Q9BX67 (JAM3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Junctional adhesion molecule C
Short name=JAM-C

Alternative name(s):
JAM-2
Junctional adhesion molecule 3
Short name=JAM-3

Gene names

Name:	JAM3
ORF Names:	UNQ859/PRO1868

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	310 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	Participates in cell-cell adhesion. It is a counter-receptor for ITGAM, mediating leukocyte-platelet interactions and is involved in the regulation of transepithelial migration of polymorphonuclear neutrophils (PMN). The soluble form is a mediator of angiogenesis. Ref.3 Ref.12 Ref.16
Subunit structure	Interacts with JAM2. Interacts with ITGAM. Ref.1 Ref.3 Ref.12
Subcellular location	Cell membrane; Single-pass type I membrane protein Potential. Cell junction › desmosome. Secreted › extracellular space. Note: In epithelial cells, it is expressed at desmosomes but not at tight junctions. Localizes at the cell surface of endothelial cells; treatment of endothelial cells with vascular endothelial growth factor stimulates recruitment of JAM3 to cell-cell contacts. Ref.12 Ref.13 Ref.16
Tissue specificity	Highest expression in placenta, brain and kidney. Significant expression is detected on platelets. Expressed in intestinal mucosa cells. Expressed in the vascular endothelium. Found in serum (at protein level). Also detected in the synovial fluid of patients with rheumatoid arthritis, psoriatic arthritis or ostearthritis (at protein level). Ref.1 Ref.3 Ref.4 Ref.12 Ref.13 Ref.16
Post-translational modification	Proteolytically cleaved from endothelial cells surface into a soluble form by ADAM10 and ADAM17; the release of soluble JAM3 is increased by proinflammatory factors. Ref.16
Involvement in disease	Defects in JAM3 are the cause of hemorrhagic destruction of the brain with subependymal calcification and cataracts (HDBSCC) [MIM:613730]. A syndrome characterized by congenital cataracts and severe brain abnormalities apparently resulting from hemorrhagic destruction of the brain tissue, including the cerebral white matter and basal ganglia. Patients manifest profound developmental delay, and other neurologic features included seizures, spasticity, and hyperreflexia. Brain imaging shows multifocal intraparenchymal hemorrhage with associated liquefaction and massive cystic degeneration, and calcification in the subependymal region and in brain tissue. Ref.15
Sequence similarities	Belongs to the immunoglobulin superfamily. Contains 1 Ig-like C2-type (immunoglobulin-like) domain. Contains 1 Ig-like V-type (immunoglobulin-like) domain.
Sequence caution	The sequence CAC94776.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Angiogenesis Cell adhesion
Cellular component	Cell junction Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	angiogenesis Inferred from direct assay Ref.16. Source: UniProtKB blood coagulation Traceable author statement. Source: Reactome cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW leukocyte migration Traceable author statement. Source: Reactome regulation of neutrophil chemotaxis Inferred from direct assay Ref.12. Source: UniProtKB
Cellular component	cell-cell contact zone Inferred from direct assay Ref.13. Source: UniProtKB desmosome Inferred from direct assay Ref.12. Source: UniProtKB extracellular space Inferred from direct assay Ref.16. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular function	integrin binding Inferred from physical interaction Ref.12. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
JAM2	P57087	2	EBI-4314733,EBI-3918416

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9BX67-1)

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: Q9BX67-2)

The sequence of this isoform differs from the canonical sequence as follows:
     85-135: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 31	31	Ref.10
	Chain	32 – 310	279	Junctional adhesion molecule C		PRO_0000015071
Regions
	Topological domain	32 – 241	210	Extracellular Potential
	Transmembrane	242 – 262	21	Helical; Potential
	Topological domain	263 – 310	48	Cytoplasmic Potential
	Domain	35 – 127	93	Ig-like V-type
	Domain	139 – 236	98	Ig-like C2-type
Amino acid modifications
	Glycosylation	104	1	N-linked (GlcNAc...) Potential
	Glycosylation	192	1	N-linked (GlcNAc...) Ref.14
	Glycosylation	198	1	N-linked (GlcNAc...) Ref.14
	Disulfide bond	53 ↔ 115		Potential
	Disulfide bond	160 ↔ 219		Potential
Natural variations
	Alternative sequence	85 – 135	51	Missing in isoform 2.		VSP_042561
Experimental info
	Sequence conflict	136	1	Q → R in AAH10690. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: CE39ADF33EA1DAB9	FASTA	310	35,020
	10 20 30 40 50 60 MALRRPPRLR LCARLPDFFL LLLFRGCLIG AVNLKSSNRT PVVQEFESVE LSCIITDSQT 70 80 90 100 110 120 SDPRIEWKKI QDEQTTYVFF DNKIQGDLAG RAEILGKTSL KIWNVTRRDS ALYRCEVVAR 130 140 150 160 170 180 NDRKEIDEIV IELTVQVKPV TPVCRVPKAV PVGKMATLHC QESEGHPRPH YSWYRNDVPL 190 200 210 220 230 240 PTDSRANPRF RNSSFHLNSE TGTLVFTAVH KDDSGQYYCI ASNDAGSARC EEQEMEVYDL 250 260 270 280 290 300 NIGGIIGGVL VVLAVLALIT LGICCAYRRG YFINNKQDGE SYKNPGKPDG VNYIRTDEEG 310 DFRHKSSFVI
	Isoform 2 [UniParc]. Checksum: 00F852424B415045	FASTA	259	29,223
	10 20 30 40 50 60 MALRRPPRLR LCARLPDFFL LLLFRGCLIG AVNLKSSNRT PVVQEFESVE LSCIITDSQT 70 80 90 100 110 120 SDPRIEWKKI QDEQTTYVFF DNKIQVKPVT PVCRVPKAVP VGKMATLHCQ ESEGHPRPHY 130 140 150 160 170 180 SWYRNDVPLP TDSRANPRFR NSSFHLNSET GTLVFTAVHK DDSGQYYCIA SNDAGSARCE 190 200 210 220 230 240 EQEMEVYDLN IGGIIGGVLV VLAVLALITL GICCAYRRGY FINNKQDGES YKNPGKPDGV 250 NYIRTDEEGD FRHKSSFVI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of human junctional adhesion molecule 3 (JAM3) and its identification as the JAM2 counter-receptor." Arrate M.P., Rodriguez J.M., Tran T.M., Brock T.A., Cunningham S.A. J. Biol. Chem. 276:45826-45832(2001) [PubMed: 11590146] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH JAM2, TISSUE SPECIFICITY. Tissue: Brain.
[2]	"Heterogeneity of endothelial junctions is reflected by differential expression and specific subcellular localization of the three JAM family members." Aurrand-Lions M.A., Johnson-Leger C., Wong C., Du Pasquier L., Imhof B.A. Blood 98:3699-3707(2001) [PubMed: 11739175] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"The junctional adhesion molecule 3 (JAM-3) on human platelets is a counterreceptor for the leukocyte integrin Mac-1." Santoso S., Sachs U.J.H., Kroll H., Linder M., Ruf A., Preissner K.T., Chavakis T. J. Exp. Med. 196:679-691(2002) [PubMed: 12208882] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH ITGAM.
[4]	"Narrowing the critical region within 11q24-qter for hypoplastic left heart and identification of a candidate gene, JAM3, expressed during cardiogenesis." Phillips H.M., Renforth G.L., Spalluto C., Hearn T., Curtis A.R.J., Craven L., Havarani B., Clement-Jones M., English C., Stumper O., Salmon T., Hutchinson S., Jackson M.S., Wilson D.I. Genomics 79:475-478(2002) [PubMed: 11944976] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Thalamus.
[6]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed: 16554811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Eye and Uterus.
[10]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 32-46.
[11]	"Leukocyte-endothelial-cell interactions in leukocyte transmigration and the inflammatory response." Muller W.A. Trends Immunol. 24:327-334(2003) [PubMed: 12810109] [Abstract] Cited for: REVIEW, NOMENCLATURE.
[12]	"JAM-C is a component of desmosomes and a ligand for CD11b/CD18-mediated neutrophil transepithelial migration." Zen K., Babbin B.A., Liu Y., Whelan J.B., Nusrat A., Parkos C.A. Mol. Biol. Cell 15:3926-3937(2004) [PubMed: 15194813] [Abstract] Cited for: FUNCTION IN NEUTROPHIL TRANSEPITHELIAL MIGRATION, INTERACTION WITH ITGAM, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[13]	"Antibody against junctional adhesion molecule-C inhibits angiogenesis and tumor growth." Lamagna C., Hodivala-Dilke K.M., Imhof B.A., Aurrand-Lions M. Cancer Res. 65:5703-5710(2005) [PubMed: 15994945] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[14]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed: 19349973] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-192 AND ASN-198, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[15]	"A homozygous mutation in the tight-junction protein JAM3 causes hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts." Mochida G.H., Ganesh V.S., Felie J.M., Gleason D., Hill R.S., Clapham K.R., Rakiec D., Tan W.H., Akawi N., Al-Saffar M., Partlow J.N., Tinschert S., Barkovich A.J., Ali B., Al-Gazali L., Walsh C.A. Am. J. Hum. Genet. 87:882-889(2010) [PubMed: 21109224] [Abstract] Cited for: INVOLVEMENT IN HDBSCC.
[16]	"Junctional adhesion molecule-C is a soluble mediator of angiogenesis." Rabquer B.J., Amin M.A., Teegala N., Shaheen M.K., Tsou P.S., Ruth J.H., Lesch C.A., Imhof B.A., Koch A.E. J. Immunol. 185:1777-1785(2010) [PubMed: 20592283] [Abstract] Cited for: FUNCTION IN ANGIOGENESIS, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE BY ADAM10 AND ADAM17.
[17]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF356518 mRNA. Translation: AAK27221.1. AJ344431 mRNA. Translation: CAC69845.1. AF448478 mRNA. Translation: AAM20925.1. AJ416101 mRNA. Translation: CAC94776.1. Different initiation. AK074769 mRNA. Translation: BAC11195.1. AK075309 mRNA. Translation: BAC11538.1. AK125071 mRNA. Translation: BAG54131.1. AY358335 mRNA. Translation: AAQ88701.1. AP000911 Genomic DNA. No translation available. AP001775 Genomic DNA. No translation available. CH471065 Genomic DNA. Translation: EAW67820.1. BC010690 mRNA. Translation: AAH10690.1. BC012147 mRNA. Translation: AAH12147.1.
IPI	IPI00152850. IPI00902570.
RefSeq	NP_001192258.1. NM_001205329.1. NP_116190.3. NM_032801.4.
UniGene	Hs.150718.
3D structure databases
ProteinModelPortal	Q9BX67.
SMR	Q9BX67. Positions 34-244.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9BX67. 1 interaction.
MINT	MINT-4085421.
STRING	Q9BX67.
Polymorphism databases
DMDM	51701611.
Proteomic databases
PRIDE	Q9BX67.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000299106; ENSP00000299106; ENSG00000166086. ENST00000441717; ENSP00000395742; ENSG00000166086.
GeneID	83700.
KEGG	hsa:83700.
UCSC	uc001qhb.2. human.
Organism-specific databases
CTD	83700.
GeneCards	GC11P133972.
HGNC	HGNC:15532. JAM3.
HPA	HPA003417.
MIM	606871. gene. 613730. phenotype.
neXtProt	NX_Q9BX67.
PharmGKB	PA29993.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG147320.
GeneTree	ENSGT00650000092897.
HOGENOM	HOG000247041.
HOVERGEN	HBG000518.
InParanoid	Q9BX67.
KO	K06785.
OrthoDB	EOG4D26QH.
Enzyme and pathway databases
Pathway_Interaction_DB	amb2_neutrophils_pathway. amb2 Integrin signaling.
Reactome	REACT_111102. Signal Transduction. REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	Q9BX67.
Bgee	Q9BX67.
CleanEx	HS_JAM3.
Genevestigator	Q9BX67.
GermOnline	ENSG00000166086. Homo sapiens.
Family and domain databases
Gene3D	G3DSA:2.60.40.10. Ig-like_fold. 2 hits.
InterPro	IPR007110. Ig-like. IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR003598. Ig_sub2. IPR013106. Ig_V-set. [Graphical view]
Pfam	PF07686. V-set. 1 hit. [Graphical view]
SMART	SM00409. IG. 1 hit. SM00408. IGc2. 1 hit. [Graphical view]
PROSITE	PS50835. IG_LIKE. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	72688.
SOURCE	Search...

Entry information

Entry name

JAM3_HUMAN

Accession

Primary (citable) accession number: Q9BX67
Secondary accession number(s): B3KWG9, Q8WWL8, Q96FL1

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 31, 2004
Last sequence update:	June 1, 2001
Last modified:	May 16, 2012
This is version 98 of the entry and version 1 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.