ID HEG_DANRE Reviewed; 977 AA.
AC Q6R8J2; Q6R8J3; Q6R8J4;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 27-MAR-2024, entry version 104.
DE RecName: Full=Protein HEG;
DE AltName: Full=Heart of glass;
DE Flags: Precursor;
GN Name=heg;
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] (ISOFORMS 1; 2 AND 3), FUNCTION, DEVELOPMENTAL
RP STAGE, AND DISRUPTION PHENOTYPE.
RC TISSUE=Embryo;
RX PubMed=14680629; DOI=10.1016/j.cub.2003.11.055;
RA Mably J.D., Mohideen M.-A.P.K., Burns C.G., Chen J.-N., Fishman M.C.;
RT "Heart of glass regulates the concentric growth of the heart in
RT zebrafish.";
RL Curr. Biol. 13:2138-2147(2003).
RN [2]
RP FUNCTION, AND INTERACTION WITH CCM2 AND KRIT1.
RX PubMed=19151727; DOI=10.1038/nm.1918;
RA Kleaveland B., Zheng X., Liu J.J., Blum Y., Tung J.J., Zou Z.,
RA Sweeney S.M., Chen M., Guo L., Lu M.M., Zhou D., Kitajewski J.,
RA Affolter M., Ginsberg M.H., Kahn M.L.;
RT "Regulation of cardiovascular development and integrity by the heart of
RT glass-cerebral cavernous malformation protein pathway.";
RL Nat. Med. 15:169-176(2009).
CC -!- FUNCTION: Receptor component of the CCM signaling pathway which is a
CC crucial regulator of heart and vessel formation and integrity. May act
CC through the stabilization of endothelial cell junctions.
CC {ECO:0000269|PubMed:14680629, ECO:0000269|PubMed:19151727}.
CC -!- SUBUNIT: Interacts with CCM2 and KRIT1; KRIT1 markedly facilitates
CC interaction with CCM2. {ECO:0000269|PubMed:19151727}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000305}; Single-
CC pass type I membrane protein {ECO:0000305}. Cell junction
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6R8J2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6R8J2-2; Sequence=VSP_025277;
CC Name=3;
CC IsoId=Q6R8J2-3; Sequence=VSP_025278;
CC -!- DEVELOPMENTAL STAGE: Expressed in the endocardium of developing heart.
CC {ECO:0000269|PubMed:14680629}.
CC -!- DISRUPTION PHENOTYPE: Death at embryonic stages due to heart growth
CC defects. {ECO:0000269|PubMed:14680629}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
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DR EMBL; AY507658; AAR87662.1; -; mRNA.
DR EMBL; AY507659; AAR87663.1; -; mRNA.
DR EMBL; AY507660; AAR87664.1; -; mRNA.
DR AlphaFoldDB; Q6R8J2; -.
DR SMR; Q6R8J2; -.
DR STRING; 7955.ENSDARP00000012786; -.
DR GlyCosmos; Q6R8J2; 11 sites, No reported glycans.
DR PaxDb; 7955-ENSDARP00000012786; -.
DR AGR; ZFIN:ZDB-GENE-040714-1; -.
DR ZFIN; ZDB-GENE-040714-1; heg1.
DR eggNOG; ENOG502QPW9; Eukaryota.
DR InParanoid; Q6R8J2; -.
DR PhylomeDB; Q6R8J2; -.
DR PRO; PR:Q6R8J2; -.
DR Proteomes; UP000000437; Genome assembly.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0007043; P:cell-cell junction assembly; IMP:ZFIN.
DR GO; GO:0007507; P:heart development; IMP:ZFIN.
DR CDD; cd00054; EGF_CA; 2.
DR Gene3D; 2.10.25.10; Laminin; 2.
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 PANTHER; PTHR24037; HEART DEVELOPMENT PROTEIN WITH EGF-LIKE DOMAINS 1; 1.
DR PANTHER; PTHR24037:SF13; PROTEIN HEG; 1.
DR Pfam; PF07645; EGF_CA; 1.
DR SMART; SM00181; EGF; 3.
DR SMART; SM00179; EGF_CA; 2.
DR SUPFAM; SSF57196; EGF/Laminin; 2.
DR PROSITE; PS00010; ASX_HYDROXYL; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 2.
DR PROSITE; PS01187; EGF_CA; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell junction; Cell membrane;
KW Developmental protein; Disulfide bond; EGF-like domain; Glycoprotein;
KW Membrane; Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..977
FT /note="Protein HEG"
FT /id="PRO_0000286982"
FT TRANSMEM 846..866
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 587..624
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 626..665
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 85..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 200..391
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 404..445
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 499..586
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 90..146
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 200..369
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 499..584
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 200
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 246
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 343
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 535
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 677
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 699
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 734
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 750
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 591..602
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 596..612
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 614..623
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 630..641
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 635..650
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 652..664
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VAR_SEQ 830..871
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14680629"
FT /id="VSP_025277"
FT VAR_SEQ 842..977
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14680629"
FT /id="VSP_025278"
SQ SEQUENCE 977 AA; 105529 MW; 8A82B3D61FE48A1A CRC64;
MMETCARRVL FTAALLVLST VIAETFSTDS DTDNPLSTET FYSRASGLKQ TSSWPGREAT
ATAVDLSSGL GEMTEIPASV SITAAREGHS PKPLQTSTNA ADWKTSTTSD ETTEHLQSDT
ELTHNATAQW ESPSSASHSI TSHHPVTETR TVRDVTDLID MDTTDSVSHT DSTYISTTNR
VGERTLLSVI SNSTFAYTQN SSISDAESQT SPWEEKTSGA TQVNEETEET VSTVSEQTDP
TFEGRNTTSA TLETERSTLS QGTESQTGQP SVTGQTAKEV TDIDNPNSTP PLTVTSRDVE
ETDATSVSSE TSYTQTSSDS ASSILPFTSS EHNVTSTSQE SHNSTLIYST NTGGSTEFST
GSVSSTAHEE TERSSTRIVD ETTLHDVTSA PPVLEDVATT IDDSLSKFPS GQSPTIPKTD
DQTNTQVVPT STHRPQVTDE ATDEVSTVYS STTTLTTTTP SVTTRQLQPH YTTVQTQTQH
TTIVTTDIIQ VLRTTPSTAH HVPTLTTSGP QAPSTADSSD VTTLHLETST ATPGNTTAHG
GRATTPFSKS SPGRTTVVVT TGHLTDKSTT ETGSATTQMP LRTSASPGHV CGPKTCANGG
HCVRSAEGSY YCQCLSAWTG PFCTEDVDEC VNSPCPQGSV CVNTGGSFSC ECDLGFDLED
GRSCTQVKTF LGTFTVNNSL HLRNLGLHEL HREIQQLLNA SLSIFHGYRR FTLGKRDGQG
VQIPVVSMFS LSSNVTSADV FNSIQMSLNN CSRTYSHCPI KLQHQLSYHV ESLCMAQKTK
CDVQYSDCSD ISGIPNCQCL PGYFKRNPED MTCRDCGDGL KLVNGKCVEC MFGFGGFNCN
NFYKLIAVVV SPAGGALLLI VVIALIVTCC KKDKNDINKI IFKSGELQMS PYAEFPKSNR
VSMEWGRETI EMQENGSTKN LLQMTDIYYS PALRNSDLER NGLYPFSGLP GSRHSCIYPA
QWNPSFLSDD SRRRDYF
//
