SCUB3_HUMAN
ID SCUB3_HUMAN Reviewed; 993 AA.
AC Q8IX30; A8K5A3; Q5CZB3; Q86UZ9; Q8NAU9;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Signal peptide, CUB and EGF-like domain-containing protein 3;
DE Flags: Precursor;
GN Name=SCUBE3 {ECO:0000312|HGNC:HGNC:13655};
GN Synonyms=CEGF3 {ECO:0000312|EMBL:AAN76808.1};
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] {ECO:0000305, ECO:0000312|EMBL:AAU08347.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBUNIT, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND GLYCOSYLATION.
RC TISSUE=Osteoblast {ECO:0000269|PubMed:15234972};
RX PubMed=15234972; DOI=10.1074/jbc.m405912200;
RA Wu B.-T., Su Y.-H., Tsai M.-T., Wasserman S.M., Topper J.N., Yang R.-B.;
RT "A novel secreted, cell-surface glycoprotein containing multiple epidermal
RT growth factor-like repeats and one CUB domain is highly expressed in
RT primary osteoblasts and bones.";
RL J. Biol. Chem. 279:37485-37490(2004).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAN76808.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Pfarr N., Bahr A., Cichutek A., Loebbert R., Zabel B.U., Schmidt E.R.,
RA Hankeln T., Winterpacht A.;
RT "Novel human gene family (CEGF) encoding mosaic proteins with EGF-like,
RT STT2R and a CUB module: cloning and expression analysis.";
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305, ECO:0000312|EMBL:BAC03798.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 45-993 (ISOFORM 2).
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] {ECO:0000305, ECO:0000312|EMBL:Z97832}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAN76808.1}
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 [6] {ECO:0000305, ECO:0000312|EMBL:AAH52263.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas {ECO:0000312|EMBL:AAH52263.2};
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 158-993 (ISOFORM 2).
RC TISSUE=Testis;
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 [8]
RP FUNCTION, INTERACTION WITH TGFBR2, TISSUE SPECIFICITY, AND PROTEOLYTIC
RP CLEAVAGE BY MMP2 AND MMP9.
RX PubMed=21441952; DOI=10.1038/onc.2011.85;
RA Wu Y.Y., Peck K., Chang Y.L., Pan S.H., Cheng Y.F., Lin J.C., Yang R.B.,
RA Hong T.M., Yang P.C.;
RT "SCUBE3 is an endogenous TGF-beta receptor ligand and regulates the
RT epithelial-mesenchymal transition in lung cancer.";
RL Oncogene 30:3682-3693(2011).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SCUBE1 AND SCUBE2,
RP INTERACTION WITH BMP2; BMP4; BMP7; BMPR1A; BMPR1B AND BMPR2, INVOLVEMENT IN
RP SSFSC2, VARIANTS SSFSC2 TRP-97; ASP-204; 573-ARG--LYS-993 DEL; THR-815 AND
RP 929-ARG--LYS-993 DEL, AND CHARACTERIZATION OF VARIANTS SSFSC2 TRP-97;
RP 573-ARG--LYS-993 DEL AND THR-815.
RX PubMed=33308444; DOI=10.1016/j.ajhg.2020.11.015;
RG Genomics England Research Consortium;
RA Lin Y.C., Niceta M., Muto V., Vona B., Pagnamenta A.T., Maroofian R.,
RA Beetz C., van Duyvenvoorde H., Dentici M.L., Lauffer P., Vallian S.,
RA Ciolfi A., Pizzi S., Bauer P., Gruening N.M., Bellacchio E.,
RA Del Fattore A., Petrini S., Shaheen R., Tiosano D., Halloun R.,
RA Pode-Shakked B., Albayrak H.M., Isik E., Wit J.M., Dittrich M.,
RA Freire B.L., Bertola D.R., Jorge A.A.L., Barel O., Sabir A.H.,
RA Al Tenaiji A.M.J., Taji S.M., Al-Sannaa N., Al-Abdulwahed H., Digilio M.C.,
RA Irving M., Anikster Y., Bhavani G.S.L., Girisha K.M., Haaf T., Taylor J.C.,
RA Dallapiccola B., Alkuraya F.S., Yang R.B., Tartaglia M.;
RT "SCUBE3 loss-of-function causes a recognizable recessive developmental
RT disorder due to defective bone morphogenetic protein signaling.";
RL Am. J. Hum. Genet. 108:115-133(2021).
CC -!- FUNCTION: Is a positive regulator of the BMP signaling pathway,
CC required for proper chondrogenesis, osteogenesis and skeletal
CC development. It acts as coreceptor for BMP ligands, particularly BMP2
CC and BMP4, facilitating their interactions with BMP type I receptors
CC (PubMed:33308444). It is required for ligand-induced recruitment of BMP
CC receptors to lipid rafts (By similarity). Binds to TGFBR2 and activates
CC TGFB signaling. In lung cancer cells, could serve as an endogenous
CC autocrine and paracrine ligand of TGFBR2, which could regulate TGFBR2
CC signaling and hence modulate epithelial-mesenchymal transition and
CC cancer progression. {ECO:0000250|UniProtKB:Q6NZL8,
CC ECO:0000269|PubMed:21441952, ECO:0000269|PubMed:33308444}.
CC -!- SUBUNIT: Forms homooligomers (PubMed:33308444). Forms heterooligomers
CC with SCUBE1 and SCUBE2 (PubMed:33308444). Interacts with TGFBR2 through
CC the CUB domain; this interaction does not affect TGFB1-binding to
CC TGFBR2. Interacts with BMP2, BMP4 and BMP7; the interaction is mediated
CC by the CUB domain (PubMed:33308444). Interacts with BMPR1A, BMPR1B and
CC BMPR2; the interaction with BMPR1A and BMPR1B is BMP2- and BMP4-
CC dependent (PubMed:33308444). {ECO:0000269|PubMed:15234972,
CC ECO:0000269|PubMed:21441952, ECO:0000269|PubMed:33308444}.
CC -!- INTERACTION:
CC Q8IX30; P08253: MMP2; NbExp=2; IntAct=EBI-4479975, EBI-1033518;
CC Q8IX30; P14780: MMP9; NbExp=2; IntAct=EBI-4479975, EBI-1382326;
CC Q8IX30; P37173: TGFBR2; NbExp=6; IntAct=EBI-4479975, EBI-296151;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15234972,
CC ECO:0000269|PubMed:33308444}. Cell surface
CC {ECO:0000269|PubMed:15234972, ECO:0000269|PubMed:33308444}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:15234972, ECO:0000269|PubMed:15489334,
CC ECO:0000269|Ref.2};
CC IsoId=Q8IX30-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334};
CC IsoId=Q8IX30-2; Sequence=VSP_052167;
CC -!- TISSUE SPECIFICITY: Highly expressed in osteoblasts. In normal lung,
CC mainly expressed in bronchial epithelial cells. Tends to be up-
CC regulated in lung cancer cells. {ECO:0000269|PubMed:15234972,
CC ECO:0000269|PubMed:21441952}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15234972}.
CC -!- PTM: Proteolytic cleavage produces a CUB-containing C-terminal fragment
CC that retains the ability to bind to TGFBR2. This reaction is catalyzed
CC in vitro by MMP2 and, to a lesser extent, by MMP9.
CC {ECO:0000269|PubMed:21441952}.
CC -!- DISEASE: Short stature, facial dysmorphism, and skeletal anomalies with
CC or without cardiac anomalies 2 (SSFSC2) [MIM:619184]: An autosomal
CC recessive disorder characterized by reduced growth, skeletal
CC abnormalities, a distinctive craniofacial appearance, and dental
CC anomalies. Cardiac anomalies have been reported in some patients.
CC {ECO:0000269|PubMed:33308444}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC03798.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY639608; AAU08347.1; -; mRNA.
DR EMBL; AF452494; AAN76808.1; -; mRNA.
DR EMBL; AK092062; BAC03798.1; ALT_INIT; mRNA.
DR EMBL; AK291218; BAF83907.1; -; mRNA.
DR EMBL; Z97832; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX03812.1; -; Genomic_DNA.
DR EMBL; BC052263; AAH52263.2; -; mRNA.
DR EMBL; CR936607; CAI56752.1; -; mRNA.
DR CCDS; CCDS4800.1; -. [Q8IX30-1]
DR RefSeq; NP_001290065.1; NM_001303136.1.
DR RefSeq; NP_689966.2; NM_152753.3. [Q8IX30-1]
DR RefSeq; XP_005249000.1; XM_005248943.1. [Q8IX30-2]
DR AlphaFoldDB; Q8IX30; -.
DR BioGRID; 128812; 1.
DR IntAct; Q8IX30; 3.
DR STRING; 9606.ENSP00000274938; -.
DR GlyGen; Q8IX30; 5 sites.
DR iPTMnet; Q8IX30; -.
DR PhosphoSitePlus; Q8IX30; -.
DR BioMuta; SCUBE3; -.
DR DMDM; 74762488; -.
DR EPD; Q8IX30; -.
DR jPOST; Q8IX30; -.
DR MassIVE; Q8IX30; -.
DR PaxDb; Q8IX30; -.
DR PeptideAtlas; Q8IX30; -.
DR PRIDE; Q8IX30; -.
DR ProteomicsDB; 70970; -. [Q8IX30-1]
DR ProteomicsDB; 70971; -. [Q8IX30-2]
DR Antibodypedia; 29465; 184 antibodies from 27 providers.
DR DNASU; 222663; -.
DR Ensembl; ENST00000274938.8; ENSP00000274938.7; ENSG00000146197.9. [Q8IX30-1]
DR GeneID; 222663; -.
DR KEGG; hsa:222663; -.
DR MANE-Select; ENST00000274938.8; ENSP00000274938.7; NM_152753.4; NP_689966.2.
DR UCSC; uc003okf.2; human. [Q8IX30-1]
DR CTD; 222663; -.
DR DisGeNET; 222663; -.
DR GeneCards; SCUBE3; -.
DR HGNC; HGNC:13655; SCUBE3.
DR HPA; ENSG00000146197; Tissue enriched (thyroid).
DR MalaCards; SCUBE3; -.
DR MIM; 614708; gene.
DR MIM; 619184; phenotype.
DR neXtProt; NX_Q8IX30; -.
DR OpenTargets; ENSG00000146197; -.
DR PharmGKB; PA134977856; -.
DR VEuPathDB; HostDB:ENSG00000146197; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000153185; -.
DR HOGENOM; CLU_013079_0_0_1; -.
DR InParanoid; Q8IX30; -.
DR OMA; HGRLHWN; -.
DR OrthoDB; 73164at2759; -.
DR PhylomeDB; Q8IX30; -.
DR TreeFam; TF351672; -.
DR PathwayCommons; Q8IX30; -.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR SignaLink; Q8IX30; -.
DR BioGRID-ORCS; 222663; 10 hits in 1014 CRISPR screens.
DR ChiTaRS; SCUBE3; human.
DR GenomeRNAi; 222663; -.
DR Pharos; Q8IX30; Tbio.
DR PRO; PR:Q8IX30; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q8IX30; protein.
DR Bgee; ENSG00000146197; Expressed in cartilage tissue and 140 other tissues.
DR Genevisible; Q8IX30; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0036122; F:BMP binding; IPI:UniProtKB.
DR GO; GO:0070700; F:BMP receptor binding; IPI:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IMP:UniProtKB.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd00041; CUB; 1.
DR Gene3D; 2.60.120.290; -; 1.
DR InterPro; IPR026823; cEGF.
DR InterPro; IPR000859; CUB_dom.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR024731; EGF_dom.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR035914; Sperma_CUB_dom_sf.
DR InterPro; IPR011641; Tyr-kin_ephrin_A/B_rcpt-like.
DR Pfam; PF12662; cEGF; 1.
DR Pfam; PF00431; CUB; 1.
DR Pfam; PF12947; EGF_3; 1.
DR Pfam; PF07645; EGF_CA; 2.
DR Pfam; PF07699; Ephrin_rec_like; 3.
DR SMART; SM00042; CUB; 1.
DR SMART; SM00181; EGF; 10.
DR SMART; SM00179; EGF_CA; 7.
DR SUPFAM; SSF49854; SSF49854; 1.
DR SUPFAM; SSF57184; SSF57184; 3.
DR PROSITE; PS00010; ASX_HYDROXYL; 6.
DR PROSITE; PS01180; CUB; 1.
DR PROSITE; PS01186; EGF_2; 7.
DR PROSITE; PS50026; EGF_3; 6.
DR PROSITE; PS01187; EGF_CA; 6.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Disease variant; Disulfide bond; Dwarfism;
KW EGF-like domain; Glycoprotein; Reference proteome; Repeat; Secreted;
KW Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..993
FT /note="Signal peptide, CUB and EGF-like domain-containing
FT protein 3"
FT /evidence="ECO:0000255"
FT /id="PRO_0000250616"
FT DOMAIN 29..69
FT /note="EGF-like 1; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 70..111
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 112..148
FT /note="EGF-like 3; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 157..198
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 199..237
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 238..276
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 277..317
FT /note="EGF-like 7; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 318..356
FT /note="EGF-like 8; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 357..398
FT /note="EGF-like 9; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 804..916
FT /note="CUB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT CARBOHYD 417
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 464
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 685
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 756
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 785
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 33..46
FT /evidence="ECO:0000255"
FT DISULFID 40..55
FT /evidence="ECO:0000255"
FT DISULFID 57..68
FT /evidence="ECO:0000255"
FT DISULFID 74..86
FT /evidence="ECO:0000255"
FT DISULFID 82..95
FT /evidence="ECO:0000255"
FT DISULFID 97..110
FT /evidence="ECO:0000255"
FT DISULFID 116..127
FT /evidence="ECO:0000255"
FT DISULFID 123..136
FT /evidence="ECO:0000255"
FT DISULFID 161..172
FT /evidence="ECO:0000255"
FT DISULFID 168..182
FT /evidence="ECO:0000255"
FT DISULFID 184..197
FT /evidence="ECO:0000255"
FT DISULFID 201..212
FT /evidence="ECO:0000255"
FT DISULFID 208..221
FT /evidence="ECO:0000255"
FT DISULFID 223..236
FT /evidence="ECO:0000255"
FT DISULFID 240..251
FT /evidence="ECO:0000255"
FT DISULFID 247..260
FT /evidence="ECO:0000255"
FT DISULFID 262..275
FT /evidence="ECO:0000255"
FT DISULFID 281..292
FT /evidence="ECO:0000255"
FT DISULFID 288..301
FT /evidence="ECO:0000255"
FT DISULFID 303..316
FT /evidence="ECO:0000255"
FT DISULFID 322..332
FT /evidence="ECO:0000255"
FT DISULFID 328..341
FT /evidence="ECO:0000255"
FT DISULFID 343..355
FT /evidence="ECO:0000255"
FT DISULFID 361..372
FT /evidence="ECO:0000255"
FT DISULFID 368..381
FT /evidence="ECO:0000255"
FT DISULFID 383..397
FT /evidence="ECO:0000255"
FT DISULFID 804..830
FT /evidence="ECO:0000255"
FT DISULFID 857..878
FT /evidence="ECO:0000255"
FT VAR_SEQ 237
FT /note="I -> IGERRLEQHIPTQAVSN (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17974005"
FT /id="VSP_052167"
FT VARIANT 97
FT /note="C -> W (in SSFSC2; decreased homodimerization; does
FT not affect heterodimerization with SCUBE1 or SCUBE2; does
FT not affect localization to the cell surface)"
FT /evidence="ECO:0000269|PubMed:33308444"
FT /id="VAR_085320"
FT VARIANT 204
FT /note="G -> D (in SSFSC2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33308444"
FT /id="VAR_085321"
FT VARIANT 410
FT /note="S -> L (in dbSNP:rs3800381)"
FT /id="VAR_048994"
FT VARIANT 573..993
FT /note="Missing (in SSFSC2; loss of stimulation of BMP
FT signaling; does not localize to the cell surface due to
FT impaired secretion)"
FT /evidence="ECO:0000269|PubMed:33308444"
FT /id="VAR_085322"
FT VARIANT 815
FT /note="I -> T (in SSFSC2; loss of stimulation of BMP
FT signaling; does not affect localization to the cell
FT surface; dbSNP:rs751478115)"
FT /evidence="ECO:0000269|PubMed:33308444"
FT /id="VAR_085323"
FT VARIANT 929..993
FT /note="Missing (in SSFSC2)"
FT /evidence="ECO:0000269|PubMed:33308444"
FT /id="VAR_085324"
FT CONFLICT 157
FT /note="Missing (in Ref. 6; AAH52263)"
FT /evidence="ECO:0000305"
FT CONFLICT 256
FT /note="T -> I (in Ref. 6; AAH52263)"
FT /evidence="ECO:0000305"
FT CONFLICT 483..484
FT /note="AS -> SP (in Ref. 3; BAC03798)"
FT /evidence="ECO:0000305"
FT CONFLICT 635
FT /note="K -> E (in Ref. 7; CAI56752)"
FT /evidence="ECO:0000305"
FT CONFLICT 856
FT /note="E -> G (in Ref. 7; CAI56752)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 993 AA; 109282 MW; 19BBE0E5627EEAF4 CRC64;
MGSGRVPGLC LLVLLVHARA AQYSKAAQDV DECVEGTDNC HIDAICQNTP RSYKCICKSG
YTGDGKHCKD VDECEREDNA GCVHDCVNIP GNYRCTCYDG FHLAHDGHNC LDVDECAEGN
GGCQQSCVNM MGSYECHCRE GFFLSDNQHT CIQRPEEGMN CMNKNHGCAH ICRETPKGGI
ACECRPGFEL TKNQRDCKLT CNYGNGGCQH TCDDTEQGPR CGCHIKFVLH TDGKTCIETC
AVNNGGCDSK CHDAATGVHC TCPVGFMLQP DRKTCKDIDE CRLNNGGCDH ICRNTVGSFE
CSCKKGYKLL INERNCQDID ECSFDRTCDH ICVNTPGSFQ CLCHRGYLLY GITHCGDVDE
CSINRGGCRF GCINTPGSYQ CTCPAGQGRL HWNGKDCTEP LKCQGSPGAS KAMLSCNRSG
KKDTCALTCP SRARFLPESE NGFTVSCGTP SPRAAPARAG HNGNSTNSNH CHEAAVLSIK
QRASFKIKDA KCRLHLRNKG KTEEAGRITG PGGAPCSECQ VTFIHLKCDS SRKGKGRRAR
TPPGKEVTRL TLELEAEVRA EETTASCGLP CLRQRMERRL KGSLKMLRKS INQDRFLLRL
AGLDYELAHK PGLVAGERAE PMESCRPGQH RAGTKCVSCP QGTYYHGQTE QCVPCPAGTF
QEREGQLSCD LCPGSDAHGP LGATNVTTCA GQCPPGQHSV DGFKPCQPCP RGTYQPEAGR
TLCFPCGGGL TTKHEGAISF QDCDTKVQCS PGHYYNTSIH RCIRCAMGSY QPDFRQNFCS
RCPGNTSTDF DGSTSVAQCK NRQCGGELGE FTGYIESPNY PGNYPAGVEC IWNINPPPKR
KILIVVPEIF LPSEDECGDV LVMRKNSSPS SITTYETCQT YERPIAFTAR SRKLWINFKT
SEANSARGFQ IPYVTYDEDY EQLVEDIVRD GRLYASENHQ EILKDKKLIK AFFEVLAHPQ
NYFKYTEKHK EMLPKSFIKL LRSKVSSFLR PYK
