SCUB2_DANRE
ID SCUB2_DANRE Reviewed; 1010 AA.
AC Q5G872; Q1W4D3; Q59I66;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Signal peptide, CUB and EGF-like domain-containing protein 2;
DE AltName: Full=Protein You {ECO:0000303|PubMed:15753045};
DE Flags: Precursor;
GN Name=scube2; Synonyms=you;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=15753045; DOI=10.1016/j.cub.2005.02.018;
RA Kawakami A., Nojima Y., Toyoda A., Takahoko M., Satoh M., Tanaka H.,
RA Wada H., Masai I., Terasaki H., Sakaki Y., Takeda H., Okamoto H.;
RT "The zebrafish-secreted matrix protein You/Scube2 is implicated in long-
RT range regulation of hedgehog signaling.";
RL Curr. Biol. 15:480-488(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15660164; DOI=10.1371/journal.pbio.0030066;
RA Woods I.G., Talbot W.S.;
RT "The you gene encodes an EGF-CUB protein essential for Hedgehog signaling
RT in zebrafish.";
RL PLoS Biol. 3:476-487(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, FUNCTION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=16626681; DOI=10.1016/j.ydbio.2006.02.032;
RA Hollway G.E., Maule J., Gautier P., Evans T.M., Keenan D.G., Lohs C.,
RA Fischer D., Wicking C., Currie P.D.;
RT "Scube2 mediates Hedgehog signalling in the zebrafish embryo.";
RL Dev. Biol. 294:104-118(2006).
CC -!- FUNCTION: Lipid-binding protein required for SHH long-range signaling
CC by binding to the dually lipid-modified SHH (ShhNp) and by promoting
CC ShhNp mobilization, solubilization and release from the cell membrane.
CC Acts by enhancing the proteolytic processing (shedding) of the lipid-
CC modified N- and C- terminal of ShhNp at the cell surface. Synergizes
CC with DISP1 to cause an increase in SHH secretion. Probable cell surface
CC coreceptor for VEGFR2 involved in VEGFR2-mediated angiogenesis.
CC {ECO:0000250|UniProtKB:Q9NQ36}.
CC -!- SUBUNIT: Interacts with SHH via the cholesterol anchor of the dually
CC lipid-modified SHH (ShhNp) (By similarity). Interacts with PTCH1 (By
CC similarity). Forms homooligomers and heterooligomers with SCUBE1 and
CC SCUBE3 (By similarity). Interacts with VEGFR2 (By similarity).
CC {ECO:0000250|UniProtKB:Q8IX30, ECO:0000250|UniProtKB:Q9NQ36}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9NQ36}. Cell
CC surface {ECO:0000250|UniProtKB:Q9NQ36}. Note=Secreted and tethered at
CC the cell surface. {ECO:0000250|UniProtKB:Q9NQ36}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the dorsal neural tube.
CC {ECO:0000269|PubMed:15753045}.
CC -!- DOMAIN: The CUB domain is important for the interaction with the
CC cholesterol-anchor of SHH. The CUB domain regulates protease
CC recruitment and activation during SHH shedding.
CC {ECO:0000250|UniProtKB:Q9NQ36}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9NQ36}.
CC -!- DISRUPTION PHENOTYPE: Zebrafish 'you class' developmental mutants are
CC grouped together based on the anormal U-shaped morphology of the
CC somites. Homozygous zebrafish mutants show disruption of the formation
CC of hedgehog-sensitive muscle fates, with an altered myotomal morphology
CC from a characteristic chevron shape to a more rounded U-shaped. One of
CC these 'you class' mutant results from disruption of the Scube2 gene.
CC These mutants lack slow twitch muscle and muscle pionneer cells, and
CC PTCH1 expression within the myotome and neural tube is essentially
CC absent. {ECO:0000269|PubMed:16626681}.
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DR EMBL; AB193554; BAD91395.1; -; mRNA.
DR EMBL; AY741664; AAW63651.1; -; mRNA.
DR EMBL; DQ438942; ABD96046.1; -; mRNA.
DR RefSeq; NP_001014813.1; NM_001014813.1.
DR AlphaFoldDB; Q5G872; -.
DR STRING; 7955.ENSDARP00000054365; -.
DR PaxDb; Q5G872; -.
DR PRIDE; Q5G872; -.
DR GeneID; 503728; -.
DR KEGG; dre:503728; -.
DR CTD; 57758; -.
DR ZFIN; ZDB-GENE-050302-80; scube2.
DR eggNOG; KOG1217; Eukaryota.
DR InParanoid; Q5G872; -.
DR OrthoDB; 73164at2759; -.
DR PhylomeDB; Q5G872; -.
DR Reactome; R-DRE-5362798; Release of Hh-Np from the secreting cell.
DR PRO; PR:Q5G872; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0009986; C:cell surface; IDA:ZFIN.
DR GO; GO:0009897; C:external side of plasma membrane; ISS:ZFIN.
DR GO; GO:0005576; C:extracellular region; IDA:ZFIN.
DR GO; GO:0005615; C:extracellular space; ISS:ZFIN.
DR GO; GO:0030141; C:secretory granule; IDA:ZFIN.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0008015; P:blood circulation; IMP:ZFIN.
DR GO; GO:0042694; P:muscle cell fate specification; IMP:ZFIN.
DR GO; GO:0007517; P:muscle organ development; IMP:ZFIN.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0007224; P:smoothened signaling pathway; IMP:ZFIN.
DR GO; GO:0001756; P:somitogenesis; IMP:ZFIN.
DR GO; GO:0051146; P:striated muscle cell differentiation; IMP:ZFIN.
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; 1.
DR Pfam; PF07699; Ephrin_rec_like; 3.
DR SMART; SM00042; CUB; 1.
DR SMART; SM00181; EGF; 10.
DR SMART; SM00179; EGF_CA; 8.
DR SUPFAM; SSF49854; SSF49854; 1.
DR SUPFAM; SSF57184; SSF57184; 4.
DR PROSITE; PS00010; ASX_HYDROXYL; 6.
DR PROSITE; PS01180; CUB; 1.
DR PROSITE; PS01186; EGF_2; 8.
DR PROSITE; PS50026; EGF_3; 6.
DR PROSITE; PS01187; EGF_CA; 6.
PE 2: Evidence at transcript level;
KW Calcium; Developmental protein; Disulfide bond; EGF-like domain;
KW Glycoprotein; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..1010
FT /note="Signal peptide, CUB and EGF-like domain-containing
FT protein 2"
FT /id="PRO_0000255582"
FT DOMAIN 28..68
FT /note="EGF-like 1; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 69..110
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 111..147
FT /note="EGF-like 3; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 160..196
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 200..235
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 269..304
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 306..346
FT /note="EGF-like 7; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 347..385
FT /note="EGF-like 8; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 386..426
FT /note="EGF-like 9; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 822..934
FT /note="CUB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT REGION 860..869
FT /note="Interaction with the cholesterol-anchor of SHH"
FT /evidence="ECO:0000250|UniProtKB:Q9JJS0"
FT CARBOHYD 249
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 488
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 703
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 774
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 803
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 982
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 32..45
FT /evidence="ECO:0000250"
FT DISULFID 39..54
FT /evidence="ECO:0000250"
FT DISULFID 56..67
FT /evidence="ECO:0000250"
FT DISULFID 73..85
FT /evidence="ECO:0000250"
FT DISULFID 81..94
FT /evidence="ECO:0000250"
FT DISULFID 96..109
FT /evidence="ECO:0000250"
FT DISULFID 115..126
FT /evidence="ECO:0000250"
FT DISULFID 122..135
FT /evidence="ECO:0000250"
FT DISULFID 310..321
FT /evidence="ECO:0000250"
FT DISULFID 317..330
FT /evidence="ECO:0000250"
FT DISULFID 332..345
FT /evidence="ECO:0000250"
FT DISULFID 351..361
FT /evidence="ECO:0000250"
FT DISULFID 357..370
FT /evidence="ECO:0000250"
FT DISULFID 372..384
FT /evidence="ECO:0000250"
FT DISULFID 390..401
FT /evidence="ECO:0000250"
FT DISULFID 397..410
FT /evidence="ECO:0000250"
FT DISULFID 412..425
FT /evidence="ECO:0000250"
FT DISULFID 822..848
FT /evidence="ECO:0000250"
FT DISULFID 875..896
FT /evidence="ECO:0000250"
FT CONFLICT 166
FT /note="G -> D (in Ref. 1; BAD91395)"
FT /evidence="ECO:0000305"
FT CONFLICT 289
FT /note="C -> R (in Ref. 3; ABD96046)"
FT /evidence="ECO:0000305"
FT CONFLICT 297
FT /note="L -> P (in Ref. 3; ABD96046)"
FT /evidence="ECO:0000305"
FT CONFLICT 414
FT /note="A -> T (in Ref. 3; ABD96046)"
FT /evidence="ECO:0000305"
FT CONFLICT 697
FT /note="E -> R (in Ref. 3; ABD96046)"
FT /evidence="ECO:0000305"
FT CONFLICT 700
FT /note="G -> E (in Ref. 1; BAD91395)"
FT /evidence="ECO:0000305"
FT CONFLICT 810
FT /note="G -> R (in Ref. 1; BAD91395)"
FT /evidence="ECO:0000305"
FT CONFLICT 932
FT /note="V -> A (in Ref. 1; BAD91395)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1010 AA; 112176 MW; 23BF1125C3510A14 CRC64;
MGAVWTVRLL CLFLLLLNTR QSAALPHNTD QCAEGSDACH IDAICQNTPT SYKCTCKTGF
KGDGKHCEDI DECDVEYNGG CVHECNNIPG NYRCTCLDGF HLAHDGHNCL DVDECVFNNG
GCQHVCVNTM GSYECRCKQG FFLSDNQHTC IHRSVEGLSC MNKEHGCGHI CKESPKGGVA
CECRPGFELA KNQRGCILTC NHGNGGCQHI CEDTEQGPIC RCHVRYMLHA DGRTCVERDE
MAPTAPDHNA TSLAEVDKRV KRRLLMETCA VNNGGCDSTC KDTSTGVRCS CPVGFTLQPD
GKSCKDIDEC ELHNGGCDHY CRNTIGSFEC SCRKGFKLLT DERSCQDIDE CFFERTCDHT
CVNSPGSFQC VCNKGYTLYG LAHCGDINEC SFNNGGCEHT CENTMGSFGC HCRAGYKLHW
NKKDCIEAED SPLVPPPARP TLNCNKQGGG ELCYLTCQSQ VHISSGAEDS YTVTCGMPLP
CHTGGQWNGS YCPGSGIKTI ATFKSGQGKC NLKRSHENLA HSFKTALSDK RATENVQFSF
VSLHCASSSR QQRSRHGRKA GEEEGSFITA QFELDVNLEE VTAEGCDLTC VRRRSEKRLR
KTIRTLRKSI NREQFHLHFA GSEYELAKKL VRPADTPDHC GTGQILLDKK CVKCSVGTYY
DGEQGRCFLC PPGTYQDEEG QVSCDVCPGP EGRGIPETAG ARNISECAGQ CRPGQFSHDG
FVPCLPCPQG TYQPEVGRTS CFTCGGSLTT KYDGSVSFQN CETKVQCSPG HYYNTSTHRC
IRCPVGTYQM EFGQNYCIAC PGNTTTDFDG STNIMQCKNR HCGGELGEFT GYIESPNYPG
NYPANIECTW TITPPPKRRI LVVVPEIYLP IEDECGDYLV MRKSSLPNSV TTYETCQTYE
RPIAFTSRSK KLWIQFRSNE GNSGKGFQVP YVTYDEDYQE LIEDIVRDGR LYASENHQEI
LKDKKLMRAL FDVLAHPQNF FNYTAQESRE MFPKSFIRFL RSKVLRFLRP
