SOSD1_HUMAN
ID SOSD1_HUMAN Reviewed; 206 AA.
AC Q6X4U4; A8MUA6; Q96HJ7; Q9Y3U3;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Sclerostin domain-containing protein 1;
DE AltName: Full=Ectodermal BMP inhibitor;
DE Short=Ectodin;
DE AltName: Full=Uterine sensitization-associated gene 1 protein;
DE Short=USAG-1;
DE Flags: Precursor;
GN Name=SOSTDC1; Synonyms=USAG1; ORFNames=CDA019;
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).
RX PubMed=14623234; DOI=10.1016/j.ydbio.2003.08.011;
RA Laurikkala J., Kassai Y., Pakkasjaervi L., Thesleff I., Itoh N.;
RT "Identification of a secreted BMP antagonist, ectodin, integrating BMP,
RT FGF, and SHH signals from the tooth enamel knot.";
RL Dev. Biol. 264:91-105(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pheochromocytoma;
RA Liu F., Xu X.R., Qian B.Z., Xiao H., Chen Z., Han Z.;
RT "A novel gene expressed in human pheochromocytoma.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA O'Shaughnessy R.F.L., Yeo W., Gautier J., Jahoda C.A.B., Christiano A.M.;
RT "A novel secreted WNT agonist is a requirement for epithelial-mesenchymal
RT interactions.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
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 PROTEIN SEQUENCE OF 24-38.
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 74-206 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [9]
RP FUNCTION, INTERACTION WITH BMP2; BMP4 AND BMP7, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=15020244; DOI=10.1016/j.bbrc.2004.02.075;
RA Yanagita M., Oka M., Watabe T., Iguchi H., Niida A., Takahashi S.,
RA Akiyama T., Miyazono K., Yanagisawa M., Sakurai T.;
RT "USAG-1: a bone morphogenetic protein antagonist abundantly expressed in
RT the kidney.";
RL Biochem. Biophys. Res. Commun. 316:490-500(2004).
CC -!- FUNCTION: May be involved in the onset of endometrial receptivity for
CC implantation/sensitization for the decidual cell reaction Enhances Wnt
CC signaling and inhibits TGF-beta signaling (By similarity). Directly
CC antagonizes activity of BMP2, BMP4, BMP6 and BMP7 in a dose-dependent
CC manner. {ECO:0000250, ECO:0000269|PubMed:15020244}.
CC -!- SUBUNIT: Interacts with BMP2, BMP4, BMP6 and BMP7 with high affinity.
CC {ECO:0000269|PubMed:15020244}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15020244}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6X4U4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6X4U4-2; Sequence=VSP_054240;
CC -!- TISSUE SPECIFICITY: Highly expressed in kidney and weakly in lung.
CC {ECO:0000269|PubMed:15020244}.
CC -!- SIMILARITY: Belongs to the sclerostin family. {ECO:0000305}.
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DR EMBL; AB059270; BAC20331.1; -; mRNA.
DR EMBL; AF361494; AAL57219.1; -; mRNA.
DR EMBL; AY255634; AAQ83296.1; -; mRNA.
DR EMBL; AK093408; BAG52710.1; -; mRNA.
DR EMBL; AC005014; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC079155; AAQ96855.1; -; Genomic_DNA.
DR EMBL; BC008484; AAH08484.1; -; mRNA.
DR EMBL; AL050024; CAB43243.2; -; mRNA.
DR CCDS; CCDS5360.1; -. [Q6X4U4-1]
DR PIR; T08710; T08710.
DR RefSeq; NP_056279.1; NM_015464.2. [Q6X4U4-1]
DR RefSeq; XP_016867432.1; XM_017011943.1.
DR AlphaFoldDB; Q6X4U4; -.
DR SMR; Q6X4U4; -.
DR BioGRID; 117428; 27.
DR STRING; 9606.ENSP00000304930; -.
DR GlyConnect; 2944; 6 N-Linked glycans (1 site).
DR GlyGen; Q6X4U4; 2 sites, 7 N-linked glycans (1 site).
DR iPTMnet; Q6X4U4; -.
DR PhosphoSitePlus; Q6X4U4; -.
DR BioMuta; SOSTDC1; -.
DR DMDM; 62287504; -.
DR MassIVE; Q6X4U4; -.
DR PaxDb; Q6X4U4; -.
DR PeptideAtlas; Q6X4U4; -.
DR PRIDE; Q6X4U4; -.
DR ProteomicsDB; 2091; -.
DR ProteomicsDB; 67782; -. [Q6X4U4-1]
DR Antibodypedia; 56432; 149 antibodies from 17 providers.
DR DNASU; 25928; -.
DR Ensembl; ENST00000307068.5; ENSP00000304930.4; ENSG00000171243.8. [Q6X4U4-1]
DR Ensembl; ENST00000396652.1; ENSP00000379889.1; ENSG00000171243.8. [Q6X4U4-2]
DR GeneID; 25928; -.
DR KEGG; hsa:25928; -.
DR MANE-Select; ENST00000307068.5; ENSP00000304930.4; NM_015464.3; NP_056279.1.
DR UCSC; uc003stg.4; human. [Q6X4U4-1]
DR CTD; 25928; -.
DR DisGeNET; 25928; -.
DR GeneCards; SOSTDC1; -.
DR HGNC; HGNC:21748; SOSTDC1.
DR HPA; ENSG00000171243; Tissue enhanced (choroid plexus, lung, stomach).
DR MIM; 609675; gene.
DR neXtProt; NX_Q6X4U4; -.
DR OpenTargets; ENSG00000171243; -.
DR PharmGKB; PA134937603; -.
DR VEuPathDB; HostDB:ENSG00000171243; -.
DR eggNOG; ENOG502QV5G; Eukaryota.
DR GeneTree; ENSGT00390000014900; -.
DR HOGENOM; CLU_087969_0_0_1; -.
DR InParanoid; Q6X4U4; -.
DR OMA; KFWARRS; -.
DR PhylomeDB; Q6X4U4; -.
DR TreeFam; TF353019; -.
DR PathwayCommons; Q6X4U4; -.
DR SignaLink; Q6X4U4; -.
DR SIGNOR; Q6X4U4; -.
DR BioGRID-ORCS; 25928; 13 hits in 1065 CRISPR screens.
DR GeneWiki; SOSTDC1; -.
DR GenomeRNAi; 25928; -.
DR Pharos; Q6X4U4; Tbio.
DR PRO; PR:Q6X4U4; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q6X4U4; protein.
DR Bgee; ENSG00000171243; Expressed in pigmented layer of retina and 143 other tissues.
DR ExpressionAtlas; Q6X4U4; baseline and differential.
DR Genevisible; Q6X4U4; HS.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0036122; F:BMP binding; IDA:UniProtKB.
DR GO; GO:0098821; F:BMP receptor activity; IDA:UniProtKB.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0072148; P:epithelial cell fate commitment; IEA:Ensembl.
DR GO; GO:0031069; P:hair follicle morphogenesis; IEA:Ensembl.
DR GO; GO:0060648; P:mammary gland bud morphogenesis; IEA:Ensembl.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IDA:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0010454; P:negative regulation of cell fate commitment; IEA:Ensembl.
DR GO; GO:2000016; P:negative regulation of determination of dorsal identity; IDA:UniProtKB.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IDA:UniProtKB.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0007389; P:pattern specification process; IEA:Ensembl.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR006207; Cys_knot_C.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR008835; Sclerostin/SOSTDC1.
DR PANTHER; PTHR14903; PTHR14903; 1.
DR Pfam; PF05463; Sclerostin; 1.
DR PROSITE; PS01225; CTCK_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Reference proteome; Secreted; Signal; Wnt signaling pathway.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 24..206
FT /note="Sclerostin domain-containing protein 1"
FT /id="PRO_0000033180"
FT DOMAIN 75..170
FT /note="CTCK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT REGION 174..206
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 189..206
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 47
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 75..133
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT DISULFID 89..147
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT DISULFID 100..163
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT DISULFID 104..165
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT VAR_SEQ 68..69
FT /note="NT -> NRTESLTRQNYFWLFPGAFLRQLQEA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054240"
FT VARIANT 189
FT /note="Q -> H (in dbSNP:rs34016012)"
FT /id="VAR_053682"
FT CONFLICT 8..14
FT /note="FYLLPLA -> LSLIPLL (in Ref. 3; AAQ83296)"
FT /evidence="ECO:0000305"
FT CONFLICT 20
FT /note="S -> N (in Ref. 3; AAQ83296)"
FT /evidence="ECO:0000305"
FT CONFLICT 41
FT /note="P -> S (in Ref. 3; AAQ83296)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="N -> S (in Ref. 3; AAQ83296)"
FT /evidence="ECO:0000305"
FT CONFLICT 69
FT /note="T -> S (in Ref. 3; AAQ83296)"
FT /evidence="ECO:0000305"
FT CONFLICT 106
FT /note="P -> L (in Ref. 8; CAB43243)"
FT /evidence="ECO:0000305"
FT CONFLICT 127
FT /note="S -> G (in Ref. 3; AAQ83296)"
FT /evidence="ECO:0000305"
FT CONFLICT 182
FT /note="M -> V (in Ref. 3; AAQ83296)"
FT /evidence="ECO:0000305"
FT CONFLICT 188
FT /note="V -> A (in Ref. 3; AAQ83296)"
FT /evidence="ECO:0000305"
FT CONFLICT 205
FT /note="M -> L (in Ref. 3; AAQ83296)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 206 AA; 23307 MW; 9FB3CC41E4B53834 CRC64;
MLPPAIHFYL LPLACILMKS CLAFKNDATE ILYSHVVKPV PAHPSSNSTL NQARNGGRHF
SNTGLDRNTR VQVGCRELRS TKYISDGQCT SISPLKELVC AGECLPLPVL PNWIGGGYGT
KYWSRRSSQE WRCVNDKTRT QRIQLQCQDG STRTYKITVV TACKCKRYTR QHNESSHNFE
SMSPAKPVQH HRERKRASKS SKHSMS
