Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9HC23 (PROK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Prokineticin-2

Short name=PK2
Alternative name(s):
Protein Bv8 homolog
Gene names
Name:PROK2
Synonyms:BV8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length129 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May function as an output molecule from the suprachiasmatic nucleus (SCN) that transmits behavioral circadian rhythm. May also function locally within the SCN to synchronize output. Potently contracts gastrointestinal (GI) smooth muscle.

Subcellular location

Secreted.

Tissue specificity

Expressed in the testis and, at low levels, in the small intestine.

Induction

Activated by CLOCK and BMAL1 heterodimers and light; inhibited by period genes (PER1, PER2 and PER3) and cryptochrome genes (CRY1 and CRY2) Probable.

Involvement in disease

Hypogonadotropic hypogonadism 4 with or without anosmia (HH4) [MIM:610628]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
Note: The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in PROK2 as well as in other HH-associated genes including PROKR2 (Ref.8). Ref.7 Ref.8

Sequence similarities

Belongs to the AVIT (prokineticin) family.

Ontologies

Keywords
   Biological processBiological rhythms
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Hypogonadotropic hypogonadism
Kallmann syndrome
   DomainSignal
   Molecular functionNeuropeptide
   PTMDisulfide bond
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Non-traceable author statement Ref.1. Source: UniProtKB

activation of MAPK activity

Traceable author statement PubMed 12728244. Source: UniProtKB

angiogenesis

Inferred from direct assay PubMed 12604792. Source: UniProtKB

cell proliferation

Inferred from direct assay PubMed 12604792. Source: UniProtKB

chemotaxis

Inferred from direct assay PubMed 12604792. Source: UniProtKB

circadian rhythm

Inferred from electronic annotation. Source: Ensembl

inflammatory response

Non-traceable author statement Ref.1. Source: UniProtKB

negative regulation of apoptotic process

Inferred from direct assay PubMed 12604792. Source: UniProtKB

neuropeptide signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of cytosolic calcium ion concentration

Traceable author statement PubMed 12728244. Source: UniProtKB

positive regulation of smooth muscle contraction

Inferred from direct assay Ref.1. Source: UniProtKB

sensory perception of pain

Traceable author statement PubMed 12728244. Source: UniProtKB

spermatogenesis

Inferred from mutant phenotype Ref.5. Source: UniProtKB

   Cellular_componentextracellular region

Traceable author statement PubMed 12466223. Source: UniProtKB

   Molecular_functionG-protein coupled receptor binding

Traceable author statement PubMed 12728244. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9HC23-1)

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: Q9HC23-2)

The sequence of this isoform differs from the canonical sequence as follows:
     75-95: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Ref.6
Chain28 – 129102Prokineticin-2
PRO_0000025809

Amino acid modifications

Disulfide bond34 ↔ 46 By similarity
Disulfide bond40 ↔ 58 By similarity
Disulfide bond45 ↔ 107 By similarity
Disulfide bond68 ↔ 115 By similarity
Disulfide bond109 ↔ 125 By similarity

Natural variations

Alternative sequence75 – 9521Missing in isoform 2.
VSP_005219
Natural variant241A → P in HH4; phenotype consistent with Kallmann syndrome; the patient also carries a mutation in PROKR2. Ref.8
VAR_069970
Natural variant321G → R in HH4; phenotype consistent with Kallmann syndrome. Ref.7
VAR_030955
Natural variant731R → C in HH4; phenotype consistent with Kallmann syndrome. Ref.7
VAR_030956

Sequences

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

Last modified September 26, 2001. Version 2.
Checksum: 0487679E8700DA55

FASTA12914,314
        10         20         30         40         50         60 
MRSLCCAPLL LLLLLPPLLL TPRAGDAAVI TGACDKDSQC GGGMCCAVSI WVKSIRICTP 

        70         80         90        100        110        120 
MGKLGDSCHP LTRKNNFGNG RQERRKRKRS KRKKEVPFFG RRMHHTCPCL PGLACLRTSF 


NRFICLAQK 

« Hide

Isoform 2 [UniParc].

Checksum: D7AF89D8551A97FC
Show »

FASTA10811,659

References

« Hide 'large scale' references
[1]"Identification of two prokineticin cDNAs: recombinant proteins potently contract gastrointestinal smooth muscle."
Li M., Bullock C.M., Knauer D.J., Ehlert F.J., Zhou Q.-Y.
Mol. Pharmacol. 59:692-698(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]"Identification and pharmacological characterization of prokineticin 2 beta as a selective ligand for prokineticin receptor 1."
Chen J., Kuei C., Sutton S., Wilson S., Yu J., Kamme F., Mazur C., Lovenberg T., Liu C.
Mol. Pharmacol. 67:2070-2076(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[5]"The mammalian homologues of frog Bv8 are mainly expressed in spermatocytes."
Wechselberger C., Puglisi R., Lepperdinger G., Boitani C., Kreil G.
FEBS Lett. 462:177-181(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-129 (ISOFORM 1).
Tissue: Testis.
[6]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 28-42.
[7]"Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2."
Dode C., Teixeira L., Levilliers J., Fouveaut C., Bouchard P., Kottler M.-L., Lespinasse J., Lienhardt-Roussie A., Mathieu M., Moerman A., Morgan G., Murat A., Toublanc J.-E., Wolczynski S., Delpech M., Petit C., Young J., Hardelin J.-P.
PLoS Genet. 2:1648-1652(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HH4 ARG-32 AND CYS-73.
[8]"Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism."
Miraoui H., Dwyer A.A., Sykiotis G.P., Plummer L., Chung W., Feng B., Beenken A., Clarke J., Pers T.H., Dworzynski P., Keefe K., Niedziela M., Raivio T., Crowley W.F. Jr., Seminara S.B., Quinton R., Hughes V.A., Kumanov P. expand/collapse author list , Young J., Yialamas M.A., Hall J.E., Van Vliet G., Chanoine J.P., Rubenstein J., Mohammadi M., Tsai P.S., Sidis Y., Lage K., Pitteloud N.
Am. J. Hum. Genet. 92:725-743(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HH4 PRO-24.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF333025 mRNA. Translation: AAK49919.1.
AY349131 mRNA. Translation: AAR06657.1.
CH471055 Genomic DNA. Translation: EAW65506.1.
BC069395 mRNA. Translation: AAH69395.1.
BC096695 mRNA. Translation: AAH96695.1.
BC098110 mRNA. Translation: AAH98110.1.
BC098162 mRNA. Translation: AAH98162.1.
AF182069 mRNA. Translation: AAG16893.2.
CCDSCCDS2916.1. [Q9HC23-2]
CCDS46868.1. [Q9HC23-1]
RefSeqNP_001119600.1. NM_001126128.1. [Q9HC23-1]
NP_068754.1. NM_021935.3. [Q9HC23-2]
UniGeneHs.528665.

3D structure databases

ProteinModelPortalQ9HC23.
SMRQ9HC23. Positions 28-128.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000295619.

PTM databases

PhosphoSiteQ9HC23.

Polymorphism databases

DMDM18202953.

Proteomic databases

MaxQBQ9HC23.
PaxDbQ9HC23.
PRIDEQ9HC23.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000295619; ENSP00000295619; ENSG00000163421. [Q9HC23-1]
ENST00000353065; ENSP00000295618; ENSG00000163421. [Q9HC23-2]
GeneID60675.
KEGGhsa:60675.
UCSCuc003doz.4. human. [Q9HC23-2]
uc003dpa.4. human. [Q9HC23-1]

Organism-specific databases

CTD60675.
GeneCardsGC03M071820.
GeneReviewsPROK2.
HGNCHGNC:18455. PROK2.
HPAHPA041408.
MIM607002. gene.
610628. phenotype.
neXtProtNX_Q9HC23.
Orphanet478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBPA38540.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39081.
HOGENOMHOG000004848.
HOVERGENHBG031845.
InParanoidQ9HC23.
OMAPLTRKNH.
OrthoDBEOG7SJD78.
PhylomeDBQ9HC23.
TreeFamTF332732.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeQ9HC23.
CleanExHS_PROK2.
GenevestigatorQ9HC23.

Family and domain databases

InterProIPR009523. Prokineticin.
IPR023569. Prokineticin_domain.
[Graphical view]
PANTHERPTHR18821. PTHR18821. 1 hit.
PfamPF06607. Prokineticin. 1 hit.
[Graphical view]
ProDomPD059788. Prokineticin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
ProtoNetSearch...

Other

GenomeRNAi60675.
NextBio65482.
PROQ9HC23.
SOURCESearch...

Entry information

Entry namePROK2_HUMAN
AccessionPrimary (citable) accession number: Q9HC23
Secondary accession number(s): Q53Z79, Q6ISR0
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: September 26, 2001
Last modified: July 9, 2014
This is version 112 of the entry and version 2 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

SIMILARITY comments

Index of protein domains and families

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM