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Protein

HLA class I histocompatibility antigen, alpha chain G

Gene

HLA-G

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

Functioni

Involved in the presentation of foreign antigens to the immune system. Plays a role in maternal tolerance of the fetus by mediating protection from the deleterious effects of natural killer cells, cytotoxic T-lymphocytes, macrophages and mononuclear cells.

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • peptide antigen binding Source: GO_Central
  • protein homodimerization activity Source: UniProtKB
  • signaling receptor binding Source: UniProtKB

GO - Biological processi

  • antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent Source: Reactome
  • antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent Source: Reactome
  • antigen processing and presentation of peptide antigen via MHC class I Source: GO_Central
  • cellular defense response Source: ProtInc
  • immune response-inhibiting cell surface receptor signaling pathway Source: BHF-UCL
  • interferon-gamma-mediated signaling pathway Source: Reactome
  • negative regulation of dendritic cell differentiation Source: BHF-UCL
  • negative regulation of immune response Source: UniProtKB
  • negative regulation of T cell proliferation Source: BHF-UCL
  • positive regulation of interleukin-12 production Source: BHF-UCL
  • positive regulation of regulatory T cell differentiation Source: BHF-UCL
  • positive regulation of T cell tolerance induction Source: BHF-UCL
  • positive regulation of tolerance induction Source: UniProtKB
  • regulation of immune response Source: Reactome
  • type I interferon signaling pathway Source: Reactome

Keywordsi

Biological processImmunity

Enzyme and pathway databases

ReactomeiR-HSA-1236974 ER-Phagosome pathway
R-HSA-1236977 Endosomal/Vacuolar pathway
R-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-877300 Interferon gamma signaling
R-HSA-909733 Interferon alpha/beta signaling
R-HSA-983170 Antigen Presentation: Folding, assembly and peptide loading of class I MHC
SIGNORiP17693

Names & Taxonomyi

Protein namesi
Recommended name:
HLA class I histocompatibility antigen, alpha chain G
Alternative name(s):
HLA G antigen
MHC class I antigen G
Gene namesi
Name:HLA-G
Synonyms:HLA-6.0, HLAG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000204632.11
HGNCiHGNC:4964 HLA-G
MIMi142871 gene
neXtProtiNX_P17693

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 308ExtracellularSequence analysisAdd BLAST284
Transmembranei309 – 332HelicalSequence analysisAdd BLAST24
Topological domaini333 – 338CytoplasmicSequence analysis6

Keywords - Cellular componenti

Cell membrane, Membrane, MHC I, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi66C → S: Abolishes homodimerization. Does not affect binding of isoform 2 to LILRB2. 2 Publications1

Organism-specific databases

DisGeNETi3135
MalaCardsiHLA-G
OpenTargetsiENSG00000204632
PharmGKBiPA35083

Polymorphism and mutation databases

BioMutaiHLA-G
DMDMi122132

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Add BLAST24
ChainiPRO_000001888625 – 338HLA class I histocompatibility antigen, alpha chain GAdd BLAST314

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi66InterchainPROSITE-ProRule annotation1 Publication
Glycosylationi110N-linked (GlcNAc...) asparagineBy similarity1
Disulfide bondi125 ↔ 188PROSITE-ProRule annotation1 Publication
Disulfide bondi227 ↔ 283PROSITE-ProRule annotation1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP17693
PaxDbiP17693
PeptideAtlasiP17693
PRIDEiP17693
ProteomicsDBi53506

PTM databases

iPTMnetiP17693
PhosphoSitePlusiP17693
SwissPalmiP17693

Expressioni

Tissue specificityi

Expressed in trophoblasts. Expressed in fetal eye and thymus (PubMed:2336406). Also expressed in adult eye (PubMed:1570318). Isoform 4: Expressed in fetal first trimester trophoblasts (PubMed:7589701). Isoform 7: Expressed in first trimester, second trimester and term placenta, fetal liver, amniotic membrane, skin, cord blood and peripheral blood mononuclear cells (PubMed:11137219).4 Publications

Gene expression databases

BgeeiENSG00000204632
CleanExiHS_HLA-G
ExpressionAtlasiP17693 baseline and differential
GenevisibleiP17693 HS

Organism-specific databases

HPAiCAB016158

Interactioni

Subunit structurei

Heterodimer of an alpha chain and a beta chain (beta-2-microglobulin). Homodimer; disulfide-linked (PubMed:12454284, PubMed:16455647). Binds to LILRB1 and LILRB2 (PubMed:16455647). Isoform 2: Forms a non-disulfide-linked homodimer and interacts with LILRB2 (PubMed:28348268).3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: UniProtKB
  • signaling receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109380, 18 interactors
DIPiDIP-46121N
IntActiP17693, 7 interactors
MINTiP17693
STRINGi9606.ENSP00000353472

Structurei

Secondary structure

1338
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi27 – 36Combined sources10
Beta strandi41 – 43Combined sources3
Beta strandi45 – 52Combined sources8
Beta strandi55 – 61Combined sources7
Beta strandi64 – 66Combined sources3
Beta strandi70 – 73Combined sources4
Helixi74 – 76Combined sources3
Helixi81 – 108Combined sources28
Beta strandi113 – 115Combined sources3
Beta strandi118 – 132Combined sources15
Beta strandi134 – 142Combined sources9
Beta strandi145 – 150Combined sources6
Beta strandi157 – 161Combined sources5
Helixi162 – 173Combined sources12
Helixi176 – 185Combined sources10
Helixi187 – 198Combined sources12
Helixi200 – 203Combined sources4
Beta strandi210 – 218Combined sources9
Turni219 – 221Combined sources3
Beta strandi222 – 235Combined sources14
Beta strandi238 – 243Combined sources6
Beta strandi246 – 248Combined sources3
Helixi249 – 251Combined sources3
Beta strandi261 – 263Combined sources3
Beta strandi265 – 274Combined sources10
Helixi278 – 280Combined sources3
Beta strandi281 – 286Combined sources6
Beta strandi290 – 292Combined sources3
Beta strandi294 – 296Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1YDPX-ray1.90A26-300[»]
2D31X-ray3.20A/D25-300[»]
2DYPX-ray2.50A25-300[»]
3BZEX-ray2.50P/Q/R/S3-11[»]
3CDGX-ray3.40P/Q3-11[»]
3CIIX-ray4.41C/F3-11[»]
3KYNX-ray2.40A26-299[»]
3KYOX-ray1.70A/C26-298[»]
ProteinModelPortaliP17693
SMRiP17693
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP17693

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini209 – 299Ig-like C1-typeAdd BLAST91

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni25 – 114Alpha-1Add BLAST90
Regioni115 – 206Alpha-2Add BLAST92
Regioni207 – 298Alpha-3Add BLAST92
Regioni299 – 308Connecting peptide10

Sequence similaritiesi

Belongs to the MHC class I family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410II5V Eukaryota
ENOG4111K8F LUCA
GeneTreeiENSGT00760000118960
HOVERGENiHBG016709
InParanoidiP17693
KOiK06751
PhylomeDBiP17693
TreeFamiTF336617

Family and domain databases

Gene3Di2.60.40.10, 1 hit
3.30.500.10, 1 hit
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003006 Ig/MHC_CS
IPR003597 Ig_C1-set
IPR011161 MHC_I-like_Ag-recog
IPR037055 MHC_I-like_Ag-recog_sf
IPR011162 MHC_I/II-like_Ag-recog
IPR001039 MHC_I_a_a1/a2
PfamiView protein in Pfam
PF07654 C1-set, 1 hit
PF00129 MHC_I, 1 hit
PRINTSiPR01638 MHCCLASSI
SMARTiView protein in SMART
SM00407 IGc1, 1 hit
SUPFAMiSSF48726 SSF48726, 1 hit
SSF54452 SSF54452, 1 hit
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit
PS00290 IG_MHC, 1 hit

Sequences (7)i

Sequence statusi: Complete.

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

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P17693-1) [UniParc]FASTAAdd to basket
Also known as: HLA-G11 Publication

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
MVVMAPRTLF LLLSGALTLT ETWAGSHSMR YFSAAVSRPG RGEPRFIAMG
60 70 80 90 100
YVDDTQFVRF DSDSACPRME PRAPWVEQEG PEYWEEETRN TKAHAQTDRM
110 120 130 140 150
NLQTLRGYYN QSEASSHTLQ WMIGCDLGSD GRLLRGYEQY AYDGKDYLAL
160 170 180 190 200
NEDLRSWTAA DTAAQISKRK CEAANVAEQR RAYLEGTCVE WLHRYLENGK
210 220 230 240 250
EMLQRADPPK THVTHHPVFD YEATLRCWAL GFYPAEIILT WQRDGEDQTQ
260 270 280 290 300
DVELVETRPA GDGTFQKWAA VVVPSGEEQR YTCHVQHEGL PEPLMLRWKQ
310 320 330
SSLPTIPIMG IVAGLVVLAA VVTGAAVAAV LWRKKSSD
Length:338
Mass (Da):38,224
Last modified:August 1, 1990 - v1
Checksum:i0678E263BE8962FF
GO
Isoform 2 (identifier: P17693-2) [UniParc]FASTAAdd to basket
Also known as: HLA-G21 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     115-206: Missing.
     207-207: D → K

Show »
Length:246
Mass (Da):27,694
Checksum:iC9B5A82501274909
GO
Isoform 3 (identifier: P17693-3) [UniParc]FASTAAdd to basket
Also known as: HLA-G31 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     115-298: Missing.

Show »
Length:154
Mass (Da):17,070
Checksum:iCECFCC7616238134
GO
Isoform 4 (identifier: P17693-4) [UniParc]FASTAAdd to basket
Also known as: HLA-G.3-51 Publication, HLA-G41 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     207-298: Missing.

Show »
Length:246
Mass (Da):27,613
Checksum:i257B982E358A94D0
GO
Isoform 5 (identifier: P17693-5) [UniParc]FASTAAdd to basket
Also known as: HLA-G1sol1 Publication, HLA-G51 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     299-338: KQSSLPTIPIMGIVAGLVVLAAVVTGAAVAAVLWRKKSSD → SKEGDGGIMSVRESRSLSEDL

Show »
Length:319
Mass (Da):36,458
Checksum:iA2010B7518A4230B
GO
Isoform 6 (identifier: P17693-6) [UniParc]FASTAAdd to basket
Also known as: HLA-G2sol1 Publication, HLA-G61 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     115-206: Missing.
     207-207: D → K
     299-338: KQSSLPTIPIMGIVAGLVVLAAVVTGAAVAAVLWRKKSSD → SKEGDGGIMSVRESRSLSEDL

Show »
Length:227
Mass (Da):25,928
Checksum:iACB75F53EE9D0AA8
GO
Isoform 7 (identifier: P17693-7) [UniParc]FASTAAdd to basket
Also known as: HLA-G71 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     116-116: S → E
     117-338: Missing.

Show »
Length:116
Mass (Da):13,286
Checksum:iFE98D2D0E1628C31
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_059191115 – 298Missing in isoform 3. 1 PublicationAdd BLAST184
Alternative sequenceiVSP_059192115 – 206Missing in isoform 2 and isoform 6. 1 PublicationAdd BLAST92
Alternative sequenceiVSP_059193116S → E in isoform 7. 1 Publication1
Alternative sequenceiVSP_059194117 – 338Missing in isoform 7. 1 PublicationAdd BLAST222
Alternative sequenceiVSP_059196207 – 298Missing in isoform 4. 2 PublicationsAdd BLAST92
Alternative sequenceiVSP_059195207D → K in isoform 2 and isoform 6. 1 Publication1
Alternative sequenceiVSP_059197299 – 338KQSSL…KKSSD → SKEGDGGIMSVRESRSLSED L in isoform 5 and isoform 6. 1 PublicationAdd BLAST40

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X17273 mRNA Translation: CAA35174.1
J03027 Genomic DNA Translation: AAA98745.1
M90683 mRNA Translation: AAA52673.1
AF055066 Genomic DNA Translation: AAC24826.1
BA000025 Genomic DNA Translation: BAB63336.1
CCDSiCCDS4668.1 [P17693-1]
PIRiA39953
RefSeqiNP_002118.1, NM_002127.5 [P17693-1]
UniGeneiHs.512152

Genome annotation databases

EnsembliENST00000360323; ENSP00000353472; ENSG00000204632 [P17693-1]
ENST00000376815; ENSP00000366011; ENSG00000204632 [P17693-3]
ENST00000383621; ENSP00000373116; ENSG00000206506 [P17693-1]
ENST00000383622; ENSP00000373117; ENSG00000206506 [P17693-3]
ENST00000415687; ENSP00000389969; ENSG00000237216 [P17693-3]
ENST00000423011; ENSP00000389522; ENSG00000233095 [P17693-1]
ENST00000423373; ENSP00000405238; ENSG00000235346 [P17693-1]
ENST00000428701; ENSP00000412927; ENSG00000204632 [P17693-1]
ENST00000428952; ENSP00000388176; ENSG00000235680 [P17693-1]
ENST00000429890; ENSP00000401326; ENSG00000235680 [P17693-3]
ENST00000444098; ENSP00000398200; ENSG00000230413 [P17693-1]
ENST00000445373; ENSP00000416408; ENSG00000230413 [P17693-3]
ENST00000448306; ENSP00000413926; ENSG00000233095 [P17693-3]
ENST00000449127; ENSP00000408773; ENSG00000237216 [P17693-1]
ENST00000457132; ENSP00000410247; ENSG00000235346 [P17693-3]
ENST00000546545; ENSP00000447762; ENSG00000230413 [P17693-1]
ENST00000546634; ENSP00000447780; ENSG00000235346 [P17693-1]
ENST00000547241; ENSP00000448085; ENSG00000233095 [P17693-1]
ENST00000547931; ENSP00000448363; ENSG00000237216 [P17693-1]
ENST00000550897; ENSP00000449903; ENSG00000235680 [P17693-1]
ENST00000553052; ENSP00000449291; ENSG00000206506 [P17693-1]
ENST00000622601; ENSP00000479399; ENSG00000276051 [P17693-3]
GeneIDi3135
KEGGihsa:3135

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiHLAG_HUMAN
AccessioniPrimary (citable) accession number: P17693
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: June 20, 2018
This is version 181 of the entry and version 1 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

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