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Protein

Neurogenic locus notch homolog protein 4

Gene

NOTCH4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. May regulate branching morphogenesis in the developing vascular system (By similarity).By similarity

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • receptor activity Source: UniProtKB

GO - Biological processi

  • cell differentiation Source: UniProtKB
  • cell fate determination Source: UniProtKB
  • embryo development Source: UniProtKB
  • endothelial cell morphogenesis Source: Ensembl
  • hemopoiesis Source: UniProtKB
  • mammary gland development Source: UniProtKB
  • morphogenesis of a branching structure Source: UniProtKB
  • negative regulation of cell differentiation Source: UniProtKB
  • negative regulation of endothelial cell differentiation Source: UniProtKB
  • Notch receptor processing Source: Reactome
  • Notch signaling pathway Source: Reactome
  • patterning of blood vessels Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription of Notch receptor target Source: BHF-UCL
  • transcription initiation from RNA polymerase II promoter Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein, Receptor

Keywords - Biological processi

Differentiation, Notch signaling pathway, Transcription, Transcription regulation

Enzyme and pathway databases

BioCyciZFISH:ENSG00000112049-MONOMER.
ReactomeiR-HSA-1912399. Pre-NOTCH Processing in the Endoplasmic Reticulum.
R-HSA-1912408. Pre-NOTCH Transcription and Translation.
R-HSA-1912420. Pre-NOTCH Processing in Golgi.
R-HSA-1980150. Signaling by NOTCH4.
R-HSA-350054. Notch-HLH transcription pathway.
R-HSA-5083630. Defective LFNG causes SCDO3.
SignaLinkiQ99466.
SIGNORiQ99466.

Names & Taxonomyi

Protein namesi
Recommended name:
Neurogenic locus notch homolog protein 4
Short name:
Notch 4
Short name:
hNotch4
Cleaved into the following 2 chains:
Gene namesi
Name:NOTCH4
Synonyms:INT3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:7884. NOTCH4.

Subcellular locationi

Notch 4 intracellular domain :
  • Nucleus

  • Note: Following proteolytical processing NICD is translocated to the nucleus.

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 1447ExtracellularSequence analysisAdd BLAST1424
Transmembranei1448 – 1468HelicalSequence analysisAdd BLAST21
Topological domaini1469 – 2003CytoplasmicSequence analysisAdd BLAST535

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • cytosol Source: Reactome
  • endoplasmic reticulum membrane Source: Reactome
  • extracellular region Source: Reactome
  • Golgi membrane Source: Reactome
  • integral component of plasma membrane Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi4855.
OpenTargetsiENSG00000204301.
ENSG00000234876.
PharmGKBiPA31686.

Chemistry databases

ChEMBLiCHEMBL3407321.

Polymorphism and mutation databases

BioMutaiNOTCH4.
DMDMi20139103.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000000770124 – 2003Neurogenic locus notch homolog protein 4Add BLAST1980
ChainiPRO_00000077021432 – 2003Notch 4 extracellular truncationBy similarityAdd BLAST572
ChainiPRO_00000077031467 – 2003Notch 4 intracellular domainBy similarityAdd BLAST537

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi28 ↔ 41By similarity
Disulfide bondi35 ↔ 51By similarity
Disulfide bondi53 ↔ 62By similarity
Disulfide bondi68 ↔ 80By similarity
Disulfide bondi74 ↔ 103By similarity
Disulfide bondi105 ↔ 114By similarity
Disulfide bondi122 ↔ 133By similarity
Disulfide bondi127 ↔ 143By similarity
Disulfide bondi145 ↔ 154By similarity
Disulfide bondi160 ↔ 171By similarity
Disulfide bondi165 ↔ 180By similarity
Disulfide bondi182 ↔ 191By similarity
Disulfide bondi198 ↔ 211By similarity
Disulfide bondi205 ↔ 220By similarity
Disulfide bondi222 ↔ 231By similarity
Disulfide bondi238 ↔ 249By similarity
Disulfide bondi243 ↔ 262By similarity
Disulfide bondi264 ↔ 273By similarity
Disulfide bondi280 ↔ 291By similarity
Disulfide bondi285 ↔ 300By similarity
Disulfide bondi302 ↔ 311By similarity
Disulfide bondi318 ↔ 332By similarity
Disulfide bondi326 ↔ 341By similarity
Disulfide bondi343 ↔ 352By similarity
Disulfide bondi359 ↔ 370By similarity
Disulfide bondi364 ↔ 379By similarity
Disulfide bondi381 ↔ 390By similarity
Disulfide bondi396 ↔ 407By similarity
Disulfide bondi401 ↔ 418By similarity
Disulfide bondi420 ↔ 429By similarity
Disulfide bondi436 ↔ 452By similarity
Disulfide bondi446 ↔ 461By similarity
Disulfide bondi463 ↔ 472By similarity
Disulfide bondi479 ↔ 490By similarity
Disulfide bondi484 ↔ 499By similarity
Disulfide bondi501 ↔ 510By similarity
Disulfide bondi517 ↔ 528By similarity
Disulfide bondi522 ↔ 537By similarity
Disulfide bondi539 ↔ 548By similarity
Disulfide bondi555 ↔ 566By similarity
Disulfide bondi560 ↔ 575By similarity
Disulfide bondi577 ↔ 586By similarity
Disulfide bondi593 ↔ 604By similarity
Disulfide bondi598 ↔ 613By similarity
Disulfide bondi615 ↔ 624By similarity
Disulfide bondi629 ↔ 640By similarity
Disulfide bondi634 ↔ 649By similarity
Disulfide bondi651 ↔ 658By similarity
Glycosylationi664N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi665 ↔ 672By similarity
Disulfide bondi667 ↔ 677By similarity
Disulfide bondi679 ↔ 688By similarity
Disulfide bondi695 ↔ 706By similarity
Disulfide bondi700 ↔ 715By similarity
Glycosylationi714N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi717 ↔ 726By similarity
Disulfide bondi733 ↔ 744By similarity
Disulfide bondi738 ↔ 753By similarity
Disulfide bondi755 ↔ 764By similarity
Disulfide bondi771 ↔ 782By similarity
Disulfide bondi776 ↔ 791By similarity
Disulfide bondi793 ↔ 802By similarity
Disulfide bondi810 ↔ 821By similarity
Disulfide bondi815 ↔ 830By similarity
Disulfide bondi832 ↔ 841By similarity
Disulfide bondi848 ↔ 859By similarity
Disulfide bondi853 ↔ 868By similarity
Disulfide bondi870 ↔ 879By similarity
Disulfide bondi886 ↔ 907By similarity
Disulfide bondi901 ↔ 916By similarity
Disulfide bondi918 ↔ 927By similarity
Disulfide bondi934 ↔ 945By similarity
Disulfide bondi939 ↔ 954By similarity
Disulfide bondi956 ↔ 965By similarity
Glycosylationi964N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi972 ↔ 983By similarity
Disulfide bondi977 ↔ 992By similarity
Disulfide bondi994 ↔ 1003By similarity
Disulfide bondi1010 ↔ 1023By similarity
Disulfide bondi1015 ↔ 1032By similarity
Disulfide bondi1034 ↔ 1043By similarity
Disulfide bondi1050 ↔ 1061By similarity
Disulfide bondi1055 ↔ 1073By similarity
Disulfide bondi1075 ↔ 1084By similarity
Disulfide bondi1091 ↔ 1102By similarity
Disulfide bondi1096 ↔ 1114By similarity
Disulfide bondi1116 ↔ 1125By similarity
Disulfide bondi1134 ↔ 1146By similarity
Disulfide bondi1140 ↔ 1159By similarity
Glycosylationi1143N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi1161 ↔ 1170By similarity
Disulfide bondi1178 ↔ 1191By similarity
Disulfide bondi1187 ↔ 1203By similarity
Disulfide bondi1214 ↔ 1238By similarity
Disulfide bondi1220 ↔ 1233By similarity
Disulfide bondi1229 ↔ 1245By similarity
Disulfide bondi1251 ↔ 1277By similarity
Disulfide bondi1259 ↔ 1272By similarity
Disulfide bondi1268 ↔ 1284By similarity

Post-translational modificationi

Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane (By similarity).By similarity
Phosphorylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ99466.
PaxDbiQ99466.
PeptideAtlasiQ99466.
PRIDEiQ99466.

PTM databases

iPTMnetiQ99466.
PhosphoSitePlusiQ99466.

Expressioni

Tissue specificityi

Highly expressed in the heart, moderately in the lung and placenta and at low levels in the liver, skeletal muscle, kidney, pancreas, spleen, lymph node, thymus, bone marrow and fetal liver. No expression was seen in adult brain or peripheral blood leukocytes.

Gene expression databases

BgeeiENSG00000204301.
CleanExiHS_NOTCH4.
GenevisibleiQ99466. HS.

Interactioni

Subunit structurei

Heterodimer of a C-terminal fragment N(TM) and a N-terminal fragment N(EC) which are probably linked by disulfide bonds (By similarity). Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH4.By similarity2 Publications

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi110917. 9 interactors.
IntActiQ99466. 1 interactor.
STRINGi9606.ENSP00000364163.

Chemistry databases

BindingDBiQ99466.

Structurei

3D structure databases

ProteinModelPortaliQ99466.
SMRiQ99466.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 63EGF-like 1PROSITE-ProRule annotationAdd BLAST40
Domaini64 – 115EGF-like 2PROSITE-ProRule annotationAdd BLAST52
Domaini118 – 155EGF-like 3PROSITE-ProRule annotationAdd BLAST38
Domaini156 – 192EGF-like 4PROSITE-ProRule annotationAdd BLAST37
Domaini194 – 232EGF-like 5; calcium-bindingPROSITE-ProRule annotationAdd BLAST39
Domaini234 – 274EGF-like 6PROSITE-ProRule annotationAdd BLAST41
Domaini276 – 312EGF-like 7; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini314 – 353EGF-like 8; calcium-bindingPROSITE-ProRule annotationAdd BLAST40
Domaini355 – 391EGF-like 9; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini392 – 430EGF-like 10PROSITE-ProRule annotationAdd BLAST39
Domaini432 – 473EGF-like 11; calcium-bindingPROSITE-ProRule annotationAdd BLAST42
Domaini475 – 511EGF-like 12; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini513 – 549EGF-like 13; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini551 – 587EGF-like 14; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini589 – 625EGF-like 15; calcium-bindingPROSITE-ProRule annotationAdd BLAST37
Domaini626 – 659EGF-like 16PROSITE-ProRule annotationAdd BLAST34
Domaini661 – 689EGF-like 17PROSITE-ProRule annotationAdd BLAST29
Domaini691 – 727EGF-like 18PROSITE-ProRule annotationAdd BLAST37
Domaini729 – 765EGF-like 19PROSITE-ProRule annotationAdd BLAST37
Domaini767 – 803EGF-like 20PROSITE-ProRule annotationAdd BLAST37
Domaini806 – 842EGF-like 21PROSITE-ProRule annotationAdd BLAST37
Domaini844 – 880EGF-like 22PROSITE-ProRule annotationAdd BLAST37
Domaini882 – 928EGF-like 23PROSITE-ProRule annotationAdd BLAST47
Domaini930 – 966EGF-like 24PROSITE-ProRule annotationAdd BLAST37
Domaini968 – 1004EGF-like 25PROSITE-ProRule annotationAdd BLAST37
Domaini1006 – 1044EGF-like 26PROSITE-ProRule annotationAdd BLAST39
Domaini1046 – 1085EGF-like 27PROSITE-ProRule annotationAdd BLAST40
Domaini1087 – 1126EGF-like 28PROSITE-ProRule annotationAdd BLAST40
Domaini1130 – 1171EGF-like 29PROSITE-ProRule annotationAdd BLAST42
Repeati1170 – 1213LNR 1Add BLAST44
Repeati1214 – 1250LNR 2Add BLAST37
Repeati1251 – 1294LNR 3Add BLAST44
Repeati1633 – 1665ANK 1Add BLAST33
Repeati1666 – 1698ANK 2Add BLAST33
Repeati1700 – 1732ANK 3Add BLAST33
Repeati1733 – 1765ANK 4Add BLAST33
Repeati1766 – 1798ANK 5Add BLAST33

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1472 – 1476Poly-Arg5

Sequence similaritiesi

Belongs to the NOTCH family.Curated
Contains 5 ANK repeats.PROSITE-ProRule annotation
Contains 29 EGF-like domains.PROSITE-ProRule annotation
Contains 3 LNR (Lin/Notch) repeats.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IR7G. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00810000125346.
HOVERGENiHBG052650.
InParanoidiQ99466.
KOiK02599.
OMAiVACHPLA.
OrthoDBiEOG091G01NU.
PhylomeDBiQ99466.
TreeFamiTF351641.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR009030. Growth_fac_rcpt_.
IPR022355. Notch_4.
IPR000800. Notch_dom.
IPR010660. Notch_NOD_dom.
IPR011656. Notch_NODP_dom.
[Graphical view]
PfamiPF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
PF00008. EGF. 12 hits.
PF07645. EGF_CA. 5 hits.
PF12661. hEGF. 3 hits.
PF06816. NOD. 1 hit.
PF07684. NODP. 1 hit.
PF00066. Notch. 3 hits.
[Graphical view]
PRINTSiPR01452. LNOTCHREPEAT.
PR01987. NOTCH4.
SMARTiSM00248. ANK. 5 hits.
SM00181. EGF. 29 hits.
SM00179. EGF_CA. 22 hits.
SM00004. NL. 3 hits.
SM01338. NOD. 1 hit.
SM01339. NODP. 1 hit.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF57184. SSF57184. 5 hits.
SSF90193. SSF90193. 2 hits.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 5 hits.
PS00010. ASX_HYDROXYL. 11 hits.
PS00022. EGF_1. 28 hits.
PS01186. EGF_2. 21 hits.
PS50026. EGF_3. 28 hits.
PS01187. EGF_CA. 9 hits.
PS50258. LNR. 3 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q99466-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MQPPSLLLLL LLLLLLCVSV VRPRGLLCGS FPEPCANGGT CLSLSLGQGT
60 70 80 90 100
CQCAPGFLGE TCQFPDPCQN AQLCQNGGSC QALLPAPLGL PSSPSPLTPS
110 120 130 140 150
FLCTCLPGFT GERCQAKLED PCPPSFCSKR GRCHIQASGR PQCSCMPGWT
160 170 180 190 200
GEQCQLRDFC SANPCVNGGV CLATYPQIQC HCPPGFEGHA CERDVNECFQ
210 220 230 240 250
DPGPCPKGTS CHNTLGSFQC LCPVGQEGPR CELRAGPCPP RGCSNGGTCQ
260 270 280 290 300
LMPEKDSTFH LCLCPPGFIG PDCEVNPDNC VSHQCQNGGT CQDGLDTYTC
310 320 330 340 350
LCPETWTGWD CSEDVDECET QGPPHCRNGG TCQNSAGSFH CVCVSGWGGT
360 370 380 390 400
SCEENLDDCI AATCAPGSTC IDRVGSFSCL CPPGRTGLLC HLEDMCLSQP
410 420 430 440 450
CHGDAQCSTN PLTGSTLCLC QPGYSGPTCH QDLDECLMAQ QGPSPCEHGG
460 470 480 490 500
SCLNTPGSFN CLCPPGYTGS RCEADHNECL SQPCHPGSTC LDLLATFHCL
510 520 530 540 550
CPPGLEGQLC EVETNECASA PCLNHADCHD LLNGFQCICL PGFSGTRCEE
560 570 580 590 600
DIDECRSSPC ANGGQCQDQP GAFHCKCLPG FEGPRCQTEV DECLSDPCPV
610 620 630 640 650
GASCLDLPGA FFCLCPSGFT GQLCEVPLCA PNLCQPKQIC KDQKDKANCL
660 670 680 690 700
CPDGSPGCAP PEDNCTCHHG HCQRSSCVCD VGWTGPECEA ELGGCISAPC
710 720 730 740 750
AHGGTCYPQP SGYNCTCPTG YTGPTCSEEM TACHSGPCLN GGSCNPSPGG
760 770 780 790 800
YYCTCPPSHT GPQCQTSTDY CVSAPCFNGG TCVNRPGTFS CLCAMGFQGP
810 820 830 840 850
RCEGKLRPSC ADSPCRNRAT CQDSPQGPRC LCPTGYTGGS CQTLMDLCAQ
860 870 880 890 900
KPCPRNSHCL QTGPSFHCLC LQGWTGPLCN LPLSSCQKAA LSQGIDVSSL
910 920 930 940 950
CHNGGLCVDS GPSYFCHCPP GFQGSLCQDH VNPCESRPCQ NGATCMAQPS
960 970 980 990 1000
GYLCQCAPGY DGQNCSKELD ACQSQPCHNH GTCTPKPGGF HCACPPGFVG
1010 1020 1030 1040 1050
LRCEGDVDEC LDQPCHPTGT AACHSLANAF YCQCLPGHTG QWCEVEIDPC
1060 1070 1080 1090 1100
HSQPCFHGGT CEATAGSPLG FICHCPKGFE GPTCSHRAPS CGFHHCHHGG
1110 1120 1130 1140 1150
LCLPSPKPGF PPRCACLSGY GGPDCLTPPA PKGCGPPSPC LYNGSCSETT
1160 1170 1180 1190 1200
GLGGPGFRCS CPHSSPGPRC QKPGAKGCEG RSGDGACDAG CSGPGGNWDG
1210 1220 1230 1240 1250
GDCSLGVPDP WKGCPSHSRC WLLFRDGQCH PQCDSEECLF DGYDCETPPA
1260 1270 1280 1290 1300
CTPAYDQYCH DHFHNGHCEK GCNTAECGWD GGDCRPEDGD PEWGPSLALL
1310 1320 1330 1340 1350
VVLSPPALDQ QLFALARVLS LTLRVGLWVR KDRDGRDMVY PYPGARAEEK
1360 1370 1380 1390 1400
LGGTRDPTYQ ERAAPQTQPL GKETDSLSAG FVVVMGVDLS RCGPDHPASR
1410 1420 1430 1440 1450
CPWDPGLLLR FLAAMAAVGA LEPLLPGPLL AVHPHAGTAP PANQLPWPVL
1460 1470 1480 1490 1500
CSPVAGVILL ALGALLVLQL IRRRRREHGA LWLPPGFTRR PRTQSAPHRR
1510 1520 1530 1540 1550
RPPLGEDSIG LKALKPKAEV DEDGVVMCSG PEEGEEVGQA EETGPPSTCQ
1560 1570 1580 1590 1600
LWSLSGGCGA LPQAAMLTPP QESEMEAPDL DTRGPDGVTP LMSAVCCGEV
1610 1620 1630 1640 1650
QSGTFQGAWL GCPEPWEPLL DGGACPQAHT VGTGETPLHL AARFSRPTAA
1660 1670 1680 1690 1700
RRLLEAGANP NQPDRAGRTP LHAAVAADAR EVCQLLLRSR QTAVDARTED
1710 1720 1730 1740 1750
GTTPLMLAAR LAVEDLVEEL IAAQADVGAR DKWGKTALHW AAAVNNARAA
1760 1770 1780 1790 1800
RSLLQAGADK DAQDNREQTP LFLAAREGAV EVAQLLLGLG AARELRDQAG
1810 1820 1830 1840 1850
LAPADVAHQR NHWDLLTLLE GAGPPEARHK ATPGREAGPF PRARTVSVSV
1860 1870 1880 1890 1900
PPHGGGALPR CRTLSAGAGP RGGGACLQAR TWSVDLAARG GGAYSHCRSL
1910 1920 1930 1940 1950
SGVGAGGGPT PRGRRFSAGM RGPRPNPAIM RGRYGVAAGR GGRVSTDDWP
1960 1970 1980 1990 2000
CDWVALGACG SASNIPIPPP CLTPSPERGS PQLDCGPPAL QEMPINQGGE

GKK
Length:2,003
Mass (Da):209,622
Last modified:March 27, 2002 - v2
Checksum:iBED10283A43A0C14
GO
Isoform 2 (identifier: Q99466-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1414: Missing.

Show »
Length:589
Mass (Da):61,262
Checksum:i0B8F267B8A5EC76B
GO
Isoform 3 (identifier: Q99466-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     378-2003: Missing.

Show »
Length:377
Mass (Da):39,617
Checksum:i77CB39F5A34F1078
GO

Sequence cautioni

The sequence BAA09708 differs from that shown. Reason: Frameshift at positions 1438 and 1463.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1431A → V in BAA09708 (PubMed:9168133).Curated1
Sequence conflicti1436A → E in BAA09708 (PubMed:9168133).Curated1
Sequence conflicti1445L → F in BAA09708 (PubMed:9168133).Curated1
Sequence conflicti1537 – 1539Missing in AAC63097 (PubMed:9693032).Curated3
Sequence conflicti1538G → A in BAA09708 (PubMed:9168133).Curated1

Polymorphismi

The poly-Leu region of NOTCH4 (in the signal peptide) is polymorphic and the number of Leu varies in the population (from 6 to 12).1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_012866117K → Q.2 PublicationsCorresponds to variant rs915894dbSNPEnsembl.1
Natural variantiVAR_033828204P → L.Corresponds to variant rs2071282dbSNPEnsembl.1
Natural variantiVAR_033829206P → L.Corresponds to variant rs2071282dbSNPEnsembl.1
Natural variantiVAR_033830244S → L.Corresponds to variant rs8192585dbSNPEnsembl.1
Natural variantiVAR_012867272D → G.Corresponds to variant rs520692dbSNPEnsembl.1
Natural variantiVAR_059271284Q → H.Corresponds to variant rs520803dbSNPEnsembl.1
Natural variantiVAR_012868317E → Q.1 Publication1
Natural variantiVAR_012869320T → A.Corresponds to variant rs422951dbSNPEnsembl.1
Natural variantiVAR_033831534G → S.Corresponds to variant rs8192591dbSNPEnsembl.1
Natural variantiVAR_048991809S → I.Corresponds to variant rs3132961dbSNPEnsembl.1
Natural variantiVAR_012870851K → R.Corresponds to variant rs2022060dbSNPEnsembl.1
Natural variantiVAR_048992942G → R.Corresponds to variant rs17604492dbSNPEnsembl.1
Natural variantiVAR_0489931346R → P.Corresponds to variant rs8192573dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0014061 – 1414Missing in isoform 2. 1 PublicationAdd BLAST1414
Alternative sequenceiVSP_001407378 – 2003Missing in isoform 3. 1 PublicationAdd BLAST1626

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D63395 mRNA. Translation: BAA09708.1. Frameshift.
D86566 Genomic DNA. Translation: BAA13116.1.
U95299 mRNA. Translation: AAC32288.1.
U89335 Genomic DNA. Translation: AAC63097.1.
AL662884 Genomic DNA. Translation: CAI18362.1.
BX284686, BX284927 Genomic DNA. Translation: CAM26209.1.
BX284927, BX284686 Genomic DNA. Translation: CAM25850.1.
CR812478 Genomic DNA. Translation: CAQ10706.1.
CR933878 Genomic DNA. Translation: CAQ09631.1.
AB023961 Genomic DNA. Translation: BAB20317.1.
AB024520 Genomic DNA. Translation: BAA88951.1.
AB024578 Genomic DNA. Translation: BAA88952.1.
CCDSiCCDS34420.1. [Q99466-1]
RefSeqiNP_004548.3. NM_004557.3. [Q99466-1]
UniGeneiHs.436100.

Genome annotation databases

EnsembliENST00000375023; ENSP00000364163; ENSG00000204301. [Q99466-1]
ENST00000425600; ENSP00000401321; ENSG00000238196.
ENST00000439349; ENSP00000408335; ENSG00000223355.
ENST00000457094; ENSP00000403447; ENSG00000234876. [Q99466-1]
GeneIDi4855.
KEGGihsa:4855.
UCSCiuc003obb.3. human. [Q99466-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism, Triplet repeat expansion

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D63395 mRNA. Translation: BAA09708.1. Frameshift.
D86566 Genomic DNA. Translation: BAA13116.1.
U95299 mRNA. Translation: AAC32288.1.
U89335 Genomic DNA. Translation: AAC63097.1.
AL662884 Genomic DNA. Translation: CAI18362.1.
BX284686, BX284927 Genomic DNA. Translation: CAM26209.1.
BX284927, BX284686 Genomic DNA. Translation: CAM25850.1.
CR812478 Genomic DNA. Translation: CAQ10706.1.
CR933878 Genomic DNA. Translation: CAQ09631.1.
AB023961 Genomic DNA. Translation: BAB20317.1.
AB024520 Genomic DNA. Translation: BAA88951.1.
AB024578 Genomic DNA. Translation: BAA88952.1.
CCDSiCCDS34420.1. [Q99466-1]
RefSeqiNP_004548.3. NM_004557.3. [Q99466-1]
UniGeneiHs.436100.

3D structure databases

ProteinModelPortaliQ99466.
SMRiQ99466.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110917. 9 interactors.
IntActiQ99466. 1 interactor.
STRINGi9606.ENSP00000364163.

Chemistry databases

BindingDBiQ99466.
ChEMBLiCHEMBL3407321.

PTM databases

iPTMnetiQ99466.
PhosphoSitePlusiQ99466.

Polymorphism and mutation databases

BioMutaiNOTCH4.
DMDMi20139103.

Proteomic databases

MaxQBiQ99466.
PaxDbiQ99466.
PeptideAtlasiQ99466.
PRIDEiQ99466.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000375023; ENSP00000364163; ENSG00000204301. [Q99466-1]
ENST00000425600; ENSP00000401321; ENSG00000238196.
ENST00000439349; ENSP00000408335; ENSG00000223355.
ENST00000457094; ENSP00000403447; ENSG00000234876. [Q99466-1]
GeneIDi4855.
KEGGihsa:4855.
UCSCiuc003obb.3. human. [Q99466-1]

Organism-specific databases

CTDi4855.
DisGeNETi4855.
GeneCardsiNOTCH4.
HGNCiHGNC:7884. NOTCH4.
MIMi164951. gene.
neXtProtiNX_Q99466.
OpenTargetsiENSG00000204301.
ENSG00000234876.
PharmGKBiPA31686.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IR7G. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00810000125346.
HOVERGENiHBG052650.
InParanoidiQ99466.
KOiK02599.
OMAiVACHPLA.
OrthoDBiEOG091G01NU.
PhylomeDBiQ99466.
TreeFamiTF351641.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000112049-MONOMER.
ReactomeiR-HSA-1912399. Pre-NOTCH Processing in the Endoplasmic Reticulum.
R-HSA-1912408. Pre-NOTCH Transcription and Translation.
R-HSA-1912420. Pre-NOTCH Processing in Golgi.
R-HSA-1980150. Signaling by NOTCH4.
R-HSA-350054. Notch-HLH transcription pathway.
R-HSA-5083630. Defective LFNG causes SCDO3.
SignaLinkiQ99466.
SIGNORiQ99466.

Miscellaneous databases

GeneWikiiNOTCH4.
GenomeRNAii4855.
PROiQ99466.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000204301.
CleanExiHS_NOTCH4.
GenevisibleiQ99466. HS.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR009030. Growth_fac_rcpt_.
IPR022355. Notch_4.
IPR000800. Notch_dom.
IPR010660. Notch_NOD_dom.
IPR011656. Notch_NODP_dom.
[Graphical view]
PfamiPF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
PF00008. EGF. 12 hits.
PF07645. EGF_CA. 5 hits.
PF12661. hEGF. 3 hits.
PF06816. NOD. 1 hit.
PF07684. NODP. 1 hit.
PF00066. Notch. 3 hits.
[Graphical view]
PRINTSiPR01452. LNOTCHREPEAT.
PR01987. NOTCH4.
SMARTiSM00248. ANK. 5 hits.
SM00181. EGF. 29 hits.
SM00179. EGF_CA. 22 hits.
SM00004. NL. 3 hits.
SM01338. NOD. 1 hit.
SM01339. NODP. 1 hit.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF57184. SSF57184. 5 hits.
SSF90193. SSF90193. 2 hits.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 5 hits.
PS00010. ASX_HYDROXYL. 11 hits.
PS00022. EGF_1. 28 hits.
PS01186. EGF_2. 21 hits.
PS50026. EGF_3. 28 hits.
PS01187. EGF_CA. 9 hits.
PS50258. LNR. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNOTC4_HUMAN
AccessioniPrimary (citable) accession number: Q99466
Secondary accession number(s): B0V183
, B0V1X5, O00306, Q5SSY7, Q99458, Q99940, Q9H3S8, Q9UII9, Q9UIJ0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: March 27, 2002
Last modified: November 2, 2016
This is version 179 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.