Q9HC23 (PROK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Prokineticin-2
Short name=PK2

Alternative name(s):
Protein Bv8 homolog

Gene names

Name:	PROK2
Synonyms:	BV8

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	129 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	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	Defects in PROK2 are the cause of Kallmann syndrome type 4 (KAL4) [MIM:610628]; also known as hypogonadotropic hypogonadism and anosmia. 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. KAL4 patients have variable degrees of olfactory and reproductive dysfunction, but do not show any of the occasional clinical anomalies reported in Kallmann syndrome such as renal agenesis, cleft lip/palate, selective tooth agenesis, and bimanual synkinesis. Ref.6
Sequence similarities	Belongs to the AVIT (prokineticin) family.

Ontologies

Keywords
Biological process	Biological rhythms
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Hypogonadotropic hypogonadism Kallmann syndrome
Domain	Signal
Molecular function	Neuropeptide
PTM	Disulfide bond
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	activation of MAPK activity Traceable author statement. Source: UniProtKB angiogenesis Inferred from direct assay. Source: UniProtKB anti-apoptosis Inferred from direct assay. Source: UniProtKB cell proliferation Inferred from direct assay. Source: UniProtKB chemotaxis Inferred from direct assay. Source: UniProtKB elevation of cytosolic calcium ion concentration Traceable author statement. Source: UniProtKB inflammatory response Non-traceable author statement Ref.1. Source: UniProtKB neuropeptide signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of smooth muscle contraction Inferred from direct assay Ref.1. Source: UniProtKB sensory perception of pain Traceable author statement. Source: UniProtKB spermatogenesis Inferred from mutant phenotype Ref.4. Source: UniProtKB
Cellular component	extracellular region Traceable author statement. Source: UniProtKB
Molecular function	G-protein coupled receptor binding Traceable author statement. 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Ref.5
	Chain	28 – 129	102	Prokineticin-2		PRO_0000025809
Amino acid modifications
	Disulfide bond	34 ↔ 46		By similarity
	Disulfide bond	40 ↔ 58		By similarity
	Disulfide bond	45 ↔ 107		By similarity
	Disulfide bond	68 ↔ 115		By similarity
	Disulfide bond	109 ↔ 125		By similarity
Natural variations
	Alternative sequence	75 – 95	21	Missing in isoform 2.		VSP_005219
	Natural variant	32	1	G → R in KAL4. Ref.6		VAR_030955
	Natural variant	73	1	R → C in KAL4. Ref.6		VAR_030956

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 26, 2001. Version 2. Checksum: 0487679E8700DA55	FASTA	129	14,314
	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
	Isoform 2 [UniParc]. Checksum: D7AF89D8551A97FC	FASTA	108	11,659
	10 20 30 40 50 60 MRSLCCAPLL LLLLLPPLLL TPRAGDAAVI TGACDKDSQC GGGMCCAVSI WVKSIRICTP 70 80 90 100 MGKLGDSCHP LTRKVPFFGR RMHHTCPCLP GLACLRTSFN RFICLAQK

References

	« Hide 'large scale' referencesShow '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: 11259612] [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: 15772293] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"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] (ISOFORM 1).
[4]	"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: 10580115] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-129 (ISOFORM 1). Tissue: Testis.
[5]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-42.
[6]	"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: 17054399] [Abstract] Cited for: VARIANTS KAL4 ARG-32 AND CYS-73.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF333025 mRNA. Translation: AAK49919.1. AY349131 mRNA. Translation: AAR06657.1. BC098162 mRNA. Translation: AAH98162.1. AF182069 mRNA. Translation: AAG16893.2.
IPI	IPI00030045. IPI00220189.
RefSeq	NP_001119600.1. NM_001126128.1. NP_068754.1. NM_021935.3.
UniGene	Hs.528665.
3D structure databases
ProteinModelPortal	Q9HC23.
SMR	Q9HC23. Positions 28-128.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9HC23.
PTM databases
PhosphoSite	Q9HC23.
Polymorphism databases
DMDM	18202953.
Proteomic databases
PRIDE	Q9HC23.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000295619; ENSP00000295619; ENSG00000163421.
GeneID	60675.
KEGG	hsa:60675.
UCSC	uc003doz.2. human. uc003dpa.2. human.
Organism-specific databases
CTD	60675.
GeneCards	GC03M071903.
H-InvDB	HIX0030733.
HGNC	HGNC:18455. PROK2.
HPA	HPA041408.
MIM	607002. gene. 610628. phenotype.
neXtProt	NX_Q9HC23.
Orphanet	478. Kallmann syndrome. 432. Normosmic congenital hypogonadotropic hypogonadism.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG20478.
GeneTree	ENSGT00390000014799.
HOGENOM	HBG713175.
HOVERGEN	HBG031845.
InParanoid	Q9HC23.
OMA	PLTRKNH.
OrthoDB	EOG42NJ21.
PhylomeDB	Q9HC23.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q9HC23.
Bgee	Q9HC23.
CleanEx	HS_PROK2.
Genevestigator	Q9HC23.
GermOnline	ENSG00000163421. Homo sapiens.
Family and domain databases
InterPro	IPR009523. Prokineticin. IPR023569. Prokineticin_domain. [Graphical view]
PANTHER	PTHR18821. Prokineticin. 1 hit.
Pfam	PF06607. Prokineticin. 1 hit. [Graphical view]
ProDom	PD059788. Prokineticin. 1 hit. [Graphical view] [Entries sharing at least one domain]
ProtoNet	Search...
Other
NextBio	65482.
SOURCE	Search...

Entry information

Entry name

PROK2_HUMAN

Accession

Primary (citable) accession number: Q9HC23
Secondary accession number(s): Q53Z79

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	September 26, 2001
Last modified:	January 25, 2012
This is version 90 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.