Reviewed, UniProtKB/Swiss-Prot P00797 (RENI_HUMAN)

Names and origin

Protein names

Recommended name:
    Renin
    EC=3.4.23.15
Alternative name(s):
    Angiotensinogenase

Gene names

Name:

REN

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	406 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	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.
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).
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)

Ontologies

Keywords
Cellular component	Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Signal
Molecular function	Aspartyl protease Hydrolase Protease
PTM	Cleavage on pair of basic residues Glycoprotein Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Uncategorized	renin activity Ref.12 Inferred from direct assay. Source: HGNC
Biological process	angiotensin maturation Ref.12 Inferred from direct assay. Source: HGNC kidney development Ref.15 Inferred from mutant phenotype. Source: UniProtKB regulation of MAPKKK cascade Ref.12 Inferred from direct assay. Source: HGNC
Cellular component	extracellular space Ref.12 Inferred from direct assay. Source: HGNC
Molecular function	receptor binding Ref.12 Inferred from physical interaction. Source: HGNC
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Molecule processing

Signal peptide

1 – 23

23

Propeptide

24 – 66

43

Activation peptide

Chain

67 – 406

340

Renin

Sites

Active site

104

1

Active site

292

1

Amino acid modifications

Glycosylation

71

1

N-linked (GlcNAc...)

Glycosylation

141

1

N-linked (GlcNAc...)

Disulfide bond

117 ↔ 124

Disulfide bond

283 ↔ 287

Disulfide bond

325 ↔ 362

Natural variations

Alternative sequence

231 – 233

3

Missing in isoform 2.

Natural variant

33

1

R → W: dbSNP rs11571098.

Natural variant

104

1

D → N in RTD.

Natural variant

160

1

Q → K: dbSNP rs11571083.

Natural variant

217

1

G → R: dbSNP rs11571117.

Natural variant

230

1

R → K in RTD.

Experimental info

Sequence conflict

55

1

R → S in AAA60364. Ref.2

Sequence conflict

189

1

E → Q in AAA60364. Ref.2

Sequence conflict

304

1

S → C in AAA60364. Ref.2

Sequence conflict

351

1

V → I Ref.7

Secondary structure

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406

Helix Strand Turn

Details...

Beta strand

74 – 77

4

Beta strand

79 – 81

3

Turn

82 – 84

3

Beta strand

85 – 92

8

Turn

93 – 96

4

Beta strand

97 – 104

8

Beta strand

110 – 114

5

Helix

122 – 124

3

Helix

132 – 134

3

Beta strand

139 – 149

11

Beta strand

152 – 165

14

Beta strand

168 – 179

12

Helix

182 – 185

4

Beta strand

189 – 195

7

Helix

199 – 201

3

Helix

203 – 205

3

Helix

209 – 216

8

Beta strand

219 – 228

10

Beta strand

240 – 246

7

Helix

249 – 251

3

Beta strand

252 – 260

9

Beta strand

268 – 271

4

Beta strand

274 – 276

3

Beta strand

279 – 282

4

Beta strand

287 – 291

5

Beta strand

296 – 300

5

Helix

302 – 312

11

Beta strand

318 – 324

7

Turn

325 – 327

3

Helix

328 – 330

3

Beta strand

334 – 338

5

Beta strand

341 – 345

5

Helix

347 – 350

4

Beta strand

360 – 368

9

Turn

373 – 375

3

Beta strand

379 – 381

3

Helix

383 – 386

4

Beta strand

389 – 394

6

Turn

395 – 398

4

Beta strand

399 – 405

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: 5AFDF8E973B21EDA	FASTA	406	45,057
	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
	Isoform 2 [UniParc]. Checksum: 4DEF0016D9EF5854		403	44,726
	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 NSQSLGGQIV 250 260 270 280 290 300 LGGSDPQHYE GNFHYINLIK TGVWQIQMKG VSVGSSTLLC EDGCLALVDT GASYISGSTS 310 320 330 340 350 360 SIEKLMEALG AKKRLFDYVV KCNEGPTLPD ISFHLGGKEY TLTSADYVFQ ESYSSKKLCT 370 380 390 400 LAIHAMDIPP PTGPTWALGA TFIRKFYTEF DRRNNRIGFA LAR

References

	« Hide 'large scale' referencesShow '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]	"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. , 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]