Reviewed, UniProtKB/Swiss-Prot P02760 (AMBP_HUMAN)

Names and origin

Protein names

Recommended name:
    AMBP protein
Cleaved into the following 3 chains:
    1- Recommended name:
            Alpha-1-microglobulin
                Short name=Protein HC
        Alternative name(s):
            Complex-forming glycoprotein heterogeneous in charge
            Alpha-1 microglycoprotein
    2- Recommended name:
            Inter-alpha-trypsin inhibitor light chain
                Short name=ITI-LC
        Alternative name(s):
            Bikunin
            HI-30
            Uronic-acid-rich protein
            EDC1
    3- Recommended name:
            Trypstatin

Gene names

Name:	AMBP
Synonyms:	HCP, ITIL

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	352 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	Inter-alpha-trypsin inhibitor inhibits trypsin, plasmin, and lysosomal granulocytic elastase. Inhibits calcium oxalate crystallization. Trypstatin is a trypsin inhibitor By similarity.
Subunit structure	I-alpha-I plasma protease inhibitors are assembled from one or two heavy chains (H1, H2 or H3) and one light chain, bikunin. Inter-alpha-inhibitor (I-alpha-I) is composed of H1, H2 and bikunin, inter-alpha-like inhibitor (I-alpha-LI) of H2 and bikunin, and pre-alpha-inhibitor (P-alpha-I) of H3 and bikunin. Alpha-1-microglobulin occurs as a monomer and also in complexes with IgA and albumin. Alpha-1-microglobulin interacts with FN1. Trypstatin is a monomer and also occurs as a complex with tryptase in mast cells By similarity. Alpha-1-microglobulin and bikunin interact (via SH3 domain) with HEV ORF3 protein.
Subcellular location	Secreted.
Tissue specificity	Expressed by the liver and secreted in plasma. Alpha-1-microglobulin occurs in many physiological fluids including plasma, urine, and cerebrospinal fluid. Inter-alpha-trypsin inhibitor is present in plasma and urine.
Post-translational modification	The precursor is proteolytically processed into separately functioning proteins. 3-hydroxykynurenine, an oxidized tryptophan metabolite that is common in biological fluids, reacts with Cys-53, Lys-111, Lys-137, and Lys-149 to form heterogeneous polycyclic chromophores including hydroxanthommatin. The reaction by alpha-1-microglobulin is autocatalytic; the human protein forms chromophore even when expressed in insect and bacterial cells. The chromophore can react with accessible cysteines forming non-reducible thioether cross-links with other molecules of alpha-1-microglobulin or with other proteins such as Ig alpha-1 chain C region 'Cys-352'. Heavy chains are interlinked with bikunin via a chondroitin 4-sulfate bridge to the their C-terminal aspartate By similarity. Addition of glycosaminoglycan chondroitin sulfate, allows cross-linking between the different components.
Miscellaneous	In vitro, the first twelve residues of the amino end of the inhibitor appear to have a reactive site capable of inhibiting the activity of a number of enzymes. Its in vivo function is not known.
Sequence similarities	In the N-terminal section; belongs to the calycin superfamily. Lipocalin family. Contains 2 BPTI/Kunitz inhibitor domains.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Secreted
Domain	Repeat Signal
Ligand	Chromophore
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Cleavage on pair of basic residues Glycoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cell adhesion Non-traceable author statement. Source: UniProtKB female pregnancy Non-traceable author statement. Source: UniProtKB heme catabolic process Non-traceable author statement. Source: UniProtKB negative regulation of JNK cascade Traceable author statement. Source: UniProtKB negative regulation of immune response Non-traceable author statement. Source: UniProtKB
Cellular component	extracellular region Non-traceable author statement. Source: UniProtKB plasma membrane Inferred from direct assay. Source: UniProtKB
Molecular function	IgA binding Inferred from direct assay. Source: UniProtKB calcium channel inhibitor activity Non-traceable author statement. Source: UniProtKB calcium oxalate binding Non-traceable author statement. Source: UniProtKB heme binding Inferred from direct assay. Source: UniProtKB plasmin inhibitor activity Traceable author statement. Source: UniProtKB protein homodimerization activity Inferred from physical interaction. Source: UniProtKB trypsin inhibitor activity Traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Signal peptide

1 – 19

19

Chain

20 – 203

184

Alpha-1-microglobulin

Chain

206 – 352

147

Inter-alpha-trypsin inhibitor light chain

Chain

284 – 344

61

Trypstatin By similarity

Regions

Domain

231 – 281

51

BPTI/Kunitz inhibitor 1

Domain

287 – 337

51

BPTI/Kunitz inhibitor 2

Region

206 – 226

21

Glycopeptide (secretory piece)

Sites

Binding site

53

1

Multimeric 3-hydroxykynurenine chromophore (covalent)

Binding site

111

1

Multimeric 3-hydroxykynurenine chromophore (covalent)

Binding site

137

1

Multimeric 3-hydroxykynurenine chromophore (covalent)

Binding site

149

1

Multimeric 3-hydroxykynurenine chromophore (covalent)

Site

241 – 242

2

Inhibitory (P1) (chymotrypsin, elastase) By similarity

Site

297 – 298

2

Inhibitory (P1) (trypsin) By similarity

Amino acid modifications

Glycosylation

24

1

O-linked (GalNAc...)

Glycosylation

36

1

N-linked (GlcNAc...) (complex)

Glycosylation

115

1

N-linked (GlcNAc...) (complex)

Glycosylation

215

1

O-linked (Xyl...) (chondroitin sulfate)

Glycosylation

250

1

N-linked (GlcNAc...)

Disulfide bond

91 ↔ 188

Disulfide bond

231 ↔ 281

Disulfide bond

240 ↔ 264

Disulfide bond

256 ↔ 277

Disulfide bond

287 ↔ 337

Disulfide bond

296 ↔ 320

Disulfide bond

312 ↔ 333

Experimental info

Sequence conflict

48 – 57

10

Missing AA sequence Ref.11

Sequence conflict

57

1

Missing Ref.10 Ref.12

Sequence conflict

137

1

Missing AA sequence Ref.11

Sequence conflict

142

1

H → T AA sequence Ref.11

Sequence conflict

145

1

Missing AA sequence Ref.11

Sequence conflict

194

1

E → Q AA sequence Ref.11

Sequence conflict

215

1

S → T AA sequence Ref.18

Sequence conflict

218

1

G → T AA sequence Ref.18

Sequence conflict

291 – 292

2

IV → VI Ref.14 Ref.15

Sequence conflict

295

1

Missing AA sequence Ref.15

Sequence conflict

343

1

G → E AA sequence Ref.14

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

352

Helix Strand Turn

Details...

Beta strand

244 – 250

7

Turn

251 – 254

4

Beta strand

255 – 261

7

Beta strand

263 – 265

3

Beta strand

271 – 273

3

Helix

274 – 281

8

Helix

284 – 288

5

Beta strand

300 – 306

7

Turn

307 – 310

4

Beta strand

311 – 317

7

Beta strand

319 – 321

3

Beta strand

327 – 329

3

Helix

330 – 337

8

Sequences

	Sequence		Length	Mass (Da)
	P02760-1 [UniParc]. Last modified August 13, 1987. Version 1. Checksum: BC001780094CBD06	FASTA	352	38,999
	10 20 30 40 50 60 MRSLGALLLL LSACLAVSAG PVPTPPDNIQ VQENFNISRI YGKWYNLAIG STCPWLKKIM 70 80 90 100 110 120 DRMTVSTLVL GEGATEAEIS MTSTRWRKGV CEETSGAYEK TDTDGKFLYH KSKWNITMES 130 140 150 160 170 180 YVVHTNYDEY AIFLTKKFSR HHGPTITAKL YGRAPQLRET LLQDFRVVAQ GVGIPEDSIF 190 200 210 220 230 240 TMADRGECVP GEQEPEPILI PRVRRAVLPQ EEEGSGGGQL VTEVTKKEDS CQLGYSAGPC 250 260 270 280 290 300 MGMTSRYFYN GTSMACETFQ YGGCMGNGNN FVTEKECLQT CRTVAACNLP IVRGPCRAFI 310 320 330 340 350 QLWAFDAVKG KCVLFPYGGC QGNGNKFYSE KECREYCGVP GDGDEELLRF SN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of a full length cDNA coding for human protein HC (alpha 1 microglobulin)." Traboni C., Cortese R. Nucleic Acids Res. 14:6340-6340(1986) [PubMed: 2428011] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The mRNA for a proteinase inhibitor related to the HI-30 domain of inter-alpha-trypsin inhibitor also encodes alpha-1-microglobulin (protein HC)." Kaumeyer J.F., Polazzi J.O., Kotick M.P. Nucleic Acids Res. 14:7839-7850(1986) [PubMed: 2430261] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"Structure of the human alpha 1-microglobulin-bikunin gene." Vetr H., Gebhard W. Biol. Chem. Hoppe-Seyler 371:1185-1196(1990) [PubMed: 1708673] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Structural analysis of the human inter-alpha-trypsin inhibitor light-chain gene." Diarra-Mehrpour M., Bourguignon J., Sesboue R., Salier J.-P., Leveillard T., Martin J.-P. Eur. J. Biochem. 191:131-139(1990) [PubMed: 1696200] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Liver.
[5]	"Identification of a human cell growth inhibition gene." Kim J.W. Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[7]	"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: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	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.,