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Protein

Lymphocyte activation gene 3 protein

Gene

LAG3

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

Functioni

Involved in lymphocyte activation. Binds to HLA class-II antigens.

GO - Molecular functioni

  • antigen binding Source: ProtInc
  • MHC class II protein binding Source: MGI
  • transmembrane signaling receptor activity Source: Ensembl

GO - Biological processi

Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Lymphocyte activation gene 3 protein
Short name:
LAG-3
Alternative name(s):
Protein FDC
CD_antigen: CD223
Gene namesi
Name:LAG3
Synonyms:FDC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:6476. LAG3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini29 – 450422ExtracellularSequence analysisAdd
BLAST
Transmembranei451 – 47121HelicalSequence analysisAdd
BLAST
Topological domaini472 – 52554CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30265.

Polymorphism and mutation databases

BioMutaiLAG3.
DMDMi251757512.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2828Add
BLAST
Chaini29 – 525497Lymphocyte activation gene 3 proteinPRO_0000014631Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi44 ↔ 160PROSITE-ProRule annotation
Glycosylationi188 – 1881N-linked (GlcNAc...)Sequence analysis
Disulfide bondi189 ↔ 241PROSITE-ProRule annotation
Glycosylationi250 – 2501N-linked (GlcNAc...)Sequence analysis
Glycosylationi256 – 2561N-linked (GlcNAc...)Sequence analysis
Disulfide bondi282 ↔ 333PROSITE-ProRule annotation
Glycosylationi343 – 3431N-linked (GlcNAc...)Sequence analysis
Disulfide bondi369 ↔ 412PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP18627.
PRIDEiP18627.

PTM databases

PhosphoSiteiP18627.

Expressioni

Tissue specificityi

On cell surface of activated NK and T-lymphocytes.

Gene expression databases

BgeeiP18627.
CleanExiHS_LAG3.
GenevisibleiP18627. HS.

Organism-specific databases

HPAiCAB002301.
HPA013967.

Interactioni

GO - Molecular functioni

  • MHC class II protein binding Source: MGI

Protein-protein interaction databases

IntActiP18627. 3 interactions.
STRINGi9606.ENSP00000203629.

Structurei

3D structure databases

ProteinModelPortaliP18627.
SMRiP18627. Positions 177-245.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini37 – 167131Ig-like V-typeAdd
BLAST
Domaini168 – 25285Ig-like C2-type 1Add
BLAST
Domaini265 – 34379Ig-like C2-type 2Add
BLAST
Domaini348 – 41972Ig-like C2-type 3Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni501 – 5242412 X 2 AA tandem repeats of E-XAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFPP. Eukaryota.
ENOG410Z3KP. LUCA.
GeneTreeiENSGT00390000017331.
HOGENOMiHOG000113275.
HOVERGENiHBG004952.
InParanoidiP18627.
KOiK06565.
OMAiERFVWSP.
OrthoDBiEOG718KC5.
PhylomeDBiP18627.
TreeFamiTF335942.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR015621. IL-1_rcpt_fam.
[Graphical view]
PANTHERiPTHR11890. PTHR11890. 2 hits.
SMARTiSM00409. IG. 3 hits.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 4 hits.
PROSITEiPS50835. IG_LIKE. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P18627-1) [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
MWEAQFLGLL FLQPLWVAPV KPLQPGAEVP VVWAQEGAPA QLPCSPTIPL
60 70 80 90 100
QDLSLLRRAG VTWQHQPDSG PPAAAPGHPL APGPHPAAPS SWGPRPRRYT
110 120 130 140 150
VLSVGPGGLR SGRLPLQPRV QLDERGRQRG DFSLWLRPAR RADAGEYRAA
160 170 180 190 200
VHLRDRALSC RLRLRLGQAS MTASPPGSLR ASDWVILNCS FSRPDRPASV
210 220 230 240 250
HWFRNRGQGR VPVRESPHHH LAESFLFLPQ VSPMDSGPWG CILTYRDGFN
260 270 280 290 300
VSIMYNLTVL GLEPPTPLTV YAGAGSRVGL PCRLPAGVGT RSFLTAKWTP
310 320 330 340 350
PGGGPDLLVT GDNGDFTLRL EDVSQAQAGT YTCHIHLQEQ QLNATVTLAI
360 370 380 390 400
ITVTPKSFGS PGSLGKLLCE VTPVSGQERF VWSSLDTPSQ RSFSGPWLEA
410 420 430 440 450
QEAQLLSQPW QCQLYQGERL LGAAVYFTEL SSPGAQRSGR APGALPAGHL
460 470 480 490 500
LLFLILGVLS LLLLVTGAFG FHLWRRQWRP RRFSALEQGI HPPQAQSKIE
510 520
ELEQEPEPEP EPEPEPEPEP EPEQL
Length:525
Mass (Da):57,449
Last modified:July 7, 2009 - v5
Checksum:i5E0BDEF20E9E36D2
GO
Isoform 2 (identifier: P18627-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     353-360: VTPKSFGS → GQPQVGKE
     361-525: Missing.

Note: No experimental confirmation available.
Show »
Length:360
Mass (Da):39,103
Checksum:iC3FDD5C8A4EB4215
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti455 – 4551I → T.3 Publications
Corresponds to variant rs870849 [ dbSNP | Ensembl ].
VAR_058295

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei353 – 3608VTPKSFGS → GQPQVGKE in isoform 2. 1 PublicationVSP_056311
Alternative sequencei361 – 525165Missing in isoform 2. 1 PublicationVSP_056312Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X51985 mRNA. Translation: CAA36243.3.
AK292104 mRNA. Translation: BAF84793.1.
AC125494 Genomic DNA. No translation available.
CH471116 Genomic DNA. Translation: EAW88741.1.
BC052589 mRNA. Translation: AAH52589.1.
CCDSiCCDS8561.1. [P18627-1]
PIRiS11246.
RefSeqiNP_002277.4. NM_002286.5. [P18627-1]
UniGeneiHs.409523.

Genome annotation databases

EnsembliENST00000203629; ENSP00000203629; ENSG00000089692. [P18627-1]
ENST00000441671; ENSP00000413825; ENSG00000089692. [P18627-2]
GeneIDi3902.
KEGGihsa:3902.
UCSCiuc001qqs.4. human. [P18627-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X51985 mRNA. Translation: CAA36243.3.
AK292104 mRNA. Translation: BAF84793.1.
AC125494 Genomic DNA. No translation available.
CH471116 Genomic DNA. Translation: EAW88741.1.
BC052589 mRNA. Translation: AAH52589.1.
CCDSiCCDS8561.1. [P18627-1]
PIRiS11246.
RefSeqiNP_002277.4. NM_002286.5. [P18627-1]
UniGeneiHs.409523.

3D structure databases

ProteinModelPortaliP18627.
SMRiP18627. Positions 177-245.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP18627. 3 interactions.
STRINGi9606.ENSP00000203629.

PTM databases

PhosphoSiteiP18627.

Polymorphism and mutation databases

BioMutaiLAG3.
DMDMi251757512.

Proteomic databases

PaxDbiP18627.
PRIDEiP18627.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000203629; ENSP00000203629; ENSG00000089692. [P18627-1]
ENST00000441671; ENSP00000413825; ENSG00000089692. [P18627-2]
GeneIDi3902.
KEGGihsa:3902.
UCSCiuc001qqs.4. human. [P18627-1]

Organism-specific databases

CTDi3902.
GeneCardsiLAG3.
H-InvDBHIX0201912.
HGNCiHGNC:6476. LAG3.
HPAiCAB002301.
HPA013967.
MIMi153337. gene.
neXtProtiNX_P18627.
PharmGKBiPA30265.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFPP. Eukaryota.
ENOG410Z3KP. LUCA.
GeneTreeiENSGT00390000017331.
HOGENOMiHOG000113275.
HOVERGENiHBG004952.
InParanoidiP18627.
KOiK06565.
OMAiERFVWSP.
OrthoDBiEOG718KC5.
PhylomeDBiP18627.
TreeFamiTF335942.

Miscellaneous databases

GeneWikiiLAG3.
GenomeRNAii3902.
NextBioi15317.
PROiP18627.
SOURCEiSearch...

Gene expression databases

BgeeiP18627.
CleanExiHS_LAG3.
GenevisibleiP18627. HS.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR015621. IL-1_rcpt_fam.
[Graphical view]
PANTHERiPTHR11890. PTHR11890. 2 hits.
SMARTiSM00409. IG. 3 hits.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 4 hits.
PROSITEiPS50835. IG_LIKE. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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] (ISOFORM 1), 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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT THR-455.
  6. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Spleen.
  7. "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.

Entry informationi

Entry nameiLAG3_HUMAN
AccessioniPrimary (citable) accession number: P18627
Secondary accession number(s): A8K7T9, Q7Z643
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: July 7, 2009
Last modified: March 16, 2016
This is version 144 of the entry and version 5 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 cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. 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.