P13489 (RINI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ribonuclease inhibitor

Alternative name(s):
Placental ribonuclease inhibitor
Short name=Placental RNase inhibitor
Ribonuclease/angiogenin inhibitor 1
Short name=RAI

Gene names

Name:	RNH1
Synonyms:	PRI, RNH

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	461 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	Ribonuclease inhibitor which inhibits RNASE1, RNASE2 and ANG. May play role in redox homeostasis. Ref.3 Ref.10 Ref.11
Subunit structure	Forms high-affinity heterodimers with RNASE1, ANG and RNASE2.
Subcellular location	Cytoplasm.
Domain	The LRR domain forms a horseshoe-shaped structure that interacts tightly with target RNAses via a large protein interaction surface on its interior side. Ref.15 Ref.16 Ref.17
Post-translational modification	The N-terminus is blocked. At least 30 of the 32 cysteine residues are in the reduced form.
Sequence similarities	Contains 15 LRR (leucine-rich) repeats.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Domain	Leucine-rich repeat Repeat
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	mRNA catabolic process Non-traceable author statement. Source: UniProtKB regulation of angiogenesis Inferred from direct assay. Source: UniProtKB
Cellular component	angiogenin-PRI complex Inferred from physical interaction. Source: UniProtKB cytoplasm Inferred from direct assay. Source: HPA
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB ribonuclease inhibitor activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ANG	P03950	2	EBI-1237106,EBI-525291
RNASE1	P07998	2	EBI-1237106,EBI-2823523
RNASE1	P61823	3	EBI-1237106,EBI-908364	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6

Chain

2 – 461

460

Ribonuclease inhibitor

PRO_0000097343

Regions

Repeat

20 – 48

29

LRR 1

Repeat

49 – 76

28

LRR 2

Repeat

77 – 105

29

LRR 3

Repeat

106 – 133

28

LRR 4

Repeat

134 – 162

29

LRR 5

Repeat

163 – 190

28

LRR 6

Repeat

191 – 219

29

LRR 7

Repeat

220 – 247

28

LRR 8

Repeat

248 – 276

29

LRR 9

Repeat

277 – 304

28

LRR 10

Repeat

305 – 333

29

LRR 11

Repeat

334 – 361

28

LRR 12

Repeat

362 – 390

29

LRR 13

Repeat

391 – 418

28

LRR 14

Repeat

419 – 447

29

LRR 15

Region

2 – 11

10

2 X 5 AA tandem repeats of S-L-D-I-Q

Amino acid modifications

Modified residue

82

1

Phosphothreonine Ref.12

Modified residue

91

1

Phosphoserine Ref.13

Natural variations

Natural variant

170

1

P → L.
Corresponds to variant rs17585 [ dbSNP | Ensembl ].

VAR_014726

Experimental info

Mutagenesis

262

1

W → A: Binding affinity decreased 5000-fold over the wild type for RNASE2; when associated with A-264 and A-319. Ref.9 Ref.10

Mutagenesis

264

1

W → A: Substantially decreased binding affinity for RNASE2. Binding affinity decreased 5000-fold over the wild type for RNASE2; when associated with A-262 and A-319. Ref.9 Ref.10

Mutagenesis

319

1

W → A: Substantially decreased binding affinity for RNASE2. Binding affinity decreased 5000-fold over the wild type for RNASE2; when associated with A-262 and A-264. Ref.9 Ref.10

Mutagenesis

376

1

W → A: 40-fold reduction in binding affinity for RNASE2. Ref.9 Ref.16

Mutagenesis

435 – 436

2

YD → AA: Substantially decreases binding affinity for RNASE1, ANG and RNASE2. Ref.9

Mutagenesis

458

1

R → A: 25-fold reduction in binding affinity for RNASE2. Ref.9 Ref.16

Mutagenesis

461

1

Missing: A significant decrease in binding affinity with RNASE1, slight decrease for the ANG ligand, no real change in binding affinity for RNASE2. Ref.8 Ref.9 Ref.10

Sequence conflict

188

1

R → H in AAH03506. Ref.5

Sequence conflict

359

1

R → A in AAL60586. Ref.3

Sequence conflict

365

1

L → P in AAL60586. Ref.3

Sequence conflict

423 – 424

2

RQ → SE in CAA32151. Ref.2

Sequence conflict

423 – 424

2

RQ → SE in AAA60249. Ref.2

Secondary structure

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461

Helix Strand Turn

Details...

Beta strand

3 – 12

10

Helix

17 – 23

7

Turn

24 – 29

6

Beta strand

31 – 38

8

Turn

42 – 44

3

Helix

45 – 53

9

Beta strand

60 – 62

3

Helix

69 – 77

9

Turn

78 – 80

3

Beta strand

89 – 91

3

Helix

99 – 101

3

Helix

102 – 111

10

Beta strand

117 – 119

3

Helix

126 – 137

12

Beta strand

146 – 148

3

Helix

156 – 158

3

Helix

159 – 168

10

Beta strand

174 – 176

3

Helix

183 – 196

14

Beta strand

203 – 205

3

Helix

215 – 225

11

Beta strand

231 – 233

3

Helix

240 – 251

12

Beta strand

260 – 262

3

Helix

270 – 280

11

Beta strand

288 – 290

3

Helix

297 – 308

12

Beta strand

317 – 319

3

Helix

327 – 329

3

Helix

330 – 339

10

Beta strand

345 – 347

3

Beta strand

350 – 352

3

Helix

354 – 365

12

Beta strand

374 – 376

3

Turn

384 – 386

3

Helix

387 – 396

10

Beta strand

402 – 404

3

Helix

412 – 423

12

Beta strand

431 – 433

3

Helix

441 – 453

13

Beta strand

458 – 460

3

Sequences

	Sequence		Length	Mass (Da)
	P13489 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 5E88CDAC95BAE5B3	FASTA	461	49,973
	10 20 30 40 50 60 MSLDIQSLDI QCEELSDARW AELLPLLQQC QVVRLDDCGL TEARCKDISS ALRVNPALAE 70 80 90 100 110 120 LNLRSNELGD VGVHCVLQGL QTPSCKIQKL SLQNCCLTGA GCGVLSSTLR TLPTLQELHL 130 140 150 160 170 180 SDNLLGDAGL QLLCEGLLDP QCRLEKLQLE YCSLSAASCE PLASVLRAKP DFKELTVSNN 190 200 210 220 230 240 DINEAGVRVL CQGLKDSPCQ LEALKLESCG VTSDNCRDLC GIVASKASLR ELALGSNKLG 250 260 270 280 290 300 DVGMAELCPG LLHPSSRLRT LWIWECGITA KGCGDLCRVL RAKESLKELS LAGNELGDEG 310 320 330 340 350 360 ARLLCETLLE PGCQLESLWV KSCSFTAACC SHFSSVLAQN RFLLELQISN NRLEDAGVRE 370 380 390 400 410 420 LCQGLGQPGS VLRVLWLADC DVSDSSCSSL AATLLANHSL RELDLSNNCL GDAGILQLVE 430 440 450 460 SVRQPGCLLE QLVLYDIYWS EEMEDRLQAL EKDKPSLRVI S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of human placental ribonuclease inhibitor." Lee F.S., Fox E.A., Zhou H.-M., Strydom D.J., Vallee B.L. Biochemistry 27:8545-8553(1988) [PubMed: 3219362] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 20-28; 35-44; 47-62; 65-72; 87-130; 147-181; 189-200; 206-226; 231-235; 239-268; 272-276; 288-295; 297-299; 303-316; 353-364; 374-394; 402-412; 424-449 AND 453-461, OXIDATION STATE OF THE CYSTEINES. Tissue: Placenta.
[2]	"The primary structure of human ribonuclease/angiogenin inhibitor (RAI) discloses a novel highly diversified protein superfamily with a common repetitive module." Schneider R., Schneider-Scherzer E., Thurnher M., Auer B., Schweiger M. EMBO J. 7:4151-4156(1988) [PubMed: 3243277] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 444-462.
[3]	"Expression of a human ribonuclease inhibitor variant in Escherichia coli and silkworm insect cell (Bombyx mori)." Huang G.H., Yang G.Z., Chen J.Y., Wu X.F. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao 35:960-963(2003) [PubMed: 14515218] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[5]	"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: Brain, Colon, Lymph and Ovary.
[6]	"Purification and characterization of human brain ribonuclease inhibitor." Nadano D., Yasuda T., Takeshita H., Uchide K., Kishi K. Arch. Biochem. Biophys. 312:421-428(1994) [PubMed: 8037455] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-14. Tissue: Brain.
[7]	"Characterisation of a tryptic peptide from human placental ribonuclease inhibitor which inhibits ribonuclease activity." Crevel-Thieffry I., Cotterill S., Schuller E. Biochim. Biophys. Acta 1122:107-112(1992) [PubMed: 1633192] [Abstract] Cited for: PROTEIN SEQUENCE OF 174-195 AND 288-302, INTERACTION WITH RNASE1.
[8]	"Site-specific mutagenesis reveals differences in the structural bases for tight binding of RNase inhibitor to angiogenin and RNase A." Chen C.Z., Shapiro R. Proc. Natl. Acad. Sci. U.S.A. 94:1761-1766(1997) [PubMed: 9050852] [Abstract] Cited for: MUTAGENESIS OF SER-461, INTERACTION WITH ANG AND RNASE1.
[9]	"Superadditive and subadditive effects of 'hot spot' mutations within the interfaces of placental ribonuclease inhibitor with angiogenin and ribonuclease A." Chen C.Z., Shapiro R. Biochemistry 38:9273-9285(1999) [PubMed: 10413501] [Abstract] Cited for: MUTAGENESIS OF 435-TYR-ASP-436, INTERACTION WITH ANG AND RNASE1.
[10]	"Mutational analysis of the complex of human RNase inhibitor and human eosinophil-derived neurotoxin (RNase 2)." Teufel D.P., Kao R.Y., Acharya K.R., Shapiro R. Biochemistry 42:1451-1459(2003) [PubMed: 12578357] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF TRP-262; TRP-264; TRP-319; 435-TYR-ASP-436 AND SER-461, INTERACTION WITH RNASE2.
[11]	"The cytosolic ribonuclease inhibitor contributes to intracellular redox homeostasis." Monti D.M., Montesano Gesualdi N., Matousek J., Esposito F., D'Alessio G. FEBS Lett. 581:930-934(2007) [PubMed: 17292889] [Abstract] Cited for: FUNCTION.
[12]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-82, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-91, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[14]	"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].
[15]	"Molecular recognition of human angiogenin by placental ribonuclease inhibitor -- an X-ray crystallographic study at 2.0-A resolution." Papageorgiou A.C., Shapiro R., Acharya K.R. EMBO J. 16:5162-5177(1997) [PubMed: 9311977] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 2-461 IN COMPLEX WITH ANG, INTERACTION WITH ANG, DOMAIN.
[16]	"Molecular recognition of human eosinophil-derived neurotoxin (RNase 2) by placental ribonuclease inhibitor." Iyer S., Holloway D.E., Kumar K., Shapiro R., Acharya K.R. J. Mol. Biol. 347:637-655(2005) [PubMed: 15755456] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 2-461 IN COMPLEX WITH RNASE2, DOMAIN, INTERACTION WITH RNASE2, MUTAGENESIS OF TRP-376 AND ARG-458.
[17]	"Inhibition of human pancreatic ribonuclease by the human ribonuclease inhibitor protein." Johnson R.J., McCoy J.G., Bingman C.A., Phillips G.N. Jr., Raines R.T. J. Mol. Biol. 368:434-449(2007) [PubMed: 17350650] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH RNASE1, DOMAIN, INTERACTION WITH RNASE1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M22414 mRNA. Translation: AAA59130.1.
M36717 mRNA. Translation: AAA60249.1.
X13973 mRNA. Translation: CAA32151.1.
AY071904 mRNA. Translation: AAL60586.1.
AL161967 mRNA. Translation: CAB82310.1.
BC000677 mRNA. Translation: AAH00677.1.
BC003506 mRNA. Translation: AAH03506.1.
BC011186 mRNA. Translation: AAH11186.1.
BC011500 mRNA. Translation: AAH11500.1.
BC014629 mRNA. Translation: AAH14629.1.
BC024037 mRNA. Translation: AAH24037.1.
BC047730 mRNA. Translation: AAH47730.1.

IPI

IPI00550069.

PIR

A31858.

RefSeq

NP_002930.2. NM_002939.3.
NP_976317.1. NM_203383.1.
NP_976318.1. NM_203384.1.
NP_976319.1. NM_203385.1.
NP_976320.1. NM_203386.2.
NP_976321.1. NM_203387.2.
NP_976322.1. NM_203388.2.
NP_976323.1. NM_203389.2.

UniGene

Hs.530687.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A4Y	X-ray	2.00	A/D	2-461	[»]
1Z7X	X-ray	1.95	W/Y	1-461	[»]
2BEX	X-ray	1.99	A/B	2-461	[»]
2Q4G	X-ray	1.95	W/Y	1-461	[»]

ProteinModelPortal

P13489.

SMR

P13489. Positions 2-461.

ModBase

Search...

Protein-protein interaction databases

IntAct

P13489. 9 interactions.

STRING

P13489.

PTM databases

PhosphoSite

P13489.

Polymorphism databases

DMDM

132573.

2D gel databases

REPRODUCTION-2DPAGE

IPI00550069.

Proteomic databases

PeptideAtlas

P13489.

PRIDE

P13489.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000354420; ENSP00000346402; ENSG00000023191.
ENST00000356187; ENSP00000348515; ENSG00000023191.
ENST00000397604; ENSP00000380729; ENSG00000023191.
ENST00000397614; ENSP00000380738; ENSG00000023191.
ENST00000397615; ENSP00000380739; ENSG00000023191.
ENST00000426245; ENSP00000390724; ENSG00000023191.
ENST00000438658; ENSP00000416589; ENSG00000023191.

GeneID

6050.

KEGG

hsa:6050.

UCSC

uc001lpk.1. human.

Organism-specific databases

CTD

6050.

GeneCards

GC11M000485.

H-InvDB

HIX0009337.

HGNC

HGNC:10074. RNH1.

HPA

HPA039223.
HPA040781.

MIM

173320. gene.

neXtProt

NX_P13489.

PharmGKB

PA34447.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19060.

HOGENOM

HBG446348.

HOVERGEN

HBG001059.

InParanoid

P13489.

OMA

SCKIQKL.

OrthoDB

EOG4DZ1VG.

PhylomeDB

P13489.

Gene expression databases

ArrayExpress

P13489.

Bgee

P13489.

CleanEx

HS_RNH1.

Genevestigator

P13489.

GermOnline

ENSG00000023191. Homo sapiens.

Family and domain databases

InterPro

IPR001611. Leu-rich_rpt.
IPR003590. Leu-rich_rpt_RNase_inh_sub-typ.
[Graphical view]

Pfam

PF00560. LRR_1. 1 hit.
[Graphical view]

SMART

SM00368. LRR_RI. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

23577.

SOURCE

Search...

Entry information

Entry name

RINI_HUMAN

Accession

Primary (citable) accession number: P13489
Secondary accession number(s): Q8IZK8 , Q96FD7, Q9BQ80, Q9UDK6

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 138 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.