P19652 (A1AG2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Alpha-1-acid glycoprotein 2
Short name=AGP 2

Alternative name(s):
Orosomucoid-2
Short name=OMD 2

Gene names

Name:	ORM2
Synonyms:	AGP2

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	201 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	Functions as transport protein in the blood stream. Binds various hydrophobic ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability. Appears to function in modulating the activity of the immune system during the acute-phase reaction. Ref.17
Subcellular location	Secreted.
Tissue specificity	Expressed by the liver and secreted in plasma.
Induction	Synthesis is controlled by glucocorticoids, interleukin-1 and interleukin-6, It increases 5- to 50-fold upon inflammation.
Domain	Contains a beta-barrel that binds various ligands in its interior. Ref.17
Post-translational modification	N-glycosylated. N-glycan heterogeneity at Asn-33: Hex5HexNAc4 (minor), Hex6HexNAc5 (major) and dHex1Hex6HexNAc5 (minor). Ref.9 Ref.10 Ref.16
Polymorphism	Many different variants of ORM2 are known.
Sequence similarities	Belongs to the calycin superfamily. Lipocalin family.
Sequence caution	The sequence CAA29873.2 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAA29874.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Acute phase Transport
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
PTM	Disulfide bond Glycoprotein Pyrrolidone carboxylic acid
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	acute-phase response Traceable author statement Ref.2. Source: ProtInc regulation of immune system process Inferred from electronic annotation. Source: InterPro transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular space Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Chain

19 – 201

183

Alpha-1-acid glycoprotein 2

PRO_0000017861

Amino acid modifications

Modified residue

19

1

Pyrrolidone carboxylic acid

Glycosylation

33

1

N-linked (GlcNAc...) (complex) Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16

Glycosylation

56

1

N-linked (GlcNAc...) Ref.9 Ref.12 Ref.13 Ref.14

Glycosylation

72

1

N-linked (GlcNAc...) Ref.9 Ref.12 Ref.13

Glycosylation

93

1

N-linked (GlcNAc...) Ref.9 Ref.10 Ref.12 Ref.13 Ref.14

Glycosylation

103

1

N-linked (GlcNAc...) Ref.9 Ref.13 Ref.14

CAR_000171

Disulfide bond

23 ↔ 165

Ref.8 Ref.17

Disulfide bond

90 ↔ 183

Ref.8 Ref.17

Natural variations

Natural variant

38

1

R → Q.
Corresponds to variant rs17650 [ dbSNP | Ensembl ].

VAR_014667

Natural variant

99

1

V → A.
Corresponds to variant rs2636889 [ dbSNP | Ensembl ].

VAR_050172

Natural variant

141

1

G → R.
Corresponds to variant rs12685968 [ dbSNP | Ensembl ].

VAR_050173

Natural variant

167

1

C → R. Ref.17
Corresponds to variant rs1126777 [ dbSNP | Ensembl ].

VAR_050174

Natural variant

174

1

M → V.
Corresponds to variant rs2636890 [ dbSNP | Ensembl ].

VAR_050175

Experimental info

Sequence conflict

32

1

T → I in CAG33211. Ref.4

Sequence conflict

102

1

E → D in BAG35159. Ref.3

Sequence conflict

125

1

T → I in BAG35159. Ref.3

Sequence conflict

162

1

A → V in BAG35159. Ref.3

Sequence conflict

189

1

Q → H in BAG35159. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

201

Helix Strand Turn

Details...

Turn

20 – 23

4

Helix

24 – 26

3

Helix

33 – 39

7

Beta strand

41 – 51

11

Helix

53 – 60

8

Beta strand

62 – 72

11

Turn

73 – 76

4

Beta strand

77 – 86

10

Beta strand

89 – 100

12

Turn

101 – 104

4

Beta strand

105 – 110

6

Beta strand

113 – 120

8

Beta strand

127 – 133

7

Turn

137 – 139

3

Beta strand

141 – 150

10

Helix

153 – 165

13

Helix

170 – 172

3

Helix

178 – 180

3

Helix

184 – 191

8

Sequences

	Sequence		Length	Mass (Da)
	P19652 [UniParc]. Last modified April 1, 1993. Version 2. Checksum: 49167ABCC22933B9	FASTA	201	23,603
	10 20 30 40 50 60 MALSWVLTVL SLLPLLEAQI PLCANLVPVP ITNATLDRIT GKWFYIASAF RNEEYNKSVQ 70 80 90 100 110 120 EIQATFFYFT PNKTEDTIFL REYQTRQNQC FYNSSYLNVQ RENGTVSRYE GGREHVAHLL 130 140 150 160 170 180 FLRDTKTLMF GSYLDDEKNW GLSFYADKPE TTKEQLGEFY EALDCLCIPR SDVMYTDWKK 190 200 DKCEPLEKQH EKERKQEEGE S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and expression of the genes coding for human alpha 1-acid glycoprotein." Dente L., Pizza M.G., Metspalu A., Cortese R. EMBO J. 6:2289-2296(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Structure and characterisation of a duplicated human alpha 1 acid glycoprotein gene." Merritt C.M., Board P.G. Gene 66:97-106(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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]. Tissue: Liver.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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]. Tissue: Skeletal muscle.
[8]	"The disulfide bonds of alpha1-acid glycoprotein." Schmid K., Buergi W., Collins J.H., Nanno S. Biochemistry 13:2694-2697(1974) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS.
[9]	"Analysis of the five glycosylation sites of human alpha 1-acid glycoprotein." Treuheit M.J., Costello C.E., Halsall H.B. Biochem. J. 283:105-112(1992) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-33; ASN-56; ASN-72; ASN-93 AND ASN-103.
[10]	"A new strategy for identification of N-glycosylated proteins and unambiguous assignment of their glycosylation sites using HILIC enrichment and partial deglycosylation." Hagglund P., Bunkenborg J., Elortza F., Jensen O.N., Roepstorff P. J. Proteome Res. 3:556-566(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PYROGLUTAMATE FORMATION AT GLN-19, GLYCOSYLATION AT ASN-33 AND ASN-93, MASS SPECTROMETRY.
[11]	"A proteomic analysis of human bile." Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H., Thuluvath P.J., Argani P., Goggins M.G., Maitra A., Pandey A. Mol. Cell. Proteomics 3:715-728(2004) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-33, MASS SPECTROMETRY. Tissue: Bile.
[12]	"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry." Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R. Proteomics 4:454-465(2004) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-33; ASN-56; ASN-72 AND ASN-93, MASS SPECTROMETRY. Tissue: Plasma.
[13]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-33; ASN-56; ASN-72; ASN-93 AND ASN-103, MASS SPECTROMETRY. Tissue: Plasma.
[14]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-33; ASN-56; ASN-93 AND ASN-103, MASS SPECTROMETRY. Tissue: Liver.
[15]	"Enrichment of glycopeptides for glycan structure and attachment site identification." Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G. Nat. Methods 6:809-811(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-33, STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY. Tissue: Cerebrospinal fluid.
[16]	"Human urinary glycoproteomics; attachment site specific analysis of N-and O-linked glycosylations by CID and ECD." Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G. Mol. Cell. Proteomics 0:0-0(2011) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-33, STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY.
[17]	"Structural insights into differences in drug-binding selectivity between two forms of human {alpha}1-acid glycoprotein genetic variants, the A and F1*S forms." Nishi K., Ono T., Nakamura T., Fukunaga N., Izumi M., Watanabe H., Suenaga A., Maruyama T., Yamagata Y., Curry S., Otagiri M. J. Biol. Chem. 286:14427-14434(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 19-201 OF VARIANT ARG-167 IN COMPLEXES WITH DISOPYRAMIDE; AMITRIPTYLINE AND CHLORPROMAZINE, FUNCTION, DISULFIDE BONDS, DOMAIN.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X06675 Genomic DNA. Translation: CAA29874.1. Sequence problems.
X05780 Genomic DNA. No translation available.
X06674 , X06676, X06677, X06678, X06679, X06680 Genomic DNA. Translation: CAA29873.2. Sequence problems.
X05784 Genomic DNA. No translation available.
M21540 Genomic DNA. Translation: AAA51549.1.
AK312226 mRNA. Translation: BAG35159.1.
CR456930 mRNA. Translation: CAG33211.1.
AL356796 Genomic DNA. Translation: CAI16860.1.
CH471090 Genomic DNA. Translation: EAW87417.1.
BC015964 mRNA. Translation: AAH15964.1.
BC056239 mRNA. Translation: AAH56239.1.

IPI

IPI00020091.

PIR

OMHU2. JT0326.

RefSeq

NP_000599.1. NM_000608.2.

UniGene

Hs.719954.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3APU	X-ray	2.10	A/B	19-201	[»]
3APV	X-ray	2.15	A/B	19-201	[»]
3APW	X-ray	2.20	A/B	19-201	[»]
3APX	X-ray	2.20	A	19-201	[»]

ProteinModelPortal

P19652.

ModBase

Search...

Protein-protein interaction databases

IntAct

P19652. 3 interactions.

STRING

9606.ENSP00000394936.

PTM databases

GlycoSuiteDB

P19652.

PhosphoSite

P19652.

Polymorphism databases

DMDM

231458.

2D gel databases

DOSAC-COBS-2DPAGE

P19652.

SWISS-2DPAGE

P19652.

Proteomic databases

PeptideAtlas

P19652.

PRIDE

P19652.

Protocols and materials databases

DNASU

5005.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000431067; ENSP00000394936; ENSG00000228278.

GeneID

5005.

KEGG

hsa:5005.

UCSC

uc004bil.3. human.

Organism-specific databases

CTD

5005.

GeneCards

GC09P117092.

HGNC

HGNC:8499. ORM2.

HPA

HPA046438.

MIM

138610. gene.

neXtProt

NX_P19652.

PharmGKB

PA32818.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HOG000125170.

HOVERGEN

HBG000035.

InParanoid

P19652.

OMA

GSHEDEL.

OrthoDB

EOG4V9TS3.

Gene expression databases

ArrayExpress

P19652.

Bgee

P19652.

Genevestigator

P19652.

GermOnline

ENSG00000204154. Homo sapiens.

Family and domain databases

Gene3D

2.40.128.20. 1 hit.

InterPro

IPR001500. A1A_glycop.
IPR012674. Calycin.
IPR011038. Calycin-like.
IPR000566. Lipocln_cytosolic_FA-bd_dom.
[Graphical view]

PANTHER

PTHR11967. PTHR11967. 1 hit.

Pfam

PF00061. Lipocalin. 1 hit.
[Graphical view]

PIRSF

PIRSF036899. AGP. 1 hit.

PRINTS

PR00708. A1AGLPROTEIN.

SUPFAM

SSF50814. Calycin. 1 hit.

PROSITE

PS00213. LIPOCALIN. False negative.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL5958.

EvolutionaryTrace

P19652.

GenomeRNAi

5005.

NextBio

19276.

SOURCE

Search...

Entry information

Entry name

A1AG2_HUMAN

Accession

Primary (citable) accession number: P19652
Secondary accession number(s): B2R5L2 , Q16571, Q5T538, Q6IB74

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	April 1, 1993
Last modified:	May 1, 2013
This is version 140 of the entry and version 2 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.