PROK1_HUMAN
ID PROK1_HUMAN Reviewed; 105 AA.
AC P58294; Q5VWD4; Q8TC69;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2001, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Prokineticin-1;
DE AltName: Full=Endocrine-gland-derived vascular endothelial growth factor;
DE Short=EG-VEGF;
DE AltName: Full=Mambakine;
DE Flags: Precursor;
GN Name=PROK1; ORFNames=UNQ600/PRO1186;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=11259612; DOI=10.1124/mol.59.4.692;
RA Li M., Bullock C.M., Knauer D.J., Ehlert F.J., Zhou Q.-Y.;
RT "Identification of two prokineticin cDNAs: recombinant proteins potently
RT contract gastrointestinal smooth muscle.";
RL Mol. Pharmacol. 59:692-698(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11528470; DOI=10.1038/35091000;
RA LeCouter J., Kowalski J., Foster J., Hass P., Zhang Z., Dillard-Telm L.,
RA Frantz G., Rangell L., DeGuzman L., Keller G.-A., Peale F., Gurney A.,
RA Hillan K.J., Ferrara N.;
RT "Identification of an angiogenic mitogen selective for endocrine gland
RT endothelium.";
RL Nature 412:877-884(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Fraser C.;
RT "Mambakine, a snake venom related endocrine hormone that controls
RT macrophages.";
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-67.
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 20-34.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [9]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15292351; DOI=10.1210/jc.2003-032024;
RA Samson M., Peale F.V. Jr., Frantz G., Rioux-Leclercq N.,
RA Rajpert-De Meyts E., Ferrara N.;
RT "Human endocrine gland-derived vascular endothelial growth factor:
RT expression early in development and in Leydig cell tumors suggests roles in
RT normal and pathological testis angiogenesis.";
RL J. Clin. Endocrinol. Metab. 89:4078-4088(2004).
RN [10]
RP FUNCTION.
RX PubMed=17289879; DOI=10.1158/1078-0432.ccr-06-2176;
RA Ngan E.S.W., Sit F.Y.L., Lee K.L., Miao X., Yuan Z., Wang W.,
RA Nicholls J.M., Wong K.K.Y., Garcia-Barcelo M., Lui V.C.H., Tam P.K.H.;
RT "Implications of endocrine gland-derived vascular endothelial growth
RT factor/prokineticin-1 signaling in human neuroblastoma progression.";
RL Clin. Cancer Res. 13:868-875(2007).
RN [11]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18339712; DOI=10.1210/en.2007-1633;
RA Evans J., Catalano R.D., Morgan K., Critchley H.O.D., Millar R.P.,
RA Jabbour H.N.;
RT "Prokineticin 1 signaling and gene regulation in early human pregnancy.";
RL Endocrinology 149:2877-2887(2008).
CC -!- FUNCTION: Potently contracts gastrointestinal (GI) smooth muscle.
CC Induces proliferation, migration and fenestration (the formation of
CC membrane discontinuities) in capillary endothelial cells derived from
CC endocrine glands. Has little or no effect on a variety of other
CC endothelial and non-endothelial cell types. Induces proliferation and
CC differentiation, but not migration, of enteric neural crest cells.
CC Directly influences neuroblastoma progression by promoting the
CC proliferation and migration of neuroblastoma cells. Positively
CC regulates PTGS2 expression and prostaglandin synthesis. May play a role
CC in placentation. May play a role in normal and pathological testis
CC angiogenesis. {ECO:0000269|PubMed:11259612,
CC ECO:0000269|PubMed:11528470, ECO:0000269|PubMed:15292351,
CC ECO:0000269|PubMed:17289879, ECO:0000269|PubMed:18339712}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Localizes to glandular epithelium, stroma and
CC vascular epithelial cells of first trimester decidua (at protein
CC level). Up-regulated in first trimester decidua when compared with non-
CC pregnant endometrium. Expressed in the steroidogenic glands, ovary,
CC testis, adrenal and placenta. {ECO:0000269|PubMed:11528470,
CC ECO:0000269|PubMed:15292351, ECO:0000269|PubMed:18339712}.
CC -!- DEVELOPMENTAL STAGE: In adult testis, is strongly expressed only in
CC Leydig cells. In testicular tumors, expressed specifically in Leydig
CC cell tumors (at protein level). Expressed from 14 weeks until birth in
CC fetal testis.
CC -!- SIMILARITY: Belongs to the AVIT (prokineticin) family. {ECO:0000305}.
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DR EMBL; AF333024; AAK49918.1; -; mRNA.
DR EMBL; AY029225; AAK33111.1; -; mRNA.
DR EMBL; AY358683; AAQ89046.1; -; mRNA.
DR EMBL; AL358215; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL390797; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471122; EAW56449.1; -; Genomic_DNA.
DR EMBL; BC025399; AAH25399.1; -; mRNA.
DR CCDS; CCDS825.1; -.
DR RefSeq; NP_115790.1; NM_032414.2.
DR AlphaFoldDB; P58294; -.
DR SMR; P58294; -.
DR BioGRID; 124072; 5.
DR STRING; 9606.ENSP00000271331; -.
DR iPTMnet; P58294; -.
DR PhosphoSitePlus; P58294; -.
DR BioMuta; PROK1; -.
DR DMDM; 17380189; -.
DR PaxDb; P58294; -.
DR PRIDE; P58294; -.
DR Antibodypedia; 20098; 318 antibodies from 30 providers.
DR DNASU; 84432; -.
DR Ensembl; ENST00000271331.4; ENSP00000271331.3; ENSG00000143125.6.
DR GeneID; 84432; -.
DR KEGG; hsa:84432; -.
DR MANE-Select; ENST00000271331.4; ENSP00000271331.3; NM_032414.3; NP_115790.1.
DR UCSC; uc001dzs.4; human.
DR CTD; 84432; -.
DR DisGeNET; 84432; -.
DR GeneCards; PROK1; -.
DR HGNC; HGNC:18454; PROK1.
DR HPA; ENSG00000143125; Group enriched (ovary, placenta, testis).
DR MIM; 606233; gene.
DR neXtProt; NX_P58294; -.
DR OpenTargets; ENSG00000143125; -.
DR PharmGKB; PA38539; -.
DR VEuPathDB; HostDB:ENSG00000143125; -.
DR eggNOG; ENOG502S1PW; Eukaryota.
DR GeneTree; ENSGT00940000161331; -.
DR HOGENOM; CLU_143202_2_0_1; -.
DR InParanoid; P58294; -.
DR OMA; GACERDI; -.
DR OrthoDB; 1517288at2759; -.
DR PhylomeDB; P58294; -.
DR TreeFam; TF332732; -.
DR PathwayCommons; P58294; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR SignaLink; P58294; -.
DR SIGNOR; P58294; -.
DR BioGRID-ORCS; 84432; 14 hits in 1054 CRISPR screens.
DR GenomeRNAi; 84432; -.
DR Pharos; P58294; Tbio.
DR PRO; PR:P58294; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P58294; protein.
DR Bgee; ENSG00000143125; Expressed in left ovary and 102 other tissues.
DR ExpressionAtlas; P58294; baseline and differential.
DR Genevisible; P58294; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IEA:Ensembl.
DR GO; GO:0045765; P:regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:0101023; P:vascular endothelial cell proliferation; IEA:Ensembl.
DR InterPro; IPR009523; Prokineticin.
DR InterPro; IPR023569; Prokineticin_domain.
DR PANTHER; PTHR18821; PTHR18821; 1.
DR Pfam; PF06607; Prokineticin; 1.
PE 1: Evidence at protein level;
KW Angiogenesis; Direct protein sequencing; Disulfide bond; Growth factor;
KW Mitogen; Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 20..105
FT /note="Prokineticin-1"
FT /id="PRO_0000025807"
FT DISULFID 26..38
FT /evidence="ECO:0000250"
FT DISULFID 32..50
FT /evidence="ECO:0000250"
FT DISULFID 37..78
FT /evidence="ECO:0000250"
FT DISULFID 60..86
FT /evidence="ECO:0000250"
FT DISULFID 80..96
FT /evidence="ECO:0000250"
FT VARIANT 67
FT /note="V -> I (in dbSNP:rs7514102)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_053610"
SQ SEQUENCE 105 AA; 11715 MW; C7E3FDE30EFB416A CRC64;
MRGATRVSIM LLLVTVSDCA VITGACERDV QCGAGTCCAI SLWLRGLRMC TPLGREGEEC
HPGSHKVPFF RKRKHHTCPC LPNLLCSRFP DGRYRCSMDL KNINF
