P18627 (LAG3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lymphocyte activation gene 3 protein
Short name=LAG-3

Alternative name(s):
Protein FDC
CD_antigen=CD223

Gene names

Name:	LAG3
Synonyms:	FDC

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	525 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	Involved in lymphocyte activation. Binds to HLA class-II antigens.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	On cell surface of activated NK and T-lymphocytes.
Sequence similarities	Contains 3 Ig-like C2-type (immunoglobulin-like) domains. Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell surface receptor signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of T cell activation Inferred from electronic annotation. Source: Compara negative regulation of interleukin-2 biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of natural killer cell mediated cytotoxicity Inferred from electronic annotation. Source: Compara
Cellular_component	external side of plasma membrane Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	MHC class II protein binding Inferred from direct assay PubMed 9159144. Source: MGI antigen binding Traceable author statement Ref.1. Source: ProtInc transmembrane signaling receptor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 28	28
	Chain	29 – 525	497	Lymphocyte activation gene 3 protein		PRO_0000014631
Regions
	Topological domain	29 – 450	422	Extracellular Potential
	Transmembrane	451 – 471	21	Helical; Potential
	Topological domain	472 – 525	54	Cytoplasmic Potential
	Domain	37 – 167	131	Ig-like V-type
	Domain	168 – 252	85	Ig-like C2-type 1
	Domain	265 – 343	79	Ig-like C2-type 2
	Domain	348 – 419	72	Ig-like C2-type 3
	Region	501 – 524	24	12 X 2 AA tandem repeats of E-X
Amino acid modifications
	Glycosylation	188	1	N-linked (GlcNAc...) Potential
	Glycosylation	250	1	N-linked (GlcNAc...) Potential
	Glycosylation	256	1	N-linked (GlcNAc...) Potential
	Glycosylation	343	1	N-linked (GlcNAc...) Potential
	Disulfide bond	44 ↔ 160		Potential
	Disulfide bond	189 ↔ 241		Potential
	Disulfide bond	282 ↔ 333		Potential
	Disulfide bond	369 ↔ 412		Potential
Natural variations
	Natural variant	455	1	I → T. Ref.1 Ref.3 Ref.5 Corresponds to variant rs870849 [ dbSNP | Ensembl ].		VAR_058295

Sequences

	Sequence		Length	Mass (Da)
	P18627 [UniParc]. Last modified July 7, 2009. Version 5. Checksum: 5E0BDEF20E9E36D2	FASTA	525	57,449
	10 20 30 40 50 60 MWEAQFLGLL FLQPLWVAPV KPLQPGAEVP VVWAQEGAPA QLPCSPTIPL QDLSLLRRAG 70 80 90 100 110 120 VTWQHQPDSG PPAAAPGHPL APGPHPAAPS SWGPRPRRYT VLSVGPGGLR SGRLPLQPRV 130 140 150 160 170 180 QLDERGRQRG DFSLWLRPAR RADAGEYRAA VHLRDRALSC RLRLRLGQAS MTASPPGSLR 190 200 210 220 230 240 ASDWVILNCS FSRPDRPASV HWFRNRGQGR VPVRESPHHH LAESFLFLPQ VSPMDSGPWG 250 260 270 280 290 300 CILTYRDGFN VSIMYNLTVL GLEPPTPLTV YAGAGSRVGL PCRLPAGVGT RSFLTAKWTP 310 320 330 340 350 360 PGGGPDLLVT GDNGDFTLRL EDVSQAQAGT YTCHIHLQEQ QLNATVTLAI ITVTPKSFGS 370 380 390 400 410 420 PGSLGKLLCE VTPVSGQERF VWSSLDTPSQ RSFSGPWLEA QEAQLLSQPW QCQLYQGERL 430 440 450 460 470 480 LGAAVYFTEL SSPGAQRSGR APGALPAGHL LLFLILGVLS LLLLVTGAFG FHLWRRQWRP 490 500 510 520 RRFSALEQGI HPPQAQSKIE ELEQEPEPEP EPEPEPEPEP EPEQL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"LAG-3, a novel lymphocyte activation gene closely related to CD4." Triebel F., Jitsukawa S., Baixeras E., Roman-Roman S., Genevee C., Viegas-Pequignot E., Hercend T. J. Exp. Med. 171:1393-1405(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-455.
[2]	Triebel F. Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO C-TERMINUS.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-455. Tissue: Synovium.
[4]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT THR-455.
[6]	"Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens." Baixeras E., Huard B., Miossec C., Jitsukawa S., Martin M., Hercend T., Auffray C., Triebel F., Piatier-Tonneau D. J. Exp. Med. 176:327-337(1992) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X51985 mRNA. Translation: CAA36243.3. AK292104 mRNA. Translation: BAF84793.1. AC125494 Genomic DNA. No translation available. CH471116 Genomic DNA. Translation: EAW88741.1.
IPI	IPI00000881.
PIR	S11246.
RefSeq	NP_002277.4. NM_002286.5.
UniGene	Hs.409523.
3D structure databases
ProteinModelPortal	P18627.
ModBase	Search...
Protein-protein interaction databases
IntAct	P18627. 3 interactions.
STRING	9606.ENSP00000203629.
Protein family/group databases
MEROPS	I43.001.
PTM databases
PhosphoSite	P18627.
Polymorphism databases
DMDM	251757512.
Proteomic databases
PaxDb	P18627.
PRIDE	P18627.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000203629; ENSP00000203629; ENSG00000089692.
GeneID	3902.
KEGG	hsa:3902.
UCSC	uc001qqt.4. human.
Organism-specific databases
CTD	3902.
GeneCards	GC12P006881.
H-InvDB	HIX0201912.
HGNC	HGNC:6476. LAG3.
HPA	CAB002301. HPA013967.
MIM	153337. gene.
neXtProt	NX_P18627.
PharmGKB	PA30265.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG45040.
HOGENOM	HOG000113275.
HOVERGEN	HBG004952.
InParanoid	P18627.
KO	K06565.
OMA	ESPHHHL.
OrthoDB	EOG480HWM.
PhylomeDB	P18627.
Gene expression databases
ArrayExpress	P18627.
Bgee	P18627.
CleanEx	HS_LAG3.
Genevestigator	P18627.
GermOnline	ENSG00000089692. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 2 hits.
InterPro	IPR007110. Ig-like_dom. IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR015621. IL1-receptor_fam. [Graphical view]
PANTHER	PTHR11890. PTHR11890. 1 hit.
SMART	SM00409. IG. 3 hits. [Graphical view]
PROSITE	PS50835. IG_LIKE. 2 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	3902.
NextBio	15317.
SOURCE	Search...

Entry information

Entry name

LAG3_HUMAN

Accession

Primary (citable) accession number: P18627
Secondary accession number(s): A8K7T9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	July 7, 2009
Last modified:	May 1, 2013
This is version 121 of the entry and version 5 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.