GP15L_HUMAN
ID GP15L_HUMAN Reviewed; 81 AA.
AC Q6UWK7;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Protein GPR15L {ECO:0000303|PubMed:28900043};
DE AltName: Full=Antimicrobial peptide with 57 amino acid residues {ECO:0000303|PubMed:25585381};
DE Short=AP-57 {ECO:0000303|PubMed:25585381};
DE Short=Antimicrobial peptide-57 {ECO:0000303|PubMed:25585381};
DE AltName: Full=Colon-derived SUSD2 binding factor {ECO:0000303|PubMed:25351403};
DE Short=CSBF {ECO:0000303|PubMed:25351403};
DE AltName: Full=Secreted protein C10orf99;
DE Flags: Precursor;
GN Name=GPR15L {ECO:0000303|PubMed:28900043};
GN Synonyms=C10orf99 {ECO:0000312|HGNC:HGNC:31428}; ORFNames=UNQ1833/PRO3446;
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP PROTEIN SEQUENCE OF 25-34, FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND INTERACTION WITH SUSD2.
RX PubMed=25351403; DOI=10.1038/srep06812;
RA Pan W., Cheng Y., Zhang H., Liu B., Mo X., Li T., Li L., Cheng X.,
RA Zhang L., Ji J., Wang P., Han W.;
RT "CSBF/C10orf99, a novel potential cytokine, inhibits colon cancer cell
RT growth through inducing G1 arrest.";
RL Sci. Rep. 4:6812-6812(2014).
RN [4]
RP PROTEIN SEQUENCE OF 44-58, FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DISULFIDE BOND.
RX PubMed=25585381; DOI=10.1016/j.bbrc.2014.12.115;
RA Yang M., Tang M., Ma X., Yang L., He J., Peng X., Guo G., Zhou L., Luo N.,
RA Yuan Z., Tong A.;
RT "AP-57/C10orf99 is a new type of mutifunctional antimicrobial peptide.";
RL Biochem. Biophys. Res. Commun. 457:347-352(2015).
RN [5]
RP FUNCTION, AND RECEPTOR BINDING.
RX PubMed=28936214; DOI=10.3389/fimmu.2017.01111;
RA Ocon B., Pan J., Dinh T.T., Chen W., Ballet R., Bscheider M., Habtezion A.,
RA Tu H., Zabel B.A., Butcher E.C.;
RT "A mucosal and cutaneous chemokine ligand for the lymphocyte
RT chemoattractant receptor GPR15.";
RL Front. Immunol. 8:1111-1111(2017).
RN [6]
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=28900043; DOI=10.1126/scisignal.aal0180;
RA Suply T., Hannedouche S., Carte N., Li J., Grosshans B., Schaefer M.,
RA Raad L., Beck V., Vidal S., Hiou-Feige A., Beluch N., Barbieri S.,
RA Wirsching J., Lageyre N., Hillger F., Debon C., Dawson J., Smith P.,
RA Lannoy V., Detheux M., Bitsch F., Falchetto R., Bouwmeester T., Porter J.,
RA Baumgarten B., Mansfield K., Carballido J.M., Seuwen K., Bassilana F.;
RT "A natural ligand for the orphan receptor GPR15 modulates lymphocyte
RT recruitment to epithelia.";
RL Sci. Signal. 10:0-0(2017).
CC -!- FUNCTION: Chemotactic factor that mediates lymphocytes recruitment to
CC epithelia through binding and activation of the G-protein coupled
CC receptor GPR15 (PubMed:28900043, PubMed:28936214). May be a tumor
CC suppressor; together with SUSD2 has a growth inhibitory effect on colon
CC cancer cells which includes G1 cell cycle arrest (PubMed:25351403).
CC {ECO:0000269|PubMed:25351403, ECO:0000269|PubMed:28900043,
CC ECO:0000269|PubMed:28936214}.
CC -!- FUNCTION: Has antimicrobial activity against Gram-positive bacteria,
CC including Staphylococcus aureus and Actinomyces spec., and Mycoplasma
CC hominis and lentivirus (PubMed:25585381).
CC {ECO:0000269|PubMed:25585381}.
CC -!- SUBUNIT: Interacts with SUSD2; the interaction is direct.
CC {ECO:0000269|PubMed:25351403}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:25351403,
CC ECO:0000269|PubMed:25585381}.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in colon, and cervix and
CC at moderate level in tonsil (PubMed:25585381, PubMed:28900043). Highly
CC reduced expression in primary colon cancer tissues compared with that
CC in adjacent tissues (PubMed:25351403). Highest levels of expression
CC detected in stomach and colon; expressed in epithelium of skin and
CC esophagus, and in some tumor and/or tumor adjacent tissues (TAT),
CC including TAT of esophagus cancer, hepatocellular carcinoma (HCC),
CC squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and invasive
CC ductal carcinoma (IDC) tissues (at protein level) (PubMed:25585381).
CC {ECO:0000269|PubMed:25585381, ECO:0000269|PubMed:28900043}.
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DR EMBL; AY358751; AAQ89111.1; -; mRNA.
DR EMBL; AC022389; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS7371.1; -.
DR RefSeq; NP_997256.1; NM_207373.2.
DR AlphaFoldDB; Q6UWK7; -.
DR STRING; 9606.ENSP00000361199; -.
DR GlyGen; Q6UWK7; 1 site.
DR iPTMnet; Q6UWK7; -.
DR PhosphoSitePlus; Q6UWK7; -.
DR BioMuta; C10orf99; -.
DR DMDM; 74749393; -.
DR MassIVE; Q6UWK7; -.
DR PaxDb; Q6UWK7; -.
DR PeptideAtlas; Q6UWK7; -.
DR PRIDE; Q6UWK7; -.
DR Antibodypedia; 62671; 7 antibodies from 6 providers.
DR DNASU; 387695; -.
DR Ensembl; ENST00000372126.4; ENSP00000361199.3; ENSG00000188373.5.
DR GeneID; 387695; -.
DR KEGG; hsa:387695; -.
DR MANE-Select; ENST00000372126.4; ENSP00000361199.3; NM_207373.3; NP_997256.1.
DR UCSC; uc001kcu.4; human.
DR CTD; 387695; -.
DR DisGeNET; 387695; -.
DR GeneCards; C10orf99; -.
DR HGNC; HGNC:31428; C10orf99.
DR HPA; ENSG00000188373; Group enriched (esophagus, intestine, vagina).
DR MIM; 617775; gene.
DR neXtProt; NX_Q6UWK7; -.
DR OpenTargets; ENSG00000188373; -.
DR PharmGKB; PA134990747; -.
DR VEuPathDB; HostDB:ENSG00000188373; -.
DR eggNOG; ENOG502TD47; Eukaryota.
DR GeneTree; ENSGT00390000015172; -.
DR HOGENOM; CLU_195436_0_0_1; -.
DR InParanoid; Q6UWK7; -.
DR OMA; LTNPKGH; -.
DR OrthoDB; 1583928at2759; -.
DR PhylomeDB; Q6UWK7; -.
DR TreeFam; TF336385; -.
DR PathwayCommons; Q6UWK7; -.
DR SignaLink; Q6UWK7; -.
DR BioGRID-ORCS; 387695; 8 hits in 1056 CRISPR screens.
DR ChiTaRS; C10orf99; human.
DR GenomeRNAi; 387695; -.
DR Pharos; Q6UWK7; Tbio.
DR PRO; PR:Q6UWK7; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q6UWK7; protein.
DR Bgee; ENSG00000188373; Expressed in gingival epithelium and 110 other tissues.
DR Genevisible; Q6UWK7; HS.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0008009; F:chemokine activity; IDA:UniProtKB.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IDA:UniProtKB.
DR GO; GO:0048018; F:receptor ligand activity; IDA:UniProtKB.
DR GO; GO:0050832; P:defense response to fungus; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0048247; P:lymphocyte chemotaxis; IDA:UniProtKB.
DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; IDA:UniProtKB.
DR GO; GO:0051782; P:negative regulation of cell division; IDA:UniProtKB.
DR GO; GO:2000404; P:regulation of T cell migration; IDA:UniProtKB.
DR InterPro; IPR031713; GPR15L.
DR Pfam; PF15854; GPR15L; 1.
PE 1: Evidence at protein level;
KW Antibiotic; Antimicrobial; Chemotaxis; Cytokine; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Reference proteome; Secreted; Signal;
KW Tumor suppressor.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:25351403"
FT CHAIN 25..81
FT /note="Protein GPR15L"
FT /id="PRO_0000260084"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 40..63
FT /evidence="ECO:0000250|UniProtKB:I3LGZ3"
FT DISULFID 41..60
FT /evidence="ECO:0000250|UniProtKB:I3LGZ3"
SQ SEQUENCE 81 AA; 9173 MW; 276E720364160B8A CRC64;
MRLLVLSSLL CILLLCFSIF STEGKRRPAK AWSGRRTRLC CHRVPSPNST NLKGHHVRLC
KPCKLEPEPR LWVVPGALPQ V
