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Protein

C-type natriuretic peptide

Gene

NPPC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hormone which plays a role in endochondral ossification through regulation of cartilaginous growth plate chondrocytes proliferation and differentiation. May also be vasoactive and natriuretic. Specifically binds and stimulates the cGMP production of the NPR2 receptor. Binds the clearance receptor NPR3 (By similarity).By similarity

GO - Molecular functioni

  1. receptor binding Source: UniProtKB

GO - Biological processi

  1. cGMP biosynthetic process Source: UniProtKB
  2. growth plate cartilage chondrocyte differentiation Source: UniProtKB
  3. growth plate cartilage chondrocyte proliferation Source: UniProtKB
  4. negative regulation of cell proliferation Source: Ensembl
  5. negative regulation of DNA metabolic process Source: Ensembl
  6. negative regulation of meiotic cell cycle Source: MGI
  7. negative regulation of oocyte maturation Source: MGI
  8. ossification Source: UniProtKB-KW
  9. positive regulation of cGMP biosynthetic process Source: Ensembl
  10. positive regulation of osteoblast differentiation Source: Ensembl
  11. positive regulation of vasodilation Source: Ensembl
  12. post-embryonic development Source: Ensembl
  13. receptor guanylyl cyclase signaling pathway Source: UniProtKB
  14. regulation of blood vessel size Source: UniProtKB-KW
  15. regulation of cAMP metabolic process Source: MGI
  16. regulation of cGMP metabolic process Source: MGI
  17. regulation of multicellular organism growth Source: Ensembl
  18. regulation of smooth muscle cell proliferation Source: Ensembl
  19. response to drug Source: Ensembl
  20. response to ethanol Source: Ensembl
  21. response to hypoxia Source: Ensembl
  22. single organism reproductive process Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hormone, Vasoactive

Keywords - Biological processi

Osteogenesis

Protein family/group databases

TCDBi1.C.46.1.1. the c-type natriuretic peptide (cnp) family.

Names & Taxonomyi

Protein namesi
Recommended name:
C-type natriuretic peptide
Cleaved into the following 3 chains:
Gene namesi
Name:NPPC
Synonyms:CNP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:7941. NPPC.

Subcellular locationi

GO - Cellular componenti

  1. extracellular space Source: Ensembl
  2. secretory granule Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA31735.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence AnalysisAdd
BLAST
Propeptidei24 – 7350PRO_0000001553Add
BLAST
Peptidei74 – 12653CNP-53PRO_0000001554Add
BLAST
Peptidei98 – 12629CNP-29PRO_0000001555Add
BLAST
Peptidei105 – 12622CNP-22PRO_0000001556Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi110 ↔ 1261 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond

Proteomic databases

PaxDbiP23582.
PRIDEiP23582.

Miscellaneous databases

PMAP-CutDBP23582.

Expressioni

Gene expression databases

BgeeiP23582.
CleanExiHS_NPPC.
ExpressionAtlasiP23582. baseline and differential.
GenevestigatoriP23582.

Organism-specific databases

HPAiHPA035362.

Interactioni

Protein-protein interaction databases

BioGridi110940. 3 interactions.
STRINGi9606.ENSP00000295440.

Structurei

Secondary structure

1
126
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni116 – 1172

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1JDPX-ray2.00H105-126[»]
ProteinModelPortaliP23582.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23582.

Family & Domainsi

Sequence similaritiesi

Belongs to the natriuretic peptide family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG43160.
GeneTreeiENSGT00390000015492.
HOGENOMiHOG000010304.
HOVERGENiHBG004229.
InParanoidiP23582.
KOiK12336.
OMAiTPPGEEV.
OrthoDBiEOG79CZ1S.
PhylomeDBiP23582.
TreeFamiTF106305.

Family and domain databases

InterProiIPR002406. C_natriurtcpep.
IPR000663. Natr_peptide.
IPR030480. Natr_peptide_CS.
[Graphical view]
PfamiPF00212. ANP. 1 hit.
[Graphical view]
PRINTSiPR00713. CNATPEPTIDE.
PR00710. NATPEPTIDES.
SMARTiSM00183. NAT_PEP. 1 hit.
[Graphical view]
PROSITEiPS00263. NATRIURETIC_PEPTIDE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P23582-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MHLSQLLACA LLLTLLSLRP SEAKPGAPPK VPRTPPAEEL AEPQAAGGGQ
60 70 80 90 100
KKGDKAPGGG GANLKGDRSR LLRDLRVDTK SRAAWARLLQ EHPNARKYKG
110 120
ANKKGLSKGC FGLKLDRIGS MSGLGC
Length:126
Mass (Da):13,246
Last modified:October 31, 1991 - v1
Checksum:i58F6E657868F9A2D
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti82 – 821R → Q.
Corresponds to variant rs5267 [ dbSNP | Ensembl ].
VAR_014583

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64710 Genomic DNA. Translation: AAA35703.1.
D90337 Genomic DNA. Translation: BAA14351.1.
AC013435 Genomic DNA. Translation: AAX88912.1.
BC069120 mRNA. Translation: AAH69120.1.
BC105065 mRNA. Translation: AAI05066.1.
BC105067 mRNA. Translation: AAI05068.1.
CCDSiCCDS2489.1.
PIRiJT0567. AWHUC.
RefSeqiNP_077720.1. NM_024409.2.
UniGeneiHs.247916.
Hs.627236.

Genome annotation databases

EnsembliENST00000295440; ENSP00000295440; ENSG00000163273.
ENST00000409852; ENSP00000387159; ENSG00000163273.
GeneIDi4880.
KEGGihsa:4880.
UCSCiuc002vsl.2. human.

Polymorphism databases

DMDMi113850.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64710 Genomic DNA. Translation: AAA35703.1.
D90337 Genomic DNA. Translation: BAA14351.1.
AC013435 Genomic DNA. Translation: AAX88912.1.
BC069120 mRNA. Translation: AAH69120.1.
BC105065 mRNA. Translation: AAI05066.1.
BC105067 mRNA. Translation: AAI05068.1.
CCDSiCCDS2489.1.
PIRiJT0567. AWHUC.
RefSeqiNP_077720.1. NM_024409.2.
UniGeneiHs.247916.
Hs.627236.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1JDPX-ray2.00H105-126[»]
ProteinModelPortaliP23582.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110940. 3 interactions.
STRINGi9606.ENSP00000295440.

Protein family/group databases

TCDBi1.C.46.1.1. the c-type natriuretic peptide (cnp) family.

Polymorphism databases

DMDMi113850.

Proteomic databases

PaxDbiP23582.
PRIDEiP23582.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000295440; ENSP00000295440; ENSG00000163273.
ENST00000409852; ENSP00000387159; ENSG00000163273.
GeneIDi4880.
KEGGihsa:4880.
UCSCiuc002vsl.2. human.

Organism-specific databases

CTDi4880.
GeneCardsiGC02M232786.
HGNCiHGNC:7941. NPPC.
HPAiHPA035362.
MIMi600296. gene.
neXtProtiNX_P23582.
PharmGKBiPA31735.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG43160.
GeneTreeiENSGT00390000015492.
HOGENOMiHOG000010304.
HOVERGENiHBG004229.
InParanoidiP23582.
KOiK12336.
OMAiTPPGEEV.
OrthoDBiEOG79CZ1S.
PhylomeDBiP23582.
TreeFamiTF106305.

Miscellaneous databases

EvolutionaryTraceiP23582.
GenomeRNAii4880.
NextBioi18784.
PMAP-CutDBP23582.
PROiP23582.
SOURCEiSearch...

Gene expression databases

BgeeiP23582.
CleanExiHS_NPPC.
ExpressionAtlasiP23582. baseline and differential.
GenevestigatoriP23582.

Family and domain databases

InterProiIPR002406. C_natriurtcpep.
IPR000663. Natr_peptide.
IPR030480. Natr_peptide_CS.
[Graphical view]
PfamiPF00212. ANP. 1 hit.
[Graphical view]
PRINTSiPR00713. CNATPEPTIDE.
PR00710. NATPEPTIDES.
SMARTiSM00183. NAT_PEP. 1 hit.
[Graphical view]
PROSITEiPS00263. NATRIURETIC_PEPTIDE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Human C-type natriuretic peptide. Characterization of the gene and peptide."
    Ogawa Y., Nakao K., Nakagawa O., Komatsu Y., Hosoda K., Suga S., Arai H., Nagata K., Yoshida N., Imura H.
    Hypertension 19:809-813(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  5. "Isolation and identification of C-type natriuretic peptide in human monocytic cell line, THP-1."
    Ishizaka Y., Kangawa K., Minamino N., Ishii K., Takano S., Eto T., Matsuo H.
    Biochem. Biophys. Res. Commun. 189:697-704(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 98-126.
  6. "Selective activation of the B natriuretic peptide receptor by C-type natriuretic peptide (CNP)."
    Koller K.J., Lowe D.G., Bennett G.L., Minamino N., Kangawa K., Matsuo H., Goeddel D.V.
    Science 252:120-123(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "Allosteric activation of a spring-loaded natriuretic peptide receptor dimer by hormone."
    He X.-L., Chow D.-C., Martick M.M., Garcia K.C.
    Science 293:1657-1662(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 105-126 IN COMPLEX WITH NPR3, DISULFIDE BOND.

Entry informationi

Entry nameiANFC_HUMAN
AccessioniPrimary (citable) accession number: P23582
Secondary accession number(s): Q4ZG41
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 1991
Last sequence update: October 31, 1991
Last modified: March 31, 2015
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.