SPON2_HUMAN
ID SPON2_HUMAN Reviewed; 331 AA.
AC Q9BUD6; D3DVN9; Q4W5N4; Q9ULW1;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 4.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Spondin-2;
DE AltName: Full=Differentially expressed in cancerous and non-cancerous lung cells 1;
DE Short=DIL-1;
DE AltName: Full=Mindin;
DE Flags: Precursor;
GN Name=SPON2; Synonyms=DIL1; ORFNames=UNQ435/PRO866;
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], TISSUE SPECIFICITY, AND VARIANT PRO-40.
RX PubMed=10512675; DOI=10.1006/geno.1999.5939;
RA Manda R., Kohno T., Matsuno Y., Takenoshita S., Kuwano H., Yokota J.;
RT "Identification of genes (SPON2 and C20orf2) differentially expressed
RT between cancerous and noncancerous lung cells by mRNA differential
RT display.";
RL Genomics 61:5-14(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS PRO-40; GLU-122 AND
RP LEU-242.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS PRO-40; GLU-122 AND
RP LEU-242.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS PRO-40 AND
RP LEU-242.
RA Mural R.J., Istrail S., Sutton 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS PRO-40; GLU-122 AND
RP LEU-242.
RC TISSUE=Colon, and Placenta;
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 X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 27-249 IN COMPLEX WITH METAL IONS,
RP PARTIAL PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, SUBUNIT,
RP GLYCOSYLATION AT TRP-283, INTERACTION WITH INTEGRIN AND BACTERIAL
RP LIPOPOLYSACCHARIDE, MUTAGENESIS OF LYS-42 AND GLU-141, AND DISULFIDE BOND.
RX PubMed=19153605; DOI=10.1038/emboj.2008.288;
RA Li Y., Cao C., Jia W., Yu L., Mo M., Wang Q., Huang Y., Lim J.-M.,
RA Ishihara M., Wells L., Azadi P., Robinson H., He Y.-W., Zhang L.,
RA Mariuzza R.A.;
RT "Structure of the F-spondin domain of mindin, an integrin ligand and
RT pattern recognition molecule.";
RL EMBO J. 28:286-297(2009).
CC -!- FUNCTION: Cell adhesion protein that promotes adhesion and outgrowth of
CC hippocampal embryonic neurons. Binds directly to bacteria and their
CC components and functions as an opsonin for macrophage phagocytosis of
CC bacteria. Essential in the initiation of the innate immune response and
CC represents a unique pattern-recognition molecule in the ECM for
CC microbial pathogens (By similarity). Binds bacterial lipopolysaccharide
CC (LPS). {ECO:0000250}.
CC -!- SUBUNIT: Monomer. Interacts with integrin.
CC {ECO:0000269|PubMed:19153605}.
CC -!- INTERACTION:
CC Q9BUD6; Q86V38: ATN1; NbExp=3; IntAct=EBI-10298801, EBI-11954292;
CC Q9BUD6; Q92876: KLK6; NbExp=3; IntAct=EBI-10298801, EBI-2432309;
CC Q9BUD6; Q15323: KRT31; NbExp=6; IntAct=EBI-10298801, EBI-948001;
CC Q9BUD6; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-10298801, EBI-742388;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in normal lung tissue but not in lung
CC carcinoma cell lines. {ECO:0000269|PubMed:10512675}.
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DR EMBL; AB027466; BAA85892.1; -; mRNA.
DR EMBL; AY358948; AAQ89307.1; -; mRNA.
DR EMBL; AK074618; BAC11092.1; -; mRNA.
DR EMBL; AK074770; BAC11196.1; -; mRNA.
DR EMBL; AC092535; AAY40988.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82604.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82606.1; -; Genomic_DNA.
DR EMBL; BC002707; AAH02707.1; -; mRNA.
DR EMBL; BC036341; AAH36341.1; -; mRNA.
DR CCDS; CCDS3347.1; -.
DR RefSeq; NP_001121797.1; NM_001128325.2.
DR RefSeq; NP_001185950.1; NM_001199021.1.
DR RefSeq; NP_036577.1; NM_012445.3.
DR PDB; 3D34; X-ray; 1.80 A; A/B=27-249.
DR PDBsum; 3D34; -.
DR AlphaFoldDB; Q9BUD6; -.
DR BioGRID; 115686; 9.
DR IntAct; Q9BUD6; 8.
DR STRING; 9606.ENSP00000483599; -.
DR GlyGen; Q9BUD6; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BUD6; -.
DR PhosphoSitePlus; Q9BUD6; -.
DR BioMuta; SPON2; -.
DR DMDM; 313104285; -.
DR jPOST; Q9BUD6; -.
DR MassIVE; Q9BUD6; -.
DR MaxQB; Q9BUD6; -.
DR PaxDb; Q9BUD6; -.
DR PeptideAtlas; Q9BUD6; -.
DR PRIDE; Q9BUD6; -.
DR ProteomicsDB; 79078; -.
DR Antibodypedia; 22210; 310 antibodies from 35 providers.
DR DNASU; 10417; -.
DR Ensembl; ENST00000290902.10; ENSP00000290902.5; ENSG00000159674.12.
DR Ensembl; ENST00000431380.5; ENSP00000394832.1; ENSG00000159674.12.
DR Ensembl; ENST00000617421.4; ENSP00000483599.1; ENSG00000159674.12.
DR GeneID; 10417; -.
DR KEGG; hsa:10417; -.
DR MANE-Select; ENST00000290902.10; ENSP00000290902.5; NM_012445.4; NP_036577.2.
DR UCSC; uc003gco.5; human.
DR CTD; 10417; -.
DR DisGeNET; 10417; -.
DR GeneCards; SPON2; -.
DR HGNC; HGNC:11253; SPON2.
DR HPA; ENSG00000159674; Tissue enhanced (endometrium).
DR MIM; 605918; gene.
DR neXtProt; NX_Q9BUD6; -.
DR OpenTargets; ENSG00000159674; -.
DR PharmGKB; PA36083; -.
DR VEuPathDB; HostDB:ENSG00000159674; -.
DR eggNOG; KOG3539; Eukaryota.
DR GeneTree; ENSGT00940000159900; -.
DR HOGENOM; CLU_034407_0_0_1; -.
DR InParanoid; Q9BUD6; -.
DR OrthoDB; 517669at2759; -.
DR PhylomeDB; Q9BUD6; -.
DR TreeFam; TF326913; -.
DR PathwayCommons; Q9BUD6; -.
DR Reactome; R-HSA-5083635; Defective B3GALTL causes PpS.
DR Reactome; R-HSA-5173214; O-glycosylation of TSR domain-containing proteins.
DR SignaLink; Q9BUD6; -.
DR BioGRID-ORCS; 10417; 10 hits in 1070 CRISPR screens.
DR ChiTaRS; SPON2; human.
DR EvolutionaryTrace; Q9BUD6; -.
DR GenomeRNAi; 10417; -.
DR Pharos; Q9BUD6; Tbio.
DR PRO; PR:Q9BUD6; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9BUD6; protein.
DR Bgee; ENSG00000159674; Expressed in granulocyte and 184 other tissues.
DR ExpressionAtlas; Q9BUD6; baseline and differential.
DR Genevisible; Q9BUD6; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0003823; F:antigen binding; IEA:Ensembl.
DR GO; GO:0001530; F:lipopolysaccharide binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0050832; P:defense response to fungus; IEA:Ensembl.
DR GO; GO:0051607; P:defense response to virus; IEA:Ensembl.
DR GO; GO:0043152; P:induction of bacterial agglutination; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002448; P:mast cell mediated immunity; IEA:Ensembl.
DR GO; GO:0008228; P:opsonization; IEA:Ensembl.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IEA:Ensembl.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR Gene3D; 2.20.100.10; -; 1.
DR Gene3D; 2.60.40.2130; -; 1.
DR InterPro; IPR009465; Spondin_N.
DR InterPro; IPR038678; Spondin_N_sf.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR InterPro; IPR044004; TSP1_spondin_dom.
DR Pfam; PF06468; Spond_N; 1.
DR Pfam; PF19028; TSP1_spondin; 1.
DR SMART; SM00209; TSP1; 1.
DR SUPFAM; SSF82895; SSF82895; 1.
DR PROSITE; PS51020; SPONDIN; 1.
DR PROSITE; PS50092; TSP1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cell adhesion; Direct protein sequencing;
KW Disulfide bond; Extracellular matrix; Glycoprotein; Immunity;
KW Innate immunity; Metal-binding; Reference proteome; Secreted; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..331
FT /note="Spondin-2"
FT /id="PRO_0000035870"
FT DOMAIN 31..221
FT /note="Spondin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00364"
FT DOMAIN 277..331
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT BINDING 141
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000305"
FT BINDING 160
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:19153605,
FT ECO:0007744|PDB:3D34"
FT BINDING 188
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:19153605,
FT ECO:0007744|PDB:3D34"
FT BINDING 192
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:19153605,
FT ECO:0007744|PDB:3D34"
FT SITE 141
FT /note="Important for metal ion-dependent interaction with
FT integrin"
FT /evidence="ECO:0000305|PubMed:19153605"
FT CARBOHYD 283
FT /note="C-linked (Man) tryptophan"
FT /evidence="ECO:0000269|PubMed:19153605"
FT DISULFID 35..171
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210,
FT ECO:0000269|PubMed:19153605"
FT VARIANT 38
FT /note="R -> G (in dbSNP:rs6836335)"
FT /id="VAR_055149"
FT VARIANT 40
FT /note="L -> P (in dbSNP:rs922697)"
FT /evidence="ECO:0000269|PubMed:10512675,
FT ECO:0000269|PubMed:12975309, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.5"
FT /id="VAR_019701"
FT VARIANT 122
FT /note="A -> E (in dbSNP:rs11247975)"
FT /evidence="ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_019702"
FT VARIANT 242
FT /note="V -> L (in dbSNP:rs2279279)"
FT /evidence="ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.5"
FT /id="VAR_019703"
FT MUTAGEN 42
FT /note="K->A: Strongly reduced metal-dependent interaction
FT with integrin; when associated with A-141."
FT /evidence="ECO:0000269|PubMed:19153605"
FT MUTAGEN 141
FT /note="E->A: Strongly reduced metal-dependent interaction
FT with integrin; when associated with A-42."
FT /evidence="ECO:0000269|PubMed:19153605"
FT STRAND 41..49
FT /evidence="ECO:0007829|PDB:3D34"
FT TURN 53..55
FT /evidence="ECO:0007829|PDB:3D34"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:3D34"
FT STRAND 67..77
FT /evidence="ECO:0007829|PDB:3D34"
FT HELIX 92..100
FT /evidence="ECO:0007829|PDB:3D34"
FT HELIX 104..117
FT /evidence="ECO:0007829|PDB:3D34"
FT STRAND 120..126
FT /evidence="ECO:0007829|PDB:3D34"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:3D34"
FT STRAND 135..143
FT /evidence="ECO:0007829|PDB:3D34"
FT STRAND 148..157
FT /evidence="ECO:0007829|PDB:3D34"
FT STRAND 159..169
FT /evidence="ECO:0007829|PDB:3D34"
FT STRAND 178..184
FT /evidence="ECO:0007829|PDB:3D34"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:3D34"
FT STRAND 215..218
FT /evidence="ECO:0007829|PDB:3D34"
FT STRAND 230..232
FT /evidence="ECO:0007829|PDB:3D34"
FT STRAND 236..243
FT /evidence="ECO:0007829|PDB:3D34"
SQ SEQUENCE 331 AA; 35788 MW; 3ABB49FEC45579EC CRC64;
MENPSPAAAL GKALCALLLA TLGAAGQPLG GESICSARAL AKYSITFTGK WSQTAFPKQY
PLFRPPAQWS SLLGAAHSSD YSMWRKNQYV SNGLRDFAER GEAWALMKEI EAAGEALQSV
HAVFSAPAVP SGTGQTSAEL EVQRRHSLVS FVVRIVPSPD WFVGVDSLDL CDGDRWREQA
ALDLYPYDAG TDSGFTFSSP NFATIPQDTV TEITSSSPSH PANSFYYPRL KALPPIARVT
LVRLRQSPRA FIPPAPVLPS RDNEIVDSAS VPETPLDCEV SLWSSWGLCG GHCGRLGTKS
RTRYVRVQPA NNGSPCPELE EEAECVPDNC V
