Q99466 (NOTC4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neurogenic locus notch homolog protein 4
Short name=Notch 4
Short name=hNotch4

Cleaved into the following 2 chains:

1. Notch 4 extracellular truncation
2. Notch 4 intracellular domain

Gene names

Name:	NOTCH4
Synonyms:	INT3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	2003 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Subunit structure	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. Ref.6 Ref.7
Subcellular location	Cell membrane; Single-pass type I membrane protein. Notch 4 intracellular domain: Nucleus. Note: Following proteolytical processing NICD is translocated to the nucleus.
Tissue specificity	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.
Post-translational modification	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. Phosphorylated By similarity.
Polymorphism	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).
Sequence similarities	Belongs to the NOTCH family. Contains 5 ANK repeats. Contains 28 EGF-like domains. Contains 3 LNR (Lin/Notch) repeats.
Sequence caution	The sequence BAA09708.1 differs from that shown. Reason: Frameshift at positions 1438 and 1463.

Ontologies

Keywords
Biological process	Differentiation Notch signaling pathway Transcription Transcription regulation
Cellular component	Cell membrane Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism Triplet repeat expansion
Domain	ANK repeat EGF-like domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Activator Developmental protein Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Notch receptor processing Traceable author statement. Source: Reactome Notch signaling pathway Traceable author statement. Source: Reactome cell fate determination Traceable author statement. Source: UniProtKB embryo development Inferred from sequence or structural similarity. Source: UniProtKB hemopoiesis Traceable author statement. Source: UniProtKB mammary gland development Inferred from direct assay. Source: UniProtKB negative regulation of endothelial cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB patterning of blood vessels Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription, DNA-dependent Traceable author statement. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	Golgi lumen Traceable author statement. Source: Reactome cell surface Inferred from direct assay. Source: UniProtKB cytosol Traceable author statement. Source: Reactome endoplasmic reticulum lumen Traceable author statement. Source: Reactome extracellular region Traceable author statement. Source: Reactome integral to plasma membrane Traceable author statement. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome
Molecular function	calcium ion binding Traceable author statement. Source: UniProtKB protein heterodimerization activity Traceable author statement. Source: UniProtKB receptor activity Traceable author statement. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: Q99466-1)

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.

Isoform 2 (identifier: Q99466-2)

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

Isoform 3 (identifier: Q99466-3)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 2003	1980	Neurogenic locus notch homolog protein 4		PRO_0000007701
	Chain	1432 – 2003	572	Notch 4 extracellular truncation By similarity		PRO_0000007702
	Chain	1467 – 2003	537	Notch 4 intracellular domain By similarity		PRO_0000007703
Regions
	Topological domain	24 – 1447	1424	Extracellular Potential
	Transmembrane	1448 – 1468	21	Helical; Potential
	Topological domain	1469 – 2003	535	Cytoplasmic Potential
	Domain	24 – 63	40	EGF-like 1
	Domain	64 – 115	52	EGF-like 2
	Domain	118 – 155	38	EGF-like 3
	Domain	156 – 192	37	EGF-like 4
	Domain	194 – 232	39	EGF-like 5; calcium-binding Potential
	Domain	234 – 274	41	EGF-like 6
	Domain	276 – 312	37	EGF-like 7; calcium-binding Potential
	Domain	314 – 353	40	EGF-like 8; calcium-binding Potential
	Domain	355 – 391	37	EGF-like 9; calcium-binding Potential
	Domain	392 – 430	39	EGF-like 10
	Domain	432 – 473	42	EGF-like 11; calcium-binding Potential
	Domain	475 – 511	37	EGF-like 12; calcium-binding Potential
	Domain	513 – 549	37	EGF-like 13; calcium-binding Potential
	Domain	551 – 587	37	EGF-like 14; calcium-binding Potential
	Domain	589 – 625	37	EGF-like 15; calcium-binding Potential
	Domain	626 – 659	34	EGF-like 16
	Domain	661 – 689	29	EGF-like 17
	Domain	691 – 727	37	EGF-like 18
	Domain	729 – 765	37	EGF-like 19
	Domain	767 – 803	37	EGF-like 20
	Domain	806 – 842	37	EGF-like 21
	Domain	844 – 880	37	EGF-like 22
	Domain	882 – 928	47	EGF-like 23
	Domain	930 – 966	37	EGF-like 24
	Domain	968 – 1004	37	EGF-like 25
	Domain	1006 – 1044	39	EGF-like 26
	Domain	1046 – 1085	40	EGF-like 27
	Domain	1087 – 1126	40	EGF-like 28
	Domain	1130 – 1171	42	EGF-like 29
	Repeat	1170 – 1213	44	LNR 1
	Repeat	1214 – 1250	37	LNR 2
	Repeat	1251 – 1294	44	LNR 3
	Repeat	1633 – 1665	33	ANK 1
	Repeat	1666 – 1698	33	ANK 2
	Repeat	1700 – 1732	33	ANK 3
	Repeat	1733 – 1765	33	ANK 4
	Repeat	1766 – 1798	33	ANK 5
	Compositional bias	1472 – 1476	5	Poly-Arg
Amino acid modifications
	Glycosylation	664	1	N-linked (GlcNAc...) Potential
	Glycosylation	714	1	N-linked (GlcNAc...) Potential
	Glycosylation	964	1	N-linked (GlcNAc...) Potential
	Glycosylation	1143	1	N-linked (GlcNAc...) Potential
	Disulfide bond	28 ↔ 41		By similarity
	Disulfide bond	35 ↔ 51		By similarity
	Disulfide bond	53 ↔ 62		By similarity
	Disulfide bond	68 ↔ 80		By similarity
	Disulfide bond	74 ↔ 103		By similarity
	Disulfide bond	105 ↔ 114		By similarity
	Disulfide bond	122 ↔ 133		By similarity
	Disulfide bond	127 ↔ 143		By similarity
	Disulfide bond	145 ↔ 154		By similarity
	Disulfide bond	160 ↔ 171		By similarity
	Disulfide bond	165 ↔ 180		By similarity
	Disulfide bond	182 ↔ 191		By similarity
	Disulfide bond	198 ↔ 211		By similarity
	Disulfide bond	205 ↔ 220		By similarity
	Disulfide bond	222 ↔ 231		By similarity
	Disulfide bond	238 ↔ 249		By similarity
	Disulfide bond	243 ↔ 262		By similarity
	Disulfide bond	264 ↔ 273		By similarity
	Disulfide bond	280 ↔ 291		By similarity
	Disulfide bond	285 ↔ 300		By similarity
	Disulfide bond	302 ↔ 311		By similarity
	Disulfide bond	318 ↔ 332		By similarity
	Disulfide bond	326 ↔ 341		By similarity
	Disulfide bond	343 ↔ 352		By similarity
	Disulfide bond	359 ↔ 370		By similarity
	Disulfide bond	364 ↔ 379		By similarity
	Disulfide bond	381 ↔ 390		By similarity
	Disulfide bond	396 ↔ 407		By similarity
	Disulfide bond	401 ↔ 418		By similarity
	Disulfide bond	420 ↔ 429		By similarity
	Disulfide bond	436 ↔ 452		By similarity
	Disulfide bond	446 ↔ 461		By similarity
	Disulfide bond	463 ↔ 472		By similarity
	Disulfide bond	479 ↔ 490		By similarity
	Disulfide bond	484 ↔ 499		By similarity
	Disulfide bond	501 ↔ 510		By similarity
	Disulfide bond	517 ↔ 528		By similarity
	Disulfide bond	522 ↔ 537		By similarity
	Disulfide bond	539 ↔ 548		By similarity
	Disulfide bond	555 ↔ 566		By similarity
	Disulfide bond	560 ↔ 575		By similarity
	Disulfide bond	577 ↔ 586		By similarity
	Disulfide bond	593 ↔ 604		By similarity
	Disulfide bond	598 ↔ 613		By similarity
	Disulfide bond	615 ↔ 624		By similarity
	Disulfide bond	629 ↔ 640		By similarity
	Disulfide bond	634 ↔ 649		By similarity
	Disulfide bond	651 ↔ 658		By similarity
	Disulfide bond	665 ↔ 672		By similarity
	Disulfide bond	667 ↔ 677		By similarity
	Disulfide bond	679 ↔ 688		By similarity
	Disulfide bond	695 ↔ 706		By similarity
	Disulfide bond	700 ↔ 715		By similarity
	Disulfide bond	717 ↔ 726		By similarity
	Disulfide bond	733 ↔ 744		By similarity
	Disulfide bond	738 ↔ 753		By similarity
	Disulfide bond	755 ↔ 764		By similarity
	Disulfide bond	771 ↔ 782		By similarity
	Disulfide bond	776 ↔ 791		By similarity
	Disulfide bond	793 ↔ 802		By similarity
	Disulfide bond	810 ↔ 821		By similarity
	Disulfide bond	815 ↔ 830		By similarity
	Disulfide bond	832 ↔ 841		By similarity
	Disulfide bond	848 ↔ 859		By similarity
	Disulfide bond	853 ↔ 868		By similarity
	Disulfide bond	870 ↔ 879		By similarity
	Disulfide bond	886 ↔ 907		By similarity
	Disulfide bond	901 ↔ 916		By similarity
	Disulfide bond	918 ↔ 927		By similarity
	Disulfide bond	934 ↔ 945		By similarity
	Disulfide bond	939 ↔ 954		By similarity
	Disulfide bond	956 ↔ 965		By similarity
	Disulfide bond	972 ↔ 983		By similarity
	Disulfide bond	977 ↔ 992		By similarity
	Disulfide bond	994 ↔ 1003		By similarity
	Disulfide bond	1010 ↔ 1023		By similarity
	Disulfide bond	1015 ↔ 1032		By similarity
	Disulfide bond	1034 ↔ 1043		By similarity
	Disulfide bond	1050 ↔ 1061		By similarity
	Disulfide bond	1055 ↔ 1073		By similarity
	Disulfide bond	1075 ↔ 1084		By similarity
	Disulfide bond	1091 ↔ 1102		By similarity
	Disulfide bond	1096 ↔ 1114		By similarity
	Disulfide bond	1116 ↔ 1125		By similarity
	Disulfide bond	1134 ↔ 1146		By similarity
	Disulfide bond	1140 ↔ 1159		By similarity
	Disulfide bond	1161 ↔ 1170		By similarity
	Disulfide bond	1178 ↔ 1191		By similarity
	Disulfide bond	1187 ↔ 1203		By similarity
	Disulfide bond	1214 ↔ 1238		By similarity
	Disulfide bond	1220 ↔ 1233		By similarity
	Disulfide bond	1229 ↔ 1245		By similarity
	Disulfide bond	1251 ↔ 1277		By similarity
	Disulfide bond	1259 ↔ 1272		By similarity
	Disulfide bond	1268 ↔ 1284		By similarity
Natural variations
	Alternative sequence	1 – 1414	1414	Missing in isoform 2.		VSP_001406
	Alternative sequence	378 – 2003	1626	Missing in isoform 3.		VSP_001407
	Natural variant	117	1	K → Q. Ref.3 Ref.4 Corresponds to variant rs915894 [ dbSNP | Ensembl ].		VAR_012866
	Natural variant	204	1	P → L. Corresponds to variant rs2071282 [ dbSNP | Ensembl ].		VAR_033828
	Natural variant	206	1	P → L. Corresponds to variant rs2071282 [ dbSNP | Ensembl ].		VAR_033829
	Natural variant	244	1	S → L. Corresponds to variant rs8192585 [ dbSNP | Ensembl ].		VAR_033830
	Natural variant	272	1	D → G. Corresponds to variant rs520692 [ dbSNP | Ensembl ].		VAR_012867
	Natural variant	284	1	Q → H. Corresponds to variant rs520803 [ dbSNP | Ensembl ].		VAR_059271
	Natural variant	317	1	E → Q. Ref.4		VAR_012868
	Natural variant	320	1	T → A. Corresponds to variant rs422951 [ dbSNP | Ensembl ].		VAR_012869
	Natural variant	534	1	G → S. Corresponds to variant rs8192591 [ dbSNP | Ensembl ].		VAR_033831
	Natural variant	809	1	S → I. Corresponds to variant rs3132961 [ dbSNP | Ensembl ].		VAR_048991
	Natural variant	851	1	K → R. Corresponds to variant rs2022060 [ dbSNP | Ensembl ].		VAR_012870
	Natural variant	942	1	G → R. Corresponds to variant rs17604492 [ dbSNP | Ensembl ].		VAR_048992
	Natural variant	1346	1	R → P. Corresponds to variant rs8192573 [ dbSNP | Ensembl ].		VAR_048993
Experimental info
	Sequence conflict	1431	1	A → V in BAA09708. Ref.1
	Sequence conflict	1436	1	A → E in BAA09708. Ref.1
	Sequence conflict	1445	1	L → F in BAA09708. Ref.1
	Sequence conflict	1537 – 1539	3	Missing in AAC63097. Ref.2
	Sequence conflict	1538	1	G → A in BAA09708. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 27, 2002. Version 2. Checksum: BED10283A43A0C14	FASTA	2,003	209,622
	10 20 30 40 50 60 MQPPSLLLLL LLLLLLCVSV VRPRGLLCGS FPEPCANGGT CLSLSLGQGT CQCAPGFLGE 70 80 90 100 110 120 TCQFPDPCQN AQLCQNGGSC QALLPAPLGL PSSPSPLTPS FLCTCLPGFT GERCQAKLED 130 140 150 160 170 180 PCPPSFCSKR GRCHIQASGR PQCSCMPGWT GEQCQLRDFC SANPCVNGGV CLATYPQIQC 190 200 210 220 230 240 HCPPGFEGHA CERDVNECFQ DPGPCPKGTS CHNTLGSFQC LCPVGQEGPR CELRAGPCPP 250 260 270 280 290 300 RGCSNGGTCQ LMPEKDSTFH LCLCPPGFIG PDCEVNPDNC VSHQCQNGGT CQDGLDTYTC 310 320 330 340 350 360 LCPETWTGWD CSEDVDECET QGPPHCRNGG TCQNSAGSFH CVCVSGWGGT SCEENLDDCI 370 380 390 400 410 420 AATCAPGSTC IDRVGSFSCL CPPGRTGLLC HLEDMCLSQP CHGDAQCSTN PLTGSTLCLC 430 440 450 460 470 480 QPGYSGPTCH QDLDECLMAQ QGPSPCEHGG SCLNTPGSFN CLCPPGYTGS RCEADHNECL 490 500 510 520 530 540 SQPCHPGSTC LDLLATFHCL CPPGLEGQLC EVETNECASA PCLNHADCHD LLNGFQCICL 550 560 570 580 590 600 PGFSGTRCEE DIDECRSSPC ANGGQCQDQP GAFHCKCLPG FEGPRCQTEV DECLSDPCPV 610 620 630 640 650 660 GASCLDLPGA FFCLCPSGFT GQLCEVPLCA PNLCQPKQIC KDQKDKANCL CPDGSPGCAP 670 680 690 700 710 720 PEDNCTCHHG HCQRSSCVCD VGWTGPECEA ELGGCISAPC AHGGTCYPQP SGYNCTCPTG 730 740 750 760 770 780 YTGPTCSEEM TACHSGPCLN GGSCNPSPGG YYCTCPPSHT GPQCQTSTDY CVSAPCFNGG 790 800 810 820 830 840 TCVNRPGTFS CLCAMGFQGP RCEGKLRPSC ADSPCRNRAT CQDSPQGPRC LCPTGYTGGS 850 860 870 880 890 900 CQTLMDLCAQ KPCPRNSHCL QTGPSFHCLC LQGWTGPLCN LPLSSCQKAA LSQGIDVSSL 910 920 930 940 950 960 CHNGGLCVDS GPSYFCHCPP GFQGSLCQDH VNPCESRPCQ NGATCMAQPS GYLCQCAPGY 970 980 990 1000 1010 1020 DGQNCSKELD ACQSQPCHNH GTCTPKPGGF HCACPPGFVG LRCEGDVDEC LDQPCHPTGT 1030 1040 1050 1060 1070 1080 AACHSLANAF YCQCLPGHTG QWCEVEIDPC HSQPCFHGGT CEATAGSPLG FICHCPKGFE 1090 1100 1110 1120 1130 1140 GPTCSHRAPS CGFHHCHHGG LCLPSPKPGF PPRCACLSGY GGPDCLTPPA PKGCGPPSPC 1150 1160 1170 1180 1190 1200 LYNGSCSETT GLGGPGFRCS CPHSSPGPRC QKPGAKGCEG RSGDGACDAG CSGPGGNWDG 1210 1220 1230 1240 1250 1260 GDCSLGVPDP WKGCPSHSRC WLLFRDGQCH PQCDSEECLF DGYDCETPPA CTPAYDQYCH 1270 1280 1290 1300 1310 1320 DHFHNGHCEK GCNTAECGWD GGDCRPEDGD PEWGPSLALL VVLSPPALDQ QLFALARVLS 1330 1340 1350 1360 1370 1380 LTLRVGLWVR KDRDGRDMVY PYPGARAEEK LGGTRDPTYQ ERAAPQTQPL GKETDSLSAG 1390 1400 1410 1420 1430 1440 FVVVMGVDLS RCGPDHPASR CPWDPGLLLR FLAAMAAVGA LEPLLPGPLL AVHPHAGTAP 1450 1460 1470 1480 1490 1500 PANQLPWPVL CSPVAGVILL ALGALLVLQL IRRRRREHGA LWLPPGFTRR PRTQSAPHRR 1510 1520 1530 1540 1550 1560 RPPLGEDSIG LKALKPKAEV DEDGVVMCSG PEEGEEVGQA EETGPPSTCQ LWSLSGGCGA 1570 1580 1590 1600 1610 1620 LPQAAMLTPP QESEMEAPDL DTRGPDGVTP LMSAVCCGEV QSGTFQGAWL GCPEPWEPLL 1630 1640 1650 1660 1670 1680 DGGACPQAHT VGTGETPLHL AARFSRPTAA RRLLEAGANP NQPDRAGRTP LHAAVAADAR 1690 1700 1710 1720 1730 1740 EVCQLLLRSR QTAVDARTED GTTPLMLAAR LAVEDLVEEL IAAQADVGAR DKWGKTALHW 1750 1760 1770 1780 1790 1800 AAAVNNARAA RSLLQAGADK DAQDNREQTP LFLAAREGAV EVAQLLLGLG AARELRDQAG 1810 1820 1830 1840 1850 1860 LAPADVAHQR NHWDLLTLLE GAGPPEARHK ATPGREAGPF PRARTVSVSV PPHGGGALPR 1870 1880 1890 1900 1910 1920 CRTLSAGAGP RGGGACLQAR TWSVDLAARG GGAYSHCRSL SGVGAGGGPT PRGRRFSAGM 1930 1940 1950 1960 1970 1980 RGPRPNPAIM RGRYGVAAGR GGRVSTDDWP CDWVALGACG SASNIPIPPP CLTPSPERGS 1990 2000 PQLDCGPPAL QEMPINQGGE GKK
	Isoform 2 [UniParc]. Checksum: 0B8F267B8A5EC76B	FASTA	589	61,262
	10 20 30 40 50 60 MAAVGALEPL LPGPLLAVHP HAGTAPPANQ LPWPVLCSPV AGVILLALGA LLVLQLIRRR 70 80 90 100 110 120 RREHGALWLP PGFTRRPRTQ SAPHRRRPPL GEDSIGLKAL KPKAEVDEDG VVMCSGPEEG 130 140 150 160 170 180 EEVGQAEETG PPSTCQLWSL SGGCGALPQA AMLTPPQESE MEAPDLDTRG PDGVTPLMSA 190 200 210 220 230 240 VCCGEVQSGT FQGAWLGCPE PWEPLLDGGA CPQAHTVGTG ETPLHLAARF SRPTAARRLL 250 260 270 280 290 300 EAGANPNQPD RAGRTPLHAA VAADAREVCQ LLLRSRQTAV DARTEDGTTP LMLAARLAVE 310 320 330 340 350 360 DLVEELIAAQ ADVGARDKWG KTALHWAAAV NNARAARSLL QAGADKDAQD NREQTPLFLA 370 380 390 400 410 420 AREGAVEVAQ LLLGLGAARE LRDQAGLAPA DVAHQRNHWD LLTLLEGAGP PEARHKATPG 430 440 450 460 470 480 REAGPFPRAR TVSVSVPPHG GGALPRCRTL SAGAGPRGGG ACLQARTWSV DLAARGGGAY 490 500 510 520 530 540 SHCRSLSGVG AGGGPTPRGR RFSAGMRGPR PNPAIMRGRY GVAAGRGGRV STDDWPCDWV 550 560 570 580 ALGACGSASN IPIPPPCLTP SPERGSPQLD CGPPALQEMP INQGGEGKK
	Isoform 3 [UniParc]. Checksum: 77CB39F5A34F1078	FASTA	377	39,617
	10 20 30 40 50 60 MQPPSLLLLL LLLLLLCVSV VRPRGLLCGS FPEPCANGGT CLSLSLGQGT CQCAPGFLGE 70 80 90 100 110 120 TCQFPDPCQN AQLCQNGGSC QALLPAPLGL PSSPSPLTPS FLCTCLPGFT GERCQAKLED 130 140 150 160 170 180 PCPPSFCSKR GRCHIQASGR PQCSCMPGWT GEQCQLRDFC SANPCVNGGV CLATYPQIQC 190 200 210 220 230 240 HCPPGFEGHA CERDVNECFQ DPGPCPKGTS CHNTLGSFQC LCPVGQEGPR CELRAGPCPP 250 260 270 280 290 300 RGCSNGGTCQ LMPEKDSTFH LCLCPPGFIG PDCEVNPDNC VSHQCQNGGT CQDGLDTYTC 310 320 330 340 350 360 LCPETWTGWD CSEDVDECET QGPPHCRNGG TCQNSAGSFH CVCVSGWGGT SCEENLDDCI 370 AATCAPGSTC IDRVGSF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Gene organization of human NOTCH4 and (CTG)n polymorphism in this human counterpart gene of mouse proto-oncogene Int3." Sugaya K., Sasanuma S., Nohata J., Kimura T., Fukagawa T., Nakamura Y., Ando A., Inoko H., Ikemura T., Mita K. Gene 189:235-244(1997) [PubMed: 9168133] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), POLYMORPHISM OF POLY-LEU REGION. Tissue: Placenta.
[2]	"Cloning, characterization, and the complete 56.8-kilobase DNA sequence of the human NOTCH4 gene." Li L., Huang G.M., Banta A.B., Deng Y., Smith T., Dong P., Friedman C., Chen L., Trask B.J., Spies T., Rowen L., Hood L. Genomics 51:45-58(1998) [PubMed: 9693032] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2 AND 3). Tissue: Bone marrow and Heart.
[3]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLN-117.
[4]	"Human notch4 gene variant." Miyagawa T., Tokunaga K., Hojho H. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-503, VARIANTS GLN-117 AND GLN-317.
[5]	"Human ligands of the Notch receptor." Gray G.E., Mann R.S., Mitsiadis E., Henrique D., Carcangiu M.-L., Banks A., Leiman J., Ward D., Ish-Horowitz D., Artavanis-Tsakonas S. Am. J. Pathol. 154:785-794(1999) [PubMed: 10079256] [Abstract] Cited for: IDENTIFICATION OF LIGANDS.
[6]	"MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors." Wu L., Aster J.C., Blacklow S.C., Lake R., Artavanis-Tsakonas S., Griffin J.D. Nat. Genet. 26:484-489(2000) [PubMed: 11101851] [Abstract] Cited for: INTERACTION WITH MAML1.
[7]	"Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors." Wu L., Sun T., Kobayashi K., Gao P., Griffin J.D. Mol. Cell. Biol. 22:7688-7700(2002) [PubMed: 12370315] [Abstract] Cited for: INTERACTION WITH MAML2 AND MAML3.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. CR933878 Genomic DNA. Translation: CAQ09631.1. AB023961 Genomic DNA. Translation: BAB20317.1. AB024520 Genomic DNA. Translation: BAA88951.1. AB024578 Genomic DNA. Translation: BAA88952.1.
IPI	IPI00785109. IPI00829649. IPI00942401.
RefSeq	NP_004548.3. NM_004557.3.
UniGene	Hs.436100.
3D structure databases
ProteinModelPortal	Q99466.
SMR	Q99466. Positions 28-469, 515-663, 698-804, 807-1436, 1544-1825.
ModBase	Search...
Protein-protein interaction databases
STRING	Q99466.
PTM databases
PhosphoSite	Q99466.
Polymorphism databases
DMDM	20139103.
Proteomic databases
PRIDE	Q99466.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000375023; ENSP00000364163; ENSG00000204301. ENST00000457094; ENSP00000403447; ENSG00000234876.
GeneID	4855.
KEGG	hsa:4855.
UCSC	uc003oba.1. human. uc003obb.1. human.
Organism-specific databases
CTD	4855.
GeneCards	GC06M032231.
HGNC	HGNC:7884. NOTCH4.
HPA	CAB012331.
MIM	164951. gene.
neXtProt	NX_Q99466.
PharmGKB	PA31686.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17252.
GeneTree	ENSGT00600000084071.
HOVERGEN	HBG052650.
InParanoid	Q99466.
OMA	VGWTGPE.
OrthoDB	EOG437RD0.
PhylomeDB	Q99466.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction. REACT_71. Gene Expression.
Gene expression databases
Bgee	Q99466.
CleanEx	HS_NOTCH4.
Genevestigator	Q99466.
GermOnline	ENSG00000204301. Homo sapiens.
Family and domain databases
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. IPR006209. EGF. IPR006210. EGF-like. IPR001881. EGF-like_Ca-bd. IPR013032. EGF-like_reg_CS. IPR000152. EGF-type_Asp/Asn_hydroxyl_site. IPR000742. EGF_3. IPR018097. EGF_Ca-bd_CS. IPR008297. Notch. IPR022355. Notch_4. IPR000800. Notch_dom. IPR011656. Notch_NODP_dom. [Graphical view]
Gene3D	G3DSA:1.25.40.20. ANK. 1 hit.
KO	K02599.
Pfam	PF12796. Ank_2. 2 hits. PF00008. EGF. 9 hits. PF07645. EGF_CA. 4 hits. PF07684. NODP. 1 hit. PF00066. Notch. 3 hits. [Graphical view]
PIRSF	PIRSF002279. Notch. 1 hit.
PRINTS	PR01452. LNOTCHREPEAT. PR01987. NOTCH4.
SMART	SM00248. ANK. 5 hits. SM00181. EGF. 17 hits. SM00179. EGF_CA. 11 hits. SM00004. NL. 3 hits. [Graphical view]
SUPFAM	SSF48403. ANK. 1 hit. SSF90193. Notch_region. 2 hits.
PROSITE	PS50297. 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]
ProtoNet	Search...
Other
NextBio	18702.
SOURCE	Search...

Entry information

Entry name

NOTC4_HUMAN

Accession

Primary (citable) accession number: Q99466
Secondary accession number(s): B0V1X5 , O00306, Q5SSY7, Q99458, Q99940, Q9H3S8, Q9UII9, Q9UIJ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 27, 2002
Last sequence update:	March 27, 2002
Last modified:	January 25, 2012
This is version 130 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.