P17693 (HLAG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
HLA class I histocompatibility antigen, alpha chain G

Alternative name(s):
HLA G antigen
MHC class I antigen G

Gene names

Name:	HLA-G
Synonyms:	HLA-6.0, HLAG

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	338 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 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.
Subunit structure	Heterodimer of an alpha chain and a beta chain (beta-2-microglobulin). Homodimer; disulfide-linked. Binds to LILRB1 and LILRB2. Ref.6 Ref.8
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Expressed in trophoblasts.
Sequence similarities	Belongs to the MHC class I family. Contains 1 Ig-like C1-type (immunoglobulin-like) domain.

Ontologies

Keywords
Biological process	Immunity
Cellular component	MHC I Membrane
Domain	Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent Traceable author statement. Source: Reactome antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent Traceable author statement. Source: Reactome cellular defense response Traceable author statement PubMed 9539768. Source: ProtInc immune response-inhibiting cell surface receptor signaling pathway Inferred from direct assay PubMed 20702625. Source: BHF-UCL interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome negative regulation of T cell proliferation Inferred from direct assay PubMed 20702625. Source: BHF-UCL negative regulation of dendritic cell differentiation Inferred from direct assay PubMed 20702625. Source: BHF-UCL positive regulation of T cell tolerance induction Inferred from mutant phenotype PubMed 20448110. Source: BHF-UCL positive regulation of interleukin-12 production Inferred from direct assay PubMed 20702625. Source: BHF-UCL positive regulation of regulatory T cell differentiation Inferred from mutant phenotype PubMed 20448110. Source: BHF-UCL type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular_component	ER to Golgi transport vesicle membrane Traceable author statement. Source: Reactome Golgi membrane Traceable author statement. Source: Reactome MHC class I protein complex Inferred from electronic annotation. Source: UniProtKB-KW early endosome membrane Traceable author statement. Source: Reactome integral to lumenal side of endoplasmic reticulum membrane Traceable author statement. Source: Reactome phagocytic vesicle membrane Traceable author statement. Source: Reactome plasma membrane Traceable author statement. Source: Reactome
Molecular_function	protein homodimerization activity Non-traceable author statement PubMed 18550825. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Chain

25 – 338

314

HLA class I histocompatibility antigen, alpha chain G

PRO_0000018886

Regions

Topological domain

25 – 308

284

Extracellular Potential

Transmembrane

309 – 332

24

Helical; Potential

Topological domain

333 – 338

6

Cytoplasmic Potential

Domain

209 – 299

91

Ig-like C1-type

Region

25 – 114

90

Alpha-1

Region

115 – 206

92

Alpha-2

Region

207 – 298

92

Alpha-3

Region

299 – 308

10

Connecting peptide

Amino acid modifications

Glycosylation

110

1

N-linked (GlcNAc...) By similarity

Disulfide bond

66

Interchain Ref.6 Ref.8

Disulfide bond

125 ↔ 188

Ref.8

Disulfide bond

227 ↔ 283

Ref.8

Experimental info

Mutagenesis

66

1

C → S: Abolishes homodimerization. Ref.6

Secondary structure

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338

Helix Strand Turn

Details...

Beta strand

27 – 36

10

Beta strand

41 – 43

3

Beta strand

45 – 52

8

Beta strand

55 – 61

7

Beta strand

64 – 66

3

Beta strand

70 – 73

4

Helix

74 – 76

3

Helix

81 – 108

28

Beta strand

113 – 115

3

Beta strand

118 – 132

15

Beta strand

134 – 142

9

Beta strand

145 – 150

6

Beta strand

157 – 161

5

Helix

162 – 173

12

Helix

176 – 185

10

Helix

187 – 198

12

Helix

200 – 203

4

Beta strand

210 – 218

9

Turn

219 – 221

3

Beta strand

222 – 235

14

Beta strand

238 – 243

6

Beta strand

246 – 248

3

Helix

249 – 251

3

Beta strand

261 – 263

3

Beta strand

265 – 274

10

Helix

278 – 280

3

Beta strand

281 – 286

6

Beta strand

290 – 292

3

Beta strand

294 – 296

3

Sequences

	Sequence		Length	Mass (Da)
	P17693 [UniParc]. Last modified August 1, 1990. Version 1. Checksum: 0678E263BE8962FF	FASTA	338	38,224
	10 20 30 40 50 60 MVVMAPRTLF LLLSGALTLT ETWAGSHSMR YFSAAVSRPG RGEPRFIAMG YVDDTQFVRF 70 80 90 100 110 120 DSDSACPRME PRAPWVEQEG PEYWEEETRN TKAHAQTDRM NLQTLRGYYN QSEASSHTLQ 130 140 150 160 170 180 WMIGCDLGSD GRLLRGYEQY AYDGKDYLAL NEDLRSWTAA DTAAQISKRK CEAANVAEQR 190 200 210 220 230 240 RAYLEGTCVE WLHRYLENGK EMLQRADPPK THVTHHPVFD YEATLRCWAL GFYPAEIILT 250 260 270 280 290 300 WQRDGEDQTQ DVELVETRPA GDGTFQKWAA VVVPSGEEQR YTCHVQHEGL PEPLMLRWKQ 310 320 330 SSLPTIPIMG IVAGLVVLAA VVTGAAVAAV LWRKKSSD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The mRNA of a human class I gene HLA G/HLA 6.0 exhibits a restricted pattern of expression." Shukla H., Swaroop A., Srivastava R., Weissman S.M. Nucleic Acids Res. 18:2189-2189(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal eye.
[2]	"A human major histocompatibility complex class I gene that encodes a protein with a shortened cytoplasmic segment." Geraghty D.E., Koller B.H., Orr H.T. Proc. Natl. Acad. Sci. U.S.A. 84:9145-9149(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	Ishitani A., Geraghty D.E. Submitted (APR-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[4]	"A 356-Kb sequence of the subtelomeric part of the MHC class I region." Hampe A., Coriton O., Andrieux N., Carn G., Lepourcelet M., Mottier S., Dreano S., Gatius M.T., Hitte C., Soriano N., Galibert F. DNA Seq. 10:263-299(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region." Shiina S., Tamiya G., Oka A., Inoko H. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Disulfide bond-mediated dimerization of HLA-G on the cell surface." Boyson J.E., Erskine R., Whitman M.C., Chiu M., Lau J.M., Koopman L.A., Valter M.M., Angelisova P., Horejsi V., Strominger J.L. Proc. Natl. Acad. Sci. U.S.A. 99:16180-16185(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, MUTAGENESIS OF CYS-66, DISULFIDE BOND AT CYS-66.
[7]	"Crystal structure of HLA-G: a nonclassical MHC class I molecule expressed at the fetal-maternal interface." Clements C.S., Kjer-Nielsen L., Kostenko L., Hoare H.L., Dunstone M.A., Moses E., Freed K., Brooks A.G., Rossjohn J., McCluskey J. Proc. Natl. Acad. Sci. U.S.A. 102:3360-3365(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 26-300.
[8]	"Efficient leukocyte Ig-like receptor signaling and crystal structure of disulfide-linked HLA-G dimer." Shiroishi M., Kuroki K., Ose T., Rasubala L., Shiratori I., Arase H., Tsumoto K., Kumagai I., Kohda D., Maenaka K. J. Biol. Chem. 281:10439-10447(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 25-300, DISULFIDE BONDS.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00015988.

PIR

A39953.

RefSeq

NP_002118.1. NM_002127.5.

UniGene

Hs.512152.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1YDP	X-ray	1.90	A	26-300	[»]
2D31	X-ray	3.20	A/D	25-300	[»]
2DYP	X-ray	2.50	A	25-300	[»]
3BZE	X-ray	2.50	P/Q/R/S	3-11	[»]
3CDG	X-ray	3.40	P/Q	3-11	[»]
3CII	X-ray	4.41	C/F	3-11	[»]
3KYN	X-ray	2.40	A	26-299	[»]
3KYO	X-ray	1.70	A/C	26-298	[»]

ProteinModelPortal

P17693.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46121N.

STRING

9606.ENSP00000387624.

PTM databases

PhosphoSite

P17693.

Polymorphism databases

DMDM

122132.

Proteomic databases

PaxDb

P17693.

PRIDE

P17693.

Protocols and materials databases

DNASU

3135.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000360323; ENSP00000353472; ENSG00000204632.
ENST00000383621; ENSP00000373116; ENSG00000206506.
ENST00000423011; ENSP00000389522; ENSG00000233095.
ENST00000423373; ENSP00000405238; ENSG00000235346.
ENST00000428701; ENSP00000412927; ENSG00000204632.
ENST00000428952; ENSP00000388176; ENSG00000235680.
ENST00000444098; ENSP00000398200; ENSG00000230413.
ENST00000449127; ENSP00000408773; ENSG00000237216.
ENST00000546545; ENSP00000447762; ENSG00000230413.
ENST00000546634; ENSP00000447780; ENSG00000235346.
ENST00000547241; ENSP00000448085; ENSG00000233095.
ENST00000547931; ENSP00000448363; ENSG00000237216.
ENST00000550897; ENSP00000449903; ENSG00000235680.
ENST00000553052; ENSP00000449291; ENSG00000206506.

GeneID

3135.

KEGG

hsa:3135.

UCSC

uc003nnw.2. human.

Organism-specific databases

CTD

3135.

GeneCards

GC06P029794.

H-InvDB

HIX0166674.
HIX0167370.

HGNC

HGNC:4964. HLA-G.

HPA

CAB016158.

MIM

142871. gene.

neXtProt

NX_P17693.

PharmGKB

PA35083.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG42056.

HOVERGEN

HBG016709.

InParanoid

P17693.

KO

K06751.

OrthoDB

EOG46DM3K.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P17693.

Bgee

P17693.

CleanEx

HS_HLA-G.

Genevestigator

P17693.

GermOnline

ENSG00000204632. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 1 hit.
3.30.500.10. 1 hit.

InterPro

IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003597. Ig_C1-set.
IPR011161. MHC_I-like_Ag-recog.
IPR011162. MHC_I/II-like_Ag-recog.
IPR001039. MHC_I_a_a1/a2.
[Graphical view]

Pfam

PF07654. C1-set. 1 hit.
PF00129. MHC_I. 1 hit.
[Graphical view]

PRINTS

PR01638. MHCCLASSI.

SMART

SM00407. IGc1. 1 hit.
[Graphical view]

SUPFAM

SSF54452. MHC_I/II-like_Ag-recog. 1 hit.

PROSITE

PS50835. IG_LIKE. 1 hit.
PS00290. IG_MHC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

HLA-G. human.

EvolutionaryTrace

P17693.

GenomeRNAi

3135.

NextBio

12439.

SOURCE

Search...

Entry information

Entry name

HLAG_HUMAN

Accession

Primary (citable) accession number: P17693

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	August 1, 1990
Last modified:	May 29, 2013
This is version 137 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.