SCUB1_HUMAN
ID SCUB1_HUMAN Reviewed; 988 AA.
AC Q8IWY4; Q5R336;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 3.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Signal peptide, CUB and EGF-like domain-containing protein 1;
DE Flags: Precursor;
GN Name=SCUBE1;
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], VARIANTS ARG-398 AND PRO-648, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX PubMed=12270931; DOI=10.1074/jbc.m207410200;
RA Yang R.-B., Ng C.K.D., Wasserman S.M., Colman S.D., Shenoy S., Mehraban F.,
RA Koemueves L.G., Tomlinson J.E., Topper J.N.;
RT "Identification of a novel family of cell-surface proteins expressed in
RT human vascular endothelium.";
RL J. Biol. Chem. 277:46364-46373(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16753137; DOI=10.1016/j.cardiores.2006.04.010;
RA Tu C.-F., Su Y.-H., Huang Y.-N., Tsai M.-T., Li L.-T., Chen Y.-L.,
RA Cheng C.-J., Dai D.-F., Yang R.-B.;
RT "Localization and characterization of a novel secreted protein SCUBE1 in
RT human platelets.";
RL Cardiovasc. Res. 71:486-495(2006).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [5]
RP INTERACTION WITH SCUBE3.
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: Could function as an adhesive molecule and its matrix bound
CC and soluble fragments may play a critical role in vascular biology.
CC {ECO:0000269|PubMed:16753137}.
CC -!- SUBUNIT: Forms homooligomers. Forms heterooligomers with SCUBE2. Forms
CC heterooligomers with SCUBE3 (PubMed:33308444). {ECO:0000250,
CC ECO:0000269|PubMed:33308444}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12270931,
CC ECO:0000269|PubMed:16753137}. Cell membrane
CC {ECO:0000269|PubMed:16753137}; Peripheral membrane protein
CC {ECO:0000269|PubMed:16753137}.
CC -!- TISSUE SPECIFICITY: Detected in endothelial cells. Highly expressed in
CC platelets. Stored in platelet alpha granules, and transferred to the
CC cell surface upon activation and aggregation. A smaller form, probably
CC produced by limited proteolysis, after being released from the storage
CC granules, is associated with thrombus and localized with the
CC subendothelial matrices in atherosclerotic plaques.
CC {ECO:0000269|PubMed:12270931, ECO:0000269|PubMed:16753137}.
CC -!- INDUCTION: Down-regulated by inflammatory cytokines.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:12270931}.
CC -!- PTM: Could be proteolytically cleaved to release a smaller active
CC fragment.
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DR EMBL; AF525689; AAN77133.1; -; mRNA.
DR EMBL; Z99756; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z82214; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS14048.1; -.
DR RefSeq; NP_766638.2; NM_173050.3.
DR AlphaFoldDB; Q8IWY4; -.
DR STRING; 9606.ENSP00000354080; -.
DR GlyGen; Q8IWY4; 6 sites.
DR iPTMnet; Q8IWY4; -.
DR PhosphoSitePlus; Q8IWY4; -.
DR BioMuta; SCUBE1; -.
DR DMDM; 145559527; -.
DR jPOST; Q8IWY4; -.
DR MassIVE; Q8IWY4; -.
DR PaxDb; Q8IWY4; -.
DR PeptideAtlas; Q8IWY4; -.
DR PRIDE; Q8IWY4; -.
DR ProteomicsDB; 70926; -.
DR Antibodypedia; 306; 100 antibodies from 22 providers.
DR DNASU; 80274; -.
DR Ensembl; ENST00000360835.9; ENSP00000354080.3; ENSG00000159307.20.
DR GeneID; 80274; -.
DR KEGG; hsa:80274; -.
DR MANE-Select; ENST00000360835.9; ENSP00000354080.3; NM_173050.5; NP_766638.2.
DR UCSC; uc003bdt.3; human.
DR CTD; 80274; -.
DR DisGeNET; 80274; -.
DR GeneCards; SCUBE1; -.
DR HGNC; HGNC:13441; SCUBE1.
DR HPA; ENSG00000159307; Tissue enhanced (ovary).
DR MIM; 611746; gene.
DR neXtProt; NX_Q8IWY4; -.
DR OpenTargets; ENSG00000159307; -.
DR PharmGKB; PA35019; -.
DR VEuPathDB; HostDB:ENSG00000159307; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000153185; -.
DR HOGENOM; CLU_013079_0_0_1; -.
DR InParanoid; Q8IWY4; -.
DR OMA; CSMSNGS; -.
DR OrthoDB; 73164at2759; -.
DR PhylomeDB; Q8IWY4; -.
DR TreeFam; TF351672; -.
DR PathwayCommons; Q8IWY4; -.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR BioGRID-ORCS; 80274; 21 hits in 1063 CRISPR screens.
DR ChiTaRS; SCUBE1; human.
DR GenomeRNAi; 80274; -.
DR Pharos; Q8IWY4; Tbio.
DR PRO; PR:Q8IWY4; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q8IWY4; protein.
DR Bgee; ENSG00000159307; Expressed in mucosa of stomach and 142 other tissues.
DR ExpressionAtlas; Q8IWY4; baseline and differential.
DR Genevisible; Q8IWY4; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005509; F:calcium ion binding; TAS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:MGI.
DR GO; GO:0007512; P:adult heart development; NAS:UniProtKB.
DR GO; GO:0007596; P:blood coagulation; NAS:UniProtKB.
DR GO; GO:0045446; P:endothelial cell differentiation; NAS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; NAS:UniProtKB.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:0009791; P:post-embryonic development; NAS: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 Calcium; Cell membrane; Disulfide bond; EGF-like domain; Glycoprotein;
KW Membrane; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..988
FT /note="Signal peptide, CUB and EGF-like domain-containing
FT protein 1"
FT /id="PRO_0000254648"
FT DOMAIN 33..73
FT /note="EGF-like 1; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 74..116
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 117..153
FT /note="EGF-like 3; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 166..202
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 206..241
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 245..280
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 282..322
FT /note="EGF-like 7; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 323..361
FT /note="EGF-like 8; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 362..402
FT /note="EGF-like 9; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 798..910
FT /note="CUB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT CARBOHYD 370
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 466
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 679
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 750
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 779
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 789
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 37..50
FT /evidence="ECO:0000250"
FT DISULFID 44..59
FT /evidence="ECO:0000250"
FT DISULFID 61..72
FT /evidence="ECO:0000250"
FT DISULFID 78..91
FT /evidence="ECO:0000250"
FT DISULFID 87..100
FT /evidence="ECO:0000250"
FT DISULFID 102..115
FT /evidence="ECO:0000250"
FT DISULFID 121..132
FT /evidence="ECO:0000250"
FT DISULFID 128..141
FT /evidence="ECO:0000250"
FT DISULFID 286..297
FT /evidence="ECO:0000250"
FT DISULFID 293..306
FT /evidence="ECO:0000250"
FT DISULFID 308..321
FT /evidence="ECO:0000250"
FT DISULFID 327..337
FT /evidence="ECO:0000250"
FT DISULFID 333..346
FT /evidence="ECO:0000250"
FT DISULFID 348..360
FT /evidence="ECO:0000250"
FT DISULFID 366..377
FT /evidence="ECO:0000250"
FT DISULFID 373..386
FT /evidence="ECO:0000250"
FT DISULFID 388..401
FT /evidence="ECO:0000250"
FT DISULFID 798..824
FT /evidence="ECO:0000250"
FT DISULFID 851..872
FT /evidence="ECO:0000250"
FT VARIANT 398
FT /note="G -> R (in dbSNP:rs129415)"
FT /evidence="ECO:0000269|PubMed:12270931"
FT /id="VAR_028850"
FT VARIANT 648
FT /note="S -> P (in dbSNP:rs138993)"
FT /evidence="ECO:0000269|PubMed:12270931"
FT /id="VAR_028851"
FT CONFLICT 53
FT /note="T -> A (in Ref. 1; AAN77133)"
FT /evidence="ECO:0000305"
FT CONFLICT 73
FT /note="E -> G (in Ref. 1; AAN77133)"
FT /evidence="ECO:0000305"
FT CONFLICT 234
FT /note="L -> P (in Ref. 1; AAN77133)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 988 AA; 107910 MW; AB2C2AB53F3D3C2B CRC64;
MGAAAVRWHL CVLLALGTRG RLAGGSGLPG SVDVDECSEG TDDCHIDAIC QNTPKSYKCL
CKPGYKGEGK QCEDIDECEN DYYNGGCVHE CINIPGNYRC TCFDGFMLAH DGHNCLDVDE
CQDNNGGCQQ ICVNAMGSYE CQCHSGFFLS DNQHTCIHRS NEGMNCMNKD HGCAHICRET
PKGGVACDCR PGFDLAQNQK DCTLTCNYGN GGCQHSCEDT DTGPTCGCHQ KYALHSDGRT
CIETCAVNNG GCDRTCKDTA TGVRCSCPVG FTLQPDGKTC KDINECLVNN GGCDHFCRNT
VGSFECGCRK GYKLLTDERT CQDIDECSFE RTCDHICINS PGSFQCLCHR GYILYGTTHC
GDVDECSMSN GSCDQGCVNT KGSYECVCPP GRRLHWNGKD CVETGKCLSR AKTSPRAQLS
CSKAGGVESC FLSCPAHTLF VPDSENSYVL SCGVPGPQGK ALQKRNGTSS GLGPSCSDAP
TTPIKQKARF KIRDAKCHLR PHSQARAKET ARQPLLDHCH VTFVTLKCDS SKKRRRGRKS
PSKEVSHITA EFEIETKMEE ASDTCEADCL RKRAEQSLQA AIKTLRKSIG RQQFYVQVSG
TEYEVAQRPA KALEGQGACG AGQVLQDSKC VACGPGTHFG GELGQCVSCM PGTYQDMEGQ
LSCTPCPSSD GLGLPGARNV SECGGQCSPG FFSADGFKPC QACPVGTYQP EPGRTGCFPC
GGGLLTKHEG TTSFQDCEAK VHCSPGHHYN TTTHRCIRCP VGTYQPEFGQ NHCITCPGNT
STDFDGSTNV THCKNQHCGG ELGDYTGYIE SPNYPGDYPA NAECVWHIAP PPKRRILIVV
PEIFLPIEDE CGDVLVMRKS ASPTSITTYE TCQTYERPIA FTSRSRKLWI QFKSNEGNSG
KGFQVPYVTY DEDYQQLIED IVRDGRLYAS ENHQEILKDK KLIKALFDVL AHPQNYFKYT
AQESKEMFPR SFIKLLRSKV SRFLRPYK
