Reviewed, UniProtKB/Swiss-Prot P78504 (JAG1_HUMAN)

Names and origin

Protein names

Recommended name:
    Protein jagged-1
      Short name=Jagged1
      Short name=hJ1
Alternative name(s):
    CD_antigen=CD339

Gene names

Name:	JAG1
Synonyms:	JAGL1

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	1218 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	Ligand for multiple Notch receptors and involved in the mediation of Notch signaling. May be involved in cell-fate decisions during hematopoiesis. Seems to be involved in early and late stages of mammalian cardiovascular development. Inhibits myoblast differentiation By similarity. Enhances fibroblast growth factor-induced angiogenesis (in vitro).
Subunit structure	Interacts with NOTCH1, NOTCH2 and NOTCH3 By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Widely expressed in adult and fetal tissues. In cervix epithelium expressed in undifferentiated subcolumnar reserve cells and squamous metaplasia. Expression is up-regulated in cervical squamous cell carcinoma. Expressed in bone marrow cell line HS-27a which supports the long-term maintenance of immature progenitor cells.
Developmental stage	Expressed in 32-52 days embryos in the distal cardiac outflow tract and pulmonary artery, major arteries, portal vein, optic vesicle, otocyst, branchial arches, metanephros, pancreas, mesocardium, around the major bronchial branches, and in the neural tube.
Involvement in disease	Defects in JAG1 are the cause of Alagille syndrome type 1 (ALGS1) [MIM:118450]. Alagille syndrome is an autosomal dominant multisystem disorder defined clinically by hepatic bile duct paucity and cholestasis in association with cardiac, skeletal, and ophthalmologic manifestations. There are characteristic facial features and less frequent clinical involvement of the renal and vascular systems. Defects in JAG1 are a cause of tetralogy of Fallot (TOF) [MIM:187500]. TOF is a congenital heart anomaly which consists of pulmonary stenosis, ventricular septal defect, dextroposition of the aorta (aorta is on the right side instead of the left) and hypertrophy of the right ventricle. This condition results in a blue baby at birth due to inadequate oxygenation. Surgical correction is emergent. The mutation Asp-274 is "leaky". Two populations of proteins are produced from this allele. One population is abnormally glycosylated and is retained intracellularly rather than being transported to the cell surface. A second population is normally glycosylated and is transported to the cell surface, where it is able to signal to the Notch receptor. The Asp-274 protein is temperature sensitive, with more abnormally glycosylated (and nonfunctional) molecules produced at higher temperatures. Carriers of this mutation therefore have more than 50% but less than 100% of the normal concentration of molecules on the cell surface. The cardiac-specific phenotype associated with this mutation suggests that the developing heart is more sensitive than the developing liver to decreased dosage of JAG1 protein.
Sequence similarities	Contains 1 DSL domain. Contains 15 EGF-like domains.
Sequence caution	The sequence AAC51323.1 differs from that shown. Reason: Frameshift at position 1187.

Ontologies

Keywords
Biological process	Notch signaling pathway
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	EGF-like domain Repeat Signal Transmembrane
Ligand	Calcium
Molecular function	Developmental protein
PTM	Glycoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	angiogenesis Ref.8 Non-traceable author statement. Source: UniProtKB cell fate determination Ref.2 Non-traceable author statement. Source: UniProtKB endothelial cell differentiation Ref.4 Non-traceable author statement. Source: UniProtKB keratinocyte differentiation Non-traceable author statement. Source: UniProtKB myoblast differentiation Ref.4 Non-traceable author statement. Source: UniProtKB nervous system development Non-traceable author statement. Source: UniProtKB regulation of cell migration Non-traceable author statement. Source: UniProtKB regulation of cell proliferation Ref.4 Non-traceable author statement. Source: UniProtKB
Cellular component	extracellular region Non-traceable author statement. Source: UniProtKB integral to plasma membrane Non-traceable author statement. Source: UniProtKB
Molecular function	Notch binding Ref.1 Non-traceable author statement. Source: UniProtKB calcium ion binding Non-traceable author statement. Source: UniProtKB growth factor activity Non-traceable author statement. Source: UniProtKB structural molecule activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 33	33	Potential
	Chain	34 – 1218	1185	Protein jagged-1		PRO_0000007625
Regions
	Topological domain	34 – 1067	1034	Extracellular Potential
	Transmembrane	1068 – 1093	26	Potential
	Topological domain	1094 – 1218	125	Cytoplasmic Potential
	Domain	185 – 229	45	DSL
	Domain	230 – 266	37	EGF-like 1; atypical
	Domain	296 – 334	39	EGF-like 2
	Domain	336 – 372	37	EGF-like 3
	Domain	374 – 410	37	EGF-like 4; calcium-binding Potential
	Domain	412 – 448	37	EGF-like 5; calcium-binding Potential
	Domain	450 – 485	36	EGF-like 6; calcium-binding Potential
	Domain	487 – 523	37	EGF-like 7; calcium-binding Potential
	Domain	525 – 561	37	EGF-like 8
	Domain	574 – 627	54	EGF-like 9
	Domain	629 – 665	37	EGF-like 10; calcium-binding Potential
	Domain	667 – 703	37	EGF-like 11; calcium-binding Potential
	Domain	705 – 741	37	EGF-like 12
	Domain	744 – 780	37	EGF-like 13
	Domain	782 – 818	37	EGF-like 14; calcium-binding Potential
	Domain	820 – 856	37	EGF-like 15; calcium-binding Potential
Amino acid modifications
	Glycosylation	143	1	N-linked (GlcNAc...) Potential
	Glycosylation	217	1	N-linked (GlcNAc...) Potential
	Glycosylation	382	1	N-linked (GlcNAc...) Potential
	Glycosylation	559	1	N-linked (GlcNAc...) Potential
	Glycosylation	745	1	N-linked (GlcNAc...) Potential
	Glycosylation	960	1	N-linked (GlcNAc...) Potential
	Glycosylation	991	1	N-linked (GlcNAc...) Potential
	Glycosylation	1045	1	N-linked (GlcNAc...) Potential
	Glycosylation	1064	1	N-linked (GlcNAc...) Potential
	Disulfide bond	234 ↔ 245		By similarity
	Disulfide bond	238 ↔ 251		By similarity
	Disulfide bond	253 ↔ 262		By similarity
	Disulfide bond	300 ↔ 312		By similarity
	Disulfide bond	306 ↔ 322		By similarity
	Disulfide bond	324 ↔ 333		By similarity
	Disulfide bond	340 ↔ 351		By similarity
	Disulfide bond	345 ↔ 360		By similarity
	Disulfide bond	362 ↔ 371		By similarity
	Disulfide bond	378 ↔ 389		By similarity
	Disulfide bond	383 ↔ 398		By similarity
	Disulfide bond	400 ↔ 409		By similarity
	Disulfide bond	416 ↔ 427		By similarity
	Disulfide bond	421 ↔ 436		By similarity
	Disulfide bond	438 ↔ 447		By similarity
	Disulfide bond	454 ↔ 464		By similarity
	Disulfide bond	458 ↔ 473		By similarity
	Disulfide bond	475 ↔ 484		By similarity
	Disulfide bond	491 ↔ 502		By similarity
	Disulfide bond	496 ↔ 511		By similarity
	Disulfide bond	513 ↔ 522		By similarity
	Disulfide bond	529 ↔ 540		By similarity
	Disulfide bond	534 ↔ 549		By similarity
	Disulfide bond	551 ↔ 560		By similarity
	Disulfide bond	578 ↔ 605		By similarity
	Disulfide bond	599 ↔ 615		By similarity
	Disulfide bond	617 ↔ 626		By similarity
	Disulfide bond	633 ↔ 644		By similarity
	Disulfide bond	638 ↔ 653		By similarity
	Disulfide bond	655 ↔ 664		By similarity
	Disulfide bond	671 ↔ 682		By similarity
	Disulfide bond	676 ↔ 691		By similarity
	Disulfide bond	693 ↔ 702		By similarity
	Disulfide bond	709 ↔ 720		By similarity
	Disulfide bond	714 ↔ 729		By similarity
	Disulfide bond	731 ↔ 740		By similarity
	Disulfide bond	748 ↔ 759		By similarity
	Disulfide bond	753 ↔ 768		By similarity
	Disulfide bond	770 ↔ 779		By similarity
	Disulfide bond	786 ↔ 797		By similarity
	Disulfide bond	791 ↔ 806		By similarity
	Disulfide bond	808 ↔ 817		By similarity
	Disulfide bond	824 ↔ 835		By similarity
	Disulfide bond	829 ↔ 844		By similarity
	Disulfide bond	846 ↔ 855		By similarity
Natural variations
	Natural variant	22 – 25	4	Missing in ALGS1.		VAR_026296
	Natural variant	31	1	A → V in ALGS1.		VAR_026297
	Natural variant	33	1	G → D in ALGS1.		VAR_026298
	Natural variant	33	1	G → S in ALGS1.		VAR_026299
	Natural variant	33	1	G → V in ALGS1.		VAR_026300
	Natural variant	37	1	L → S in ALGS1.		VAR_013186
	Natural variant	39	1	I → S in ALGS1.		VAR_026301
	Natural variant	40	1	L → P in ALGS1.		VAR_026302
	Natural variant	45	1	V → L in biliary atresia; extrahepatic.		VAR_026303
	Natural variant	53	1	N → D in biliary atresia; extrahepatic.		VAR_026304