyen G., Delarue F., Burckle C., Bouzhir L., Giller T., Sraer J.-D.
J. Clin. Invest. 109:1417-1427(2002) [PubMed: 12045255] [Abstract]
Cited for: INTERACTION WITH ATP6AP2, CHARACTERIZATION.
[15]"Structure of recombinant human renin, a target for cardiovascular-active drugs, at 2.5-A resolution."
Sielecki A.R., Hayakawa K., Fujinaga M., Murphy M.E.P., Fraser M., Muir A.K., Carilli C.T., Lewicki J.A., Baxter J.D., James M.N.G.
Science 243:1346-1351(1989) [PubMed: 2493678] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[16]"X-ray analyses of peptide-inhibitor complexes define the structural basis of specificity for human and mouse renins."
Dhanaraj V., Dealwis C.G., Frazao C., Badasso M., Sibanda B.L., Tickle I.J., Cooper J.B., Driessen H.P.C., Newman M., Aguilar C., Wood S.P., Blundell T.L., Hobart P.M., Geoghegan K.F., Ammirati M.J., Danley D.E., O'Connor B.A., Hoover D.J.
Nature 357:466-472(1992) [PubMed: 1608447] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
[17]"Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis."
Gribouval O., Gonzales M., Neuhaus T., Aziza J., Bieth E., Laurent N., Bouton J.M., Feuillet F., Makni S., Ben Amar H., Laube G., Delezoide A.-L., Bouvier R., Dijoud F., Ollagnon-Roman E., Roume J., Joubert M., Antignac C., Gubler M.-C.
Nat. Genet. 37:964-968(2005) [PubMed: 16116425] [Abstract]
Cited for: VARIANTS RTD ASN-104 AND LYS-230.
[18]"Dominant renin gene mutations associated with early-onset hyperuricemia, anemia, and chronic kidney failure."
Zivna M., Hulkova H., Matignon M., Hodanova K., Vylet'al P., Kalbacova M., Baresova V., Sikora J., Blazkova H., Zivny J., Ivanek R., Stranecky V., Sovova J., Claes K., Lerut E., Fryns J.P., Hart P.S., Hart T.C. expand/collapse author list , Adams J.N., Pawtowski A., Clemessy M., Gasc J.M., Guebler M.C., Antignac C., Elleder M., Kapp K., Grimbert P., Bleyer A.J., Kmoch S.
Am. J. Hum. Genet. 85:204-213(2009) [PubMed: 19664745] [Abstract]
Cited for: VARIANT HNFJ2 ARG-16, CHARACTERIZATION OF VARIANT HNFJ2 ARG-16.
+Additional computationally mapped references.

Web resources

Wikipedia

Renin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L00073 expand/collapse EMBL AC list , L00064, L00065, L00066, L00067, L00068, L00069, L00070, L00071, L00072 Genomic DNA. Translation: AAA60363.1.
M26901, M26899, M26900 Genomic DNA. Translation: AAA60364.1.
M10152 expand/collapse EMBL AC list , M10030, M10128, M10150, M10151 Genomic DNA. Translation: AAD03461.1.
AY436324 Genomic DNA. Translation: AAR03502.1.
CR536498 mRNA. Translation: CAG38737.1.
EU332871 Genomic DNA. Translation: ABY87560.1.
AL592114, AL592146 Genomic DNA. Translation: CAH71224.1.
AL592146, AL592114 Genomic DNA. Translation: CAI16594.1.
BC033474 mRNA. Translation: AAH33474.1.
BC047752 mRNA. Translation: AAH47752.1.
M15410 Genomic DNA. Translation: AAA60263.1.
M26440 Genomic DNA. Translation: AAA60365.1.
M13253 Genomic DNA. Translation: AAA60262.1.
IPIIPI00019644.
IPI00552207.
PIRREHUK. A21454.
RefSeqNP_000528.1. NM_000537.3.
UniGeneHs.3210.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1BBSX-ray2.80A/B67-406[»]
1BILX-ray2.40A/B70-406[»]
1BIMX-ray2.80A/B70-406[»]
1HRNX-ray1.80A/B70-406[»]
1RNEX-ray2.40A67-406[»]
2BKSX-ray2.20A/B67-406[»]
2BKTX-ray2.30A/B67-406[»]
2FS4X-ray2.20A/B74-406[»]
2G1NX-ray2.90A/B74-406[»]
2G1OX-ray2.70A/B74-406[»]
2G1RX-ray2.42A/B74-406[»]
2G1SX-ray2.50A/B74-406[»]
2G1YX-ray2.50A/B74-406[»]
2G20X-ray2.40A/B74-406[»]
2G21X-ray2.20A/B74-406[»]
2G22X-ray2.50A/B74-406[»]
2G24X-ray1.90A/B74-406[»]
2G26X-ray2.10A/B74-406[»]
2G27X-ray2.90A/B74-406[»]
2I4QX-ray2.30A/B73-406[»]
2IKOX-ray1.90A/B67-406[»]
2IKUX-ray2.60A/B67-406[»]
2IL2X-ray2.24A/B67-406[»]
2RENX-ray2.50A67-406[»]
2V0ZX-ray2.20C/O67-406[»]
2V10X-ray3.10C/O67-406[»]
2V11X-ray3.10C/O67-406[»]
2V12X-ray3.20C/O67-406[»]
2V13X-ray2.80A67-406[»]
2V16X-ray2.80C/O67-406[»]
2X0BX-ray4.33A/C/E/G24-406[»]
3D91X-ray2.20A/B67-406[»]
3G6ZX-ray2.00A/B67-406[»]
3G70X-ray2.00A/B67-406[»]
3G72X-ray1.90A/B67-406[»]
3GW5X-ray2.00A/B70-406[»]
3K1WX-ray1.50A/B67-406[»]
3KM4X-ray1.90A/B70-406[»]
3O9LX-ray2.40A/C67-232[»]
B/D237-406[»]
3OADX-ray2.17A/C67-232[»]
B/D237-406[»]
3OAGX-ray2.30A/C67-232[»]
B/D237-406[»]
3OOTX-ray2.55A/B67-406[»]
3OQFX-ray2.78A/B67-406[»]
3OQKX-ray2.90A/B67-406[»]
3OWNX-ray2.00A/B67-406[»]
3Q3TX-ray2.60A/B67-406[»]
3Q4BX-ray2.19A/B67-406[»]
3Q5HX-ray2.16A/B67-406[»]
3SFCX-ray2.10A/B67-406[»]
ProteinModelPortalP00797.
SMRP00797. Positions 31-406.
ModBaseSearch...

Protein-protein interaction databases

IntActP00797. 1 interaction.
MINTMINT-1381167.
STRINGP00797.

Protein family/group databases

MEROPSA01.007.

PTM databases

GlycoSuiteDBP00797.

Polymorphism databases

DMDM132326.

Proteomic databases

PRIDEP00797.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000272190; ENSP00000272190; ENSG00000143839.
GeneID5972.
KEGGhsa:5972.
UCSCuc001haq.1. human.

Organism-specific databases

CTD5972.
GeneCardsGC01M204123.
H-InvDBHIX0023538.
HGNCHGNC:9958. REN.
HPACAB025903.
HPA005131.
MIM179820. gene.
267430. phenotype.
613092. phenotype.
neXtProtNX_P00797.
Orphanet217330. Hyperuricemia - anemia - renal failure.
97369. Renal tubular dysgenesis of genetic origin.
PharmGKBPA297.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG05915.
HOGENOMHBG590923.
HOVERGENHBG000482.
OMASYITGPA.
OrthoDBEOG4W3SN8.
PhylomeDBP00797.

Gene expression databases

ArrayExpressP00797.
BgeeP00797.
CleanExHS_REN.
GenevestigatorP00797.
GermOnlineENSG00000143839. Homo sapiens.

Family and domain databases

InterProIPR001461. Peptidase_A1.
IPR021109. Peptidase_aspartic.
IPR001969. Peptidase_aspartic_AS.
IPR009007. Peptidase_aspartic_catalytic.
IPR012848. Propep_A1.
[Graphical view]
Gene3DG3DSA:2.40.70.10. Pept_Aspartc_cat. 2 hits.
KOK01380.
PANTHERPTHR13683. Peptidase_A1. 1 hit.
PfamPF07966. A1_Propeptide. 1 hit.
PF00026. Asp. 1 hit.
[Graphical view]
PRINTSPR00792. PEPSIN.
SUPFAMSSF50630. Pept_Aspartic. 1 hit.
PROSITEPS00141. ASP_PROTEASE. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

BindingDBP00797.
DrugBankDB01258. Aliskiren.
DB00212. Remikiren.
NextBio23249.
PMAP-CutDBP00797.
SOURCESearch...

Entry information

Entry nameRENI_HUMAN
AccessionPrimary (citable) accession number: P00797
Secondary accession number(s): Q6FI38, Q6T5C2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 1, 1988
Last modified: January 25, 2012
This is version 153 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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.

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families