HEG1_MOUSE
ID HEG1_MOUSE Reviewed; 1337 AA.
AC E9Q7X6; Q3TR26; Q6GQS6; Q8CED0;
DT 25-JAN-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=Protein HEG homolog 1;
DE Flags: Precursor;
GN Name=Heg1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1007-1240 (ISOFORM 1).
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 [5]
RP IDENTIFICATION, FUNCTION, INTERACTION WITH CCM2 AND KRIT1, SUBCELLULAR
RP LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
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).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1315, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Receptor component of the CCM signaling pathway which is a
CC crucial regulator of heart and vessel formation and integrity. May be
CC acting by stabilizing endothelial cell junctions.
CC {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: Cell membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Cell junction
CC {ECO:0000269|PubMed:19151727}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=E9Q7X6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=E9Q7X6-2; Sequence=VSP_042234;
CC Name=3;
CC IsoId=E9Q7X6-3; Sequence=VSP_042234, VSP_042235, VSP_042236;
CC -!- DEVELOPMENTAL STAGE: Expressed in the endothelium of the developing
CC heart and aorta and in the neural tube at 10.5 dpc, and in the arterial
CC endothelium, smooth muscle, endocardium of the heart and brain
CC vasculature at 14.5 dpc. {ECO:0000269|PubMed:19151727}.
CC -!- DISRUPTION PHENOTYPE: Some mutant animals die in utero, but most die
CC postnatally, about half before weaning as a result of pulmonary
CC hemorrhage. Midgestation mutant embryos show cardiac defects
CC characterized by invagination of the ventricular cavity into, and often
CC through, the compact layer of ventricular myocardium. The septal
CC myocardium is similarly honeycombed by endothelial-lined extensions
CC from the ventricular cavity, a defect accompanied by the presence of
CC ventricular septal defects in most late-gestation embryos. Neonatal
CC mice also show defective cardiac integrity manifested by a blood-filled
CC pericardial sac, due to the rupture of the low-pressure atrial chamber
CC of the heart. Cardiac or pulmonary integrity defects are observed in
CC half of the animals. About 10% of neonatal mutant mice exhibit dilated
CC lymphatic vessel malformations. {ECO:0000269|PubMed:19151727}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be due to an intron retention.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH72651.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK163128; BAE37205.1; -; mRNA.
DR EMBL; AK028518; BAC25987.1; -; mRNA.
DR EMBL; AC121570; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466521; EDK97850.1; -; Genomic_DNA.
DR EMBL; BC072651; AAH72651.1; ALT_INIT; mRNA.
DR AlphaFoldDB; E9Q7X6; -.
DR CORUM; E9Q7X6; -.
DR STRING; 10090.ENSMUSP00000119790; -.
DR GlyGen; E9Q7X6; 1 site.
DR iPTMnet; E9Q7X6; -.
DR PhosphoSitePlus; E9Q7X6; -.
DR EPD; E9Q7X6; -.
DR jPOST; E9Q7X6; -.
DR MaxQB; E9Q7X6; -.
DR PaxDb; E9Q7X6; -.
DR PRIDE; E9Q7X6; -.
DR ProteomicsDB; 269558; -. [E9Q7X6-1]
DR ProteomicsDB; 269559; -. [E9Q7X6-2]
DR ProteomicsDB; 269560; -. [E9Q7X6-3]
DR Antibodypedia; 2617; 20 antibodies from 9 providers.
DR Ensembl; ENSMUST00000126532; ENSMUSP00000119790; ENSMUSG00000075254. [E9Q7X6-1]
DR UCSC; uc007zah.1; mouse. [E9Q7X6-3]
DR MGI; MGI:1924696; Heg1.
DR VEuPathDB; HostDB:ENSMUSG00000075254; -.
DR eggNOG; ENOG502QPW9; Eukaryota.
DR GeneTree; ENSGT00710000106813; -.
DR InParanoid; E9Q7X6; -.
DR OMA; GMQKCVN; -.
DR PhylomeDB; E9Q7X6; -.
DR ChiTaRS; Heg1; mouse.
DR PRO; PR:E9Q7X6; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; E9Q7X6; protein.
DR Bgee; ENSMUSG00000075254; Expressed in embryonic post-anal tail and 146 other tissues.
DR ExpressionAtlas; E9Q7X6; baseline and differential.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0003209; P:cardiac atrium morphogenesis; IMP:MGI.
DR GO; GO:0055017; P:cardiac muscle tissue growth; IGI:MGI.
DR GO; GO:0007043; P:cell-cell junction assembly; IEA:InterPro.
DR GO; GO:0045216; P:cell-cell junction organization; IMP:MGI.
DR GO; GO:0001885; P:endothelial cell development; IGI:MGI.
DR GO; GO:0001886; P:endothelial cell morphogenesis; IMP:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0030324; P:lung development; IMP:MGI.
DR GO; GO:0003017; P:lymph circulation; IMP:MGI.
DR GO; GO:0001945; P:lymph vessel development; IMP:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IGI:MGI.
DR GO; GO:1905709; P:negative regulation of membrane permeability; ISS:UniProtKB.
DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; ISS:UniProtKB.
DR GO; GO:2000299; P:negative regulation of Rho-dependent protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0060039; P:pericardium development; IMP:MGI.
DR GO; GO:0090271; P:positive regulation of fibroblast growth factor production; IGI:MGI.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:1902414; P:protein localization to cell junction; ISS:UniProtKB.
DR GO; GO:0050878; P:regulation of body fluid levels; IMP:MGI.
DR GO; GO:0001944; P:vasculature development; IGI:MGI.
DR GO; GO:0001570; P:vasculogenesis; IGI:MGI.
DR GO; GO:0048845; P:venous blood vessel morphogenesis; IGI:MGI.
DR GO; GO:0003281; P:ventricular septum development; IMP:MGI.
DR GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; IGI:MGI.
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; IPR028720; HEG.
DR PANTHER; PTHR24037; PTHR24037; 2.
DR Pfam; PF00008; EGF; 1.
DR Pfam; PF07645; EGF_CA; 1.
DR SMART; SM00181; EGF; 3.
DR SMART; SM00179; EGF_CA; 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; Phosphoprotein; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..1337
FT /note="Protein HEG homolog 1"
FT /id="PRO_0000415377"
FT TOPO_DOM 32..1204
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1205..1225
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1226..1337
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 941..979
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 981..1019
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 28..149
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 175..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 235..296
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 313..675
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 723..767
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 860..909
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 96..149
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 175..208
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 247..296
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 341..364
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 481..522
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 543..621
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 649..675
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 723..764
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 860..886
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1315
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 1093
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 945..956
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 950..967
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 969..978
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 985..996
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 990..1005
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1007..1018
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VAR_SEQ 83..179
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_042234"
FT VAR_SEQ 510..550
FT /note="LTGLSYTREHGSDAGQRTSSDHTDHGYVPSTFTKGERTLLS -> REFLVHG
FT NRHRVLGCVWSFDLPKHTLGKEFHYSQAIILLAD (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_042235"
FT VAR_SEQ 551..1337
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_042236"
SQ SEQUENCE 1337 AA; 141899 MW; 80D24CAAC1AD77BF CRC64;
MATPRAPRWP PPSLLLLLLL PLLLLPPAAP GARGSLPSPA HRTLLPVAGP LSPPGAGHTA
PGPGVATRRG RSGRVPRGVS AAAARNRWLE SNNPEPHIGC SPSYQSQEDH SGSRKGVTAQ
NARMSHSSSE GPENPPLLPE TSAEWSNMAS SHRADIAGLR RGPSPEITTA PTAHSSLLSL
ESLPESPSSS RSQRRITPSQ TESGTSLGFL ERTRELPEEG TVHTQVAGTW VSRQASHPAL
EPGEPTVLSQ KRNSSGQEHS GPPFSWSQSH PPPSDHPSSS GSIKNGNNFT ALQNPSVTQT
KSMLITDTYT NGVPRTLRSL PVGVDPADET EGFPEHSRLG ITSMSVRSSP SVKDSRTNSG
LTEHLGDGEG TELSTENGYG LPSIHWQSDA PSFGGRQLAS SSEAGDGRAM PLTEAVFRSD
PSIGGGESTG RWILTKKKTS TDAAESSALH PEAGGAGGLT QSSHAAQQPR GGGEDSGMGG
RSYAESSSSS SSTSSSESLD SSAPLREHSL TGLSYTREHG SDAGQRTSSD HTDHGYVPST
FTKGERTLLS ITDNTSYSEA SESSTSSVKI SDSPSQAQPK QSSMSSDDDE PAQSSTESPV
LHTSNLPTYT STVNMPNTLV LDTGTKPVED PSDSRVPSTQ PSPSQPQPFS SALPSTRSPG
STSETTTSSP SPSPISLLVS TLAPYSVSQT TFPHPSSTLV PHRPREPRVT SVQMSTAISA
IALIPSNQTA NPKNQSTPQQ EKPITEAKSP SLVSPPTDST KAVTVSLPPG APWSPALTGF
STGPALPATS TSLAQMSPAL TSAMPQTTHS PVTSPSTLSH VEALTSGAVV VHTTPKKPHL
PTNPEILVPH ISTEGAITTE GNREHTDPTT QPIPLTTSTT SAGERTTELG RAEESSPSHF
LTPSSPQTTD VSTAEMLTSR YITFAAQSTS QSPTALPPLT PVNSCTVNPC LHDGKCIVDL
TGRGYRCVCP PAWQGENCSV DVNECLSSPC PPLATCNNTQ GSFTCRCPVG YQLEKGICNL
VRTFVTEFKL KKTFLNTTAE NHSNTQELEN EIAQTLNVCF STLPGYIRTT AHVSREPSTV
FISLKTTFAL ASNVTLFDLA DRIQKYVNSC RSSAEVCQLL GSQRRVFRAG SLCKRKSPEC
DKETSICTDL DGVALCQCKS GYFQFNKMDH SCRACEDGYR LENETCMSCP FGLGGLNCGN
PYQLITVVIA AAGGGLLLIL GVALIVTCCR KSKNDISKLI FKSGDFQMSP YTDVPKNPRS
QEWGREAIEM HENGSTKNLL QMTDVYYSPT NVRNPELERN GLYPAYTGLP GSRHSCIFPG
QYNPSFISDE SRRRDYF
