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Protein

Nitrophorin-4

Gene
N/A
Organism
Rhodnius prolixus (Triatomid bug)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Heme-based protein that delivers nitric oxide gas (NO) to the victim while feeding, resulting in vasodilation and inhibition of platelet aggregation. Also bind tightly to histamine, which is released by the host to induce wound healing. NO release is pH dependent and linked to loop dynamics.5 Publications

Catalytic activityi

3 nitrite + 2 H+ = 2 nitric oxide + nitrate + H2O.1 Publication

Cofactori

heme b1 PublicationNote: Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi80 – 801Iron (heme proximal ligand); via tele nitrogen9 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase, Vasoactive, Vasodilator

Keywords - Ligandi

Heme, Iron, Metal-binding

Enzyme and pathway databases

BRENDAi1.7.6.1. 5379.

Names & Taxonomyi

Protein namesi
Recommended name:
Nitrophorin-41 Publication (EC:1.7.6.11 Publication)
Short name:
NP41 Publication
Alternative name(s):
Nitrite dismutaseCurated
OrganismiRhodnius prolixus (Triatomid bug)
Taxonomic identifieri13249 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraParaneopteraHemipteraEuhemipteraHeteropteraPanheteropteraCimicomorphaReduviidaeTriatominaeRhodnius
Proteomesi
  • UP000015103 Componenti: Unassembled WGS sequence

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi51 – 511D → A or N: Loss of NO-induced conformational change and strongly reduced pH dependence for NO release. Stabilization of the ferric-NO heme center and decreased nitrite disproportionation. 3 Publications
Mutagenesisi76 – 761E → Q: Stabilization of the ferric-NO heme center. 1 Publication
Mutagenesisi142 – 1421T → V: No effect on NO-induced conformational change or on pH dependence for NO release. Increased NO association rates. 1 Publication
Mutagenesisi150 – 1512DL → AA: Loss of NO-induced conformational change and loss of pH dependence for NO release. 1 Publication
Mutagenesisi151 – 1511L → R: Coordination of the heme iron center and inhibition of nitrite disproportionation. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Add
BLAST
Chaini22 – 205184Nitrophorin-4PRO_0000021826Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi23 ↔ 1432 Publications
Disulfide bondi62 ↔ 1922 Publications

Keywords - PTMi

Disulfide bond

Expressioni

Tissue specificityi

Expressed by the salivary glands.

Structurei

Secondary structure

1
205
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi35 – 384Combined sources
Beta strandi40 – 5314Combined sources
Helixi54 – 563Combined sources
Beta strandi62 – 709Combined sources
Beta strandi73 – 819Combined sources
Turni83 – 853Combined sources
Beta strandi88 – 9912Combined sources
Beta strandi102 – 1109Combined sources
Beta strandi116 – 1183Combined sources
Beta strandi124 – 13310Combined sources
Beta strandi135 – 14612Combined sources
Beta strandi153 – 1619Combined sources
Helixi168 – 1769Combined sources
Helixi181 – 1833Combined sources
Beta strandi184 – 1863Combined sources
Helixi188 – 1903Combined sources
Helixi196 – 2027Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1D2UX-ray1.15A22-205[»]
1D3SX-ray1.40A22-205[»]
1EQDX-ray1.60A22-205[»]
1ERXX-ray1.40A22-205[»]
1IKEX-ray1.50A22-205[»]
1IKJX-ray1.27A22-205[»]
1KOIX-ray1.08A22-205[»]
1ML7X-ray1.25A22-205[»]
1NP4X-ray1.50A22-205[»]
1SXUX-ray1.40A22-205[»]
1SXWX-ray1.05A22-205[»]
1SXXX-ray1.01A22-205[»]
1SXYX-ray1.07A22-205[»]
1SY0X-ray1.15A22-205[»]
1SY1X-ray1.01A22-205[»]
1SY2X-ray1.00A22-205[»]
1SY3X-ray1.00A22-205[»]
1U0XX-ray1.45A22-205[»]
1X8NX-ray1.08A22-205[»]
1X8OX-ray1.01A22-205[»]
1X8PX-ray0.85A22-205[»]
1X8QX-ray0.85A22-205[»]
1YWAX-ray0.89A22-205[»]
1YWBX-ray0.97A22-205[»]
1YWCX-ray1.00A22-205[»]
1YWDX-ray1.08A22-205[»]
2AT0X-ray1.00X22-205[»]
2AT3X-ray1.00X22-205[»]
2AT5X-ray1.22X22-205[»]
2AT6X-ray1.22X22-205[»]
2AT8X-ray1.00X22-205[»]
2OFMX-ray1.11X22-205[»]
2OFRX-ray1.00X22-205[»]
3C76X-ray1.07X22-205[»]
3C77X-ray1.08X22-205[»]
3C78X-ray0.98X22-205[»]
3FLLX-ray1.50A22-205[»]
3MVFX-ray1.40A22-205[»]
3TGAX-ray1.30A22-205[»]
3TGBX-ray1.35A22-205[»]
3TGCX-ray1.40A22-205[»]
4GNWX-ray1.15A/B22-205[»]
4GRJX-ray1.15A/B22-205[»]
4HPAX-ray1.50A22-205[»]
4HPBX-ray1.60A22-205[»]
4HPCX-ray1.40A22-205[»]
4HPDX-ray1.30A22-205[»]
ProteinModelPortaliQ94734.
SMRiQ94734. Positions 22-205.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ94734.

Family & Domainsi

Sequence similaritiesi

Belongs to the calycin superfamily. Nitrophorin family.Curated

Keywords - Domaini

Signal

Family and domain databases

Gene3Di2.40.128.20. 1 hit.
InterProiIPR012674. Calycin.
IPR011038. Calycin-like.
IPR023613. Nitrophorin.
IPR002351. Nitrophorin_domain.
[Graphical view]
PfamiPF02087. Nitrophorin. 1 hit.
[Graphical view]
PRINTSiPR00788. NITROPHORIN.
SUPFAMiSSF50814. SSF50814. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q94734-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKSYTSLLAV AILCLFGGVN GACTKNAIAQ TGFNKDKYFN GDVWYVTDYL
60 70 80 90 100
DLEPDDVPKR YCAALAAGTA SGKLKEALYH YDPKTQDTFY DVSELQVESL
110 120 130 140 150
GKYTANFKKV DKNGNVKVAV TAGNYYTFTV MYADDSSALI HTCLHKGNKD
160 170 180 190 200
LGDLYAVLNR NKDAAAGDKV KSAVSAATLE FSKFISTKEN NCAYDNDSLK

SLLTK
Length:205
Mass (Da):22,406
Last modified:February 1, 1997 - v1
Checksum:i9BAACA12001527F2
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U70584 mRNA. Translation: AAB09590.1.
PIRiD56385.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U70584 mRNA. Translation: AAB09590.1.
PIRiD56385.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1D2UX-ray1.15A22-205[»]
1D3SX-ray1.40A22-205[»]
1EQDX-ray1.60A22-205[»]
1ERXX-ray1.40A22-205[»]
1IKEX-ray1.50A22-205[»]
1IKJX-ray1.27A22-205[»]
1KOIX-ray1.08A22-205[»]
1ML7X-ray1.25A22-205[»]
1NP4X-ray1.50A22-205[»]
1SXUX-ray1.40A22-205[»]
1SXWX-ray1.05A22-205[»]
1SXXX-ray1.01A22-205[»]
1SXYX-ray1.07A22-205[»]
1SY0X-ray1.15A22-205[»]
1SY1X-ray1.01A22-205[»]
1SY2X-ray1.00A22-205[»]
1SY3X-ray1.00A22-205[»]
1U0XX-ray1.45A22-205[»]
1X8NX-ray1.08A22-205[»]
1X8OX-ray1.01A22-205[»]
1X8PX-ray0.85A22-205[»]
1X8QX-ray0.85A22-205[»]
1YWAX-ray0.89A22-205[»]
1YWBX-ray0.97A22-205[»]
1YWCX-ray1.00A22-205[»]
1YWDX-ray1.08A22-205[»]
2AT0X-ray1.00X22-205[»]
2AT3X-ray1.00X22-205[»]
2AT5X-ray1.22X22-205[»]
2AT6X-ray1.22X22-205[»]
2AT8X-ray1.00X22-205[»]
2OFMX-ray1.11X22-205[»]
2OFRX-ray1.00X22-205[»]
3C76X-ray1.07X22-205[»]
3C77X-ray1.08X22-205[»]
3C78X-ray0.98X22-205[»]
3FLLX-ray1.50A22-205[»]
3MVFX-ray1.40A22-205[»]
3TGAX-ray1.30A22-205[»]
3TGBX-ray1.35A22-205[»]
3TGCX-ray1.40A22-205[»]
4GNWX-ray1.15A/B22-205[»]
4GRJX-ray1.15A/B22-205[»]
4HPAX-ray1.50A22-205[»]
4HPBX-ray1.60A22-205[»]
4HPCX-ray1.40A22-205[»]
4HPDX-ray1.30A22-205[»]
ProteinModelPortaliQ94734.
SMRiQ94734. Positions 22-205.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

BRENDAi1.7.6.1. 5379.

Miscellaneous databases

EvolutionaryTraceiQ94734.

Family and domain databases

Gene3Di2.40.128.20. 1 hit.
InterProiIPR012674. Calycin.
IPR011038. Calycin-like.
IPR023613. Nitrophorin.
IPR002351. Nitrophorin_domain.
[Graphical view]
PfamiPF02087. Nitrophorin. 1 hit.
[Graphical view]
PRINTSiPR00788. NITROPHORIN.
SUPFAMiSSF50814. SSF50814. 1 hit.
ProtoNetiSearch...

Publicationsi

  1. Champagne D.E., Ribeiro J.M.C.
    Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Salivary gland.
  2. "Nitric oxide interaction with insect nitrophorins and thoughts on the electron configuration of the {FeNO}6 complex."
    Walker F.A.
    J. Inorg. Biochem. 99:216-236(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  3. "Reduction of the lipocalin type heme containing protein nitrophorin -- sensitivity of the fold-stabilizing cysteine disulfides toward routine heme-iron reduction."
    Knipp M., Taing J.J., He C.
    J. Inorg. Biochem. 105:1405-1412(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BOND.
  4. "pH-Dependent conformational changes in proteins and their effect on experimental pK(a)s: the case of Nitrophorin 4."
    Di Russo N.V., Estrin D.A., Marti M.A., Roitberg A.E.
    PLoS Comput. Biol. 8:E1002761-E1002761(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "pH-dependent picosecond structural dynamics in the distal pocket of nitrophorin 4 investigated by 2D IR spectroscopy."
    Cheng M., Brookes J.F., Montfort W.R., Khalil M.
    J. Phys. Chem. B 117:15804-15811(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "The crystal structure of nitrophorin 4 at 1.5-A resolution: transport of nitric oxide by a lipocalin-based heme protein."
    Andersen J.F., Weichsel A., Balfour C.A., Champagne D.E., Montfort W.R.
    Structure 6:1315-1327(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 22-205 IN COMPLEX WITH HEME.
  7. "Nitric oxide binding to nitrophorin 4 induces complete distal pocket burial."
    Weichsel A., Andersen J.F., Roberts S.A., Montfort W.R.
    Nat. Struct. Biol. 7:551-554(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 22-205 IN COMPLEX WITH HEME AND NITRIC OXIDE.
  8. "Ligand-induced heme ruffling and bent NO geometry in ultra-high-resolution structures of nitrophorin 4."
    Roberts S.A., Weichsel A., Qiu Y., Shelnutt J.A., Walker F.A., Montfort W.R.
    Biochemistry 40:11327-11337(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.08 ANGSTROMS) OF 22-205 IN COMPLEX WITH HEME; NITRIC OXIDE; AMMONIA; HISTAMINE AND IMIDAZOLE.
  9. "Role of binding site loops in controlling nitric oxide release: structure and kinetics of mutant forms of nitrophorin 4."
    Maes E.M., Weichsel A., Andersen J.F., Shepley D., Montfort W.R.
    Biochemistry 43:6679-6690(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, X-RAY CRYSTALLOGRAPHY (1.00 ANGSTROMS) OF 22-205 IN COMPLEX WITH HEME; NITRIC OXIDE; AMMONIA AND IMIDAZOLE, MUTAGENESIS OF ASP-51; THR-142 AND 150-ASP-LEU-151.
  10. "Protein functional cycle viewed at atomic resolution: conformational change and mobility in nitrophorin 4 as a function of pH and NO binding."
    Kondrashov D.A., Roberts S.A., Weichsel A., Montfort W.R.
    Biochemistry 43:13637-13647(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (0.85 ANGSTROMS) OF 22-205 IN COMPLEX WITH HEME AND NITRIC OXIDE, DISULFIDE BOND.
  11. "Structural dynamics controls nitric oxide affinity in nitrophorin 4."
    Nienhaus K., Maes E.M., Weichsel A., Montfort W.R., Nienhaus G.U.
    J. Biol. Chem. 279:39401-39407(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 22-205 IN COMPLEX WITH HEME.
  12. "Axial ligand complexes of the Rhodnius nitrophorins: reduction potentials, binding constants, EPR spectra, and structures of the 4-iodopyrazole and imidazole complexes of NP4."
    Berry R.E., Ding X.D., Shokhireva T.K.H., Weichsel A., Montfort W.R., Walker F.A.
    J. Biol. Inorg. Chem. 9:135-144(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 22-205 IN COMPLEX WITH HEME AND 4-IODOPYRAZOLE.
  13. "Ultrahigh resolution structures of nitrophorin 4: heme distortion in ferrous CO and NO complexes."
    Maes E.M., Roberts S.A., Weichsel A., Montfort W.R.
    Biochemistry 44:12690-12699(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (0.89 ANGSTROMS) OF 22-205 IN COMPLEX WITH HEME; NITRIC OXYDE AND CARBON MONOXIDE.
  14. "Apo-nitrophorin 4 at atomic resolution."
    Amoia A.M., Montfort W.R.
    Protein Sci. 16:2076-2081(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.11 ANGSTROMS) OF 22-205.
  15. "Effect of mutation of carboxyl side-chain amino acids near the heme on the midpoint potentials and ligand binding constants of nitrophorin 2 and its NO, histamine, and imidazole complexes."
    Berry R.E., Shokhirev M.N., Ho A.Y., Yang F., Shokhireva T.K., Zhang H., Weichsel A., Montfort W.R., Walker F.A.
    J. Am. Chem. Soc. 131:2313-2327(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 22-205 IN COMPLEX WITH HEME AND NITRIC OXYDE, MUTAGENESIS OF ASP-51 AND GLU-76.
  16. "Formation of the complex of nitrite with the ferriheme b beta-barrel proteins nitrophorin 4 and nitrophorin 7."
    He C., Ogata H., Knipp M.
    Biochemistry 49:5841-5851(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 22-205 IN COMPLEX WITH HEME AND NITRITE.
  17. "Guanidine-ferroheme coordination in the mutant protein nitrophorin 4(L130R)."
    He C., Fuchs M.R., Ogata H., Knipp M.
    Angew. Chem. Int. Ed. Engl. 51:4470-4473(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 22-205 IN COMPLEX WITH HEME, MUTAGENESIS OF LEU-151.
  18. "Insertion of an H-bonding residue into the distal pocket of the ferriheme protein nitrophorin 4: effect on nitrite-iron coordination and nitrite disproportionation."
    He C., Ogata H., Knipp M.
    Chem. Biodivers. 9:1761-1775(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 22-205 IN COMPLEX WITH HEME AND NITRITE, MUTAGENESIS OF ASP-51 AND LEU-151.
  19. "Complexes of ferriheme nitrophorin 4 with low-molecular weight thiol(ate)s occurring in blood plasma."
    He C., Nishikawa K., Erdem O.F., Reijerse E., Ogata H., Lubitz W., Knipp M.
    J. Inorg. Biochem. 122:38-48(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 22-205 IN COMPLEX WITH HEME; L-CYSTEINE AND L-HOMOCYSTEINE.

Entry informationi

Entry nameiNP4_RHOPR
AccessioniPrimary (citable) accession number: Q94734
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: February 1, 1997
Last modified: October 14, 2015
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)

Miscellaneousi

Miscellaneous

Superposition of the structures of NP4 in the presence of ammonia or nitrite shows a conformational change of the protein upon NO2- binding.5 Publications

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.