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Protein

Protein AMBP

Gene

AMBP

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

Functioni

Inter-alpha-trypsin inhibitor inhibits trypsin, plasmin, and lysosomal granulocytic elastase. Inhibits calcium oxalate crystallization.1 Publication
Trypstatin is a trypsin inhibitor.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei53 – 531Multimeric 3-hydroxykynurenine chromophore (covalent)
Binding sitei111 – 1111Multimeric 3-hydroxykynurenine chromophore (covalent)
Binding sitei137 – 1371Multimeric 3-hydroxykynurenine chromophore (covalent)
Binding sitei149 – 1491Multimeric 3-hydroxykynurenine chromophore (covalent)
Sitei241 – 2422Inhibitory (P1) (chymotrypsin, elastase)By similarity
Sitei297 – 2982Inhibitory (P1) (trypsin)By similarity

GO - Molecular functioni

  • calcium channel inhibitor activity Source: UniProtKB
  • calcium oxalate binding Source: UniProtKB
  • heme binding Source: UniProtKB
  • IgA binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • serine-type endopeptidase inhibitor activity Source: UniProtKB
  • small molecule binding Source: InterPro

GO - Biological processi

  • cell adhesion Source: UniProtKB
  • female pregnancy Source: UniProtKB
  • heme catabolic process Source: UniProtKB
  • negative regulation of immune response Source: UniProtKB
  • negative regulation of JNK cascade Source: UniProtKB
  • protein catabolic process Source: Ensembl
  • protein-chromophore linkage Source: UniProtKB-KW
  • receptor-mediated endocytosis Source: Reactome
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Keywords - Biological processi

Host-virus interaction

Keywords - Ligandi

Chromophore

Enzyme and pathway databases

ReactomeiR-HSA-2168880. Scavenging of heme from plasma.

Protein family/group databases

MEROPSiI02.005.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein AMBP
Cleaved into the following 3 chains:
Alpha-1-microglobulin
Short name:
Protein HC
Alternative name(s):
Alpha-1 microglycoprotein
Complex-forming glycoprotein heterogeneous in charge
Alternative name(s):
Bikunin
EDC1
HI-30
Uronic-acid-rich protein
Gene namesi
Name:AMBP
Synonyms:HCP, ITIL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:453. AMBP.

Subcellular locationi

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • cell surface Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
  • extracellular space Source: UniProtKB
  • intracellular membrane-bounded organelle Source: Ensembl
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA24759.

Chemistry

DrugBankiDB00062. Human Serum Albumin.
DB00064. Serum albumin iodonated.

Polymorphism and mutation databases

BioMutaiAMBP.
DMDMi122801.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 19193 PublicationsAdd
BLAST
Chaini20 – 203184Alpha-1-microglobulinPRO_0000017886Add
BLAST
Chaini206 – 352147Inter-alpha-trypsin inhibitor light chainPRO_0000017887Add
BLAST
Chaini284 – 34461TrypstatinBy similarityPRO_0000318926Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi24 – 241O-linked (GalNAc...)1 PublicationCAR_000172
Glycosylationi36 – 361N-linked (GlcNAc...) (complex)1 Publication
Disulfide bondi91 ↔ 188
Glycosylationi115 – 1151N-linked (GlcNAc...) (complex)2 Publications
Glycosylationi215 – 2151O-linked (Xyl...) (chondroitin sulfate)3 Publications
Disulfide bondi231 ↔ 281
Disulfide bondi240 ↔ 264
Glycosylationi250 – 2501N-linked (GlcNAc...) (complex)2 Publications
Disulfide bondi256 ↔ 277
Disulfide bondi287 ↔ 337
Disulfide bondi296 ↔ 320
Disulfide bondi312 ↔ 333

Post-translational modificationi

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
N- and O-glycosylated. N-glycan heterogeneity at Asn-115: Hex5HexNAc4 (major), Hex6HexNAc5 (minor) and dHex1Hex6HexNAc5 (minor). N-glycan at Asn-250: Hex5HexNAc4. O-linkage of the glycosaminoglycan, chondroitin sulfate, at Ser-215 allows cross-linking between the three polypeptide chains.5 Publications

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP02760.
PaxDbiP02760.
PeptideAtlasiP02760.
PRIDEiP02760.

2D gel databases

SWISS-2DPAGEP02760.

PTM databases

iPTMnetiP02760.
PhosphoSiteiP02760.
UniCarbKBiP02760.

Miscellaneous databases

PMAP-CutDBP02760.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiENSG00000106927.
CleanExiHS_AMBP.
ExpressionAtlasiP02760. baseline and differential.
GenevisibleiP02760. HS.

Organism-specific databases

HPAiCAB069436.
HPA001497.

Interactioni

Subunit structurei

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.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CTSBP078584EBI-2115136,EBI-715062
FHL3Q136433EBI-2115136,EBI-741101

GO - Molecular functioni

  • IgA binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi106757. 13 interactions.
IntActiP02760. 11 interactions.
MINTiMINT-1367019.
STRINGi9606.ENSP00000265132.

Structurei

Secondary structure

1
352
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi37 – 393Combined sources
Beta strandi42 – 5110Combined sources
Helixi54 – 596Combined sources
Helixi60 – 623Combined sources
Beta strandi66 – 727Combined sources
Beta strandi78 – 8710Combined sources
Beta strandi90 – 10011Combined sources
Beta strandi106 – 1116Combined sources
Turni112 – 1154Combined sources
Beta strandi116 – 12510Combined sources
Beta strandi127 – 14216Combined sources
Beta strandi145 – 15511Combined sources
Helixi159 – 17012Combined sources
Turni171 – 1733Combined sources
Helixi176 – 1783Combined sources
Beta strandi179 – 1813Combined sources
Beta strandi244 – 2507Combined sources
Turni251 – 2544Combined sources
Beta strandi255 – 2617Combined sources
Beta strandi263 – 2653Combined sources
Beta strandi271 – 2733Combined sources
Helixi274 – 2818Combined sources
Helixi284 – 2885Combined sources
Beta strandi300 – 3067Combined sources
Turni307 – 3104Combined sources
Beta strandi311 – 3177Combined sources
Beta strandi319 – 3213Combined sources
Beta strandi327 – 3293Combined sources
Helixi330 – 3378Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BIKX-ray2.50A206-352[»]
3QKGX-ray2.30A20-202[»]
4ES7X-ray2.00A27-193[»]
4U30X-ray2.50W/X/Y/Z283-340[»]
ProteinModelPortaliP02760.
SMRiP02760. Positions 28-193, 230-339.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP02760.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini231 – 28151BPTI/Kunitz inhibitor 1PROSITE-ProRule annotationAdd
BLAST
Domaini287 – 33751BPTI/Kunitz inhibitor 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni206 – 22621Glycopeptide (secretory piece)Add
BLAST

Sequence similaritiesi

In the N-terminal section; belongs to the calycin superfamily. Lipocalin family.Curated
Contains 2 BPTI/Kunitz inhibitor domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG4295. Eukaryota.
ENOG410XQNP. LUCA.
GeneTreeiENSGT00740000114929.
HOVERGENiHBG000225.
InParanoidiP02760.
OrthoDBiEOG091G09P2.
PhylomeDBiP02760.
TreeFamiTF351222.

Family and domain databases

Gene3Di2.40.128.20. 1 hit.
4.10.410.10. 2 hits.
InterProiIPR002968. A1-microglobln.
IPR029856. AMBP.
IPR012674. Calycin.
IPR011038. Calycin-like.
IPR002223. Kunitz_BPTI.
IPR002345. Lipocalin.
IPR022272. Lipocalin_CS.
IPR000566. Lipocln_cytosolic_FA-bd_dom.
IPR020901. Prtase_inh_Kunz-CS.
[Graphical view]
PANTHERiPTHR10083:SF18. PTHR10083:SF18. 1 hit.
PfamiPF00014. Kunitz_BPTI. 2 hits.
PF00061. Lipocalin. 1 hit.
[Graphical view]
PRINTSiPR01215. A1MCGLOBULIN.
PR00759. BASICPTASE.
PR00179. LIPOCALIN.
SMARTiSM00131. KU. 2 hits.
[Graphical view]
SUPFAMiSSF50814. SSF50814. 1 hit.
SSF57362. SSF57362. 2 hits.
PROSITEiPS00280. BPTI_KUNITZ_1. 2 hits.
PS50279. BPTI_KUNITZ_2. 2 hits.
PS00213. LIPOCALIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P02760-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRSLGALLLL LSACLAVSAG PVPTPPDNIQ VQENFNISRI YGKWYNLAIG
60 70 80 90 100
STCPWLKKIM DRMTVSTLVL GEGATEAEIS MTSTRWRKGV CEETSGAYEK
110 120 130 140 150
TDTDGKFLYH KSKWNITMES YVVHTNYDEY AIFLTKKFSR HHGPTITAKL
160 170 180 190 200
YGRAPQLRET LLQDFRVVAQ GVGIPEDSIF TMADRGECVP GEQEPEPILI
210 220 230 240 250
PRVRRAVLPQ EEEGSGGGQL VTEVTKKEDS CQLGYSAGPC MGMTSRYFYN
260 270 280 290 300
GTSMACETFQ YGGCMGNGNN FVTEKECLQT CRTVAACNLP IVRGPCRAFI
310 320 330 340 350
QLWAFDAVKG KCVLFPYGGC QGNGNKFYSE KECREYCGVP GDGDEELLRF

SN
Length:352
Mass (Da):38,999
Last modified:August 13, 1987 - v1
Checksum:iBC001780094CBD06
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti48 – 5710Missing AA sequence (PubMed:6164372).Curated
Sequence conflicti57 – 571Missing AA sequence (PubMed:6198962).Curated
Sequence conflicti57 – 571Missing AA sequence (Ref. 12) Curated
Sequence conflicti137 – 1371Missing AA sequence (PubMed:6164372).Curated
Sequence conflicti142 – 1421H → T AA sequence (PubMed:6164372).Curated
Sequence conflicti145 – 1451Missing AA sequence (PubMed:6164372).Curated
Sequence conflicti194 – 1941E → Q AA sequence (PubMed:6164372).Curated
Sequence conflicti215 – 2151S → T AA sequence (PubMed:7676539).Curated
Sequence conflicti218 – 2181G → T AA sequence (PubMed:7676539).Curated
Sequence conflicti291 – 2922IV → VI AA sequence (PubMed:2408638).Curated
Sequence conflicti291 – 2922IV → VI AA sequence (PubMed:1469060).Curated
Sequence conflicti295 – 2951Missing AA sequence (PubMed:1469060).Curated
Sequence conflicti343 – 3431G → E AA sequence (PubMed:2408638).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04225 mRNA. Translation: CAA27803.1.
X04494 mRNA. Translation: CAA28182.1.
X54816, X54817, X54818 Genomic DNA. Translation: CAA38585.1.
X54817 Genomic DNA. Translation: CAA38586.1.
X54818 Genomic DNA. Translation: CAA38587.1.
M88249
, M88165, M88243, M88244, M88246, M88247 Genomic DNA. Translation: AAA59196.1.
AY544123 mRNA. Translation: AAT11154.1.
AK290837 mRNA. Translation: BAF83526.1.
AL137850 Genomic DNA. Translation: CAI15899.1.
CH471090 Genomic DNA. Translation: EAW87404.1.
BC041593 mRNA. Translation: AAH41593.1.
CCDSiCCDS6800.1.
PIRiS13433. HCHU.
RefSeqiNP_001624.1. NM_001633.3.
UniGeneiHs.436911.

Genome annotation databases

EnsembliENST00000265132; ENSP00000265132; ENSG00000106927.
GeneIDi259.
UCSCiuc004bie.5. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04225 mRNA. Translation: CAA27803.1.
X04494 mRNA. Translation: CAA28182.1.
X54816, X54817, X54818 Genomic DNA. Translation: CAA38585.1.
X54817 Genomic DNA. Translation: CAA38586.1.
X54818 Genomic DNA. Translation: CAA38587.1.
M88249
, M88165, M88243, M88244, M88246, M88247 Genomic DNA. Translation: AAA59196.1.
AY544123 mRNA. Translation: AAT11154.1.
AK290837 mRNA. Translation: BAF83526.1.
AL137850 Genomic DNA. Translation: CAI15899.1.
CH471090 Genomic DNA. Translation: EAW87404.1.
BC041593 mRNA. Translation: AAH41593.1.
CCDSiCCDS6800.1.
PIRiS13433. HCHU.
RefSeqiNP_001624.1. NM_001633.3.
UniGeneiHs.436911.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BIKX-ray2.50A206-352[»]
3QKGX-ray2.30A20-202[»]
4ES7X-ray2.00A27-193[»]
4U30X-ray2.50W/X/Y/Z283-340[»]
ProteinModelPortaliP02760.
SMRiP02760. Positions 28-193, 230-339.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106757. 13 interactions.
IntActiP02760. 11 interactions.
MINTiMINT-1367019.
STRINGi9606.ENSP00000265132.

Chemistry

DrugBankiDB00062. Human Serum Albumin.
DB00064. Serum albumin iodonated.

Protein family/group databases

MEROPSiI02.005.

PTM databases

iPTMnetiP02760.
PhosphoSiteiP02760.
UniCarbKBiP02760.

Polymorphism and mutation databases

BioMutaiAMBP.
DMDMi122801.

2D gel databases

SWISS-2DPAGEP02760.

Proteomic databases

MaxQBiP02760.
PaxDbiP02760.
PeptideAtlasiP02760.
PRIDEiP02760.

Protocols and materials databases

DNASUi259.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265132; ENSP00000265132; ENSG00000106927.
GeneIDi259.
UCSCiuc004bie.5. human.

Organism-specific databases

CTDi259.
GeneCardsiAMBP.
HGNCiHGNC:453. AMBP.
HPAiCAB069436.
HPA001497.
MIMi176870. gene.
neXtProtiNX_P02760.
PharmGKBiPA24759.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4295. Eukaryota.
ENOG410XQNP. LUCA.
GeneTreeiENSGT00740000114929.
HOVERGENiHBG000225.
InParanoidiP02760.
OrthoDBiEOG091G09P2.
PhylomeDBiP02760.
TreeFamiTF351222.

Enzyme and pathway databases

ReactomeiR-HSA-2168880. Scavenging of heme from plasma.

Miscellaneous databases

EvolutionaryTraceiP02760.
GeneWikiiAlpha-1-microglobulin/bikunin_precursor.
GenomeRNAii259.
PMAP-CutDBP02760.
PROiP02760.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000106927.
CleanExiHS_AMBP.
ExpressionAtlasiP02760. baseline and differential.
GenevisibleiP02760. HS.

Family and domain databases

Gene3Di2.40.128.20. 1 hit.
4.10.410.10. 2 hits.
InterProiIPR002968. A1-microglobln.
IPR029856. AMBP.
IPR012674. Calycin.
IPR011038. Calycin-like.
IPR002223. Kunitz_BPTI.
IPR002345. Lipocalin.
IPR022272. Lipocalin_CS.
IPR000566. Lipocln_cytosolic_FA-bd_dom.
IPR020901. Prtase_inh_Kunz-CS.
[Graphical view]
PANTHERiPTHR10083:SF18. PTHR10083:SF18. 1 hit.
PfamiPF00014. Kunitz_BPTI. 2 hits.
PF00061. Lipocalin. 1 hit.
[Graphical view]
PRINTSiPR01215. A1MCGLOBULIN.
PR00759. BASICPTASE.
PR00179. LIPOCALIN.
SMARTiSM00131. KU. 2 hits.
[Graphical view]
SUPFAMiSSF50814. SSF50814. 1 hit.
SSF57362. SSF57362. 2 hits.
PROSITEiPS00280. BPTI_KUNITZ_1. 2 hits.
PS50279. BPTI_KUNITZ_2. 2 hits.
PS00213. LIPOCALIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAMBP_HUMAN
AccessioniPrimary (citable) accession number: P02760
Secondary accession number(s): P00977
, P02759, P78491, Q2TU33, Q5TBD7, Q9UC58, Q9UDI8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: August 13, 1987
Last modified: September 7, 2016
This is version 197 of the entry and version 1 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

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.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.