ID   ESM1_HUMAN              Reviewed;         184 AA.
AC   Q9NQ30; B2R4G3; Q15330; Q3V4E3; Q96ES3;
DT   27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT   27-APR-2001, sequence version 2.
DT   24-JAN-2024, entry version 167.
DE   RecName: Full=Endothelial cell-specific molecule 1;
DE            Short=ESM-1;
DE   Flags: Precursor;
GN   Name=ESM1;
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] (ISOFORM 1).
RC   TISSUE=Umbilical vein endothelial cell;
RX   PubMed=8702785; DOI=10.1074/jbc.271.34.20458;
RA   Lassalle P., Molet S., Janin A., Vander-Heyden J.E., Tavernier J.,
RA   Fiers W., Devos R.E., Tonnel A.-B.;
RT   "ESM-1 is a novel human endothelial cell-specific molecule expressed in
RT   lung and regulated by cytokines.";
RL   J. Biol. Chem. 271:20458-20464(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Leukocyte;
RA   Vedrenne C., Kervoaze G., Lassalle P.;
RT   "Sequencing of the human ESM-1 gene and analysis of its 5' flanking
RT   region.";
RL   Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA   Depontieu F., Grigoriu B., Scherpereel A., Adam E., Lafitte J.J.,
RA   Ouatas T., Delehedde M., Lyon M., Copin M.C., Janin A., Tonnel A.B.,
RA   Tsicopoulos A., Lassalle P.;
RT   "Exon 2 of the endocan gene contributes to tumorigenesis and its expression
RT   is increased in human lung tumor vascular cells.";
RL   Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Thalamus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA   Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA   Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA   Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA   Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA   Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA   Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Lung;
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   [7]
RP   FUNCTION.
RX   PubMed=20616313; DOI=10.1161/circresaha.110.217257;
RA   Brutsch R., Liebler S.S., Wustehube J., Bartol A., Herberich S.E.,
RA   Adam M.G., Telzerow A., Augustin H.G., Fischer A.;
RT   "Integrin cytoplasmic domain-associated protein-1 attenuates sprouting
RT   angiogenesis.";
RL   Circ. Res. 107:592-601(2010).
RN   [8]
RP   GLYCOSYLATION AT SER-156.
RX   PubMed=20581009; DOI=10.1093/glycob/cwq100;
RA   Sarrazin S., Lyon M., Deakin J.A., Guerrini M., Lassalle P., Delehedde M.,
RA   Lortat-Jacob H.;
RT   "Characterization and binding activity of the chondroitin/dermatan sulfate
RT   chain from Endocan, a soluble endothelial proteoglycan.";
RL   Glycobiology 20:1380-1388(2010).
RN   [9]
RP   GLYCOSYLATION AT SER-156.
RX   PubMed=32337544; DOI=10.1093/glycob/cwaa039;
RA   Toledo A.G., Pihl J., Spliid C.B., Persson A., Nilsson J., Pereira M.A.,
RA   Gustavsson T., Choudhary S., Oo H.Z., Black P.C., Daugaard M., Esko J.D.,
RA   Larson G., Salanti A., Clausen T.M.;
RT   "An affinity chromatography and glycoproteomics workflow to profile the
RT   chondroitin sulfate proteoglycans that interact with malarial VAR2CSA in
RT   the placenta and in cancer.";
RL   Glycobiology 30:989-1002(2020).
CC   -!- FUNCTION: Involved in angiogenesis; promotes angiogenic sprouting. May
CC       have potent implications in lung endothelial cell-leukocyte
CC       interactions. {ECO:0000269|PubMed:20616313}.
CC   -!- SUBUNIT: Monomer.
CC   -!- INTERACTION:
CC       Q9NQ30; O43184-4: ADAM12; NbExp=3; IntAct=EBI-12260294, EBI-12006944;
CC       Q9NQ30; Q49AR9: ANKS1A; NbExp=3; IntAct=EBI-12260294, EBI-11954519;
CC       Q9NQ30; P29972: AQP1; NbExp=3; IntAct=EBI-12260294, EBI-745213;
CC       Q9NQ30; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-12260294, EBI-11524452;
CC       Q9NQ30; Q9H5Z6-2: FAM124B; NbExp=3; IntAct=EBI-12260294, EBI-11986315;
CC       Q9NQ30; O43559: FRS3; NbExp=3; IntAct=EBI-12260294, EBI-725515;
CC       Q9NQ30; Q8WUI4-6: HDAC7; NbExp=3; IntAct=EBI-12260294, EBI-12094670;
CC       Q9NQ30; P49639: HOXA1; NbExp=3; IntAct=EBI-12260294, EBI-740785;
CC       Q9NQ30; O60333-2: KIF1B; NbExp=3; IntAct=EBI-12260294, EBI-10975473;
CC       Q9NQ30; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12260294, EBI-16439278;
CC       Q9NQ30; Q16656-4: NRF1; NbExp=3; IntAct=EBI-12260294, EBI-11742836;
CC       Q9NQ30; Q7Z417: NUFIP2; NbExp=3; IntAct=EBI-12260294, EBI-1210753;
CC       Q9NQ30; O43741: PRKAB2; NbExp=3; IntAct=EBI-12260294, EBI-1053424;
CC       Q9NQ30; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-12260294, EBI-396669;
CC       Q9NQ30; A8MV65-2: VGLL3; NbExp=3; IntAct=EBI-12260294, EBI-11957216;
CC       Q9NQ30; O76024: WFS1; NbExp=3; IntAct=EBI-12260294, EBI-720609;
CC       Q9NQ30; P25490: YY1; NbExp=3; IntAct=EBI-12260294, EBI-765538;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9NQ30-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9NQ30-2; Sequence=VSP_042631;
CC   -!- TISSUE SPECIFICITY: Expressed in lung, on the vascular capillary
CC       network within alveolar walls, and also at lower level in kidney.
CC   -!- INDUCTION: By TNF and IL1B/interleukin-1 beta, but not IL4/interleukin-
CC       4.
CC   -!- PTM: May contain intrachain disulfide bonds.
CC   -!- PTM: O-glycosylated; contains chondroitin sulfate and dermatan sulfate.
CC       {ECO:0000269|PubMed:20581009}.
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DR   EMBL; X89426; CAA61597.1; -; mRNA.
DR   EMBL; AJ401091; CAB94771.1; -; Genomic_DNA.
DR   EMBL; AJ401092; CAB94771.1; JOINED; Genomic_DNA.
DR   EMBL; AJ973643; CAJ13737.1; -; mRNA.
DR   EMBL; AK300634; BAG62324.1; -; mRNA.
DR   EMBL; AK311817; BAG34760.1; -; mRNA.
DR   EMBL; AC010436; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC034238; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC011989; AAH11989.1; -; mRNA.
DR   CCDS; CCDS3963.1; -. [Q9NQ30-1]
DR   CCDS; CCDS47206.1; -. [Q9NQ30-2]
DR   RefSeq; NP_001129076.1; NM_001135604.1. [Q9NQ30-2]
DR   RefSeq; NP_008967.1; NM_007036.4. [Q9NQ30-1]
DR   AlphaFoldDB; Q9NQ30; -.
DR   BioGRID; 116265; 15.
DR   IntAct; Q9NQ30; 17.
DR   STRING; 9606.ENSP00000370812; -.
DR   GlyCosmos; Q9NQ30; 1 site, No reported glycans.
DR   GlyGen; Q9NQ30; 1 site.
DR   iPTMnet; Q9NQ30; -.
DR   PhosphoSitePlus; Q9NQ30; -.
DR   BioMuta; ESM1; -.
DR   DMDM; 13431509; -.
DR   MassIVE; Q9NQ30; -.
DR   PaxDb; 9606-ENSP00000370812; -.
DR   PeptideAtlas; Q9NQ30; -.
DR   ProteomicsDB; 82061; -. [Q9NQ30-1]
DR   ProteomicsDB; 82062; -. [Q9NQ30-2]
DR   Antibodypedia; 23370; 291 antibodies from 27 providers.
DR   DNASU; 11082; -.
DR   Ensembl; ENST00000381403.4; ENSP00000370810.4; ENSG00000164283.13. [Q9NQ30-2]
DR   Ensembl; ENST00000381405.5; ENSP00000370812.4; ENSG00000164283.13. [Q9NQ30-1]
DR   GeneID; 11082; -.
DR   KEGG; hsa:11082; -.
DR   MANE-Select; ENST00000381405.5; ENSP00000370812.4; NM_007036.5; NP_008967.1.
DR   UCSC; uc003jpk.4; human. [Q9NQ30-1]
DR   AGR; HGNC:3466; -.
DR   CTD; 11082; -.
DR   DisGeNET; 11082; -.
DR   GeneCards; ESM1; -.
DR   HGNC; HGNC:3466; ESM1.
DR   HPA; ENSG00000164283; Tissue enhanced (kidney, thyroid gland).
DR   MIM; 601521; gene.
DR   neXtProt; NX_Q9NQ30; -.
DR   OpenTargets; ENSG00000164283; -.
DR   PharmGKB; PA27883; -.
DR   VEuPathDB; HostDB:ENSG00000164283; -.
DR   eggNOG; KOG1218; Eukaryota.
DR   GeneTree; ENSGT00390000018810; -.
DR   HOGENOM; CLU_103395_0_0_1; -.
DR   InParanoid; Q9NQ30; -.
DR   OMA; TAWSAKY; -.
DR   OrthoDB; 5341363at2759; -.
DR   PhylomeDB; Q9NQ30; -.
DR   PathwayCommons; Q9NQ30; -.
DR   SignaLink; Q9NQ30; -.
DR   BioGRID-ORCS; 11082; 8 hits in 1139 CRISPR screens.
DR   GeneWiki; ESM1; -.
DR   GenomeRNAi; 11082; -.
DR   Pharos; Q9NQ30; Tbio.
DR   PRO; PR:Q9NQ30; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; Q9NQ30; Protein.
DR   Bgee; ENSG00000164283; Expressed in islet of Langerhans and 111 other cell types or tissues.
DR   ExpressionAtlas; Q9NQ30; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005171; F:hepatocyte growth factor receptor binding; IPI:UniProtKB.
DR   GO; GO:0005178; F:integrin binding; IPI:UniProtKB.
DR   GO; GO:0001525; P:angiogenesis; IEP:UniProtKB.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR   GO; GO:1902204; P:positive regulation of hepatocyte growth factor receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0002040; P:sprouting angiogenesis; IMP:UniProtKB.
DR   Gene3D; 4.10.40.20; -; 1.
DR   InterPro; IPR038850; ESM1.
DR   InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR   InterPro; IPR000867; IGFBP-like.
DR   PANTHER; PTHR15428:SF0; ENDOTHELIAL CELL-SPECIFIC MOLECULE 1; 1.
DR   PANTHER; PTHR15428; ENDOTHELIAL CELL-SPECIFIC MOLECULE 1 ESM-1; 1.
DR   Pfam; PF00219; IGFBP; 1.
DR   SMART; SM00121; IB; 1.
DR   SUPFAM; SSF57184; Growth factor receptor domain; 1.
DR   PROSITE; PS51323; IGFBP_N_2; 1.
DR   Genevisible; Q9NQ30; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Angiogenesis; Disulfide bond; Glycoprotein;
KW   Proteoglycan; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   CHAIN           20..184
FT                   /note="Endothelial cell-specific molecule 1"
FT                   /id="PRO_0000014394"
FT   DOMAIN          24..102
FT                   /note="IGFBP N-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   CARBOHYD        156
FT                   /note="O-linked (Xyl...) (chondroitin sulfate) serine"
FT                   /evidence="ECO:0000269|PubMed:20581009,
FT                   ECO:0000269|PubMed:32337544"
FT   DISULFID        28..51
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        32..53
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        37..54
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        43..57
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        65..83
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        77..99
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   VAR_SEQ         101..150
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3"
FT                   /id="VSP_042631"
FT   CONFLICT        44
FT                   /note="K -> E (in Ref. 6; AAH11989)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        151
FT                   /note="Missing (in Ref. 2; CAB94771)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   184 AA;  20095 MW;  2AD15EDEC74BC8CE CRC64;
     MKSVLLLTTL LVPAHLVAAW SNNYAVDCPQ HCDSSECKSS PRCKRTVLDD CGCCRVCAAG
     RGETCYRTVS GMDGMKCGPG LRCQPSNGED PFGEEFGICK DCPYGTFGMD CRETCNCQSG
     ICDRGTGKCL KFPFFQYSVT KSSNRFVSLT EHDMASGDGN IVREEVVKEN AAGSPVMRKW
     LNPR
//